William K. Redekop

The CarerQol instrument: A new instrument to measure care-related quality of life of informal caregivers for use in economic evaluations

The societal perspective in economic evaluations dictates that costs and effects of informal care are included in the analyses. However, this incorporation depends on practically applicable, reliable and valid methods to register the impact of informal care. This paper presents the conceptualisation and a first test of the CarerQol instrument, aimed at measuring care-related quality of life in informal caregivers. The instrument combines the information density of a burden instrument (encompassing seven important burden dimensions) with a valuation component (a VAS scale for happiness). The instrument was tested in a Dutch sample of heterogeneous caregivers (n = 175) approached through regional caregiver support centres. This first test describes the feasibility as well as convergent and clinical validity of the CarerQol instrument. The seven burden dimensions related well with differences in VAS scores. In all instances, the average CarerQol-VAS scores decreased as the severity of problems increased. Multivariate analyses showed that the seven burden dimensions explained 37–43% of the variation in CarerQol-VAS scores, depending on the model used. The CarerQol seems a promising new instrument to register the impact of informal caregivers in economic evaluations.

A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.

BACKGROUND Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy. METHODS We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks. RESULTS A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events. CONCLUSIONS Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).

Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of anticoagulant therapy (EU-PACT) trial design

The narrow therapeutic range and wide interpatient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients require frequent monitoring to avert adverse effects and maintain therapeutic efficacy. Polymorphisms in VKORC1 and CYP2C9 jointly account for about 40% of the interindividual variability in dose requirements. To date, several pharmacogenetic-guided dosing algorithms for coumarin derivatives, predominately for warfarin, have been developed. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomized settings. The European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) trial will assess, in a single-blinded and randomized controlled trial with a follow-up period of 3 months, the safety and clinical utility of genotype-guided dosing in daily practice for the three main coumarin derivatives used in Europe. The primary outcome measure is the percentage time in the therapeutic range for international normalized ratio. This report describes the design and protocol for the trial.

Comparing methodologies for the cost estimation of hospital services

The aim of the study was to determine whether the total cost estimate of a hospital service remains reliable when the cost components of bottom-up microcosting were replaced by the cost components of top-down microcosting or gross costing. Total cost estimates were determined in representative general hospitals in the Netherlands for appendectomy, normal delivery, stroke and acute myocardial infarction for 2005. It was concluded that restricting the use of bottom-up microcosting to those cost components that have a great impact on the total costs (i.e., labour and inpatient stay) would likely result in reliable cost estimates.

Blood pressure patterns in rural, semi-urban and urban children in the Ashanti region of Ghana, West Africa

BackgroundHigh blood pressure, once rare, is rapidly becoming a major public health burden in sub-Saharan/Africa. It is unclear whether this is reflected in children. The main purpose of this study was to assess blood pressure patterns among rural, semi-urban, and urban children and to determine the association of blood pressure with locality and body mass index (BMI) in this sub-Saharan Africa setting.MethodsWe conducted a cross-sectional survey among school children aged 8–16 years in the Ashanti region of Ghana (West-Africa). There were 1277 children in the study (616 boys and 661 females). Of these 214 were from rural, 296 from semi-urban and 767 from urban settings.ResultsBlood pressure increased with increasing age in rural, semi-urban and urban areas, and in both boys and girls. The rural boys had a lower systolic and diastolic blood pressure than semi-urban boys (104.7/62.3 vs. 109.2/66.5; p < 0.001) and lower systolic blood pressure than urban boys (104.7 vs. 107.6; p < 0.01). Girls had a higher blood pressure than boys (109.1/66.7 vs. 107.5/63.8; p < 0.01). With the exception of a lower diastolic blood pressure amongst rural girls, no differences were found between rural girls (107.4/64.4) and semi-urban girls (108.0/66.1) and urban girls (109.8/67.5). In multiple linear regression analysis, locality and BMI were independently associated with blood pressure in both boys and girls.ConclusionThese findings underscore the urgent need for public health measures to prevent increasing blood pressure and its sequelae from becoming another public health burden. More work on blood pressure in children in sub-Saharan African and other developing countries is needed to prevent high blood pressure from becoming a major burden in many of these countries.

Pharmacogenetic-guided dosing of coumarin anticoagulants : Algorithms for warfarin, acenocoumarol and phenprocoumon

Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose-response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials.

Quality of life of patients with type I diabetes mellitus

The objective of this study was to assess health related quality of life (QOL) in patients with type I diabetes mellitus (DMT1) and to compare their QOL with the QOL of persons of comparable age in the general population. Furthermore we wanted to investigate which factors mostly influence QOL. In a Dutch cohort of 281 patients with DMT1 QOL was assessed using two generic instruments: the EuroQol and the RAND-36. We performed regression analyses to investigate relationships between several demographic (e.g. sex, age, marital status) and diabetes-specific variables (e.g. HbA1c, frequency of insulin injection, presence of acute and chronic complications) and QOL. The Spearman rank correlations between RAND-36 domains and EuroQol were analysed. RAND-36 results showed, for almost all domains, a QOL comparable with persons of comparable age in the general population. In contrast the QOL measured with the EuroQol was lower for subjects with DMT1. Hyperglycaemic complaints and macrovascular complications had a profound negative influence on QOL. Most correlations between the RAND-36 results and the EuroQol results corresponded with our expectations. Longitudinal data and comparison with results of several diabetes-specific questionnaires should help to establish which instrument might be most appropriate to measure QOL in patients with DMT1.

Diabetes prevalence in populations of South Asian Indian and African origins: a comparison of England and the Netherlands

Background: We determined whether the overall lower prevalence of type II diabetes in England versus the Netherlands is observed in South-Asian-Indian and African-Caribbean populations. Additionally, we assessed the contribution of health behavior, body size, and socioeconomic position to observed differences between countries. Methods: Secondary analyses of population-based standardized individual-level data of 3386 participants were conducted. Results: Indian and African-Caribbean populations had higher prevalence rates of diabetes than whites in both countries. In cross-country comparisons (and similar to whites), Indians residing in England had a lower prevalence of diabetes than those residing in the Netherlands; the prevalence ratio (PR) was 0.35 (95% confidence interval = 0.22 to 0.55) in women and 0.74 (0.50 to 1.10) in men after adjustment for other covariates. Among people of African descent as well, diabetes prevalence was lower in England than in the Netherlands; for women, PR = 0.43 (0.20 to 0.89) and for men, 0.57 (0.21 to 1.49). Conclusions: The increasing prevalence of diabetes after migration may be modified by the context in which ethnic minority groups live.

Real‐world health care costs of relapsed/refractory multiple myeloma during the era of novel cancer agents

What is known and objective:  High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real‐world costs and cost‐effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real‐world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice.

Resource consumption and costs in Dutch patients with Type 2 diabetes mellitus. Results from 29 general practices

Aims The aims of this study were to estimate the costs incurred by Dutch patients with Type 2 diabetes, examine which patient and/or treatment characteristics are associated with costs, and estimate the medical and non‐medical costs of patients with Type 2 diabetes in The Netherlands.