Approaches for setting micronutrient recommendations : a case study of vitamin B12 for adults and elderly people

Background: Most countries in Europe provide recommendations on the micronutrient composition of diets to fulfil requirements of nearly all individuals in the general apparently healthy population. However as each country uses its own methods for deriving such recommendations, there is large variation between countries in the recommended micronutrient intakes. The objectives of this thesis are to signal key issues for harmonizing approaches for establishing micronutrient recommendations for adults and elderly across Europe and to illustrate standardized and transparent review methods that can be used to summarize and evaluate the evidence-base for setting recommendations, using vitamin B12 as a case micronutrient. Methods: First the need for harmonization is substantiated by a descriptive study on the variation in published micronutrient recommendations across Europe. In addition methodological factors were identified that should be considered for alignment of recommended intakes across Europe. Secondly, the evidence-base for establishing recommended vitamin B12 intakes was summarized in two systematic reviews. One review focused on requirements for the compensation of daily obligatory losses (factorial approach) and the other review evaluated the relation of vitamin B12 intake and status with cognitive performance (dose-response approach). Whether interactions between folate and vitamin B12 on cognitive performance should be considered for establishing recommended vitamin B12 intakes was evaluated using data from 2203 Norwegian elderly from the Hordaland Homocysteine Study. Results: For harmonizing approaches for establishing micronutrient recommendations, standard methods are needed to a)-select health indicators and define adequate biomarker concentrations, b)-make assumptions about inter-individual variation in requirements, c)-derive bioavailability factors, and d)-select and interpret evidence on requirements. The first systematic review showed that daily vitamin B12 losses in apparently healthy adults and elderly probably range between 2.6-3.9 µg and bioavailability from the usual diet may range between 29 and 37% rather than the generally assumed 50%. Dose-response evidence from 2 randomized controlled trials and 19 prospective cohort studies showed no or inconsistent associations between vitamin B12 intake or status and dementia, Alzheimer’s Disease, global cognitive function or domain-specific cognitive function in adults and elderly people. Cross-sectional analyses in the Norwegian cohort study showed that low plasma vitamin B12 in combination with high folate was associated with better cognitive performance. However, these associations were not observed for sensitive markers of vitamin B12 status. Conclusion: The main conclusion of this thesis is that evidence underlying current recommended vitamin B12 intakes is old and has large uncertainties, whereas the available evidence on the relation between vitamin B12 and cognitive performance is yet not convincing and thereby limits its use as an outcome for estimating vitamin B12 requirements. The relation between vitamin B12 intake and markers of vitamin B12 status seems the best alternative, but sound statistical methods to define recommendations based on these dose-response data should be further developed. </p

Restarting from scratch: humanist initiatives as an option for strengthening civil society in the new member states of the European Union

Topic: Inclusion and exclusion are direct results of how the concepts of human dignity, equality and justice are valued. This always held true for the European Union (EU) since it was formed, but is even more topical now that recently twelve new countries of Central- and Eastern Europe have joined. Therefore at the moment, a major process of reorientation on the question how to construct stable societies is going on. Research question: In this essay research is done on the question whether - and if so how - humanist initiatives might be an option for strengthening civil society in the new member states. Conclusion: All together one can say that in the effort to integrate - and therewith include - the new European member states as well as possible into the new European Union, the rebuilding of civil society is crucial. Humanism seems to be able to attribute to that, by the fact that some core values of this philosophy of life, of this movement that started in the Renaissance and goes back to the ancient times, are similar to the ones needed for the development of civil society. Those key-notes being: autonomy, solidarity, and responsibility. Another explanation for the fact that humanism seems to successfully function as a source of inspiration for the development of common European ideas how to organize society, is because of the common history Western, Northern, Middle and Eastern Europe share in this tradition. It reaffirms the common roots all those parts of Europe share as part of their cultural and historical background

A note on the expressive power of linear orders

This article shows that there exist two particular linear orders such that first-order logic with these two linear orders has the same expressive power as first-order logic with the Bit-predicate FO(Bit). As a corollary we obtain that there also exists a built-in permutation such that first-order logic with a linear order and this permutation is as expressive as FO(Bit)

Nutri-RecQuest: a web-based search engine on current micronutrient recommendations

Background: The EURRECA (EURopean micronutrient RECommendations Aligned) Network of Excellence collated current micronutrient recommendations. A user-friendly tool, Nutri-RecQuest, was developed to allow access to the collated data and to create a database source for use in other nutritional software tools. Methods: Recommendations, that is, intakes of micronutrients sufficient to meet the requirements of the majority of healthy individuals of that population, from 37 European countries/organizations and eight key non-European countries/regions comprising 29 micronutrients were entered into a database. General information on the source of the recommendations, as well scientific background information, was added. Results: A user-friendly web-based interface was developed to provide efficient search, comparison, display, print and export functions. Conclusion: Easy access to existing recommendations through the web-based tool may be valuable for bodies responsible for setting recommendations, as well as for users of recommendations including scientists, policy makers, health professionals and industry. Adding related dietary reference values such as average nutrient requirements and upper limits may extend the utility of the tool. European Journal of Clinical Nutrition (2010) 64, S43-S47; doi:10.1038/ejcn.2010.6

Prevention and management of adverse events related to regorafenib

Regorafenib is an oral multikinase inhibitor that has shown antitumor activity in a range of solid tumors. Based on data from phase III clinical trials, regorafenib is indicated for the treatment of adult patients with metastatic colorectal cancer who have previously been treated with, or are not considered candidates for, other available therapies, and in patients with advanced gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to other appropriate treatments. A panel of oncology nurses, research coordinators, and other medical oncology experts, experienced in the care of patients treated with regorafenib, met to discuss the best practice for the management of regorafenib-associated adverse events (AEs). The panel agreed that, in clinical trials and daily practice with regorafenib, AEs are common but mostly manageable. The most common and/or important AEs associated with regorafenib were considered to be hand-foot skin reaction, rash or desquamation, stomatitis, diarrhea, hypertension, liver abnormalities, and fatigue. This manuscript describes the experience and recommendations of the panel for managing these AEs in everyday clinical practice. Appropriate education, monitoring, and management are considered essential for reducing the incidence, duration, and severity of regorafenib-associated AEs. © 2013 The Author(s)