One-year efficacy and safety of routine prasugrel in patients with acute coronary syndromes treated with percutaneous coronary intervention

Objective: To investigate 1‑year outcomes with routine prasugrel treatment after acute coronary syndrome (ACS) in a large-scale registry. Methods: The Rijnmond Collective Cardiology Research registry is a prospective, observational study that enrolled 4,258 consecutive ACS patients treated with percutaneous coronary intervention (PCI) with 1‑year follow-up. Patients received prasugrel as first-choice antiplatelet agent, except for increased bleeding risk patients in which clopidogrel was recommended. Events were validated by an independent clinical endpoint committee. Results: A total number of 2,677 patients received prasugrel at discharge after the index event. Eighty-one percent of the target population was on prasugrel treatment at hospital discharge. At 1 year, the primary endpoint, a composite of all-cause mortality and myocardial infarction, occurred in 2.4% of patients receiving prasugrel. All-cause mortality occurred in 1.0%, myocardial infarction in 1.5%, target-vessel revascularisation in 3.1%, stent thrombosis in 0.6%, and stroke in 0.5% of the patients treated with prasugrel. Thrombolysis in Myocardial Infarction defined major bleeding episodes not related to coronary artery bypass grafting were observed in 1.4% of patients receiving prasugrel. Conclusions: In routine practice, a tailored approach of prasugrel prescription in ACS patients undergoing PCI, resulted in low ischaemic and low bleeding rates up to 1 year post PCI

Development and measurement of guidelines-based quality indicators of caesarean section care in the Netherlands: A RAND-modified delphi procedure and retrospective medical chart review

Background There is an ongoing discussion on the rising CS rate worldwide. Suboptimal guideline adherence may be an important contributor to this rise. Before improvement of care can be established, optimal CS care in different settings has to be defined. This study aimed to develop and measure quality indicators to determine guideline adherence and identify target groups for improvement of care with direct effect on caesarean section (CS) rates. Method Eighteen obstetricians and midwives participated in an expert panel for systematic CS quality indicator development according to the RAND-modified Delphi method. A multi-center study was performed and medical charts of 1024 women with a CS and a stratified and weighted randomly selected group of 1036 women with a vaginal delivery were analysed. Quality indicator frequency and adherence were scored in 2060 women with a CS or vaginal delivery. Results The expert panel developed 16 indicators on planned CS and 11 indicators on unplanned CS. Indicator adherence was calculated, defined as the number of women in a specific obstetrical situation in which care was performed as recommended in both planned and unplanned CS settings. The most frequently occurring obstetrical situations with low indicator adherence were: 1) suspected fetal distress (frequency 17%, adh

Is routine karyotyping required in prenatal samples with a molecular or metabolic referral?

As a routine, karyotyping of invasive prenatal samples is performed as an adjunct to referrals for DNA mutation detection and metabolic testing. We performed a retrospective study on 500 samples to assess the diagnostic value of this procedure. These samples included 454 (90.8%) chorionic villus (CV) and 46 (9.2%) amniocenteses specimens. For CV samples karyotyping was based on analyses of both short-term culture (STC) and long-term culture (LTC) cells. Overall, 19 (3.8%) abnormal karyotypes were denoted: four with a common aneuploidy (trisomy 21, 18 and 13), two with a sex chromosomal aneuploidy (Klinefelter syndrome), one with a sex chromosome mosaicism and twelve with various autosome mosaicisms. In four cases a second invasive test was performed because of an abnormal finding in the STC. Taken together, we conclude that STC and LTC karyotyping has resulted in a diagnostic yield of 19 (3.8%) abnormal cases, including 12 cases (2.4%) with an uncertain significance. From a diagnostic point of view, it is desirable to limit uncertain test results as secondary test findings. Therefore, we recommend a more targeted assay, such as e.g. QF-PCR, as a replacement of the STC and to provide parents the autonomy to choose between karyotyping and QF-PCR

Biologically relevant effects of mRNA amplification on gene expression profiles

BACKGROUND: Gene expression microarray technology permits the analysis of global gene expression profiles. The amount of sample needed limits the use of small excision biopsies and/or needle biopsies from human or animal tissues. Linear amplification techniques have been developed to increase the amount of sample derived cDNA. These amplified samples can be hybridised on microarrays. However, little information is available whether microarrays based on amplified and unamplified material yield comparable results. In the present study we compared microarray data obtained from amplified mRNA derived from biopsies of rat cardiac left ventricle and non-amplified mRNA derived from the same organ. Biopsies were linearly amplified to acquire enough material for a microarray experiment. Both amplified and unamplified samples were hybridized to the Rat Expression Set 230 Array of Affymetrix. RESULTS: Analysis of the microarray data showed that unamplified material of two different left ventricles had 99.6% identical gene expression. Gene expression patterns of two biopsies obtained from the same parental organ were 96.3% identical. Similarly, gene expression pattern of two biopsies from dissimilar organs were 92.8% identical to each other. Twenty-one percent of reporters called present in parental left ventricular tissue disappeared after amplification in the biopsies. Those reporters were predominantly seen in the low intensity range. Sequence analysis showed that reporters that disappeared after amplification had a GC-content of 53.7+/-4.0%, while reporters called present in biopsy- and whole LV-samples had an average GC content of 47.8+/-5.5% (P <0.001). Those reporters were also predicted to form significantly more (0.76+/-0.07 versus 0.38+/-0.1) and longer (9.4+/-0.3 versus 8.4+/-0.4) hairpins as compared to representative control reporters present before and after amplification. CONCLUSION: This study establishes that the gene expression profile obtained after amplification of mRNA of left ventricular biopsies is representative for the whole left ventricle of the rat heart. However, specific gene transcripts present in parental tissues were undetectable in the minute left ventricular biopsies. Transcripts that were lost due to the amplification process were not randomly distributed, but had higher GC-content and hairpins in the sequence and were mainly found in the lower intensity range which includes many transcription factors from specific signalling pathways

Sex-Related Bleeding Risk in Acute Coronary Syndrome Patients Receiving Dual Antiplatelet Therapy with Aspirin and a P2Y12 Inhibitor

Objective: The aim of this work was to study sex differences in major bleeding risk in relation to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Methods and Results: The Rijnmond Collective Cardiology Research registry was designed to evaluate the application and outcomes of DAPT after ACS/PCI in the Rijnmond region in the Netherlands. Overall, 1,172 women (median age 67.5 years) and 3,087 men (median age 62.2 years) with ACS/PCI were enrolled between August 2011 and June 2013. Based on a tailored regional DAPT guideline aiming at bleeding risk minimization, 52.6% women and 66.9% men received prasugrel as first-choice P2Y12 inhibitor, in addition to aspirin. Women more frequently had contraindications for the use of prasugrel (and therefore received clopidogrel) than men (47.9 vs. 26.9%, p < 0.001). Femoral access was more common in women than in men (47.6 vs. 38.1%, p < 0.001). Women had higher incidence of major bleeding at 1 year than men (2.6 vs. 1.6%, p = 0.018). After adjustment for established bleeding risk factors, female sex was associated with over two-fold higher risk of major bleeding (adjusted hazard ratio 2.33; 95% confidence interval 1.26-4.32). This difference was apparent at discharge and appeared to be caused by access site bleedings (0.9 vs. 0.1%, p < 0.001). No sex differences were found in non-access site-related major bleeding up to 1 year. Conclusion: Women with ACS/PCI receiving DAPT had higher major bleeding risk caused by an excess in access site bleeds, mainly in relation to the femoral approach

Ontwikkeling van een meetlat voor immuuncompetentie in varkens, vleeskuikens en vleeskalveren

Het doel van dit project is om een “meetlat” te ontwikkelen die de effecten van (voedings)interventies gericht op de verbetering van de immuuncompetentie van varkens, pluimvee en vleeskalveren kan vaststellen. Immuuncompetentie is binnen dit project gedefinieerd als het vermogen van dieren om effectieve responsen van het immuunsysteem te tonen op het moment dat de gezondheid van het dier onder druk wordt gezet. Een meetlat voor immuuncompetentie kan in de toekomst door de diervoedingssector gebruikt worden bij de ontwikkeling en evaluatie van nieuwe voerconcepten, ingrediënten en additieven gericht op de verbetering en ondersteuning van diergezondheid. Het is bekend dat de samenstelling van de voeding van jonge dieren invloed heeft op de functionele ontwikkeling van het maagdarmkanaal en op de samenstelling van de daarin aanwezige microbiota. De interacties tussen de microbiota en de weefsels van het darmkanaal (cross talk) hebben een belangrijke invloed op de ontwikkeling van immuuncompetentie. Daarom wordt in dit project gefocust op de effecten van (voedings)interventies op de microbiota, genexpressie veranderingen in darmweefsel, en morfologische en immunologische veranderen in de darm. De hier gepresenteerde meetlat voor immuuncompetentie is gebaseerd op de resultaten van onderzoek binnen het VDI programma van Feed4Foodure (projecten VDI-11; vleeskuikens, VDI-12; biggen, VDI- 13; gespeende biggen en kalveren) waarin m.b.v. model interventies de effecten van variatie in voersamenstelling op de microbiota samenstelling in het darmkanaal, de biologische responsen van darmweefsel en de zoötechnische dierprestaties zijn onderzocht. In de hier gepresenteerde meetlat worden gemeten effecten in deze studies aan elkaar gerelateerd en functioneel inzichtelijk gemaakt. Dit rapport beschrijft de ontwikkeling en totstandkoming van een eerste versie van de meetlat. Hierbij worden gemaakte keuzes, beperkingen en mogelijkheden van de meetlat bediscussieerd. Tenslotte wordt inzicht gegeven in de mogelijkheden tot verdere verfijningen en de toepasbaarheid van de meetlat

Improving Distributed Intelligence in Complex Innovation Systems

Science and technology (S&T) are considered to be a central source, or at least a basic medium, of societal and industrial innovation, while innovation is conceived to basically feed the regeneration of our welfare. The suppliers of S&T in Europe as well as the users of their „products“, are confronted with a number of challenges today. We want to stress here that it was not the primary goal of our Advanced Science & Technology Policy Planning (ASTPP) Network to come up with proposals how the strategic character of European S&T policies could be strengthened. The ASTPP-network instead focuses on one aspect: the provision of strategic intelligence necessary to identify and develop strategic choices. The underlying hypothesis is that the existing body of experiences with technology foresight, technology assessment and S/T policy evaluation provides a basis for the development of an advanced S&T policy „planning“ approach by trying to enhance, interlink or even integrate the growing, but still dispersed experience in these three areas of intelligence. By „intelligent“ we mean that the inter-relatedness of S&T, industrial efforts, societal needs and political interventions becomes more transparent so that interactive collaboration between them will be facilitated