Perception et communication du risque: du diabète à la maladie cardiovasculaire [Risk perception and communication: from diabetes to cardiovascular diseases].

Evidence-based medicine has enabled to approach disease in a more rational and scientific way. Clinical research has identified behaviours and risk factors that could cause disease often "silent" at the beginning, such as diabetes. Despite the clear impact of these evidences on public health, it seems that the individual risk perception level remains weak. To mention as well, the health professionals very often have a different views, which makes it difficult to communicate the risk with patients. In this article we describe the principles of risk perception, the diabetes related risk perception concerning cardiovascular complications, and suggest some practical strategies and tools which could improve risk communication in the everyday practice.

Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.

BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase. RESULTS: All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score. CONCLUSIONS: The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be different.

The Sequential Organ Failure Assessment score and copeptin for predicting survival in ventilator-associated pneumonia.

INTRODUCTION: Ventilator-associated pneumonia remains the most common nosocomial infection in the critically ill and contributes to significant morbidity. Eventual decisions regarding withdrawal or maximal therapy are demanding and rely on physicians' experience. Additional objective tools for risk assessment may improve medical judgement. Copeptin, reflecting vasopressin release, as well as the Sequential Organ Failure Assessment (SOFA) score, reflecting the individual degree of organ dysfunction, might qualify for survival prediction in ventilator-associated pneumonia. We investigated the predictive value of the SOFA score and copeptin in ventilator-associated pneumonia. METHODS: One hundred one patients with ventilator-associated pneumonia were prospectively assessed. Death within 28 days after ventilator-associated pneumonia onset was the primary end point. RESULTS: The SOFA score and the copeptin levels at ventilator-associated pneumonia onset were significantly elevated in nonsurvivors (P = .002 and P = .017, respectively). Both markers had different time courses in survivors and nonsurvivors (P < .001 and P = .006). Mean SOFA (average SOFA of 10 days after VAP onset) was superior in predicting 28-day survival as compared with SOFA and copeptin at ventilator-associated pneumonia onset (area under the curve, 0.90 vs 0.73 and 0.67, respectively). CONCLUSIONS: The predictive value of serial-measured SOFA significantly exceeds those of single SOFA and copeptin measurements. Serial SOFA scores accurately predict outcome in ventilator-associated pneumonia.

Small dense lipoproteins, apolipoprotein B, and risk of coronary events in HIV-infected patients on antiretroviral therapy: the Swiss HIV Cohort Study.

OBJECTIVES: HIV infection and exposure to certain antiretroviral drugs is associated with dyslipidemia and increased risk for coronary events. Whether this risk is mediated by highly atherogenic lipoproteins is unclear. We investigated the association of highly atherogenic small dense low-density lipoproteins (LDLs) and apolipoprotein B and coronary events in HIV-infected individuals receiving antiretroviral therapy. METHODS: We conducted a case-control study nested into the Swiss HIV Cohort Study to investigate the association of small dense LDL and apolipoprotein B and coronary events in 98 antiretroviral drug-treated patients with a first coronary event (19 fatal and 79 nonfatal coronary events with 53 definite and 15 possible myocardial infarctions, 11 angioplasties or bypasses) and 393 treated controls matched for age, gender, and smoking status. Lipids were measured by ultracentrifugation. RESULTS: In models including cholesterol, triglycerides, high-density lipoprotein cholesterol, blood pressure, central obesity, diabetes, and family history, there was an independent association between small dense LDL and coronary events [odds ratio (OR) for 1 mg/dL increase: 1.06, 95% confidence interval (CI): 1.00 to 1.11] and apolipoprotein B (OR for 10 mg/dL increase: 1.16, 95% CI: 1.02 to 1.32). When adding HIV and antiretroviral therapy-related variables, ORs were 1.04 (95% CI: 0.99 to 1.10) for small dense LDL and 1.13 (95% CI: 0.99 to 1.30) for apolipoprotein B. In both models, blood pressure and HIV viral load was independently associated with the odds for coronary events. CONCLUSIONS: HIV-infected patients receiving antiretroviral therapy with elevate small dense LDL and apolipoprotein B are at increased risk for coronary events as are patients without sustained HIV suppression.

A reflection about the social and technological aspects in flood risk management - the case of the Italian Civil Protection

The right of a person to be protected from natural hazards is a characteristic of the social and economical development of the society. This paper is a contribution to the reflection about the role of Civil Protection organizations in a modern society. The paper is based in the inaugural conference made by the authors on the 9th Plinius Conference on Mediterranean Storms. Two major issues are considered. The first one is sociological; the Civil Protection organizations and the responsible administration of the land use planning should be perceived as reliable as possible, in order to get consensus on the restrictions they pose, temporary or definitely, on the individual free use of the territory as well as in the entire warning system. The second one is technological: in order to be reliable they have to issue timely alert and warning to the population at large, but such alarms should be as "true" as possible. With this aim, the paper summarizes the historical evolution of the risk assessment, starting from the original concept of "hazard", introducing the concepts of "scenario of event" and "scenario of risk" and ending with a discussion about the uncertainties and limits of the most advanced and efficient tools to predict, to forecast and to observe the ground effects affecting people and their properties. The discussion is centred in the case of heavy rains and flood events in the North-West of Mediterranean Region.

Bilan préopératoire pour la chirurgie cardio-vasculaire en urgence [Preoperative assessment in emergency cardiovascular surgery].

In the emergency situation, preoperative patient work-up for cardio-vascular surgery is quite different from the elective setting. We have analyzed a consecutive series of 5576 cases out of which 823 underwent emergency procedures (14.8%). The most frequent problems requiring emergent intervention were peripheral vascular (186 cases; 22.6% of the emergent procedure), followed by coronary artery disease (156 cases; 19.0%), thoracic aortic aneurysms (86 cases; 10.4%), abdominal aortic aneurysms (54 cases; 6.6%), congenital heart disease (36 cases: 4.4%), heart and heart lung transplantation (31 cases; 3.8%), problems with cardiac rythm (25 cases: 3.0%), and others (267 cases: 32.4%). Classification by proportion of urgent procedures with reference to elective operations shows a different picture. As a matter of fact transplantations were always emergency procedures (100%), whereas repair of aortic dissections type A and B was an emergency procedure in 81.5%. Emergency thoracic and abdominal aortic aneurysm repair accounted for 30% and 20% respectively and the corresponding proportion for peripheral vascular surgery is 19%. However, emergency surgery for acute coronary ischemia, valvular and congenital heart disease accounted for somewhat less than 10% for each group of these pathologies. Systematic pre-operative diagnostic work-up is a recognized tool for procedure related risk assessment and superior management of diseases. However, hemodynamic instability and other time related events correlated with negative outcome, are the main driving forces for accelerated diagnostic pathways

Prevalence of cardiovascular risk factors in a middle-income country and estimated cost of a treatment strategy.

BACKGROUND: We assessed the prevalence of risk factors for cardiovascular disease (CVD) in a middle-income country in rapid epidemiological transition and estimated direct costs for treating all individuals at increased cardiovascular risk, i.e. following the so-called "high risk strategy". METHODS: Survey of risk factors using an age- and sex-stratified random sample of the population of Seychelles aged 25-64 in 2004. Assessment of CVD risk and treatment modalities were in line with international guidelines. Costs are expressed as USD per capita per year. RESULTS: 1255 persons took part in the survey (participation rate of 80.2%). Prevalence of main risk factors was: 39.6% for high blood pressure (> or =140/90 mmHg or treatment) of which 59% were under treatment; 24.2% for high cholesterol (> or =6.2 mmol/l); 20.8% for low HDL-cholesterol (<1.0 mmol/l); 9.3% for diabetes (fasting glucose > or =7.0 mmol/l); 17.5% for smoking; 25.1% for obesity (body mass index > or =30 kg/m2) and 22.1% for the metabolic syndrome. Overall, 43% had HBP, high cholesterol or diabetes and substantially increased CVD risk. The cost for medications needed to treat all high-risk individuals amounted to USD 45.6, i.e. 11.2 dollars for high blood pressure, 3.8 dollars for diabetes, and 30.6 dollars for dyslipidemia (using generic drugs except for hypercholesterolemia). Cost for minimal follow-up medical care and laboratory tests amounted to 22.6 dollars. CONCLUSION: High prevalence of major risk factors was found in a rapidly developing country and costs for treatment needed to reduce risk factors in all high-risk individuals exceeded resources generally available in low or middle income countries. Our findings emphasize the need for affordable cost-effective treatment strategies and the critical importance of population strategies aimed at reducing risk factors in the entire population.

Risque thrombotique sous procréation médicalement assistée [Thrombotic risk in assisted reproductive technology].

Use of assisted reproductive technology (ART) is increasing in many developed countries. Arterial and venous thromboembolic complications are reported during ART with an incidence of 0.1%. The development of these events has been mainly ascribed to the presence of ovarian hyperstimulation syndrome (OHSS). Precise mechanisms by which OHSS and exogenous hormonal stimulation used in ART induce thromboembolic events remain unclear. However, vascular endothelial growth factor secreted during OHSS, high estradiol concentrations, and blood hyperviscosity play a major role in inducing a prothrombotic state. Therefore, before planning an ART, individual thromboembolic risk should be assessed and thromboprophylaxis offered to high risk patients. Prophylaxis should be initiated in women who develop moderate-to-severe OHSS.

External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study.

BACKGROUND: We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. METHODS: For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. FINDINGS: Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. INTERPRETATION: In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Assessing alpine plant vulnerability to climate change: A modeling perspective

The potential ecological impact of ongoing climate change has been much discussed. High mountain ecosystems were identified early on as potentially very sensitive areas. Scenarios of upward species movement and vegetation shift are commonly discussed in the literature. Mountains being characteristically conic in shape, impact scenarios usually assume that a smaller surface area will be available as species move up. However, as the frequency distribution of additional physiographic factors (e.g., slope angle) changes with increasing elevation (e.g., with few gentle slopes available at higher elevation), species migrating upslope may encounter increasingly unsuitable conditions. As a result, many species could suffer severe reduction of their habitat surface, which could in turn affect patterns of biodiversity. In this paper, results from static plant distribution modeling are used to derive climate change impact scenarios in a high mountain environment. Models are adjusted with presence/absence of species. Environmental predictors used are: annual mean air temperature, slope, indices of topographic position, geology, rock cover, modeled permafrost and several indices of solar radiation and snow cover duration. Potential Habitat Distribution maps were drawn for 62 higher plant species, from which three separate climate change impact scenarios were derived. These scenarios show a great range of response, depending on the species and the degree of warming. Alpine species would be at greatest risk of local extinction, whereas species with a large elevation range would run the lowest risk. Limitations of the models and scenarios are further discussed.

Mesure de la pression artérielle: meilleur moyen d'évaluer le risque cardiovasculaire [Measurement of blood pressure: best way to assess cardiovascular risk?]

Measurement of the blood pressure by the physician remains an essential step in the evaluation of cardiovascular risk. Ambulatory measurement and self-measurement of blood pressure are ways of counteracting the "white coat" effect which is the rise in blood pressure many patients experience in the presence of doctors. Thus, it is possible to define the cardiovascular risk of hypertension and identify the patients with the greatest chance of benefiting from antihypertensive therapy. However, it must be realised that normotensive subjects during their everyday activities and becoming hypertensive in the doctor's surgery, may become hypertensive with time, irrespective of the means used to measure blood pressure. These patients should be followed up regularly even if the decision to treat has been postponed.

Assessment of the occurrence of nanoparticles in Swiss industry and evaluation of the appropriatenesss of the measurement devices to determine the workforce exposure

Abstract : The occupational health risk involved with handling nanoparticles is the probability that a worker will experience an adverse health effect: this is calculated as a function of the worker's exposure relative to the potential biological hazard of the material. Addressing the risks of nanoparticles requires therefore knowledge on occupational exposure and the release of nanoparticles into the environment as well as toxicological data. However, information on exposure is currently not systematically collected; therefore this risk assessment lacks quantitative data. This thesis aimed at, first creating the fundamental data necessary for a quantitative assessment and, second, evaluating methods to measure the occupational nanoparticle exposure. The first goal was to determine what is being used where in Swiss industries. This was followed by an evaluation of the adequacy of existing measurement methods to assess workplace nanopaiticle exposure to complex size distributions and concentration gradients. The study was conceived as a series of methodological evaluations aimed at better understanding nanoparticle measurement devices and methods. lt focused on inhalation exposure to airborne particles, as respiration is considered to be the most important entrance pathway for nanoparticles in the body in terms of risk. The targeted survey (pilot study) was conducted as a feasibility study for a later nationwide survey on the handling of nanoparticles and the applications of specific protection means in industry. The study consisted of targeted phone interviews with health and safety officers of Swiss companies that were believed to use or produce nanoparticles. This was followed by a representative survey on the level of nanoparticle usage in Switzerland. lt was designed based on the results of the pilot study. The study was conducted among a representative selection of clients of the Swiss National Accident Insurance Fund (SUVA), covering about 85% of Swiss production companies. The third part of this thesis focused on the methods to measure nanoparticles. Several pre- studies were conducted studying the limits of commonly used measurement devices in the presence of nanoparticle agglomerates, This focus was chosen, because several discussions with users and producers of the measurement devices raised questions about their accuracy measuring nanoparticle agglomerates and because, at the same time, the two survey studies revealed that such powders are frequently used in industry. The first preparatory experiment focused on the accuracy of the scanning mobility particle sizer (SMPS), which showed an improbable size distribution when measuring powders of nanoparticle agglomerates. Furthermore, the thesis includes a series of smaller experiments that took a closer look at problems encountered with other measurement devices in the presence of nanoparticle agglomerates: condensation particle counters (CPC), portable aerosol spectrometer (PAS) a device to estimate the aerodynamic diameter, as well as diffusion size classifiers. Some initial feasibility tests for the efficiency of filter based sampling and subsequent counting of carbon nanotubes (CNT) were conducted last. The pilot study provided a detailed picture of the types and amounts of nanoparticles used and the knowledge of the health and safety experts in the companies. Considerable maximal quantities (> l'000 kg/year per company) of Ag, Al-Ox, Fe-Ox, SiO2, TiO2, and ZnO (mainly first generation particles) were declared by the contacted Swiss companies, The median quantity of handled nanoparticles, however, was 100 kg/year. The representative survey was conducted by contacting by post mail a representative selection of l '626 SUVA-clients (Swiss Accident Insurance Fund). It allowed estimation of the number of companies and workers dealing with nanoparticles in Switzerland. The extrapolation from the surveyed companies to all companies of the Swiss production sector suggested that l'309 workers (95%-confidence interval l'073 to l'545) of the Swiss production sector are potentially exposed to nanoparticles in 586 companies (145 to l'027). These numbers correspond to 0.08% (0.06% to 0.09%) of all workers and to 0.6% (0.2% to 1.1%) of companies in the Swiss production sector. To measure airborne concentrations of sub micrometre-sized particles, a few well known methods exist. However, it was unclear how well the different instruments perform in the presence of the often quite large agglomerates of nanostructured materials. The evaluation of devices and methods focused on nanoparticle agglomerate powders. lt allowed the identification of the following potential sources of inaccurate measurements at workplaces with considerable high concentrations of airborne agglomerates: - A standard SMPS showed bi-modal particle size distributions when measuring large nanoparticle agglomerates. - Differences in the range of a factor of a thousand were shown between diffusion size classifiers and CPC/SMPS. - The comparison between CPC/SMPS and portable aerosol Spectrometer (PAS) was much better, but depending on the concentration, size or type of the powders measured, the differences were still of a high order of magnitude - Specific difficulties and uncertainties in the assessment of workplaces were identified: the background particles can interact with particles created by a process, which make the handling of background concentration difficult. - Electric motors produce high numbers of nanoparticles and confound the measurement of the process-related exposure. Conclusion: The surveys showed that nanoparticles applications exist in many industrial sectors in Switzerland and that some companies already use high quantities of them. The representative survey demonstrated a low prevalence of nanoparticle usage in most branches of the Swiss industry and led to the conclusion that the introduction of applications using nanoparticles (especially outside industrial chemistry) is only beginning. Even though the number of potentially exposed workers was reportedly rather small, it nevertheless underscores the need for exposure assessments. Understanding exposure and how to measure it correctly is very important because the potential health effects of nanornaterials are not yet fully understood. The evaluation showed that many devices and methods of measuring nanoparticles need to be validated for nanoparticles agglomerates before large exposure assessment studies can begin. Zusammenfassung : Das Gesundheitsrisiko von Nanopartikel am Arbeitsplatz ist die Wahrscheinlichkeit dass ein Arbeitnehmer einen möglichen Gesundheitsschaden erleidet wenn er diesem Stoff ausgesetzt ist: sie wird gewöhnlich als Produkt von Schaden mal Exposition gerechnet. Für eine gründliche Abklärung möglicher Risiken von Nanomaterialien müssen also auf der einen Seite Informationen über die Freisetzung von solchen Materialien in die Umwelt vorhanden sein und auf der anderen Seite solche über die Exposition von Arbeitnehmenden. Viele dieser Informationen werden heute noch nicht systematisch gesarnmelt und felilen daher für Risikoanalysen, Die Doktorarbeit hatte als Ziel, die Grundlagen zu schaffen für eine quantitative Schatzung der Exposition gegenüber Nanopartikel am Arbeitsplatz und die Methoden zu evaluieren die zur Messung einer solchen Exposition nötig sind. Die Studie sollte untersuchen, in welchem Ausmass Nanopartikel bereits in der Schweizer Industrie eingesetzt werden, wie viele Arbeitnehrner damit potentiel] in Kontakt komrrien ob die Messtechnologie für die nötigen Arbeitsplatzbelastungsmessungen bereits genügt, Die Studie folcussierte dabei auf Exposition gegenüber luftgetragenen Partikel, weil die Atmung als Haupteintrittspforte iïlr Partikel in den Körper angesehen wird. Die Doktorarbeit besteht baut auf drei Phasen auf eine qualitative Umfrage (Pilotstudie), eine repräsentative, schweizerische Umfrage und mehrere technische Stndien welche dem spezitischen Verständnis der Mëglichkeiten und Grenzen einzelner Messgeräte und - teclmikeri dienen. Die qualitative Telephonumfrage wurde durchgeführt als Vorstudie zu einer nationalen und repräsentativen Umfrage in der Schweizer Industrie. Sie zielte auf Informationen ab zum Vorkommen von Nanopartikeln, und den angewendeten Schutzmassnahmen. Die Studie bestand aus gezielten Telefoninterviews mit Arbeit- und Gesundheitsfachpersonen von Schweizer Unternehmen. Die Untemehmen wurden aufgrund von offentlich zugànglichen lnformationen ausgewählt die darauf hinwiesen, dass sie mit Nanopartikeln umgehen. Der zweite Teil der Dolctorarbeit war die repräsentative Studie zur Evalniernng der Verbreitnng von Nanopaitikelanwendungen in der Schweizer lndustrie. Die Studie baute auf lnformationen der Pilotstudie auf und wurde mit einer repräsentativen Selektion von Firmen der Schweizerischen Unfall Versicherungsanstalt (SUVA) durchgeüihxt. Die Mehrheit der Schweizerischen Unternehmen im lndustrieselctor wurde damit abgedeckt. Der dritte Teil der Doktorarbeit fokussierte auf die Methodik zur Messung von Nanopartikeln. Mehrere Vorstudien wurden dnrchgefîihrt, um die Grenzen von oft eingesetzten Nanopartikelmessgeräten auszuloten, wenn sie grösseren Mengen von Nanopartikel Agglomeraten ausgesetzt messen sollen. Dieser F okns wurde ans zwei Gründen gewählt: weil mehrere Dislcussionen rnit Anwendem und auch dem Produzent der Messgeràte dort eine Schwachstelle vermuten liessen, welche Zweifel an der Genauigkeit der Messgeräte aufkommen liessen und weil in den zwei Umfragestudien ein häufiges Vorkommen von solchen Nanopartikel-Agglomeraten aufgezeigt wurde. i Als erstes widmete sich eine Vorstndie der Genauigkeit des Scanning Mobility Particle Sizer (SMPS). Dieses Messgerät zeigte in Präsenz von Nanopartikel Agglorneraten unsinnige bimodale Partikelgrössenverteilung an. Eine Serie von kurzen Experimenten folgte, welche sich auf andere Messgeräte und deren Probleme beim Messen von Nanopartikel-Agglomeraten konzentrierten. Der Condensation Particle Counter (CPC), der portable aerosol spectrometer (PAS), ein Gerät zur Schàtzung des aerodynamischen Durchniessers von Teilchen, sowie der Diffusion Size Classifier wurden getestet. Einige erste Machbarkeitstests zur Ermittlnng der Effizienz von tilterbasierter Messung von luftgetragenen Carbon Nanotubes (CNT) wnrden als letztes durchgeiührt. Die Pilotstudie hat ein detailliiertes Bild der Typen und Mengen von genutzten Nanopartikel in Schweizer Unternehmen geliefert, und hat den Stand des Wissens der interviewten Gesundheitsschntz und Sicherheitsfachleute aufgezeigt. Folgende Typen von Nanopaitikeln wurden von den kontaktierten Firmen als Maximalmengen angegeben (> 1'000 kg pro Jahr / Unternehrnen): Ag, Al-Ox, Fe-Ox, SiO2, TiO2, und ZnO (hauptsächlich Nanopartikel der ersten Generation). Die Quantitäten von eingesetzten Nanopartikeln waren stark verschieden mit einem ein Median von 100 kg pro Jahr. ln der quantitativen Fragebogenstudie wurden l'626 Unternehmen brieflich kontaktiert; allesamt Klienten der Schweizerischen Unfallversicherringsanstalt (SUVA). Die Resultate der Umfrage erlaubten eine Abschätzung der Anzahl von Unternehmen und Arbeiter, welche Nanopartikel in der Schweiz anwenden. Die Hochrechnung auf den Schweizer lndnstriesektor hat folgendes Bild ergeben: ln 586 Unternehmen (95% Vertrauensintervallz 145 bis 1'027 Unternehmen) sind 1'309 Arbeiter potentiell gegenüber Nanopartikel exponiert (95%-Vl: l'073 bis l'545). Diese Zahlen stehen für 0.6% der Schweizer Unternehmen (95%-Vl: 0.2% bis 1.1%) und 0.08% der Arbeiternehmerschaft (95%-V1: 0.06% bis 0.09%). Es gibt einige gut etablierte Technologien um die Luftkonzentration von Submikrometerpartikel zu messen. Es besteht jedoch Zweifel daran, inwiefern sich diese Technologien auch für die Messurrg von künstlich hergestellten Nanopartikeln verwenden lassen. Aus diesem Grund folcussierten die vorbereitenden Studien für die Arbeitsplatzbeurteilnngen auf die Messung von Pulverri, welche Nan0partike1-Agg10merate enthalten. Sie erlaubten die ldentifikation folgender rnöglicher Quellen von fehlerhaften Messungen an Arbeitsplätzen mit erhöhter Luft-K0nzentrati0n von Nanopartikel Agglomeratenz - Ein Standard SMPS zeigte eine unglaubwürdige bimodale Partikelgrössenverteilung wenn er grössere Nan0par'til<e1Agg10merate gemessen hat. - Grosse Unterschiede im Bereich von Faktor tausend wurden festgestellt zwischen einem Diffusion Size Classiîier und einigen CPC (beziehungsweise dem SMPS). - Die Unterschiede zwischen CPC/SMPS und dem PAS waren geringer, aber abhängig von Grosse oder Typ des gemessenen Pulvers waren sie dennoch in der Grössenordnung von einer guten Grössenordnung. - Spezifische Schwierigkeiten und Unsicherheiten im Bereich von Arbeitsplatzmessungen wurden identitiziert: Hintergrundpartikel können mit Partikeln interagieren die während einem Arbeitsprozess freigesetzt werden. Solche Interaktionen erschweren eine korrekte Einbettung der Hintergrunds-Partikel-Konzentration in die Messdaten. - Elektromotoren produzieren grosse Mengen von Nanopartikeln und können so die Messung der prozessbezogenen Exposition stören. Fazit: Die Umfragen zeigten, dass Nanopartikel bereits Realitàt sind in der Schweizer Industrie und dass einige Unternehmen bereits grosse Mengen davon einsetzen. Die repräsentative Umfrage hat diese explosive Nachricht jedoch etwas moderiert, indem sie aufgezeigt hat, dass die Zahl der Unternehmen in der gesamtschweizerischen Industrie relativ gering ist. In den meisten Branchen (vor allem ausserhalb der Chemischen Industrie) wurden wenig oder keine Anwendungen gefunden, was schliessen last, dass die Einführung dieser neuen Technologie erst am Anfang einer Entwicklung steht. Auch wenn die Zahl der potentiell exponierten Arbeiter immer noch relativ gering ist, so unterstreicht die Studie dennoch die Notwendigkeit von Expositionsmessungen an diesen Arbeitsplätzen. Kenntnisse um die Exposition und das Wissen, wie solche Exposition korrekt zu messen, sind sehr wichtig, vor allem weil die möglichen Auswirkungen auf die Gesundheit noch nicht völlig verstanden sind. Die Evaluation einiger Geräte und Methoden zeigte jedoch, dass hier noch Nachholbedarf herrscht. Bevor grössere Mess-Studien durgefîihrt werden können, müssen die Geräte und Methodem für den Einsatz mit Nanopartikel-Agglomeraten validiert werden.

Risk of falls and major bleeds in patients on oral anticoagulation therapy.

BACKGROUND: The risk of falls is the most commonly cited reason for not providing oral anticoagulation, although the risk of bleeding associated with falls on oral anticoagulants is still debated. We aimed to evaluate whether patients on oral anticoagulation with high falls risk have an increased risk of major bleeding. METHODS: We prospectively studied consecutive adult medical patients who were discharged on oral anticoagulants. The outcome was the time to a first major bleed within a 12-month follow-up period adjusted for age, sex, alcohol abuse, number of drugs, concomitant treatment with antiplatelet agents, and history of stroke or transient ischemic attack. RESULTS: Among the 515 enrolled patients, 35 patients had a first major bleed during follow-up (incidence rate: 7.5 per 100 patient-years). Overall, 308 patients (59.8%) were at high risk of falls, and these patients had a nonsignificantly higher crude incidence rate of major bleeding than patients at low risk of falls (8.0 vs 6.8 per 100 patient-years, P=.64). In multivariate analysis, a high falls risk was not statistically significantly associated with the risk of a major bleed (hazard ratio 1.09; 95% confidence interval, 0.54-2.21). Overall, only 3 major bleeds occurred directly after a fall (incidence rate: 0.6 per 100 patient-years). CONCLUSIONS: In this prospective cohort, patients on oral anticoagulants at high risk of falls did not have a significantly increased risk of major bleeds. These findings suggest that being at risk of falls is not a valid reason to avoid oral anticoagulants in medical patients.

Prescription de statines en prévention primaire: quel score de risque cardiovasculaire faut-il utiliser en Suisse? [Statin prescription in primary prevention: which cardiovascular risk score should be used in Switzerland?]

La prévention primaire des maladies cardiovasculaires par les médecins s'effectue par une prise en charge individualisée des facteurs de risque. L'indication à un traitement par statines se base sur une estimation du risque de survenue d'une maladie cardiovasculaire et sur le taux de LDL-cholestérol. Trois scores de risque sont couramment utilisés: le score PROCAM, le score Framingham, et le SCORE européen. En Suisse, le Groupe Suisse Lipides et Athérosclérose (GSLA) recommande en première instance l'utilisation du score PROCAM avec une adaptation du niveau de risque pour la Suisse. Une enquête a aussi montré que c'est le score le plus utilisé en Suisse. Dans cet article, les particularités de ces scores et leurs applications pratiques en ce qui concerne la prescription de statines en prévention primaire sont discutées. Les conséquences et les bénéfices potentiels de l'application de ces scores en Suisse sont également abordés. [Abstract] Primary prevention of cardiovascular disease by physicians is achieved by management of individual risk factors. The eligibility for treatment with statins is based on both an estimate of the risk of developing cardiovascular disease and the LDL-cholesterol. Three risk scores are commonly used : the PROCAM score, the Framingham score, and the European score. In Switzerland, the Swiss Group Lipids and Atherosclerosis (GSLA) recommends to use the PROCAM score with an adjustment of the level of risk for Switzerland. A survey also showed that PROCAM is the most used in Switzerland. In this article, the differences of these scores and their practical applications regarding the prescription of statins in primary prevention are discussed. The consequences and potential benefits of applying these scores in Switzerland are also discussed.

Minimal analytical characterisation of engineered nanomaterials need for hazard assessment in biological matrices

The safe and responsible development of engineered nanomaterials (ENM), nanotechnology-based materials and products, together with the definition of regulatory measures and implementation of "nano"-legislation in Europe require a widely supported scientific basis and sufficient high quality data upon which to base decisions. At the very core of such a scientific basis is a general agreement on key issues related to risk assessment of ENMs which encompass the key parameters to characterise ENMs, appropriate methods of analysis and best approach to express the effect of ENMs in widely accepted dose response toxicity tests. The following major conclusions were drawn: Due to high batch variability of ENMs characteristics of commercially available and to a lesser degree laboratory made ENMs it is not possible to make general statements regarding the toxicity resulting from exposure to ENMs. 1) Concomitant with using the OECD priority list of ENMs, other criteria for selection of ENMs like relevance for mechanistic (scientific) studies or risk assessment-based studies, widespread availability (and thus high expected volumes of use) or consumer concern (route of consumer exposure depending on application) could be helpful. The OECD priority list is focussing on validity of OECD tests. Therefore source material will be first in scope for testing. However for risk assessment it is much more relevant to have toxicity data from material as present in products/matrices to which men and environment are be exposed. 2) For most, if not all characteristics of ENMs, standardized methods analytical methods, though not necessarily validated, are available. Generally these methods are only able to determine one single characteristic and some of them can be rather expensive. Practically, it is currently not feasible to fully characterise ENMs. Many techniques that are available to measure the same nanomaterial characteristic produce contrasting results (e.g. reported sizes of ENMs). It was recommended that at least two complementary techniques should be employed to determine a metric of ENMs. The first great challenge is to prioritise metrics which are relevant in the assessment of biological dose response relations and to develop analytical methods for characterising ENMs in biological matrices. It was generally agreed that one metric is not sufficient to describe fully ENMs. 3) Characterisation of ENMs in biological matrices starts with sample preparation. It was concluded that there currently is no standard approach/protocol for sample preparation to control agglomeration/aggregation and (re)dispersion. It was recommended harmonization should be initiated and that exchange of protocols should take place. The precise methods used to disperse ENMs should be specifically, yet succinctly described within the experimental section of a publication. 4) ENMs need to be characterised in the matrix as it is presented to the test system (in vitro/ in vivo). 5) Alternative approaches (e.g. biological or in silico systems) for the characterisation of ENMS are simply not possible with the current knowledge. Contributors: Iseult Lynch, Hans Marvin, Kenneth Dawson, Markus Berges, Diane Braguer, Hugh J. Byrne, Alan Casey, Gordon Chambers, Martin Clift, Giuliano Elia1, Teresa F. Fernandes, Lise Fjellsbø, Peter Hatto, Lucienne Juillerat, Christoph Klein, Wolfgang Kreyling, Carmen Nickel1, and Vicki Stone.