PIH22 Cost-Effectiveness Of Cyp2d6 Genotyping In Older Depressed Patients, Starting With Nortriptyline Therapy

Objectives: Genotyping for the cytochrome P450-2D6 has the potency to predict differences in metabolism of nortriptyline. This information could optimize treatment. We explored if possible benefits could outweigh genotyping costs for Dutch depressed patients in clinical psychiatry. Methods: First, a decision-tree was created to model the first weeks of nortriptyline therapy. In the model, costs of hospitalization, therapeutic drug monitoring, and drug costs were captured. Based on the patients genetics, patients were distributed among three health states: correctly, sub-, or supra-therapeutically dosed. Utilities for each of these health states and at different points in time were obtained from an expert opinion (nine clinicians). Second, an improvement in sub or supra-therapeutically dosed patients to correctly dosed patients, was simulated, assuming genotyping would prevent under or overdosing. In the base case the improvement was 36%. In addition, we assumed genotyping could reduce hospitalization days with a maximum of 3.7 days (average: 28.6 days). Results from the model without genotyping were compared with the genotyping model. In a scenario analyses we varied the effects of genotyping to reach cost-effectiveness at € 20 000/quality adjusted life year (QALY) or € 50 000/ QALY. In a univariate sensitivity analysis, effects of lowering genotyping costs were examined. A probabilistic sensitivity analysis (PSA) was performed to investigate influence of parameter uncertainty. Results: In the base case, the incremental cost-effectiveness ratio (ICER) was € 32 697/QALY. For an ICER of € 20 000/QALY, a genotyping facilitated improvement of 45% was needed and for € 50 000/QALY this was 27%. Lowering the genotype price to € 162 made genotyping cost-saving. Results of the PSA indicated a probability of 0.95 for a willingness-to-pay threshold of € 46000/ QALY. Conclusions: Genotyping could be cost-effective and even be cost-saving when genotyping costs drops. However, there is a need for more clinical evidence to support assumptions made in this model

Cultural tailoring for the promotion of Hepatitis B screening in Turkish Dutch: a protocol for a randomized controlled trial

Background. Chronic hepatitis B virus infection (HBV) is an important health problem in the Turkish community in the Netherlands, and promotion of screening for HBV in this risk group is necessary. An individually tailored intervention and a culturally tailored intervention have been developed to promote screening in first generation 16-40 year old Turkish immigrants. This paper describes the design of the randomized controlled trial, which will be used to evaluate the effectiveness of the two tailored internet interventions as compared to generic online information o

Awareness, knowledge and self-reported test rates regarding Hepatitis B in Turkish-Dutch: a survey

Background: Hepatitis B virus infection is an important health problem in the Turkish community in the Netherlands. To prevent transmission and progression of the disease in this community, increased screening is necessary. This study aimed to determine 1) the levels of awareness and knowledge regarding hepatitis B, comparing these in tested and non-tested Turkish-Dutch in Rotterdam; 2) the self-reported hepatitis B test status in this population, and how this is related to demographic characteristics, knowledge and awareness. Methods: We conducted a postal survey amongst first and second generation migrants, aged 16 - 40 years. Results: The response rate was 30.2% (n = 355 respondents). Levels of awareness and knowledge regarding hepatitis B were low, as the majority of respondents (73%) never thought about the disease and 58% of the respondents scored 5 or less out of ten knowledge items. Weighted analysis of self-reports showed a test rate of 15%, and a vaccination rate of 3%. Regression analys

Landbouwpraktijk en waterkwaliteit op landbouwbedrijven aangemeld voor de derogatie. Beschrijving van de meetnetopzet voor de periode 2006-2009 en de inhoud van de rapportages vanaf 2008

Translation of RIVM report 680717001. Alleen digitaal verschenenHet RIVM en het LEI hebben in 2006 in Nederland een monitoringnetwerk opgezet dat de gevolgen meet als landbouwbedrijven mogen afwijken (derogatie) van de Europese gebruiksnorm voor dierlijke mest. Het meetnet volgt driehonderd landbouwbedrijven die zich hebben aangemeld voor derogatie. Het legt de gevolgen vast voor de landbouwpraktijk en de waterkwaliteit. In dit rapport is de opzet van het monitoringnetwerk beschreven, evenals de wijze waarop vanaf 2008 over de resultaten zal worden gerapporteerd. Het rapport geeft onder andere aan wanneer welke cijfers beschikbaar zijn, en welke rekenmethoden gebruikt zullen worden om onder andere de bemesting en gewasopbrengst te berekenen. De Europese Nitraatrichtlijn verplicht lidstaten het stikstofgebruik via dierlijke mest te beperken tot maximaal 170 kg per hectare. Een lidstaat kan de Europese Commissie vragen hiervan onder voorwaarden af te wijken. Nederland heeft in december 2005 toestemming gekregen om vanaf 2006 tot en met 2009 onder voorwaarden af te mogen wijken van de gestelde norm. Dit betekent dat landbouwbedrijven 250 kilo stikstof per hectare mogen toedienen via dierlijke mest afkomstig van graasdieren (vooral koeien). Een van die voorwaarden is dat minimaal 70 procent van het totale areaal grasland is. Daarnaast is de Nederlandse overheid verplicht een monitoringnetwerk in te richten en de Commissie over de resultaten daarvan te rapporteren. De driehonderd deelnemers die worden gevolgd, zijn een steekproef van de circa 27.000 Nederlandse landbouwbedrijven die zich hebben aangemeld voor derogatie. Het netwerk is een onderdeel van het Landelijk Meetnet effecten Mestbeleid (LMM).In 2006 RIVM and LEI set up a monitoring network that measures the consequences of the option for farmers to deviate from the European use-standard for animal manure (derogation). The monitoring network follows three hundred farms benefiting from individual derogations and records the consequences for agricultural practice and water quality. This report describes the design and set-up of the monitoring network, as well as the content and layout of the annual reports from 2008 onwards containing results of the monitoring network. The report indicates, for example, what data will be available at a certain point in time, and what methods will be used to calculate such factors as fertilisation and yield. The Nitrates Directive obliges Member States to limit the use of animal manure to a maximum of 170 kg of nitrogen per hectare. A Member State may request the European Commission to deviate from this obligation under certain conditions. In December 2005, the European Commission granted the Netherlands the right to derogate from the obligation from 2006 till 2009 inclusive, implying that farmers could use up to 250 kg of nitrogen via manure of grazing livestock (particularly cows). One of the conditions is that 70% or more of the acreage available for manure application is grass. The Netherlands authorities are also obliged to set up a monitoring network and to report the results of this network to the European Commission. The 300 farms participating in the monitoring represent a sample taken from the approximately 27,000 Netherlands farms benefiting from individual derogations. The network is part of the National Programme for Monitoring the Effectiveness of the Minerals Policy (LMM).VROM-BWLLNV-D

Amniotic fluid embolism incidence, risk factors and outcomes: a review and recommendations

<p>Abstract</p> <p>Background</p> <p>Amniotic fluid embolism (AFE) is a rare but severe complication of pregnancy. A recent systematic review highlighted apparent differences in the incidence, with studies estimating the incidence of AFE to be more than three times higher in North America than Europe. The aim of this study was to examine population-based regional or national data from five high-resource countries in order to investigate incidence, risk factors and outcomes of AFE and to investigate whether any variation identified could be ascribed to methodological differences between the studies.</p> <p>Methods</p> <p>We reviewed available data sources on the incidence of AFE in Australia, Canada, the Netherlands, the United Kingdom and the USA. Where information was available, the risk factors and outcomes of AFE were examined.</p> <p>Results</p> <p>The reported incidence of AFE ranged from 1.9 cases per 100 000 maternities (UK) to 6.1 per 100 000 maternities (Australia). There was a clear distinction between rates estimated using different methodologies. The lowest estimated incidence rates were obtained through validated case identification (range 1.9-2.5 cases per 100 000 maternities); rates obtained from retrospective analysis of population discharge databases were significantly higher (range 5.5-6.1 per 100 000 admissions with delivery diagnosis). Older maternal age and induction of labour were consistently associated with AFE.</p> <p>Conclusions</p> <p>Recommendation 1: Comparisons of AFE incidence estimates should be restricted to studies using similar methodology. The recommended approaches would be either population-based database studies using additional criteria to exclude false positive cases, or tailored data collection using existing specific population-based systems.</p> <p>Recommendation 2: Comparisons of AFE incidence between and within countries would be facilitated by development of an agreed case definition and an agreed set of criteria to minimise inclusion of false positive cases for database studies.</p> <p>Recommendation 3: Groups conducting detailed population-based studies on AFE should develop an agreed strategy to allow combined analysis of data obtained using consistent methodologies in order to identify potentially modifiable risk factors.</p> <p>Recommendation 4: Future specific studies on AFE should aim to collect information on management and longer-term outcomes for both mothers and infants in order to guide best practice, counselling and service planning.</p

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

Haemorrhagia post partum; an implementation study on the evidence-based guideline of the Dutch Society of Obstetrics and Gynaecology (NVOG) and the MOET (Managing Obstetric Emergencies and Trauma-course) instructions; the Fluxim study

Contains fulltext : 88435.pdf (publisher's version ) (Open Access)BACKGROUND: One of the most important causes of maternal mortality and severe morbidity worldwide is post partum haemorrhage (PPH). Factors as substandard care are frequently reported in the international literature and there are similar reports in the Netherlands. The incidence of PPH in the Dutch population is 5% containing 10.000 women a year. The introduction of an evidence-based guideline on PPH by the Dutch society of Obstetrics and Gynaecology (NVOG) and the initiation of the MOET course (Managing Obstetrics Emergencies and Trauma) did not lead to a reduction of PPH. This implies the possibility of an incomplete implementation of both the NVOG guideline and MOET-instructions. Therefore, the aim of this study is to develop and test a tailored strategy to implement both the NVOG guideline and MOET-instructions METHODS/DESIGN: One step in the development procedure is to evaluate the implementation of the guideline and MOET-instructions in the current care. Therefore measurement of the actual care will be performed in a representative sample of 20 hospitals. This will be done by prospective observation of the third stage of labour of 320 women with a high risk of PPH using quality indicators extracted from the NVOG guideline and MOET instructions. In the next step barriers and facilitators for guideline adherence will be analyzed by performance of semi structured interviews with 30 professionals and 10 patients, followed by a questionnaire study among all Dutch gynaecologists and midwives to quantify the barriers mentioned. Based on the outcomes, a tailored strategy to implement the NVOG guideline and MOET-instructions will be developed and tested in a feasibility study in 4 hospitals, including effect-, process- and cost evaluation. DISCUSSION: This study will provide insight into current Dutch practice, in particular to what extent the PPH guidelines of the NVOG and the MOET-instructions have been implemented in the actual care, and into the barriers and facilitators regarding guideline adherence. The knowledge of the feasibility study regarding the effects and costs of the tailored strategy and the experiences of the users can be used in countries with a relatively high incidence of PPH. TRIAL REGISTRATION: ClinicTrials.gov NCT00928863