Cost-effectiveness of Transcatheter Mitral Valve Leaflet Repair for the Treatment of Mitral Regurgitation in Heart Failure

Contexte: La régurgitation mitrale (RM) est une maladie valvulaire nécessitant une intervention dans les cas les plus grave. Une réparation percutanée de la valve mitrale avec le dispositif MitraClip est un traitement sécuritaire et efficace pour les patients à haut risque chirurgical. Nous voulons évaluer les résultats cliniques et l'impact économique de cette thérapie par rapport à la gestion médicale des patients en insuffisance cardiaque avec insuffisance mitrale symptomatique. Méthodes: L'étude a été composée de deux phases; une étude d'observation de patients souffrant d'insuffisance cardiaque et de régurgitation mitrale traitée avec une thérapie médicale ou le MitraClip, et un modèle économique. Les résultats de l'étude observationnelle ont été utilisés pour estimer les paramètres du modèle de décision, qui a estimé les coûts et les avantages d'une cohorte hypothétique de patients atteints d'insuffisance cardiaque et insuffisance mitrale sévère traitée avec soit un traitement médical standard ou MitraClip. Résultats: La cohorte de patients traités avec le système MitraClip était appariée par score de propension à une population de patients atteints d'insuffisance cardiaque, et leurs résultats ont été comparés. Avec un suivi moyen de 22 mois, la mortalité était de 21% dans la cohorte MitraClip et de 42% dans la cohorte de gestion médicale (p = 0,007). Le modèle de décision a démontré que MitraClip augmente l'espérance de vie de 1,87 à 3,60 années et des années de vie pondérées par la qualité (QALY) de 1,13 à 2,76 ans. Le coût marginal était 52.500 $ dollars canadiens, correspondant à un rapport coût-efficacité différentiel (RCED) de 32,300.00 $ par QALY gagné. Les résultats étaient sensibles à l'avantage de survie. Conclusion: Dans cette cohorte de patients atteints d'insuffisance cardiaque symptomatique et d insuffisance mitrale significative, la thérapie avec le MitraClip est associée à une survie supérieure et est rentable par rapport au traitement médical.

An Assessment of the Penalties System for Infringements of EU Competition Law: Can Personal Sanctions be the Missing Piece of the Puzzle? IES WORKING PAPER 6/2013

Competition law seeks to protect competition on the market as a means of enhancing consumer welfare and of ensuring an efficient allocation of resources. In order to be successful, therefore, competition authorities should be adequately equipped and have at their disposal all necessary enforcement tools. However, at the EU level the current enforcement system of competition rules allows only for the imposition of administrative fines by the European Commission to liable undertakings. The main objectives, in turn, of an enforcement policy based on financial penalties are two fold: to impose sanctions on infringing undertakings which reflect the seriousness of the violation, and to ensure that the risk of penalties will deter both the infringing undertakings (often referred to as 'specific deterrence') and other undertakings that may be considering anti-competitive activities from engaging in them (often referred to as 'general deterrence'). In all circumstances, it is important to ensure that pecuniary sanctions imposed on infringing undertakings are proportionate and not excessive. Although pecuniary sanctions against infringing undertakings are a crucial part of the arsenal needed to deter competition law violations, they may not be sufficient. One alternative option in that regard is the strategic use of sanctions against the individuals involved in, or responsible for, the infringements. Sanctions against individuals are documented to focus the minds of directors and employees to comply with competition rules as they themselves, in addition to the undertakings in which they are employed, are at risk of infringements. Individual criminal penalties, including custodial sanctions, have been in fact adopted by almost half of the EU Member States. This is a powerful tool but is also limited in scope and hard to implement in practice mostly due to the high standards of proof required and the political consensus that needs first to be built. Administrative sanctions for individuals, on the other hand, promise to deliver up to a certain extent the same beneficial results as criminal sanctions whilst at the same time their adoption is not likely to meet strong opposition and their implementation in practice can be both efficient and effective. Directors’ disqualification, in particular, provides a strong individual incentive for each member, or prospective member, of the Board as well as other senior executives, to take compliance with competition law seriously. It is a flexible and promising tool that if added to the arsenal of the European Commission could bring balance to the current sanctioning system and that, in turn, would in all likelihood make the enforcement of EU competition rules more effective. Therefore, it is submitted that a competition law regime in order to be effective should be able to deliver policy objectives through a variety of tools, not simply by imposing significant pecuniary sanctions to infringing undertakings. It is also clear that individual sanctions, mostly of an administrative nature, are likely to play an increasingly important role as they focus the minds of those in business who might otherwise be inclined to regard infringing the law as a matter of corporate risk rather than of personal risk. At the EU level, in particular, the adoption of directors’ disqualification promises to deliver more effective compliance and greater overall economic impact.

The Political Response of Firms to the 1992 Single Market Program: The Case of the German Automobile Industry Pamela Camer. CES Germany & Europe Working Papers, No. 03.1, 1994

This paper examines the political responses of German automobile firms to the 1992 Single Market initiative. I argue that the decision by firms to try to influence EC policies depends on the perceived economic impact of the single market and ,the market alternative open to firms, while the decision on how to lobby depends on the size of the finn and the institutional and strategic environment in which a firm operates. I use this framework to explain why German automobile firms were slow in responding the single market initiative and why, when they did choose to lobby, the firms pursued different political strategies. The research suggests that we should not limit our studies to the political activity of trade associations and sectors, but should also examine the political strategies and activities of individual firms. It also suggests that, as integration efforts in Europe proceed, there is likely to be increased activity by individual firms and national associations because European trade associations may not be able to agree on specific EC policy proposals.

The Geostrategic Implications of TTIP. CEPS Special Report No. 105/April 2015

This paper analyses the strategic considerations that define the perceived need for transatlantic renewal, and examines the geo-economic impact of the Transatlantic Trade and Investment Partnership (TTIP) on both emerging powers and poorer countries. It argues that TTIP has the potential to be a catalyst for trade liberalisation at the global level, as long as the US and the EU are proactive about making the ‘open architecture’ of TTIP a reality.

Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs) previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for therapy of bovine and canine neosporosis.

The Performance of Swiss and German Family Firms: Investigating Strategies, Orientations and SEW as Determinants

In this chapter we center our attention on the performance drivers of family firms in Switzerland and Germany and compare the corresponding results with the findings generated in the US. Investigating family firms is justified as this organizational form not only constitutes the majority of all firms globally (Sharma and Carney, 2012), but in particular in Switzerland and Germany. In fact, more than 88 percent of all firms in Switzerland are defined as family firms (Frey, Halter, Klein, and Zellweger, 2004), and numbers for Germany are similar (Klein, 2000). While more than 99 percent of all companies in Switzerland are small and medium-sized (Frey et al., 2004), the share of family firms varies with firm size; more specifically, the share of family firms decreases with increasing firm size, which is in line with findings from Germany (Klein, 2000). The social and economic impact of family firms is remarkable. In Germany for instance, family controlled firms provide 60 percent of all jobs and account for 51 percent of the total sales of the German economy (cf. www.familienunternehmen.de). Even though the interest of both academics and practitioners in family firms has been rising significantly in recent years, the existing body of knowledge in the field is still rather fragmented (Sharma, 2004; Sharma and Carney, 2012).

An investigation of truck size and weight limits - technical supplement. Volume 2: truck and rail cost effects of truck size and weight limits. Final report.

Transportation Department, Office of the Assistant Secretary for Policy and International Affairs, Washington, D.C.

Highways and the economy. Final report.

Federal Highway Administration, Office of Program and Policy Planning, Washington, D.C.

Effects of regulatory reform on unemployment in the trucking industry. Report to the Honorable Dennis DeConcini, United States Senate.

Mode of access: Internet.

Final regulatory analysis of the model year 1982 light truck fuel economy standards.

Mode of access: Internet.

Terror Lake project, no. 2743 - Alaska : applicant, Kodiak Electric Association, Inc. /

"August 1981."

Rulemaking support paper - light truck fuel economy standards - model year 1981.

Mode of access: Internet.

The contributions of automotive regulation. Preliminary report.

Mode of access: Internet.

Market analysis and consumer impacts source document. Part I: the motor vehicle market in the late 1970's. Final report.

National Highway Traffic Safety Administration, Office of Research and Development, Washington, D.C.

Market analysis and consumer impacts source document. Part II: review of motor vehicle market and consumer expenditures on motor vehicle transportation. Final report.

National Highway Traffic Safety Administration, Office of Research and Development, Washington, D.C.