The association between a genetic risk score for allergy and the risk of developing allergies in childhood-Results of the WHISTLER cohort.

Background: Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy based on findings in adults and study its predictive capacity for allergy in children.

Methods: A GRS was constructed based on 10 SNPs previously associated with allergies in adults.

High incidence of oral corticosteroids prescriptions in children with asthma in early childhood.

Objective: Severe asthma exacerbations are often treated with short courses of oral corticosteroids (OCS). This study assessed the incidence of OCS being prescribed in asthmatic children of various age groups and calculated their chances of receiving subsequent OCS prescriptions.

Methods: Longitudinal Dutch community pharmacy data of 2272 children who were regular users of asthma medication was analyzed retrospectively.

Characteristics and severity of asthma in children with and without atopic conditions: a cross-sectional study.

Background: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children with certain combinations of co-morbid allergic conditions.

[Threshold value for reimbursement of costs of new drugs: cost-effectiveness research and modelling are essential links].

There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations.

Pharmacogenetic analysis of GLCCI1 in three north European pediatric asthma populations with a reported use of inhaled corticosteroids.

Background: GLCCI1 rs37972 has previously been associated with decreased lung function improvement upon treatment with inhaled corticosteroids (ICS) in asthmatics.

Aim: To assess whether variation in rs37972 is associated with altered ICS efficacy in north European asthmatic children and young adults with a reported use of ICS.

Patients & Methods: rs37972 was genotyped in three cohort studies of asthmatic children with a reported use of ICS.

The fiduciary obligation of the physician-researcher in phase IV trials.

Background: In this manuscript, we argue that within the context of phase IV, physician-researchers retain their fiduciary obligation to treat the patient-participants.

Discussion: We first clarify why the perspective that research ethics ought to be differentiated from clinical ethics is not applicable in phase IV, and therefore, why therapeutic orientation is most convivial in this phase. Next, assuming that ethics guidelines may be representative of common morality, we show that ethics guidelines see physician-researchers primarily as physicians and only secondarily as researchers.

Restoring trust in the pharmaceutical sector on the basis of the SSRI case.

The lack of public trust in the pharmaceutical sector (i.e. industry, authorities and doctors) could compromise the future of drug development and the regulatory system.

Arg16 ADRB2 genotype increases the risk of asthma exacerbation in children with a reported use of long-acting β2-agonists: results of the PACMAN cohort.

Background: Current evidence suggests that asthma patients with the ADRB2 Arg16 genotype have a poorer response to long-acting β2-agonists (LABA), but the results remain inconsistent.

Aim: This study assessed the association between Arg16 variants and treatment outcome in children treated with inhaled corticosteroids (ICS) and LABA.

Materials & Methods: ADRB2 Arg16 was genotyped in 597 children (4-12 years of age) participating in the PACMAN cohort study.

The impact of structural uncertainty on cost-effectiveness models for adjuvant endocrine breast cancer treatments: the need for disease-specific model standardization and improved guidance.

Introduction: Structural uncertainty relates to differences in model structure and parameterization. For many published health economic analyses in oncology, substantial differences in model structure exist, leading to differences in analysis outcomes and potentially impacting decision-making processes. The objectives of this analysis were (1) to identify differences in model structure and parameterization for cost-effectiveness analyses (CEAs) comparing tamoxifen and anastrazole for adjuvant breast cancer (ABC) treatment; and (2) to quantify the impact of these differences on analysis outcome metrics.

The cloudy crystal ball of cost-effectiveness studies.

Despite the use of identical clinical trial data (Anastrazole, Tamoxifen, Alone or in Combination for the adjuvant treatment of postmenopausal women with localised hormone receptor-positive breast cancer data), not dependent on differences between countries, the outcome of 11 published cost-effectiveness analyses varied more than 20-fold. The observed wide variation in predicted life-years gained (a parameter derived from clinical trial data) demonstrates that authors used substantially different methods for handling the same data. We therefore consider it to be of utmost importance to strive for standardization of and better guidance for disease-specific modeling in economic evaluations.

Inflammatory phenotypes underlying uncontrolled childhood asthma despite inhaled corticosteroid treatment: rationale and design of the PACMAN2 study.

Background: The diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to similarly presenting clinical symptoms, but may nonetheless require different treatment approaches. Distinct underlying inflammatory patterns are thought to influence responsiveness to standard asthma medication.

Methods/design: The purpose of the PACMAN2 study is to identify inflammatory phenotypes that can discriminate uncontrolled childhood asthma from controlled childhood asthma by measures in peripheral blood and exhaled air.

Development of a framework for cohort simulation in cost-effectiveness analyses using a multistep ordinary differential equation solver algorithm in R.

Introduction: Dynamic processes in cost-effectiveness analysis (CEA) are typically described using cohort simulations, which can be implemented as Markov models, or alternatively using systems of ordinary differential equations (ODEs). In the field of CEA, simple and potentially inaccurate single-step algorithms are commonly used for solving ODEs, which can potentially induce bias, especially if an incorrect step size is used. The aims of this project were 1) to implement and demonstrate the use of a modern and well-established hybrid linear multistep ODE solver algorithm (LSODA) in the context of CEA using the statistical scripting language R and 2) to quantify bias in outcome for a case example CEA as generated by a commonly used single-step ODE solver algorithm.

Decision theory and the evaluation of risks and benefits of clinical trials.

Research ethics committees (RECs) are tasked to assess the risks and the benefits of a clinical trial. In previous studies, it was shown that RECs find this task difficult, if not impossible, to do. The current approaches to benefit-risk assessment (i.

Exhaled NO is a poor marker of asthma control in children with a reported use of asthma medication: a pharmacy-based study.

Background: A high fraction of nitric oxide in exhaled breath (FeNO) has been suggested to be a marker of ongoing airway inflammation and poorly controlled disease in asthma. The usefulness of FeNO to monitor asthma control is still debated today.

Aim: To assess the validity of FeNO as a marker of asthma control in children with reported use of asthma medication.

The risk-benefit task of research ethics committees: an evaluation of current approaches and the need to incorporate decision studies methods.

Background: Research ethics committees (RECs) are tasked to assess the risks and the benefits of a trial. Currently, two procedure-level approaches are predominant, the Net Risk Test and the Component Analysis.

Discussion: By looking at decision studies, we see that both procedure-level approaches conflate the various risk-benefit tasks, i.

Knowledge of actions of inhaled corticosteroids in patients who did not persist drug treatment early.

Objective: To evaluate, among new users of inhaled corticosteroids that did not persist treatment, knowledge of inhaled corticosteroids' actions and whether they were instructed on the use of their inhaler.

Setting: Fifteen community pharmacies in The Netherlands. Methods Patients were interviewed by telephone.

Reviewing the cost-effectiveness of endocrine early breast cancer therapies: influence of differences in modeling methods on outcomes.

Objectives: The purpose of this systematic review is primarily to identify published cost-effectiveness analyses and cost-utility analyses of endocrine therapies for the treatment of early breast cancer. A secondary objective is to identify whether differences in seven modeling characteristics are related to differences in outcome of these cost-effectiveness and cost-utility analyses.

Methods: A systematic literature review was conducted to identify peer-reviewed full economic evaluations of endocrine treatments of early breast cancer published in the English language between 2000 and December 2010.

Inhaled corticosteroid adherence in paediatric patients: the PACMAN cohort study.

Aims: Poor adherence with inhaled corticosteroids (ICSs) has been reported frequently and may be associated with uncontrolled asthma. A better understanding of factors influencing adherence may help to achieve higher adherence rates for a larger part of the population, which will eventually lead to better asthma control. The aim of this study was to investigate factors associated with adherence in paediatric ICS users.

Asthma symptoms in pediatric patients: differences throughout the seasons.

Introduction: Seasonal variation in asthma has been widely recognized. The aim of this study was to describe seasonal patterns of asthma symptoms and asthma medication use in a cohort of pediatric asthma medication users and to study determinants of seasonal childhood asthma.

Methods: For this study, 602 children participating in the Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects) cohort were included.

Limited agreement between current and long-term asthma control in children: the PACMAN cohort study.

Background: Several studies have shown that predictors of asthma treatment outcomes differ depending on the definition of the outcome chosen. This provides evidence that different outcomes studied may reflect distinct aspects of asthma control. To assess predictors of asthma control, we need firm outcome phenotypes.