Assessing the impact of health technology assessment in the Netherlands

Copyright © Cambridge University Press 2008Objectives: Investments in health research should lead to improvements in health and health care. This is also the remit of the main HTA program in the Netherlands. The aims of this study were to assess whether the results of this program have led to such improvements and to analyze how best to assess the impact from health research.Methods: We assessed the impact of individual HTA projects by adapting the "payback framework" developed in the United Kingdom. We conducted dossier reviews and sent a survey to principal investigators of forty-three projects awarded between 2000 and 2003. We then provided an overview of documented output and outcome that was assessed by ten HTA experts using a scoring method. Finally, we conducted five case studies using information from additional dossier review and semistructured key informant interviews.Results: The findings confirm that the payback framework is a useful approach to assess the impact of HTA projects. We identified over 101 peer reviewed papers, more than twenty-five PhDs, citations of research in guidelines (six projects), and implementation of new treatment strategies (eleven projects). The case studies provided greater depth and understanding about the levels of impact that arise and why and how they have been achieved.Conclusions: It is generally too early to determine whether the HTA program led to actual changes in healthcare policy and practice. However, the results can be used as a baseline measurement for future evaluation and can help funding organizations or HTA agencies consider how to assess impact, possibly routinely. This, in turn, could help inform research strategies and justify expenditure for health research.This research is funded by ZonMw, the Netherlands organization for health research and development (project 945-15-001)

Integrating Traditional and Social Media Data to Predict Bilateral Migrant Stocks in the European Union

Although up-to-date information on the nature and extent of migration within the European Union (EU) is important for policymaking, timely and reliable statistics on the number of EU citizens residing in or moving across other member states are difficult to obtain. In this paper, we develop a statistical model that integrates data on EU migrant stocks using traditional sources such as census, population registers and Labour Force Survey, with novel data sources, primarily from the Facebook Advertising Platform. Findings suggest that combining different data sources provides near real-time estimates that can serve as early warnings about shifts in EU mobility patterns. Estimated migrant stocks match relatively well to the observed data, despite some overestimation of smaller migrant populations and underestimation for larger migrant populations in Germany and the United Kingdom. In addition, the model estimates missing stocks for migrant corridors and years where no data are available, offering timely now-casted estimates

Pancreatic acinar cell carcinoma : an analysis of cell lineage markers, P53 expression, and Ki-ras mutation

In a series of 22 pancreatic acinar cell carcinomas, including two acinar cystadenocarcinomas, cellular differentiation was analyzed by immunocytochemistry and electron microscopy. In addition, overexpression of p53 protein and Ki-ras codon 12 mutation was studied. Four of the 20 noncystic acinar cell carcinomas showed a pure acinar pattern, nine an acinar-solid, and seven a solid pattern. All tumors stained for at least one of the following pancreatic acinar markers: trypsin (21 of 22), lipase (19 of 22), chymotrypsin (13 of 22), phospholipase A2 (nine of 22), and pancreatic stone protein (19 of 22). One-third of the tumors expressed neuroendocrine markers (synaptophysin, eight of 22; chromogranin A, six of 21) and duct cell markers (CA19.9, nine of 21; B72.3, six of 21). Cellular coexpression of trypsin and synaptophysin was demonstrated in one tumor. Electron microscopy revealed zymogen granules (nine of nine). In only one of 16 tumors a Ki-ras mutation at codon 12 was found, whereas in none of 19 tumors could overexpression of p53 protein be demonstrated. The results suggest that acinar cell carcinomas show obvious capacity to differentiate into several directions, but nevertheless constitute an entity different from ductal adenocarcinomas or endocrine tumors

Light-controlled inhibition of BRAFV600E kinase

Metastatic melanoma is amongst the most difficult types of cancer to treat, with current therapies mainly relying on the inhibition of the BRAFV600E mutant kinase. However, systemic inhibition of BRAF by small molecule drugs in cancer patients results - paradoxically - in increased wild-type BRAF activity in healthy tissue, causing side-effects and even the formation of new tumors. Here we show the development of BRAFV600E kinase inhibitors of which the activity can be switched on and off reversibly with light, offering the possibility to overcome problems of systemic drug activity by selectively activating the drug at the desired site of action. Based on a known inhibitor, eight photoswitchable effectors containing an azobenzene photoswitch were designed, synthesized and evaluated. The most promising inhibitor showed an approximately 10-fold increase in activity upon light-activation. This research offers inspiration for the development of therapies for metastatic melanoma in which tumor tissue is treated with an active BRAFV600E inhibitor with high spatial and temporal resolution, thus limiting the damage to other tissues

Litter mixture interactions at the level of plant functional types are additive.

It is very difficult to estimate litter decomposition rates in natural ecosystems because litters of many species are mixed and idiosyncratic interactions occur among those litters. A way to tackle this problem is to investigate litter mixing effects not at the species level but at the level of Plant Functional Types (PFTs). We tested the hypothesis that at the PFT level positive and negative interactions balance each other, causing an overall additive effect (no significant interactions among PFTs). Thereto, we used litter of four PFTs from a temperate peatland in which random draws were taken from the litter species pool of each PFT for every combination of 2, 3, and 4 PFTs. Decomposition rates clearly differed among the 4 PFTs (Sphagnum spp. < graminoids = N-fixing tree < forbs) and showed little variation within the PFTs (notably for the Sphagnum mosses and the graminoids). Significant positive interactions (4 out of 11) in the PFT mixtures were only found after 20 weeks and in all these combinations Sphagnum was involved. After 36 and 56 weeks of incubation interactions were not significantly different from zero. However, standard deviations were larger than the means, indicating that positive and negative interactions balanced each other. Thus, when litter mixture interactions are considered at the PFT level the interactions are additive. From this we conclude that for estimating litter decomposition rates at the ecosystem level, it is sufficient to use the weighted (by litter production) average decomposition rates of the contributing PFTs. © 2009 The Author(s)

Gendered self-views across 62 countries: A test of competing models

Social role theory posits that binary gender gaps in agency and communion should be larger in less egalitarian countries, reflecting these countries’ more pronounced sex-based power divisions. Conversely, evolutionary and self-construal theorists suggest that gender gaps in agency and communion should be larger in more egalitarian countries, reflecting the greater autonomy support and flexible self-construction processes present in these countries. Using data from 62 countries (N = 28,640), we examine binary gender gaps in agentic and communal self-views as a function of country-level objective gender equality (the Global Gender Gap Index) and subjective distributions of social power (the Power Distance Index). Findings show that in more egalitarian countries, gender gaps in agency are smaller and gender gaps in communality are larger. These patterns are driven primarily by cross-country differences in men’s self-views and by the Power Distance Index (PDI) more robustly than the Global Gender Gap Index (GGGI). We consider possible causes and implications of these findings.info:eu-repo/semantics/acceptedVersio

Neighbour identity hardly affects litter-mixture effects on decomposition rates of New Zealand forest species.

The mass loss of litter mixtures is often different than expected based on the mass loss of the component species. We investigated if the identity of neighbour species affects these litter-mixing effects. To achieve this, we compared decomposition rates in monoculture and in all possible two-species combinations of eight tree species, widely differing in litter chemistry, set out in two contrasting New Zealand forest types. Litter from the mixed-species litter bags was separated into its component species, which allowed us to quantify the importance of litter-mixing effects and neighbour identity, relative to the effects of species identity, litter chemistry and litter incubation environment. Controlling factors on litter decomposition rate decreased in importance in the order: species identity (litter quality) >> forest type >> neighbour species. Species identity had the strongest influence on decomposition rate. Interspecific differences in initial litter lignin concentration explained a large proportion of the interspecific differences in litter decomposition rate. Litter mass loss was higher and litter-mixture effects were stronger on the younger, more fertile alluvial soils than on the older, less-fertile marine terrace soils. Litter-mixture effects only shifted percentage mass loss within the range of 1.5%. There was no evidence that certain litter mixtures consistently showed interactive effects. Contrary to common theory, adding a relatively fast-decomposing species generally slowed down the decomposition of the slower decomposing species in the mixture. This study shows that: (1) species identity, litter chemistry and forest type are quantitatively the most important drivers of litter decomposition in a New Zealand rain forest; (2) litter-mixture effects—although statistically significant—are far less important and hardly depend on the identity and the chemical characteristics of the neighbour species; (3) additive effects predominate in this ecosystem, so that mass dynamics of the mixtures can be predicted from the monocultures

Assay for high glucose-mediated islet cell sensitization to apoptosis induced by streptozotocin and cytokines

Pancreatic β-cell apoptosis is known to participate in the β-cell destruction process that occurs in diabetes. It has been described that high glucose level induces a hyperfunctional status which could provoke apoptosis. This phenomenon is known as glucotoxicity and has been proposed that it can play a role in type 1 diabetes mellitus pathogenesis. In this study we develop an experimental design to sensitize pancreatic islet cells by high glucose to streptozotocin (STZ) and proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor (TNF)-α and interferon (IFN)-γ]-induced apoptosis. This method is appropriate for subsequent quantification of apoptotic islet cells stained with Tdt-mediated dUTP Nick-End Labeling (TUNEL) and protein expression assays by Western Blotting (WB)

The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett’s esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett’s Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%–88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients