De patient bestaat niet

Rede, Uitgesproken bij aanvaarding van van het ambt van bijzonder hoogleraar met als leeropdracht klinische farmacologie aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 16 september 2011. De klinische farmacologie is de wetenschap die zich bezighoudt met het bestuderen van de toepassing van geneesmiddelen bij de mens. De basis wordt gevormd door kennis over de werkingsmechanismen van geneesmiddelen en de pathofysiologie van ziektebeelden. De klinische farmacologie verbindt als het ware de basale farmacologische principes met de klinische praktijk. Het uiteindelijke doel is het beter inzetten van geneesmiddelen bij de behandeling van patiënten, waarbij gestreefd wordt naar optimale effectiviteit en naar het beperken van bijwerkingen. De veronderstelling dat geneeskunde en farmacie hierbij gecombineerd worden is dus ook niet zo gek. Sterker nog, om de klinische farmacologie optimaal te benutten is een nauwe samenwerking tussen artsen en apothekers van groot belang

Comparison of climate and production in closed, semi-closed and open greenhouses

A (semi-)closed greenhouse is a novel greenhouse with an active cooling system and temporary heat storage in an aquifer. Air is cooled, heated and dehumidified by air treatment units. Climate in (semi-)closed greenhouses differs from that of conventional open greenhouses. The aims of our research were first, to analyze the effect of active cooling on greenhouse climate, in terms of stability, gradient and average levels; second, to determine crop growth and production in closed and semi-closed greenhouses. An experiment with tomato crop was conducted from December 2007 until November 2008 in a closed greenhouse with 700 W m-2 cooling capacity, two semi-closed greenhouses with 350 and 150 W m-2 cooling capacity, respectively, and an open greenhouse. The higher the cooling capacity, the more independent the greenhouse climate was of the outside climate. As the cooling ducts were placed underneath the plants, cooling led to a remarkable vertical temperature gradient. Under sunny conditions temperature could be 5°C higher at the top than at the bottom of the canopy in the closed greenhouse. Cumulative production in the semi-closed greenhouses with 350 and 150 W m-2 cooling capacity were 10% (61 kg m-2) and 6% (59 kg m-2) higher than that in the open greenhouse (55 kg m-2), respectively. Cumulative production in the closed greenhouse was 14% higher than in the open greenhouse in week 29 after planting but at the end of the experiment the cumulative increase was only 4% due to botrytis. Model calculations showed that the production increase in the closed and semi-closed greenhouses was explained by higher CO2 concentratio

First-Order Provenance Games

We propose a new model of provenance, based on a game-theoretic approach to query evaluation. First, we study games G in their own right, and ask how to explain that a position x in G is won, lost, or drawn. The resulting notion of game provenance is closely related to winning strategies, and excludes from provenance all "bad moves", i.e., those which unnecessarily allow the opponent to improve the outcome of a play. In this way, the value of a position is determined by its game provenance. We then define provenance games by viewing the evaluation of a first-order query as a game between two players who argue whether a tuple is in the query answer. For RA+ queries, we show that game provenance is equivalent to the most general semiring of provenance polynomials N[X]. Variants of our game yield other known semirings. However, unlike semiring provenance, game provenance also provides a "built-in" way to handle negation and thus to answer why-not questions: In (provenance) games, the reason why x is not won, is the same as why x is lost or drawn (the latter is possible for games with draws). Since first-order provenance games are draw-free, they yield a new provenance model that combines how- and why-not provenance

Knowledge Cartography for Controversies: The Iraq Debate

In analysing controversies and debates—which would include reviewing a literature in order to plan research, or assessing intelligence to formulate policy—there is no one worldview which can be mapped, for instance as a single, coherent concept map. The cartographic challenge is to show which facts are agreed and contested, and the different kinds of narrative links that use facts as evidence to define the nature of the problem, what to do about it, and why. We will use the debate around the invasion of Iraq to demonstrate the methodology of using a knowledge mapping tool to extract key ideas from source materials, in order to classify and connect them within and across a set of perspectives of interest to the analyst. We reflect on the value that this approach adds, and how it relates to other argument mapping approaches

How cyclosporine reduces mycophenolic acid exposure by 40% while other calcineurin inhibitors do not

The most frequently used immunosuppressive treatment in kidney transplant recipients is the combination therapy of a calcineurin inhibitor (CNI) and mycophenolate mofetil, with or without corticosteroids. Cyclosporine and tacrolimus are the 2 CNIs registered for this indication. Also, in the treatment of glomerular diseases, CNIs and mycophenolate are being used on a worldwide scale, either alone or as combined treatment. In January 2021, the US Food and Drug Administration approved voclosporin, a novel CNI, for the treatment of adult patients with active lupus nephritis. There is a clinically relevant drug-drug interaction between cyclosporine and mycophenolate. As a result of cyclosporine-induced inhibition of the enterohepatic recirculation of mycophenolate, the mycophenolic acid area under the curve is significantly lower (40%) in case of cyclosporine coadministration compared with cotreatment with either tacrolimus or voclosporin (or no CNI cotreatment). The aim of this mini review is to summarize this potential drug-drug interaction and explain how cyclosporine affects the pharmacokinetics of mycophenolate. The optimal dose of mycophenolate mofetil is likely to depend on the CNI with which it is coadministered. Furthermore, clinical implications are discussed, including the potential emergence of mycophenolic acid-related adverse effects after discontinuation of cyclosporine cotreatment.Personalised Therapeutic

A future orientation intervention delivered through a smartphone application and virtual reality: study protocol for a randomized controlled trial

Background: Short-term mindsets are associated with self-defeating behaviors, such as delinquency and alcohol use. In contrast, people who consider the longer-term consequences of their decisions tend to report positive outcomes, like feeling more competent and enhanced goal achievement. We evaluate an intervention, FutureU, that aims to stimulate future-oriented thinking, increase goal achievement, and reduce self-defeating behavior, by strengthening people’s identification with their future self. The intervention will be delivered through a smartphone application (app) or immersive Virtual Reality (VR). We test the effectiveness of FutureU for both delivery methods, examine working mechanisms, and identify potential moderators of intervention effects.Methods: In this Randomized Controlled Trial, a total of 240 first-year university students (n = 80 per condition) will be randomized into one of three conditions: (1) a smartphone condition, (2) a VR condition, and (3) an active control condition. We will assess proximal (i.e., future self-identification) and distal intervention outcomes (e.g., future orientation, self-defeating behaviors, goal achievement), user engagement, and examine usage data and goal content. Assessments will take place at baseline, during the intervention, immediately after the intervention, and at 3- and 6-months follow-up.Discussion: This study will provide information on the effectiveness of the intervention and allows for comparisons between delivery methods using novel technologies, a smartphone app versus immersive VR. Knowledge gained through this study can be used for further intervention development as well as theory building

Treatment of a life-threatening dapsone intoxication

The case report describes a case of a severe dapsone (more than 200 tablets dapsone 100 mg) and mild methotrexate intoxication (10 tablets methotrexate 10 mg) as an attempt to commit suicide, resulting in severe cyanosis with elevation in methemoglobin concentration, treated with methylene blue, ascorbic acid, folinic acid, multidose activated charcoal and hemodialysis. Measurements of blood gases, dapsone and methotrexate levels were performed. Furthermore a hepatitis, pulmonary artery thrombus and a strange taste sensation were diagnosed, probably related to dapsone. The patient recovered and was discharged from hospital after five days. Acute intoxication from excessive dapsone intake is uncommon and clear treatment guidelines are lacking. We here report the treatment modalities as a result of a dapsone intoxication, including the effects on the overall condition of the patient.</p