4 research outputs found
European regulation on orphan medicinal products: 10 years of experience and future perspectives.
In 2000, regulation on orphan medicinal products was adopted in the European Union with the aim of benefiting patients who suffer from serious, rare conditions for which there is currently no satisfactory treatment. Since then, more than 850 orphan drug designations have been granted by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products (COMP), and more than 60 orphan drugs have received marketing authorization in Europe. Here, stimulated by the tenth anniversary of the COMP, we reflect on the outcomes and experience gained in the past decade, and contemplate issues for the future, such as catalysing drug development for the large number of rare diseases that still lack effective treatments
Large-scale gene-centric analysis identifies novel variants for coronary artery disease.
Coronary artery disease (CAD) has a significant genetic contribution that is
incompletely characterized. To complement genome-wide association (GWA) studies,
we conducted a large and systematic candidate gene study of CAD susceptibility,
including analysis of many uncommon and functional variants. We examined 49,094
genetic variants in 3c2,100 genes of cardiovascular relevance, using a customised
gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733
controls of European descent; 4,394 cases and 4,259 controls of South Asian
origin). We attempted to replicate putative novel associations in an additional
17,121 CAD cases and 40,473 controls. Potential mechanisms through which the
novel variants could affect CAD risk were explored through association tests with
vascular risk factors and gene expression. We confirmed associations of several
previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19);
1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2,
ZC3HC1, CYP17A1:p<5
710(-7)). However, we found essentially null results for most
previously suggested CAD candidate genes. In our replication study of 24
promising common variants, we identified novel associations of variants in or
near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk
with each of the novel variants ranging from 1.06-1.09. Associations with
variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data
or effects on lipid levels. Apart from the previously reported variants in LPA,
none of the other 3c4,500 low frequency and functional variants showed a strong
effect. Associations in South Asians did not differ appreciably from those in
Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27
respectively; P for heterogeneity\u200a=\u200a0.003). This large-scale gene-centric
analysis has identified several novel genes for CAD that relate to diverse
biochemical and cellular functions and clarified the literature with regard to
many previously suggested genes
Garantenstellung des Wohnungsinhabers bei Angriffen auf einen Gast
Garantenstellung des Wohnungsinhabers bei Angriffen auf einen Gast. - In: Juristische Schulung. 18. 1978. S. 308-31
Risk factors for unfavourable postoperative outcome in patients with Crohn's disease undergoing right hemicolectomy or ileocaecal resection. An international audit by ESCP and S-ECCO
Aim: Patient- and disease-related factors, as well as operation technique, all have the potential to impact on postoperative outcome in Crohn's disease. The available evidence is based on small series and often displays conflicting results. The aim was to investigate the effect of preoperative and intra-operative risk factors on 30-day postoperative outcome in patients undergoing surgery for Crohn's disease. Method: This was an international prospective snapshot audit including consecutive patients undergoing right hemicolectomy or ileocaecal resection. The study analysed a subset of patients who underwent surgery for Crohn's disease. The primary outcome measure was the overall Clavien\u2013Dindo postoperative complication rate. The key secondary outcomes were anastomotic leak, reoperation, surgical site infection and length of stay in hospital. Multivariable binary logistic regression analyses were used to produce odds ratios and 95% confidence intervals. Results: In all, 375 resections in 375 patients were included. The median age was 37 and 57.1% were women. In multivariate analyses, postoperative complications were associated with preoperative parenteral nutrition (OR 2.36, 95% CI 1.10\u20134.97), urgent/expedited surgical intervention (OR 2.00, 95% CI 1.13\u20133.55) and unplanned intra-operative adverse events (OR 2.30, 95% CI 1.20\u20134.45). The postoperative length of stay in hospital was prolonged in patients who received preoperative parenteral nutrition (OR 31, 95% CI 1.08\u20131.61) and those who had urgent/expedited operations (OR 1.21, 95% CI 1.07\u20131.37). Conclusion: Preoperative parenteral nutritional support, urgent/expedited operation and unplanned intra-operative adverse events were associated with unfavourable postoperative outcome. Enhanced preoperative optimization and improved planning of operation pathways and timings may improve outcomes for patients