Assessing patient's belief on HIV testing before elective surgery: room for improvements in Switzerland !

Background: ln Switzerland no HIV test is performed without the patient's consent based on a Voluntary Counseling and Testing policy (VCT). We hypothesized that a substantial proportion of patients going through an elective surgery falsely believed that an HIV test was performed on a routine basis and that the lack of transmission of result was interpreted as being HIV negative. Method: All patients with elective orthopedic surgery during 2007 were contacted by phone in 2008. A structured questionnaire assessed their belief about routine preoperative blood analysis (diabetes, coagulation function, HIV test and cholesterol level) as well as result awareness and interpretation. Variables included age and gender. Analysis were conducted using the software JMP 6.0.3. Results: 1123 patients were included. 130 (12 %) were excluded (Le. unreachable, unable to communicate on the phone, not operated). 993 completed the survey (89 %). Median age was 51 (16-79). 50 % were female. 376 (38 %) patients thought they had an HIV test performed before surgery but none of them had one. 298 (79 %) interpreted the absence of result as a negative HIV test. A predictive factor to believe an HIV test had been done was an age below 50 years old (45 % vs 33 % for 16-49 years old and 50-79 years old respectively, p < 0.001). No difference was observed between genders. Conclusion: ln Switzerland, nearly 40 % of the patients falsely thought an HIV test had been performed on a routine basis before surgery and were erroneously reassured about their HIV status. These results should either improve the information given to the patient regarding preoperative exams, or motivate public health policy to consider HIV opt-out screening instead of VCT strategy.

Virtual Library Services for a Virtual University : User-Oriented Virtual Sites in an Open Library

La llegada de las tecnologías de la información, y su uso cada vez mayor y generalizado que se está haciendo de ellas, ha permitido para que una nueva situación aparezca que, a su vez, ha originado - de hecho, que ha precipitado - una serie de cambios de gran importancia en todos los niveles, pero especialmente en los niveles sociales, económicos y culturales. Este nueva escena ha tenido una gran influencia en el entorno pedagógico. De hecho, la aparición de nuevos modelos educativos como resultado de este cambio ha estado sucediendo de una manera continuada e ininterrumpida durante la década pasada. Estos cambios recientes en los sistemas actuales de enseñanza y de aprendizaje han significado un aumento y un cambio en el tipo de demandas hechas desde las bibliotecas y los centros de documentación.

Testing Delivery Systems in Transnational virtual learning: the vocational management training for the european tourism industry (VocMat) case study

This article discusses the lessons learned from developing and delivering the Vocational Management Training for the European Tourism Industry (VocMat) online training programme, which was aimed at providing flexible, online distance learning for the European tourism industry. The programme was designed to address managers ‘need for flexible, senior management level training which they could access at a time and place which fitted in with their working and non-work commitments. The authors present two main approaches to using the Virtual Learning Environment, the feedback from the participants, and the implications of online Technology in extending tourism training opportunities

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.

Consensus statement of the European guidelines on clinical management of HIV-1 tropism testing

Introduction: Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. To date, in most European countries HIV tropism is determined using a phenotypic test. Recently, new data have emerged supporting the use of a genotypic HIV V3-loop sequence analysis as the basis for tropism determination. The European guidelines group on clinical management of HIV-1 tropism testing was established to make recommendations to clinicians and virologists. Methods: We searched online databases for articles from Jan 2006 until March 2010 with the terms: tropism or CCR5-antagonist or CCR5 antagonist or maraviroc or vicriviroc. Additional articles and/or conference abstracts were identified by hand searching. This strategy identified 712 potential articles and 1240 abstracts. All were reviewed and finally 57 papers and 42 abstracts were included and used by the panel to reach a consensus statement. Results: The panel recommends HIV-tropism testing for the following indications: i) drug-naïve patients in whom toxicity or limited therapeutic options are foreseen; ii) patients experiencing therapy failure whenever a treatment change is considered. Both the phenotypic Enhanced Trofile assay (ESTA) and genotypic population sequencing of the V3-loop are recommended for use in clinical practice. Although the panel does not recommend one methodology over another it is anticipated that genotypic testing will be used more frequently because of its greater accessibility, lower cost and shorter turnaround time. The panel also provides guidance on technical aspects and interpretation issues. If using genotypic methods, triplicate PCR amplification and sequencing testing is advised using the G2P interpretation tool (clonal model) with an FPR of 10%. If the viral load is below the level of reliable amplification, proviral DNA can be used, and the panel recommends performing triplicate testing and use of an FPR of 10%. If genotypic DNA testing is not performed in triplicate the FPR should be increased to 20%. Conclusions: The European guidelines on clinical management of HIV-1 tropism testing provide an overview of current literature, evidence-based recommendations for the clinical use of tropism testing and expert guidance on unresolved issues and current developments. Current data support both the use of genotypic population sequencing and ESTA for co-receptor tropism determination. For practical reasons genotypic population sequencing is the preferred method in Europe.

In vitro activity of fosfomycin against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: comparison of susceptibility testing procedures

The agar dilution, broth microdilution, and disk diffusion methods were compared to determine the in vitro susceptibility of 428 extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin. Fosfomycin showed very high activity against all ESBL-producing strains. Excellent agreement between the three susceptibility methods was found for E. coli, whereas marked discrepancies were observed for K. pneumoniae.

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung: a dialog between aerosol science and biology

The introduction of engineered nanostructured materials into a rapidly increasing number of industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of (consumer) products. The dynamic development of nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety.In this consensus document from a workshop on in-vitro cell systems for nanoparticle toxicity testing11Workshop on 'In-Vitro Exposure Studies for Toxicity Testing of Engineered Nanoparticles' sponsored by the Association for Aerosol Research (GAeF), 5-6 September 2009, Karlsruhe, Germany. an overview is given of the main issues concerning exposure to airborne nanoparticles, lung physiology, biological mechanisms of (adverse) action, in-vitro cell exposure systems, realistic tissue doses, risk assessment and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanoparticle toxicity. For the investigation of lung toxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they more closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. An important aspect, which is frequently overlooked, is the comparison of typically used in-vitro dose levels with realistic in-vivo nanoparticle doses in the lung. If we consider average ambient urban exposure and occupational exposure at 5mg/m3 (maximum level allowed by Occupational Safety and Health Administration (OSHA)) as the boundaries of human exposure, the corresponding upper-limit range of nanoparticle flux delivered to the lung tissue is 3×10-5-5×10-3μg/h/cm2 of lung tissue and 2-300particles/h/(epithelial) cell. This range can be easily matched and even exceeded by almost all currently available cell exposure systems.The consensus statement includes a set of recommendations for conducting in-vitro cell exposure studies with pulmonary cell systems and identifies urgent needs for future development. As these issues are crucial for the introduction of safe nanomaterials into the marketplace and the living environment, they deserve more attention and more interaction between biologists and aerosol scientists. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

Postmortem circulation: a new model for testing endovascular devices and training clinicians in their use.

The development of new medical devices, such as aortic valves, requires numerous preliminary studies on animals and training of personnel on cadavers before the devices can be used in patients. Postmortem circulation, a technique used for postmortem angiography, allows the vascular system to be reperfused in a way similar to that in living persons. This technique is used for postmortem investigations to visualize the human vascular system and to make vascular diagnoses. Specific material for reperfusing a human body was developed recently. Our aim was to investigate whether postmortem circulation that imitates in vivo conditions allows for the testing of medical materials on cadavers. We did this by delivering an aortic valve using minimally invasive methods. Postmortem circulation was established in eight corpses to recreate an environment as close as possible to in vivo conditions. Mobile fluoroscopy and a percutaneous catheterization technique were used to deliver the material to the correct place. Once the valve was implanted, the heart and primary vessels were extracted to confirm its position. Postmortem circulation proved to be essential in several of the cadavers because it helped the clinicians to deliver the material and improve their implantation techniques. Due to the intravascular circulation, sites with substantial arteriosclerotic stenosis could be bypassed, which would have been impossible without perfusion. Although originally developed for postmortem investigations, this reperfusion technique could be useful for testing new medical devices intended for living patients.

Testing of Diagnostic Methods for Detection of Influenza Virusfor Optimal Performance in the Context of an Influenza Surveillance Network

Influenza surveillance networks must detect early the viruses that will cause the forthcoming annual epidemics and isolate the strains for further characterization. We obtained the highest sensitivity (95.4%) with a diagnostic tool that combined a shell-vial assay and reverse transcription-PCR on cell culture supernatants at 48 h, and indeed, recovered the strain

Inventory and perspectives of chronic disease management programs in Switzerland: an exploratory survey.

OBJECTIVE: To describe chronic disease management programs active in Switzerland in 2007, using an exploratory survey. METHODS: We searched the internet (Swiss official websites and Swiss web-pages, using Google), a medical electronic database (Medline), reference lists of pertinent articles, and contacted key informants. Programs met our operational definition of chronic disease management if their interventions targeted a chronic disease, included a multidisciplinary team (>/=2 healthcare professionals), lasted at least six months, and had already been implemented and were active in December 2007. We developed an extraction grid and collected data pertaining to eight domains (patient population, intervention recipient, intervention content, delivery personnel, method of communication, intensity and complexity, environment, clinical outcomes). RESULTS: We identified seven programs fulfilling our operational definition of chronic disease management. Programs targeted patients with diabetes, hypertension, heart failure, obesity, psychosis and breast cancer. Interventions were multifaceted; all included education and half considered planned follow-ups. The recipients of the interventions were patients, and healthcare professionals involved were physicians, nurses, social workers, psychologists and case managers of various backgrounds. CONCLUSIONS: In Switzerland, a country with universal healthcare insurance coverage and little incentive to develop new healthcare strategies, chronic disease management programs are scarce. For future developments, appropriate evaluations of existing programs, involvement of all healthcare stakeholders, strong leadership and political will are, at least, desirable.

The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease

Among the pathophysiological derangements operating in the chronic phase of Chagas disease, parasite persistence is likely to constitute the main mechanism of myocardial injury in patients with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi in the heart causes a low-grade, but relentless, inflammatory process and induces myocardial autoimmune injury. These facts suggest that trypanocidal therapy may positively impact the clinical course of patients with chronic Chagas heart disease. However, the experimental and clinical evidence currently available is insufficient to support the routine use of etiologic treatment in these patients. The BENEFIT project - Benznidazole Evaluation for Interrupting Trypanosomiasis - is an international, multicenter, double-blind, placebo-controlled trial of trypanocidal treatment with benznidazole in patients with chronic Chagas heart disease. This project is actually comprised of two studies. The pilot study investigates whether etiologic treatment significantly reduces parasite burden, as assessed by polymerase chain reaction-based techniques and also determines the safety and tolerability profile of the trypanocidal drug in this type of chagasic population. The full-scale study determines whether antitrypanosomal therapy with benznidazole reduces mortality and other major cardiovascular clinical outcomes in patients with chronic Chagas heart disease.

Compositional hypotheses of subcompositional stability and specific perturbation change and their testing

In standard multivariate statistical analysis common hypotheses of interest concern changes in mean vectors and subvectors. In compositional data analysis it is now well established that compositional change is most readily described in terms of the simplicial operation of perturbation and that subcompositions replace the marginal concept of subvectors. To motivate the statistical developments of this paper we present two challenging compositional problems from food production processes.Against this background the relevance of perturbations and subcompositions can beclearly seen. Moreover we can identify a number of hypotheses of interest involvingthe specification of particular perturbations or differences between perturbations and also hypotheses of subcompositional stability. We identify the two problems as being the counterpart of the analysis of paired comparison or split plot experiments and of separate sample comparative experiments in the jargon of standard multivariate analysis. We then develop appropriate estimation and testing procedures for a complete lattice of relevant compositional hypotheses

Resource dimensioning aspect of heterogeneous traffic with different service requirements: Integration versus segregation

In this paper, we consider the ATM networks in which the virtual path concept is implemented. The question of how to multiplex two or more diverse traffic classes while providing different quality of service requirements is a very complicated open problem. Two distinct options are available: integration and segregation. In an integration approach all the traffic from different connections are multiplexed onto one VP. This implies that the most restrictive QOS requirements must be applied to all services. Therefore, link utilization will be decreased because unnecessarily stringent QOS is provided to all connections. With the segregation approach the problem can be much simplified if different types of traffic are separated by assigning a VP with dedicated resources (buffers and links). Therefore, resources may not be efficiently utilized because no sharing of bandwidth can take place across the VP. The probability that the bandwidth required by the accepted connections exceeds the capacity of the link is evaluated with the probability of congestion (PC). Since the PC can be expressed as the CLP, we shall simply carry out bandwidth allocation using the PC. We first focus on the influence of some parameters (CLP, bit rate and burstiness) on the capacity required by a VP supporting a single traffic class using the new convolution approach. Numerical results are presented both to compare the required capacity and to observe which conditions under each approach are preferred

The agreement between ipsative and normative questionnaires using compositional data analysis techniques

The main instrument used in psychological measurement is the self-report questionnaire. One of its majordrawbacks however is its susceptibility to response biases. A known strategy to control these biases hasbeen the use of so-called ipsative items. Ipsative items are items that require the respondent to makebetween-scale comparisons within each item. The selected option determines to which scale the weight ofthe answer is attributed. Consequently in questionnaires only consisting of ipsative items everyrespondent is allotted an equal amount, i.e. the total score, that each can distribute differently over thescales. Therefore this type of response format yields data that can be considered compositional from itsinception.Methodological oriented psychologists have heavily criticized this type of item format, since the resultingdata is also marked by the associated unfavourable statistical properties. Nevertheless, clinicians havekept using these questionnaires to their satisfaction. This investigation therefore aims to evaluate bothpositions and addresses the similarities and differences between the two data collection methods. Theultimate objective is to formulate a guideline when to use which type of item format.The comparison is based on data obtained with both an ipsative and normative version of threepsychological questionnaires, which were administered to 502 first-year students in psychology accordingto a balanced within-subjects design. Previous research only compared the direct ipsative scale scoreswith the derived ipsative scale scores. The use of compositional data analysis techniques also enables oneto compare derived normative score ratios with direct normative score ratios. The addition of the secondcomparison not only offers the advantage of a better-balanced research strategy. In principle it also allowsfor parametric testing in the evaluation

Methods for testing association between uncertain genotypes and quantitative traits.

Interpretability and power of genome-wide association studies can be increased by imputing unobserved genotypes, using a reference panel of individuals genotyped at higher marker density. For many markers, genotypes cannot be imputed with complete certainty, and the uncertainty needs to be taken into account when testing for association with a given phenotype. In this paper, we compare currently available methods for testing association between uncertain genotypes and quantitative traits. We show that some previously described methods offer poor control of the false-positive rate (FPR), and that satisfactory performance of these methods is obtained only by using ad hoc filtering rules or by using a harsh transformation of the trait under study. We propose new methods that are based on exact maximum likelihood estimation and use a mixture model to accommodate nonnormal trait distributions when necessary. The new methods adequately control the FPR and also have equal or better power compared to all previously described methods. We provide a fast software implementation of all the methods studied here; our new method requires computation time of less than one computer-day for a typical genome-wide scan, with 2.5 M single nucleotide polymorphisms and 5000 individuals.