Reform of the EU Institutions: Implications for the EU’s Performance in Climate Negotiations. CEPS Policy Brief No. 40, September 2003

This CEPS Policy Brief assesses the potential impact of the draft Constitutional Treaty of the Convention on the Future of Europe on the way the EU operates in international climate negotiations. Although Treaty revisions in the EU are ultimately decided by the EU member states, the Convention’s draft can be seen as an important blueprint that forms the starting point of the negotiations between the member states due to start in October 2003. Among the relevant issues that the authors identify are: A change in the number and form of the Council of Ministers formations. There is a chance that the Environment Council as it exists today will be changed, since most of its agenda – the adoption of legislation – will be transferred to the proposed Legislative Council. The transfer of remaining issues such as decision-making on multilateral environmental agreements to the Foreign Affairs Council or to an ‘Internal Market Council’ might offer some new perspectives, but it might also lead to a loss of environmental knowledge; The establishment of a Union Minister of Foreign Affairs (with a European External Action Service). Involvement of the Foreign Minister could offer an opportunity for more integration of foreign policy aspects in the EU’s position for climate change negotiations; Changes regarding the rotating Presidency. Currently the rotating Presidency has an important role in both preparing and negotiating the EU’s position in the climate negotiations. The proposal of a longer-term chair of the Council of Ministers (at least one year) is likely to increase the consistency of EU negotiation positions; More transparent procedures on how the Council of Ministers nominates the negotiator or leader of the Union’s negotiating team (Art III-227). The paper concludes that the Convention’s draft Constitution offers some interesting proposals that could lead to more integration of the broader range of external policies into the EU’s position for climate negotiations. Furthermore, there might be improvements related to the consistency of the EU’s position

Portugal and the Netherlands: punching above their weight?

This chapter explores attitudes and actions of Greek and Slovenian diplomacies towards the European External Action Service (EEAS). It examines the two countries' attitudes towards the EEAS, its leadership and its relations with other institutional actors, including the national diplomacies. The core objective of Slovenian foreign policy after gaining independence was to consolidate its place in the Euro-Atlantic security community in order to deflect any potential security threat from its immediate neighbourhood. The only new area in which there has been significant potential for Greece has been in regional energy cooperation given the discovery of energy resources in the eastern Mediterranean. Slovenia and Greece share a foreign policy goal, namely to ensure the European Union (EU) perspective of the countries of Southeast Europe. The empirical research we conducted suggested that the Hellenic Ministry of Foreign Affairs is currently still in the process of accustoming itself with the operation of the EEAS

Upholding the World Health Organization: Next steps for the EU

Before the COVID-19 pandemic, the European Union (EU) was neither a strong pro­moter of global health nor a strong supporter of the World Health Organization (WHO). The Global Health Council Conclusions from 2010 were never comprehensively implemented and quickly forgotten. With the pandemic greatly affecting EU member states, the EU is increasingly interested in upholding multilateral cooperation in the global health field. Therefore, the EU should aim for an upgrading of the EU’s status in WHO, the establishment of a global health unit in the European External Action Service (EEAS), and an overhaul of the formal relationship between the European Com­mission and WHO. (Autorenreferat

Policy Coherence for Development in the EU Council: Strategies for the Way Forward. CEPS Paperbacks. July 2006

In recognition of the fact that EU policies in non-development areas, such as trade, energy and migration, can also profoundly affect the poor in developing countries, the EU has affirmed ‘Policy Coherence for Development’ as an important principle for achieving more effective development cooperation. This new CEPS study analyses whether policy-making processes in the EU Council provide sufficient scope for development inputs to be made in 12 key policy areas: trade, environment, climate change, security, agriculture, fisheries, social dimension of globalisation, employment and decent work, migration, research and innovation, information society, transport and energy. The study also includes coverage of the policy-making processes in the European Commission as it initiates and defends most of the policies being discussed in the EU Council. Its findings point to the highly segregated character of EU policy-making and provide interesting insights into the internal challenges the EU will need to address in order to fulfil its goal of achieving greater coherency in its (external) policy-making. To strengthen the potential for PCD the study suggests six proposals for structural reform as well as a set of specific recommendations

Unterstützung für die Weltgesundheitsorganisation: welche Schritte die EU als Nächstes einleiten sollte

Vor der Covid‑19-Pandemie galt die Europäische Union (EU) weder als Motor für globale Gesundheit noch als bedeutende Unterstützerin der Weltgesundheits­organisation (WHO). 2010 verabschiedete der Rat der EU Schlussfolgerungen zur Rolle der Union im Bereich globaler Gesundheit; sie gerieten in Vergessenheit und wurden nie umfassend umgesetzt. Da einige EU-Mitglied­staaten zu den besonders von der Pandemie betroffenen Ländern gehören, ist die EU verstärkt an multilateraler Zusammenarbeit auf dem Gebiet der globalen Gesundheit interessiert. Drei Dinge könnten dafür hilfreich sein: eine Auf­wertung ihres Status in der WHO, die Einrichtung eines Referats für globale Gesundheit im Europäischen Auswärtigen Dienst (EAD) sowie eine Überarbeitung der formellen Beziehungen zwischen EU und WHO. (Autorenreferat

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: Recent developments and ethnic considerations

Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression.Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations.Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a ∼ 40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4∗22, CYP3A4∗26, and POR∗28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping

A population pharmacokinetic model to predict the individual starting dose of tacrolimus in adult renal transplant recipients

AIMS The aims of this study were to describe the pharmacokinetics of tacrolimus immediately after kidney transplantation, and to develop a clinical tool for selecting the best starting dose for each patient. METHODS Data on tacrolimus exposure were collected for the first 3 months following renal transplantation. A population pharmacokinetic analysis was conducted using nonlinear mixed-effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. RESULTS A total of 4527 tacrolimus blood samples collected from 337 kidney transplant recipients were available. Data were best described using a two-compartment model. The mean absorption rate was 3.6 h1 , clearance was 23.0 l h–1 (39% interindividual variability, IIV), central volume of distribution was 692 l (49% IIV) and the peripheral volume of distribution 5340 l (53% IIV). Interoccasion variability was added to clearance (14%). Higher body surface area (BSA), lower serum creatinine, younger age, higher albumin and lower haematocrit levels were identified as covariates enhancing tacrolimus clearance. Cytochrome P450 (CYP) 3A5 expressers had a significantly higher tacrolimus clearance (160%), whereas CYP3A4*22 carriers had a significantly lower clearance (80%). From these significant covariates, age, BSA, CYP3A4 and CYP3A5 genotype were incorporated in a second model to individualize the tacrolimus starting dose: Both models were successfully internally and externally validated. A clinical trial was simulated to demonstrate the added value of the starting dose model. CONCLUSIONS For a good prediction of tacrolimus pharmacokinetics, age, BSA, CYP3A4 and CYP3A5 genotype are important covariates. These covariates explained 30% of the variability in CL/F. The model proved effective in calculating the optimal tacrolimus dose based on these parameters and can be used to individualize the tacrolimus dose in the early period after transplantation

Avoiding Tacrolimus Underexposure and Overexposure with a Dosing Algorithm for Renal Transplant Recipients: A Single Arm Prospective Intervention Trial

Bodyweight-based tacrolimus dosing followed by therapeutic drug monitoring is standard clinical care after renal transplantation. However, after transplantation, a meager 38% of patients are on target at first steady-state and it can take up to 3 weeks to reach the target tacrolimus predose concentration (C0). Tacrolimus underexposure and overexposure is associated with an increased risk of rejection and drug-related toxicity, respectively. To minimize subtherapeutic and supratherapeutic tacrolimus exposure in the immediate post-transplant phase, a previously developed dosing algorithm to predict an individual’s tacrolimus starting dose was tested prospectively. In this single-arm, prospective, therapeutic