Trends in direct oral anticoagulant (DOAC) use:Health benefits and patient preference

In 2012, the Dutch Health Council published a report addressing barriers for an early and broad introduction of direct oral anticoagulants (DOACs). The report raised concerns about the lack of an antidote, adherence, lack of monitoring in the case of overdose and the increased budget impact at DOAC introduction. In the past decade, international studies have shown that DOACs can provide healthcare benefits for a large number of patients. This has led to an increase in the prescription of DOACs, as they are an effective and user-friendly alternative to vitamin K antagonists (VKAs). Unlike VKAs, DOACs do not need monitoring of the international normalized ratio due to more predictable pharmacokinetics. However, the number of prescriptions of DOACs in the Netherlands is still lagging, compared to other European countries. This article highlights the potential health gains in the Netherlands if the use of DOACs were to increase, based on current international experience

Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon

Coumarin oral anticoagulant drugs have proven to be effective for the prevention of thromboembolic events. World-wide,warfarin is the most prescribed drug. In Europe, acenocoumarol and phenprocoumon are also administered. Yet it has been proven that variant alleles of the VKORC1 and CYP2C9 genotypes influence the pharmacokinetics and pharmacodynamics of these drugs. The combination of these two variant genotypes is a major cause of the inter-individual differences in coumarin anticoagulant drug dosage. Individuals who test positive for both variant genotypes are at increased risk of major bleeding. The impact of the CYP2C9 and VKORC1 genotype is most significant during the initial period of coumarin anticoagulant therapy. The effect of VKORC1 allelic variants is relatively similar for all three VKAs. The CYP2C9 polymorphism is associated with delayed stabilisation for coumarin anticoagulants. The effects of CYP2C9 polymorphisms on the pharmacokinetics and anticoagulant response are least pronounced in the case of phenprocoumon. In the long term, patients using phenprocoumon have more often international normalised ratio (INR) values in the therapeutic range, requiring fewer monitoring visits. This leads us to conclude that in the absence of pharmacogenetic testing, phenprocoumon seems preferable for use in long-term therapeutic anticoagulation. Pharmacogenetic testing before initiating coumarin oral anticoagulants may add to the safety of all coumarin anticoagulants especially in the elderly receiving multiple drugs

KNOWLEDGE TRANSFER IN THE CHINESE AUTOMOTIVE INDUSTRY

The automotive industry has been subject to a turbulent shift in the last decades as its markets, production and focus has shifted its center of gravity towards the East, specifically to China. When Western automotive companies seek to establish themselves on the Chinese automotive market they have been forced to engage in joint ventures with Chinese counterparts. As the motivation for the Chinese partners is to accumulate knowledge, experience and competencies from their mature and sophisticated Western partners, the Western partners are faced with the difficult process of transferring competencies and knowledge that have been accumulated over long periods of time and which can be tacit or hard to codify. The question of how to transfer knowledge and competencies successfully to their Chinese joint venture subsidiaries therefore becomes evident. Our aim with this thesis was to identify how Western multinational corporations can upgrade the competencies of their joint venture subsidiaries in China through the transfer of knowledge. We engaged in research of empirical data concerning both the problems faced by the Chinese automotive industry as well as the study of how Western parent firms successfully can transfer knowledge and competencies to their Chinese joint venture subsidiaries. The empirical data consisted of both secondary data as well as primary data collected through interviews. We formulated our hypothesis on the analysis of our empirical data and a theoretical framework on knowledge transfer. Our study shows that the Western automotive parent firms should focus on knowledge transfer associated to the establishment of new organizational structures and managerial principles. Most of the problems faced by the Chinese automotive industry derives from difficulties of retaining skilled personnel, which makes competence building hard, and that the Chinese organizations are not knowledge sharing, accumulating and creating organizations, which deprives them of innovativeness and development. By creating knowledge orientated organizations, not only will the Chinese subsidiaries be able to absorb competencies associated directly to the faced issues but it will also facilitate any future knowledge transfer between the organizations

Optimization of vitamin K antagonist drug dose finding by replacement of the international normalized ratio by a bidirectional factor:validation of a new algorithm

UNLABELLED: Essentials We developed a new algorithm to optimize vitamin K antagonist dose finding. Validation was by comparing actual dosing to algorithm predictions. Predicted and actual dosing of well performing centers were highly associated. The method is promising and should be tested in a randomized trial. SUMMARY: Background Oral vitamin K antagonists (VKAs) have a narrow therapeutic window and thus require frequent monitoring of its intensity by the international normalized ratio (INR). Improvement of VKA dosing defined as more time in therapeutic range (TTR) can reduce thrombotic disease and bleeding. Computerized decision support programs (CDSs) are used to optimize VKA dosing, but the effects are heterogeneous. CDSs significantly improve the proportion of time in the therapeutic INR range for initiation therapy but not the quality of anticoagulant management in an outpatient setting. One of the major problems of VKA dose finding is that the INR is a ratio and does not present linearity. We developed a new dose-finding algorithm, based on a novel bidirectional factor (BF). This BF is linear transformation of the nonlinear INR. Methods We compared the outcomes of the new algorithm, called BF-N, with dose finding performed at three highly ranked Dutch anticoagulation centers, using both acenocoumarol and phenprocoumon. Results The outcomes of the BF-N algorithm showed a linear correlation with VKA doses of the three centers (y = 1.001x, r(2) 0.999 for acenocoumarol and y = 0.999x, r(2) 0.999 for phenprocoumon), with a standard deviation of 3.83%. The rate of automated dosage proposals increased to 100%. Conclusion The BF-N algorithm performs well in real-life settings and increases the rate of automated dosage proposals. The algorithm can be easily built into existing CDSs. Experienced staff remains necessary for complicated situations. The new algorithm needs to be evaluated in a prospective trial