International comparability of reference unit costs of education services: when harmonizing methodology is not enough (PECUNIA project).

BACKGROUND: Health problems can lead to costs in the education sector. However, these costs are rarely incorporated in health economic evaluations due to the lack of reference unit costs (RUCs), cost per unit of service, of education services and of validated methods to obtain them. In this study, a standardized unit cost calculation tool developed in the PECUNIA project, the PECUNIA RUC Template for services, was applied to calculate the RUCs of selected education services in five European countries. METHODS: The RUCs of special education services and of educational therapy were calculated using the information collected via an exploratory gray literature search and contact with service providers. RESULTS: The RUCs of special education services ranged from €55 to €189 per school day. The RUCs of educational therapy ranged from €6 to €25 per contact and from €5 to €35 per day. Variation was observed in the type of input data and measurement unit, among other. DISCUSSION: The tool helped reduce variability in the RUCs related to costing methodology and gain insights into other aspects that contribute to the variability (e.g. data availability). Further research and efforts to generate high quality input data are required to reduce the variability of the RUCs.

Magnitude of terminological bias in international health services research: a disambiguation analysis in mental health.

AIMS: Health services research (HSR) is affected by a widespread problem related to service terminology including non-commensurability (using different units of analysis for comparisons) and terminological unclarity due to ambiguity and vagueness of terms. The aim of this study was to identify the magnitude of the terminological bias in health and social services research and health economics by applying an international classification system. METHODS: This study, that was part of the PECUNIA project, followed an ontoterminology approach (disambiguation of technical and scientific terms using a taxonomy and a glossary of terms). A listing of 56 types of health and social services relevant for mental health was compiled from a systematic review of the literature and feedback provided by 29 experts in six European countries. The disambiguation of terms was performed using an ontology-based classification of services (Description and Evaluation of Services and DirectoriEs - DESDE), and its glossary of terms. The analysis focused on the commensurability and the clarity of definitions according to the reference classification system. Interrater reliability was analysed using κ. RESULTS: The disambiguation revealed that only 13 terms (23%) of the 56 services selected were accurate. Six terms (11%) were confusing as they did not correspond to services as defined in the reference classification system (non-commensurability bias), 27 (48%) did not include a clear definition of the target population for which the service was intended, and the definition of types of services was unclear in 59% of the terms: 15 were ambiguous and 11 vague. The κ analyses were significant for agreements in unit of analysis and assignment of DESDE codes and very high in definition of target population. CONCLUSIONS: Service terminology is a source of systematic bias in health service research, and certainly in mental healthcare. The magnitude of the problem is substantial. This finding has major implications for the international comparability of resource use in health economics, quality and equality research. The approach presented in this paper contributes to minimise differentiation between services by taking into account key features such as target population, care setting, main activities and type and number of professionals among others. This approach also contributes to support financial incentives for effective health promotion and disease prevention. A detailed analysis of services in terms of cost measurement for economic evaluations reveals the necessity and usefulness of defining services using a coding system and taxonomical criteria rather than by 'text-based descriptions'.

Most important barriers and facilitators of HTA usage in decision-making in Europe.

BACKGROUND: To enhance usage of health technology assessment (HTA) in decision-making, it is important to prioritise important barriers and facilitators to the uptake of HTA. This study aims to quantify and compare the relative importance of barriers and facilitators regarding the use of HTA in several European countries. METHODS: A survey containing two best-worst scaling (BWS) object case studies (i.e. barriers and facilitators) were conducted among 136 policy makers and HTA researchers from the Netherlands, Germany, France, and United Kingdom. Hierarchical Bayes analysis generated the mean relative importance score (RIS) for each factor and subgroup analyses assessed differences between countries. RESULTS: Six barriers (RIS≥5) and five facilitators (RIS≥6) were deemed highly important. Eleven barriers and ten facilitators differed in their importance between countries. Policy characteristics, research & researcher characteristics, and organisation & resources were particularly important to facilitate uptake of HTA, such as an explicit framework for decision-making and research of sufficient quality. CONCLUSION: The most paramount barriers and facilitators to HTA usage were quantified. For all countries it is crucial to create an explicit framework for the decision-making context to include HTA evidence. Country differences in the quality of research emphasize the need for enhanced international collaboration in HTA.

INVESTIGATION OF THE EXTENDED RANGE REM-COUNTER SMARTREM-LINUS IN REFERENCE AND WORKPLACE FIELDS EXPECTED AROUND HIGH-ENERGY ACCELERATORS.

Radiation survey instrumentation is adequate for the use around high-energy accelerators if capable to measure the dose arising from neutrons with energies ranging from thermal up to a few gigaelectronvolts. The SmartREM-LINUS is a commercial extended range rem-counter, consisting of a central (3)He-proportional counter surrounded by a spherical moderator made of borated polyethylene with an internal shield made of lead. The dose rate indicated by the SmartREM-LINUS was investigated for two different irradiation conditions. The linearity and the angular dependence of the indicated dose rate were investigated using reference neutron fields produced by (241)AmBe and (252)Cf. Additional measurements were performed in two different workplace fields with a component of neutrons with energies >20 MeV, namely the CERN-EU high-energy reference field and near the beam dump of the SwissFEL injector test facility. The measured dose rates were compared to a commercial rem-counter (WENDI2) and the results of Monte Carlo simulations.

Video sequence compared to conventional freeze image documentation: a way to improve the sonographic assessment of breast lesions?

PURPOSE: To compare video sequence and conventional freeze image documentation of breast ultrasound findings with respect to lesion assessment and the diagnostic power of established ultrasound characteristics. MATERIALS AND METHODS: Digitally stored freeze images and corresponding video sequences of 50 breast lesions were randomly arranged and interpreted by eight investigators with breast ultrasound training and experience. Established ultrasound criteria were documented on a standardized classification form for every lesion. The investigators were blinded to the clinical and radiological findings, patient characteristics including age, and lesion histology. Statistical analysis compared both groups and correlated the results with the lesion histology. A receiver operating characteristics (ROC) analysis was performed to evaluate the diagnostic performance of ultrasound criteria in lesions documented by video sequences compared to freeze images. RESULTS: Breast lesions were assessed almost identically in video sequences and freeze images. Only the features echogenic halo, orientation, and margin varied among both groups. The dynamic features compressibility and mobility were highly statistically significant correlated with the lesion histology in the video sequence interpretation (p < 0.0001). ROC analysis revealed almost identical diagnostic accuracy in both groups (area under the curve 0.719 for video sequences and 0.762 for freeze images). CONCLUSION: Video sequences are an appropriate tool to document lesions in breast ultrasound. In contrast to our hypothesis, however, this tool did not improve the diagnostic power of established ultrasound characteristics compared to freeze image documentation.

Characterisation of the PSI whole body counter by radiographic imaging.

A joint project between the Paul Scherrer Institut (PSI) and the Institute of Radiation Physics was initiated to characterise the PSI whole body counter in detail through measurements and Monte Carlo simulation. Accurate knowledge of the detector geometry is essential for reliable simulations of human body phantoms filled with known activity concentrations. Unfortunately, the technical drawings provided by the manufacturer are often not detailed enough and sometimes the specifications do not agree with the actual set-up. Therefore, the exact detector geometry and the position of the detector crystal inside the housing were determined through radiographic images. X-rays were used to analyse the structure of the detector, and (60)Co radiography was employed to measure the core of the germanium crystal. Moreover, the precise axial alignment of the detector within its housing was determined through a series of radiographic images with different incident angles. The hence obtained information enables us to optimise the Monte Carlo geometry model and to perform much more accurate and reliable simulations.

[Comparison of laparoscopic splenectomy in supine position with hanging-spleen technique in idiopathic thrombocytopenic purpura]. / Vergleich der laparoskopischen Splenektomie in Steinschnittlage mit der Hanging-Spleen-Technik bei idiopathischer thrombozytopenischer Purpura.

BACKGROUND: Laparoscopic splenectomy has become the gold standard intervention for elective splenectomy. Several techniques have been described, which differ in trocar localisations and patient positions. The hanging-spleen technique was examined in comparison to the conventional laparoscopic splenectomy in the supine position among the patient population in our institution over a period of 8 years. PATIENTS AND METHODS: On the basis of a retrospective analysis, data were collected on all patients who underwent elective laparoscopic splenectomy for idiopathic thrombocytopenic purpura between May 1994 and April 2002 and were examined for operation time, blood loss and peri-operative complications. Two types of operation were compared, the conventional laparoscopic splenectomy in the supine position (group A) and the hanging-spleen technique (group B). Finally, the costs of materials of the two operation techniques were compared. RESULTS: For 51 patients (43.1 % men, 56.9 % women) (mean age: 45.5 ± 17.5 years) the mean operation times were 134.2 ± 47.3 min (group A) and 9.8 ± 39.9 min (group B). The mean blood losses were 691.3 ± 544.4 mL in group A and 638.3 ± 1050.6 mL in group B. The perioperative complications were 38.8 % in group A and 21.2 % in group B. There was no significant difference found for operation time, blood loss and perioperative complications in a multivariate analysis. The cost of materials was reduced in group B (use of Endo-GIA 42.4 % in group B, 100 % in group A). In group A 4 incisions, in group B 3 incisions were necessary. CONCLUSIONS: Regarding operation time, blood loss and perioperative complications the 2 laparoscopic techniques for splenectomy do not differ significantly. Merely reduced material costs and a reduction of incisions were found in patients -operated with the hanging-spleen technique. Whether the hanging-spleen technique is the method of choice will have to be shown by further prospective studies.

Response of neutron detectors to high-energy mixed radiation fields.

Radiation protection around CERN's high-energy accelerators represents a major challenge due to the presence of complex, mixed radiation fields. Behind thick shielding neutrons dominate and their energy ranges from fractions of eV to about 1 GeV. In this work the response of various portable detectors sensitive to neutrons was studied at CERN's High-Energy Reference Field Facility (CERF). The measurements were carried out with conventional rem counters, which usually cover neutron energies up to 20 MeV, the Thermo WENDI-2, which is specified to measure neutrons up to several GeV, and a tissue-equivalent proportional counter. The experimentally determined neutron dose equivalent results were compared with Monte Carlo (MC) simulations. Based on these studies field calibration factors can be determined, which result in a more reliable estimate of H*(10) in an unknown, but presumably similar high-energy field around an accelerator than a calibration factor determined in a radiation field of a reference neutron source.

Declaration of patent applications as financial interests: a survey of practice among authors of papers on molecular biology in Nature.

OBJECTIVES: To determine whether authors of scientific publications in molecular biology declare patents and other potential financial interests. DESIGN: Survey of a 6-month sample of papers related to molecular biology in Nature. METHODS: The esp@cenet worldwide patent search engine was used to search for patents applied for by the authors of scientific papers in Nature that were related to molecular biology and genetics, between January and June 2005. RESULTS: Of the 79 papers considered, four had declared that certain authors had competing financial interests. Seven papers in which no financial interests were declared had authors with patent applications that were based on the research in the paper or were closely related to it. Another paper had two authors with connections to biotechnology companies that were not disclosed. CONCLUSION: Two thirds of the papers in which authors had patent applications or company affiliations that might be considered to be competing financial interests did not disclose them. Failure to disclose such information may have negative implications on the perception of science in society and on its quality if the possible bias is hidden. Journals should make greater efforts to ensure full disclosure, and scientific institutions should consider failure to disclose financial interests as an example of scientific malpractice. Establishing a register of interests for scientists is one way to increase transparency and openness.

Benchmark studies of induced radioactivity produced in LHC materials, Part I: Specific activities.

Samples of materials which will be used in the LHC machine for shielding and construction components were irradiated in the stray radiation field of the CERN-EU high-energy reference field facility. After irradiation, the specific activities induced in the various samples were analysed with a high-precision gamma spectrometer at various cooling times, allowing identification of isotopes with a wide range of half-lives. Furthermore, the irradiation experiment was simulated in detail with the FLUKA Monte Carlo code. A comparison of measured and calculated specific activities shows good agreement, supporting the use of FLUKA for estimating the level of induced activity in the LHC.

Benchmark studies of induced radioactivity produced in LHC materials, Part II: Remanent dose rates.

A new method to estimate remanent dose rates, to be used with the Monte Carlo code FLUKA, was benchmarked against measurements from an experiment that was performed at the CERN-EU high-energy reference field facility. An extensive collection of samples of different materials were placed downstream of, and laterally to, a copper target, intercepting a positively charged mixed hadron beam with a momentum of 120 GeV c(-1). Emphasis was put on the reduction of uncertainties by taking measures such as careful monitoring of the irradiation parameters, using different instruments to measure dose rates, adopting detailed elemental analyses of the irradiated materials and making detailed simulations of the irradiation experiment. The measured and calculated dose rates are in good agreement.

Hazard identification by methods of animal-based toxicology.

This paper is one of several prepared under the project "Food Safety In Europe: Risk Assessment of Chemicals in Food and Diet" (FOSIE), a European Commission Concerted Action Programme, organised by the International Life Sciences Institute, Europe (ILSI). The aim of the FOSIE project is to review the current state of the science of risk assessment of chemicals in food and diet, by consideration of the four stages of risk assessment, that is, hazard identification, hazard characterisation, exposure assessment and risk characterisation. The contribution of animal-based methods in toxicology to hazard identification of chemicals in food and diet is discussed. The importance of first applying existing technical and chemical knowledge to the design of safety testing programs for food chemicals is emphasised. There is consideration of the presently available and commonly used toxicity testing approaches and methodologies, including acute and repeated dose toxicity, reproductive and developmental toxicity, neurotoxicity, genotoxicity, carcinogenicity, immunotoxicity and food allergy. They are considered from the perspective of whether they are appropriate for assessing food chemicals and whether they are adequate to detect currently known or anticipated hazards from food. Gaps in knowledge and future research needs are identified; research on these could lead to improvements in the methods of hazard identification for food chemicals. The potential impact of some emerging techniques and toxicological issues on hazard identification for food chemicals, such as new measurement techniques, the use of transgenic animals, assessment of hormone balance and the possibilities for conducting studies in which common human diseases have been modelled, is also considered.

Assessment of intake from the diet.

Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals; (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including, for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks. Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for "worst case" situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however, require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general; (2) to assess the consumption patterns for the foods containing these substances, including especially those parts of the population with high consumption and thus potentially high intakes; and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances. It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a "worst case" estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These will be needed if initially high intakes are indicated for at least parts of the population. Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend, refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities, accuracy, etc.) will guide future data collection.

Precautionary approaches to the appraisal of risk: a case study of a genetically modified crop.

There are strong scientific reasons for holding the broader scope of precautionary approaches to be more consistent with the scientific foundations of rational choice and probability theory than are conventional narrow risk-assessment techniques. The imperatives both of science and precaution can be seen to pull in the same direction. The regulatory appraisal of risk should become more systematic and broader in scope. In particular, a set of criteria can be developed concerning the need for greater humility, completeness, transparency, and participation in regulatory appraisal, with specific attention to the comparison of different options (including mixtures of options), the consideration of benefits and justifications, and the systematic "mapping" of the ways in which different framing assumptions lead to different pictures of performance. A case study of a pilot exercise applying a multi-criteria mapping method to the regulatory appraisal of a genetically modified crop is reported. The results are more complete than orthodox risk assessment, in that they embody consideration of an unlimited array of issues and include consideration of a wide range of different strategic alternatives to the use of GM technologies. It is concluded that conventional regulatory appraisal might be adapted to better address the imperatives of both science and precaution.

Cost and outcome of mechanical ventilation for life-threatening stroke.

BACKGROUND AND PURPOSE: Hospital mortality rates of 50% to 90% have been reported for stroke patients treated with mechanical ventilation. These data have raised serious questions about the cost-effectiveness of this intervention. We sought to determine how often stroke patients are mechanically ventilated, identify predictors of 30-day survival among ventilated patients, and evaluate the cost-effectiveness of this intervention. METHODS: We identified mechanically ventilated patients in a population-based multiethnic cohort of 510 incidence stroke patients who were hospitalized between July 1993 and June 1996. Factors affecting 30-day survival were identified in a multiple logistic regression analysis. We calculated the cost per patient discharged alive, life-year saved, and quality-adjusted life-year saved using a zero-cost, zero-life assumption. RESULTS: Ten percent of patients (n=52) were mechanically ventilated. Thirty-day mortality was 65% overall and did not differ significantly by stroke subtype. Glasgow Coma Scale score on the day of intubation (P:<0.01) and subsequent neurological deterioration (P:=0.02) were identified as predictors of 30-day mortality. The cost (1996 US dollars) of hospitalization per patient discharged alive was $89 400; the cost per year of life saved was $37 600; and the cost per quality-adjusted life-year saved was $174 200. Functional status of most survivors was poor; at 6 months, half were severely disabled and completely dependent. In a worst-case scenario of quality of life preferences, mechanical ventilation resulted in a net deficit of meaningful survival. CONCLUSIONS: Two thirds of mechanically ventilated stroke patients die during their hospitalization, and most survivors are severely disabled. Survival is particularly unlikely if patients are deeply comatose or clinically deteriorate after intubation. In our multiethnic urban population, mechanical ventilation for stroke was relatively cost-effective for extending life but not for preserving quality of life.

Thoughts on the Jewish perspective regarding organ transplantation.

The purpose of this article is to convey some understanding of Orthodox Jewish thought on organ donation and transplantation. This perspective is particularly important as practitioners become more culturally diverse and medical care becomes more globalized. The Jewish ethical position, found in the Compendium on Medical Ethics: Jewish Moral, Ethical and Religious Principles in Medical Practice, is described. Points of view for determining death in Jewish law as well as some halakic (Jewish law) issues for the donor and recipient are also indicated.