Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre, prospective, cluster randomised, crossover clinical trial

Objectives: Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treatment is superior to standard treatment for invasive aspergillosis. Methods: A multicentre (n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged ≥18 years treated with voriconazole. All patients received standard voriconazole dose at the start of treatment. Blood/serum/plasma was periodically collected after treatment initiation of voriconazole and repeated during treatment in both groups. The TDM group had measured voriconazole concentrations reported back, with dose adjustments made as appropriate, while the non-TDM group had voriconazole concentrations measured only after study completion. The composite primary endpoint included response to treatment and voriconazole treatment discontinuation due to an adverse drug reaction related to voriconazole within 28 days after treatment initiation. Results: In total, 189 patients were enrolled in the study. For the composite primary endpoint, 74 patients were included in the non-TDM group and 68 patients in the TDM group. Here, no significant difference was found between both groups (P = 0.678). However, more trough concentrations were found within the generally accepted range of 1–6 mg/L for the TDM group (74.0%) compared with the non-TDM group (64.0%) (P < 0.001). Conclusions: In this trial, TDM-guided dosing of voriconazole did not show improved treatment outcome compared with standard dosing. We believe that these findings should open up the discussion for an approach to voriconazole TDM that includes drug exposure, pathogen susceptibility and host defence. Clinical trial registration: ClinicalTrials.gov registration no. NCT00893555

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study

Contains fulltext : 87274.pdf (publisher's version ) (Open Access)BACKGROUND: Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective. METHODS/DESIGN: A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness. DISCUSSION: This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies

School, Bewegen en Sport

Onderzoek naar relaties tussen de school(omgeving) en het beweeg- en sportgedrag van leerlingen. In een dagboekje beschreven ruim 7.000 leerlingen van bijna 200 scholen 10 beweegrijke activiteiten. Beweeggedrag binnen en buiten de school is te vergelijken

Dutch norms for the Bayley III

The Bayley III was adapted for dutch children and Dutch norms were created in order to develop the Bayley-III-NL The Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) are frequently used to assess early child development worldwide. However, the original standardization only included US children, and it is still unclear whether or not these norms are adequate for use in other populations. Recently, norms for the Dutch version of the Bayley-III (The Bayley-III-NL) were made. Scores based on Dutch and US norms were compared to study the need for population-specific norms. Scaled scores based on Dutch and US norms were compared for 1912 children between 14 days and 42 months 14 days. Next, the proportions of children scoring < 1-SD and < -2 SD based on the two norms were compared, to identify over- or under-referral for developmental delay resulting from non-population-based norms

Study Adolescent Depression (SAD)

Data on research project on adolescent depression. Depression during adolescence is a serious mental health problem. Difficulties in regulating evoked emotions after stressful life events are considered to lead to depression. The research project examined if depressive symptoms were mediated by various cognitive emotion regulation strategies after stressful life events, more specifically, the loss of a loved one, health threats or relational challenges