OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.

Background: The OARSI Standing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains (pain, function, and patient's global assessment) as a single variable for clinical trials (1). For each domain, a response was defined by both a relative and an absolute change, with different cut-offs with regard to the drug, the route of administration and the OA localization. Objective: To propose a simplified set of responder criteria with a similar cut-off, whatever the drug, the route or the OA localization. Methods: Data driven approach: (1) Two databases were considered The 'elaboration' database with which the formal OARSI sets of responder criteria were elaborated and The 'revisit' database. (2) Six different scenarios were evaluated: The two formal OARSI sets of criteria Four proposed scenarios of simplified sets of criteria Data from clinical randomized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different databases ('elaboration' versus 'revisit') and those of the four proposed simplified scenarios within the 'revisit' database. The placebo effect, active effect, treatment effect, and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios. Experts' opinion approach: Results were discussed among the participants of the OMERACT VI meeting, who voted to select the definite OMERACT-OARSI set of criteria (one of the six evaluated scenarios). Results: Data driven approach: Fourteen trials totaling 1886 CA patients and fifteen studies involving 8164 CA patients were evaluated in the 'elaboration' and the 'revisit' databases respectively. The variability of the performances observed in the 'revisit' database when using the different simplified scenarios was similar to that observed between the two databases ('elaboration' versus 'revisit') when using the formal scenarios. The treatment effect and the required sample arm size were similar for each set of criteria. Experts' opinion approach: According to the experts, these two previous performances were the most important of an optimal set of responder criteria. They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response, with similar cut-offs whatever the drug, the route of administration or the CA localization. Conclusion: This data driven and experts' opinion approach is the basis for proposing an optimal simplified set of responder criteria for CA clinical trials. Other studies, using other sets of CA patients, are required in order to further validate this proposed OMERACT - OARSI set of criteria. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

International evaluation of current and future requirements for environmental engineering education

The field of environmental engineering is developing as a result of changing environmental requirements. In response, environmental engineering education (E3) needs to ensure that it provides students with the necessary tools to address these challenges. In this paper the current status and future development of E3 is evaluated based on a questionnaire sent to universities and potential employers of E3 graduates. With increasing demands on environmental quality, the complexity of environmental engineering problems to be solved can be expected to increase. To find solutions environmental engineers will need to work in interdisciplinary teams. Based on the questionnaire there was a broad agreement that the best way to prepare students for these future challenges is to provide them with a fundamental education in basic sciences and related engineering fields. Many exciting developments in the environmental engineering profession will be located at the interface between engineering, science, and society. Aspects of all three areas need to be included in E3 and the student needs to be exposed to the tensions associated with linking the three.

Antibiotic therapy for Klebsiella pneumoniae bacteremia: Implications of production of extended-spectrum beta-lactamases

The prevalence of extended-spectrum beta-lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL-producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem ( primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

Computerizing the welfare state: An international comparison of computerization in social security

Although computer technology is central to the operation of the modern welfare state, there has been little analysis of its role or of the factors shaping the way in which it is used. Using data generated by expert informants from 13 OECD countries, this paper provides an indicative comparison of the aims of computerization in national social security systems over a 15-year period from 1985 to 2000. The paper seeks to identify and explain patterns in the data and outlines and examines four hypotheses. Building on social constructivist accounts of technology, the first three hypotheses attribute variations in the aims of computerization to different welfare state regimes, forms of capitalism, and structures of public administration. The fourth hypothesis, which plays down the importance of social factors, assumes that computerization is adopted as a means of improving operational efficiency and generating expenditure savings. The findings suggest that, in all 13 countries, computerization was adopted in the expectation that it would lead to increased productivity and higher standards of performance, thus providing most support for the fourth hypothesis. However, variations between countries suggest that the sociopolitical values associated with different welfare state regimes have also had some effect in shaping the ways in which computer technology has been used in national social security systems.

Diabetes as a tracer condition in international benchmarking of health systems

OBJECTIVE - To assess the performance of health systems using diabetes as a tracer condition. RESEARCH DESIGN AND METHODS - We generated a measure of case-fatality among young people with diabetes Using the mortalily-to-incidence ratio (M/I ratio) for 29 industrialized countries using published data on diabetes incidence and mortality. Standardized incidence rates for ages 0-14 years were extracted from the World Health Organization DiaMond Study for the period 1990-1994; data on death from diabetes for ages 0-39 years were obtained from the World Health Organization Mortality database and converted into age-standardized death rates for the period 1994-1998, using the European standard population. RESULTS - The MA ratio varied > 10-fold. These relative differences appear similar to those observed in cohort studies of mortality among young people with type I diabetes in five countries. A sensitivity analysis showed that using plausible assumptions about potential overestimation of diabetes as a cause of death and underestimation of incidence rates in the U.S. yields an M/I ratio that would still be twice as high as in the U.K. or Canada. CONCLUSIONS - The M/I ratio for diabetes provides a means of differentiating countries on quality of care for people with diabetes. It is solely an indicator of potential problems, a basis for Stimulating more detailed assessments of whether such problems exist, and what can be done to address them.

Genetic uniformity of international isolates of Leifsonia xyli subsp xyli, causal agent of ratoon stunting disease of sugarcane

An international collection of the sugarcane ratoon stunting disease pathogen, Leifsonia xyli subsp. xyli, was analysed to assess genetic diversity. DNA fingerprinting using BOX primers was performed on 105 isolates, comprising 65 Australian isolates and an additional 40 isolates from Indonesia (n = 8), Japan (n = 1), USA (n = 3), Brazil (n = 2), Mali (n = 2), Zimbabwe (n = 13), South Africa (n = 9) and Reunion (n = 2). Sixty-two of these isolates were also screened using ERIC primers. No variation was found among any of the isolates. The intergenic spacer (IGS) region of the ribosomal RNA genes from 54 isolates was screened for sequence variation using single-stranded conformational polymorphism (SSCP), but none was observed. Direct sequencing of the IGS from a subset of nine isolates, representing all of the countries sampled in this study, confirmed the results of the SSCP analysis. Likewise, no sequence variation was found in the 16S ribosomal RNA genes of the same subset. Four Colombian isolates from sugarcane, morphologically similar to L. xyli subsp. xyli, were putatively shown to be an undescribed Agrococcus species of unknown pathogenicity. The lack of genetic variation among L. xyli subsp. xyli isolates, independent of time of sampling, cultivar of isolation, or country of origin, suggests the worldwide spread of a single pathogenic clone, and further suggests that sugarcane cultivars resistant to ratoon stunting disease in one area should retain this property in other regions.

The properties of the International Classification of the External Cause of Injury when used as an instrument for injury prevention research

Objective: To demonstrate properties of the International Classification of the External Cause of Injury (ICECI) as a tool for use in injury prevention research. Methods: The Childhood Injury Prevention Study (CHIPS) is a prospective longitudinal follow up study of a cohort of 871 children 5 - 12 years of age, with a nested case crossover component. The ICECI is the latest tool in the International Classification of Diseases (ICD) family and has been designed to improve the precision of coding injury events. The details of all injury events recorded in the study, as well as all measured injury related exposures, were coded using the ICECI. This paper reports a substudy on the utility and practicability of using the ICECI in the CHIPS to record exposures. Interrater reliability was quantified for a sample of injured participants using the Kappa statistic to measure concordance between codes independently coded by two research staff. Results: There were 767 diaries collected at baseline and event details from 563 injuries and exposure details from injury crossover periods. There were no event, location, or activity details which could not be coded using the ICECI. Kappa statistics for concordance between raters within each of the dimensions ranged from 0.31 to 0.93 for the injury events and 0.94 and 0.97 for activity and location in the control periods. Discussion: This study represents the first detailed account of the properties of the ICECI revealed by its use in a primary analytic epidemiological study of injury prevention. The results of this study provide considerable support for the ICECI and its further use.

International Union of Pharmacology. LXVI. Orphan nuclear receptors

Half of the members of the nuclear receptors superfamily are so-called orphan receptors because the identity of their ligand, if any, is unknown. Because of their important biological roles, the study of orphan receptors has attracted much attention recently and has resulted in rapid advances that have helped in the discovery of novel signaling pathways. In this review we present the main features of orphan receptors, discuss the structure of their ligand-binding domains and their biological functions. The paradoxical existence of a pharmacology of orphan receptors, a rapidly growing and innovative field, is highlighted.