Health-related Quality of Life using the EQ-5D-5L:normative utility scores in a Dutch female population

PURPOSE: Normative utility scores represent the health related quality of life of the general population, are of utmost importance in cost-effectiveness studies and should reflect relevant sexes and age groups. The aim of this study was to estimate EQ-5D-5L normative utility scores in a population of Dutch females, stratified by age, and to compare these scores to those of female populations of three other countries. METHODS: Dutch women completed the EQ-5D-5L online between January and July 2020. Mean normative utilities were computed using the Dutch EQ-5D-5L value set, stratified by age, tested for differences using the Kruskall–Wallis test, and compared to normative utility scores of female populations elsewhere. Additionally, to support the use of the Dutch EQ-5D-5L data in other settings, normative utility scores were also calculated by applying the value sets of Germany, United Kingdom and USA. RESULTS: Data of 9037 women were analyzed and the weighted mean utility score was 0.911 (SD 0.155, 95% CI 0.908–0.914). The mean normative utility scores differed between age groups, showing lower scores in older females. Compared to other normative utility scores of female populations, Dutch mean utilities were consistently higher except for age groups 18–24 and 25–34. With the three country-specific value sets, new age-specific mean normative utility scores were provided. CONCLUSION: This study provides mean normative utility scores of a large cohort of Dutch females per age group, which were found to be lower in older age groups. Utility scores calculated with three other value sets were made available. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11136-022-03271-3

Health utility values of breast cancer treatments and the impact of varying quality of life assumptions on cost-effectiveness

In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs). Four hundred sixty four female patients with breast cancer treated at Erasmus MC, the Netherlands, completed EQ-5D-5L questionnaires from diagnosis throughout their treatment. Average utilities were calculated stratified by age and treatment. These utilities were applied in CEAs analysing 920 breast cancer screening policies differing in eligible ages and screening interval simulated by the MISCAN-Breast microsimulation model, using a willingness-to-pay threshold of €20,000. The CEAs included varying sets on normative, breast cancer treatment and screening and follow-up utilities. Efficiency frontiers were compared to assess the impact of the utility sets. The calculated average patient utilities were reduced at breast cancer diagnosis and 6 months after surgery and increased toward normative utilities 12 months after surgery. When using normative utility values of 1 in CEAs, QALYs were overestimated compared to using average gender and age-specific values. Only small differences in QALYs gained were seen when varying treatment utilities in CEAs. The CEAs varying screening and follow-up utilities showed only small changes in QALYs gained and the efficiency frontier. Throughout all variations in utility sets, the optimal strategy remained robust; biennial for ages 40-76 years and occasionally biennial 40-74 years. In sum, we recommend to use gender and age stratified normative utilities in CEAs, and patient-based breast cancer utilities stratified by age and treatment or disease stage. Furthermore, despite varying utilities, the optimal screening scenario seems very robust.</p

Health utility values of breast cancer treatments and the impact of varying quality of life assumptions on cost-effectiveness

In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs). Four hundred sixty four female patients with breast cancer treated at Erasmus MC, the Netherlands, completed EQ-5D-5L questionnaires from diagnosis throughout their treatment. Average utilities were calculated stratified by age and treatment. These utilities were applied in CEAs analysing 920 breast cancer screening policies differing in eligible ages and screening interval simulated by the MISCAN-Breast microsimulation model, using a willingness-to-pay threshold of €20,000. The CEAs included varying sets on normative, breast cancer treatment and screening and follow-up utilities. Efficiency frontiers were compared to assess the impact of the utility sets. The calculated average patient utilities were reduced at breast cancer diagnosis and 6 months after surgery and increased toward normative utilities 12 months after surgery. When using normative utility values of 1 in CEAs, QALYs were overestimated compared to using average gender and age-specific values. Only small differences in QALYs gained were seen when varying treatment utilities in CEAs. The CEAs varying screening and follow-up utilities showed only small changes in QALYs gained and the efficiency frontier. Throughout all variations in utility sets, the optimal strategy remained robust; biennial for ages 40-76 years and occasionally biennial 40-74 years. In sum, we recommend to use gender and age stratified normative utilities in CEAs, and patient-based breast cancer utilities stratified by age and treatment or disease stage. Furthermore, despite varying utilities, the optimal screening scenario seems very robust.</p

Health-related quality of life (HRQoL) after different axillary treatments in women with breast cancer:a 1-year longitudinal cohort study

Purpose: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. Methods: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. Results: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p &lt; 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p &lt; 0.05). Conclusion: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.</p

Functional and Morphologic Analysis of the Fluid-Conducting Meshwork in Xenografted Cutaneous and Primary Uveal Melanoma

PURPOSE. In primary uveal and cutaneous melanoma lesions, extracellular matrix (ECM) is often deposited in arcs, loops, and network patterns. Based on prognostic relevance, these patterns appear to play a significant role in facilitating metastasis. It has been demonstrated that these patterns were capable of transmitting fluid. The current study was undertaken to elucidate further the functional role of these patterns in tumor perfusion and to examine the composition of the patterns by immunohistochemistry. METHODS. To study the role of these patterns in perfusion, fluorochrome-labeled bovine serum albumin, bovine insulin, and dextrans of different molecular sizes were injected intravenously into nude mice bearing subcutaneous human cutaneous melanoma xenografts. Distribution of the human melanoma cells and murine host cells was analyzed by DNA in situ hybridization. To elucidate the composition of these patterns, human uveal melanoma tissues were analyzed for expression of ECM components by immunohistochemistry. RESULTS. Small molecules (Stokes&apos; radius Ͻ4.4 nm) crossed the vessel wall and spread along the ECM patterns within 2 to 10 minutes, whereas larger molecules (Stokes&apos; radius ϳ5.8 nm) required 30 to 45 minutes to enter. Murine host cells were found exclusively in the ECM pattern compartment. In primary uveal melanoma, different types of collagen, ECM-associated heparan sulfate proteoglycans, and different types of cells were present in the patterns. CONCLUSIONS. The data suggest that the ECM deposited as arcs, loops, and network patterns, accommodate the transport of plasma-derived molecules, (e.g., nutrients), to the tumor lesion, thus enhancing tumor growth and progression, and facilitating infiltration of tumor tissue by host-derived cells. (Invest Ophthalmol Vis Sci. 2005;46:3013-3020

Report on existing vocational European Fission Training Schemes and their accreditation

This report was produced as a deliverable in the frame of the ENEN Plus project. It provides an overview of all twenty-five projects carried out under the Euratom Fission Training Schemes (EFTS) and their main achievements. Almost all projects are completed to date except for three. The EFTS's ultimate goal is to develop a European passport for Continuous Professional Development, which relies on the principles of modularity of courses and common qualification criteria, a common mutual recognition system, and the facilitation of teacher, student and worker mobility across the EU. The conclusions of this review will be published in a separate report.JRC.G.10-Knowledge for Nuclear Security and Safet

Neutron Resonance Capture Analysis (NRCA), elemental compositions of bronze age objects

Prehistory of Nortwestern Europ

Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts

Angiogenesis is a multistep process that is limited and carefully regulated in normal adult tissue, but in tumours this regulation is disrupted and the process remains ‘switched on’ (Hanahan and Folkman, 1996). Ample experimental data support the fact that tumour growth requires access to blood vessels and subsequent expansion of host vessels to provide nutrients for the growing tumour mass (Folkman, 1995a). Furthermore, many studies in a variety of tumour types have reported a correlation between the extent of tumour vasculature and poor prognosis or increased metastases (Weidner et al, 1991; Folkman, 1995b; Weidner and Folkman, 1996). Thus, accurate assessment of the vasculature of tumours could provide valuable information regarding treatment outcomes and the likelihood of metastatic spread to other sites. Angiogenesis can be regulated by a variety of factors. Several cytokines produced by immune cells also have been shown to affect the process of angiogenesis. One of the most noteworthy is interleukin (IL)-12, which is produced by antigen presenting cells (APC), such as macrophages and dendritic cells (DC) in response to bacterial stimuli or other inflammatory cytokines. Thus, IL-12 plays an important role in both the innate and adaptive immune responses (Trinchieri, 1998). Owing to its central role in stimulating immunity, it has been examined for possible therapeutic effects in the treatment of tumours. In addition to its effects on the immune system, IL-12 has also been shown to inhibit angiogenesis (Voest et al, 1995; Sgadari et al, 1996). Despite studies in both experimental models and in patients (reviewed in Trinchieri and Scott, 1999), and clear demonstrations of therapeutic efficacy, relatively little is known about how it alters vessel formation within tumours. In part, this is due to the difficulty in assessing the three-dimensional structure of vessels and other cellular components within the tumour. Assessment of tumour vessels is generally based on immunohistochemistry of tumour sections. Although use of this technique has led to a great deal of important information, these procedures are extremely time consuming and provide only a limited two-dimensional view of the vessels. This makes it very difficult to visualise the structure of the microvasculature and identify differences among different tumour types or changes following treatment regimens. To more easily and accurately visualise vessels within tumours, we developed a whole-tissue mount technique that provides a three-dimensional view of the tumour vasculature relative to other components of the tumour tissue. This technique was first validated by studying vessels from transgenic mice that express green fluorescent protein (GFP) (Wu et al, 2000), and then used to investigate the mechanism by which IL-12 influences the vessel architecture within B16 tumours