E. W. M. Grijseels

The evidence-based approach in health policy and health care delivery

Evidence-based approaches are prominent on the national and international agendas for health policy and health research. It is unclear what the implications of this approach are for the production and distribution of health in populations, given the notion of multiple determinants in health. It is equally unclear what kind of barriers there are to the adoption of evidence-based approaches in health care practice. This paper sketches some developments in the way in which health policy is informed by the results from health research. It summarises evidence-based approaches in health at three impact levels: intersectoral assessment, national health care policy, and evidence-based medicine in everyday practice. Consensus is growing on the role of broad and specific health determinants, including health care, as well as on priority setting based on the burden of diseases. In spite of methodological constraints, there is a demand for intersectoral assessments, especially in health sector reform. Initiators of policy changes in other sectors may be held responsible for providing the evidence related to health. There are limited possibilities for priority setting at the national health care policy level. Hence, there is a decentralisation of responsibilities for resource use. Health care providers are encouraged to assume agency roles for both patients and society and asked to promote and deliver effective and efficient health care. Governments will have to design a national framework to facilitate their organisation and legal framework to enhance evidence-based health policy. Treatment guidelines supported by evidence on effectiveness and efficiency will be one essential element in this process. With the increasing number of advocates for the enhancement of population health in the policy arenas, evidence-based approaches provide the information and some of the tools to help with priority setting.

Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS study

Currently, up to 50% of the operations in early-stage non-small cell lung cancer (NSCLC) are futile owing to the presence of locally advanced tumour or distant metastases. More accurate pre-operative staging is required in order to reduce the number of futile operations. The cost-effectiveness of fluorine-18 fluorodeoxyglucose positron emission tomography (18FDG-PET) added to the conventional diagnostic work-up was studied in the PLUS study. Prior to invasive staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU was based on prevailing guidelines. Pre-operative staging was followed by 1 year of follow-up. Outcomes are expressed in the percentage of correctly staged patients and the associated costs. The cost price of PET varied between €736 and €1,588 depending on the (hospital) setting and the procurement of 18FDG commercially or from on-site production. In the CWU group, 41% of the patients underwent a futile thoracotomy, whereas in the PET group 21% of the thoracotomies were considered futile (P=0.003). The average costs per patient in the CWU group were €9,573 and in the PET group, €8,284. The major cost driver was the number of hospital days related to recovery from surgery. Sensitivity analysis on the cost and accuracy of PET showed that the results were robust, i.e. in favour of the PET group. The addition of PET to CWU prevented futile surgery in one out of five patients with suspected NSCLC. Despite the additional PET costs, the total costs were lower in the PET group, mainly due to a reduction in the number of futile operations. The additional use of PET in the staging of patients with NSCLC is feasible, safe and cost saving from a clinical and from an economic perspective.

Pre- and postnatal diagnosis and outcome of fetuses and neonates with esophageal atresia and tracheoesophageal fistula

Clinical symptoms and ultrasound signs during pregnancy could suggest the presence of esophageal atresia (EA). However, most often EA is diagnosed postnatally. The aim of our study is to evaluate the course and outcome for prenatally and postnatally diagnosed EA. In addition, we studied the outcome of isolated versus nonisolated EA.

Costs and effects of various analgesic treatments for patients with rheumatoid arthritis and osteoarthritis in The Netherlands

OBJECTIVE To assess the balance between costs and upper gastrointestinal (GI) side effects of treatment with celecoxib, nonsteroidal antiinflammatory drugs (NSAIDs) alone, NSAID plus misoprostol, NSAID plus histamine-2 receptor antagonist (H(2)RA), NSAID plus proton pump inhibitor (PPI), and Arthrotec in The Netherlands. METHODS A model was used to convene data from various sources on the probability of GI side effects and resource use. The probabilities of GI side effects for celecoxib and NSAIDs alone were derived from trial data. Calculations were based on 6 months of treatment, and were from a societal perspective. Distinction was made between low-, medium-, and high-risk patients. An extensive probabilistic sensitivity analysis was performed to address uncertainty. RESULTS Assuming an average patient, the total costs per 6 months of therapy were: celecoxib 255 Euro, NSAIDs alone 166 Euro, NSAID plus misoprostol 285 Euro, NSAID plus H(2)RA 284 Euro, NSAID plus PPI 243 Euro, and Arthrotec 187 Euro. Treatment with celecoxib was associated with the lowest number of GI side effects and related deaths. Incremental costs per life-year saved for Arthrotec compared to NSAIDs alone were 5676 Euro for all patients and 526 Euro for medium-to-high-risk patients, whereas for high-risk patients, Arthrotec dominated NSAID alone. For celecoxib compared to Arthrotec, the incremental cost-effectiveness ratios (ICERs) were 56,667 Euro, 33,684 Euro, and 15,429 Euro, respectively. CONCLUSION Assuming a limit of 20,000 Euro per life-year gained, from an economic point of view, Arthrotec is the preferred treatment when all patients or medium-to-high-risk patients are considered. In high-risk patients, celecoxib is the preferred treatment strategy.

Isolated or non-isolated duodenal obstruction: Perinatal outcome following prenatal or postnatal diagnosis

To determine whether the pre‐ or postnatal diagnosis of either isolated or non‐isolated duodenal obstruction (DO) is associated with different outcomes.

Three‐dimensional sonography of prenatal skull base development

To explore longitudinally the development of the fetal skull base using three‐dimensional (3D) sonography.

Outcome of pregnancies complicated by oligohydramnios or anhydramnios of renal origin

To evaluate the outcome of fetuses with oligohydramnios due to kidney anomalies.

Comparable Low-Level Mosaicism in Affected and Non Affected Tissue of a Complex CDH Patient

In this paper we present the detailed clinical and cytogenetic analysis of a prenatally detected complex Congenital Diaphragmatic Hernia (CDH) patient with a mosaic unbalanced translocation (5;12). High-resolution whole genome SNP array confirmed a low-level mosaicism (20%) in uncultured cells, underlining the value of array technology for identification studies. Subsequently, targeted Fluorescence In-Situ Hybridization in postmortem collected tissues demonstrated a similar low-level mosaicism, independently of the affected status of the tissue. Thus, a higher incidence of the genetic aberration in affected organs as lung and diaphragm cannot explain the severe phenotype of this complex CDH patient. Comparison with other described chromosome 5p and 12p anomalies indicated that half of the features presented in our patient (including the diaphragm defect) could be attributed to both chromosomal areas. In contrast, a few features such as the palpebral downslant, the broad nasal bridge, the micrognathia, microcephaly, abnormal dermatoglyphics and IUGR better fitted the 5p associated syndromes only. This study underlines the fact that low-level mosaicism can be associated with severe birth defects including CDH. The contribution of mosaicism to human diseases and specifically to congenital anomalies and spontaneous abortions becomes more and more accepted, although its phenotypic consequences are poorly described phenomena leading to counseling issues. Therefore, thorough follow–up of mosaic aberrations such as presented here is indicated in order to provide genetic counselors a more evidence based prediction of fetal prognosis in the future.

P01.04: Outcome of pregnancies complicated by oligohydramnios or anhydramnios of renal origin

Objective: An ARSA is diagnosed when the vessel arises separately from the aortic arch and courses behind the trachea, instead of from the brachiocephalic trunk. It is detected by applying color Doppler at the level of the three-vessel-trachea view. An ARSA is found in approx. 1.5% of the normal population and was described to be more common in fetuses with Trisomy 21. The aim of the present study was to find out the prevalence of this vascular variant in fetuses with Trisomy 21. Patients: In the four years study (2004–2008) fetuses with trisomy 21 between 11 weeks and term and a documented course of the right subclavian artery (RSA) were included in the evaluation. Results: A total of 66 fetuses could be assessed and an ARSA was found in 13 cases (19.6%). The prevalence was the same in the group undergoing 11–14 weeks screening (7/33 = 21%). Conclusions: This study confirms earlier observations on the common finding of an ARSA in fetuses with trisomy 21, but the prevalence is lower than first described. 20% prevalence in trisomy 21 fetuses versus 1,5% in the normal population results in a likelihood ratio of 13× increased risk. This sign can be added to first and second trimester genetic scan.

Phenotypic Variability Associated with a Large Recurrent 1q21.1 Microduplication in a Three-Generation Family

Recurrent copy number variants of the q21.1 region of chromosome 1 have been associated with variable clinical features, including developmental delay, mild to moderate intellectual disability, psychiatric and behavioral problems, congenital heart malformations, and craniofacial abnormalities. A subset of individuals is clinically unaffected. We describe a unique 3-generation family with a large recurrent 1q21.1 microduplication (BP2-BP4). Our observations underline the incomplete penetrance and phenotypic variability of this rearrangement. We also confirm the association with congenital heart malformations, chronic depression, and anxiety. Furthermore, we report a broader range of dysmorphic features. The extreme phenotypic heterogeneity observed in this family suggests that additional factors modify the clinical phenotype.