The "help" question doesn't help when screening for major depression: external validation of the three-question screening test for primary care patients managed for physical complaints.

BACKGROUND: Major depression, although frequent in primary care, is commonly hidden behind multiple physical complaints that are often the first and only reason for patient consultation. Major depression can be screened by two validated questions that are easier to use in primary care than the full DSM-IV criteria. A third question, called the "help" question, improves the specificity without apparently decreasing the sensitivity of this screening procedure. We validated the abbreviated screening procedure for major depression with and without the "help" question in primary care patients managed for a physical complaint. METHODS: This diagnostic accuracy study used data from a cohort study called SODA (for SOmatisation Depression Anxiety ) conducted by 24 general practitioners (GPs) in western Switzerland that included patients over 18 years of age with at least one physical complaint at index consultation. Major depression was identified with the full Patient Health Questionnaire. GPs were asked to screen patients for major depression with the three screening questions one year after inclusion. RESULTS: Out of 937 patients with at least one physical complaint, 751 were eligible one year after index consultation. Major depression was diagnosed in 69/724 (9.5%) patients. The sensitivity and specificity of the two-question method alone were 91.3% (95% confidence interval 81.4-96.4%) and 65.0% (95% confidence interval 61.2-68.6%), respectively. Adding the "help" question decreased the sensitivity (59.4% ; 95% confidence interval 47.0-70.9%) but improved the specificity (88.2% ; 95% confidence interval 85.4-90.5%) of the three-question method. CONCLUSIONS: The use of two screening questions for major depression was associated with high sensitivity and low specificity in primary care patients presenting a physical complaint. Adding the "help" question improved the specificity but clearly decreased the sensitivity; when using the "help" question; four out of ten patients with depression will be missed, compared to only one out of ten with the two-question method. Therefore, the "help" question is not useful as a screening question, but may help discussing management strategies.

Anti-leishmania effector functions of CD4+ Th1 cells and early events instructing Th2 cell development and susceptibility to Leishmania major in BALB/c mice.

Resistance and susceptibility to infection with the intracellular parasite, Leishmania major, are mediated by parasite-specific CD4+ Th1 and Th2 cells, respectively. It is well established that the protective effect of parasite-specific CD4+ Th1 cells is largely dependent upon the IFN-gamma produced. However, recent results indicate that the effect of Th1 cells on resolution of lesions induced by L. major in genetically resistant mice also requires a functional Fas-FasL pathway of cytotoxicity. In contrast to resistant mice, susceptible BALB/c mice develop aberrant Th2 responses following infection with L. major and consequently suffer progressive disease. These outcomes clearly depends upon the production of interleukin 4 (IL-4) early after infection. We have shown that a burst of IL-4 mRNA, peaking in draining lymph nodes of BALB/c mice 16 hrs after infection, occurs within CD4+ T cells that express V beta 4-V alpha 8 T cell receptors. In contrast to control and V beta 6-deficient mice, V beta 4-deficient BALB/c mice were resistant to infection, demonstrating the role of these cells in Th2 development. The early IL-4 response was absent in these mice, and Th1 responses occurred following infection. The LACK antigen of L. major induced comparable IL-4 production in V beta 4-V alpha 8 CD4+ T cells. Thus, the IL-4 required for Th2 development and susceptibility to L. major is produced by a restricted population of V beta 4-V alpha 8 CD4+ T cells after cognate interaction with a single antigen from this complex parasite. The IL-4 produced rapidly by these CD4+ T cells induces within 48 hours a state of unresponsiveness to IL-12 among parasite-specific CD4+ T cell precursors by downregulating the IL-12 receptor beta 2 chain expression.

Major influencing factors of indoor radon concentrations in Switzerland.

PURPOSE: In Switzerland, nationwide large-scale radon surveys have been conducted since the early 1980s to establish the distribution of indoor radon concentrations (IRC). The aim of this work was to study the factors influencing IRC in Switzerland using univariate analyses that take into account biases caused by spatial irregularities of sampling. METHODS: About 212,000 IRC measurements carried out in more than 136,000 dwellings were available for this study. A probability map to assess risk of exceeding an IRC of 300 Bq/m(3) was produced using basic geostatistical techniques. Univariate analyses of IRC for different variables, namely the type of radon detector, various building characteristics such as foundation type, year of construction and building type, as well as the altitude, the average outdoor temperature during measurement and the lithology, were performed comparing 95% confidence intervals among classes of each variable. Furthermore, a map showing the spatial aggregation of the number of measurements was generated for each class of variable in order to assess biases due to spatially irregular sampling. RESULTS: IRC measurements carried out with electret detectors were 35% higher than measurements performed with track detectors. Regarding building characteristics, the IRC of apartments are significantly lower than individual houses. Furthermore, buildings with concrete foundations have the lowest IRC. A significant decrease in IRC was found in buildings constructed after 1900 and again after 1970. Moreover, IRC decreases at higher outdoor temperatures. There is also a tendency to have higher IRC with altitude. Regarding lithology, carbonate rock in the Jura Mountains produces significantly higher IRC, almost by a factor of 2, than carbonate rock in the Alps. Sedimentary rock and sediment produce the lowest IRC while carbonate rock from the Jura Mountains and igneous rock produce the highest IRC. Potential biases due to spatially unbalanced sampling of measurements were identified for several influencing factors. CONCLUSIONS: Significant associations were found between IRC and all variables under study. However, we showed that the spatial distribution of samples strongly affected the relevance of those associations. Therefore, future methods to estimate local radon hazards should take the multidimensionality of the process of IRC into account.

IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB/c mice.

BALB/c mice develop aberrant T helper 2 (Th2) responses and suffer progressive disease after infection with Leishmania major. These outcomes depend on the production of interleukin-4 (IL-4) early after infection. Here we demonstrate that the burst of IL-4 mRNA, peaking in draining lymph nodes of BALB/c mice 16 hr after infection, occurs within CD4+ T cells that express V beta 4 V alpha 8 T cell receptors. In contrast to control and V beta 6-deficient BALB/c mice, V beta 4-deficient BALB/c mice were resistant to infection, demonstrating the role of these cells in Th2 development. The early IL-4 response was absent in these mice, and T helper 1 responses occurred following infection. Recombinant LACK antigen from L. major induced comparable IL-4 production in V beta 4 V alpha 8 CD4+ cells. Thus, the IL-4 required for Th2 development and susceptibility to L. major is produced by a restricted population of V beta 4 V alpha 8 CD4+ T cells after cognate interaction with a single antigen from this complex organism.

The Complete Chromosomal Organization of the Reference Strain of the Leishmania Genome Project, L. major ;Friedlin'.

In recent years, analysis of the genomes of many organisms has received increasing international attention. The bulk of the effort to date has centred on the Human Genome Project and analysis of model organisms such as yeast, Drosophila and Caenorhabditis elegans. More recently, the revolution in genome sequencing and gene identification has begun to impact on infectious disease organisms. Initially, much of the effort was concentrated on prokaryotes, but small eukaryotic genomes, including the protozoan parasites Plasmodium, Toxoplasma and trypanosomatids (Leishmania, Trypanosoma brucei and T. cruzi), as well as some multicellular organisms, such as Brugia and Schistosoma, are benefiting from the technological advances of the genome era. These advances promise a radical new approach to the development of novel diagnostic tools, chemotherapeutic targets and vaccines for infectious disease organisms, as well as to the more detailed analysis of cell biology and function.Several networks or consortia linking laboratories around the world have been established to support these parasite genome projects[1] (for more information, see http://www.ebi.ac.uk/ parasites/paratable.html). Five of these networks were supported by an initiative launched in 1994 by the Specific Programme for Research and Tropical Diseases (TDR) of the WHO[2, 3, 4, 5, 6]. The Leishmania Genome Network (LGN) is one of these[3]. Its activities are reported at http://www.ebi.ac.uk/parasites/leish.html, and its current aim is to map and sequence the genome of Leishmania by the year 2002. All the mapping, hybridization and sequence data are also publicly available from LeishDB, an AceDB-based genome database (http://www.ebi.ac.uk/parasites/LGN/leissssoft.html).

Trachea, lung, and tracheobronchial lymph nodes are the major sites where antigen-presenting cells are detected after nasal vaccination of mice with human papillomavirus type 16 virus-like particles.

Vaccination by the nasal route has been successfully used for the induction of immune responses. Either the nasal-associated lymphoid tissue (NALT), the bronchus-associated lymphoid tissue, or lung dendritic cells have been mainly involved. Following nasal vaccination of mice with human papillomavirus type 16 (HPV16) virus-like-particles (VLPs), we have previously shown that interaction of the antigen with the lower respiratory tract was necessary to induce high titers of neutralizing antibodies in genital secretions. However, following a parenteral priming, nasal vaccination with HPV16 VLPs did not require interaction with the lung to induce a mucosal immune response. To evaluate the contribution of the upper and lower respiratory tissues and associated lymph nodes (LN) in the induction of humoral responses against HPV16 VLPs after nasal vaccination, we localized the immune inductive sites and identified the antigen-presenting cells involved using a specific CD4(+) T-cell hybridoma. Our results show that the trachea, the lung, and the tracheobronchial LN were the major sites responsible for the induction of the immune response against HPV16 VLP, while the NALT only played a minor role. Altogether, our data suggest that vaccination strategies aiming to induce efficient immune responses against HPV16 VLP in the female genital tract should target the lower respiratory tract.

Trends in mortality from major cancers in the americas : 1980-2010

BACKGROUND: Between the 1970's and 2000 mortality in Latin America showed favorable trends for some common cancer sites, including stomach and male lung cancer in most countries. However, major concerns were related to mortality patterns from other cancers, particularly in women. We provide an up-to-date picture of patterns and trends in cancer mortality in Latin America. METHODS: We analyzed data from the World Health Organization mortality database in 2005-2009 for 20 cancer sites in 11 Latin American countries and, for comparative purposes, in the USA and Canada. We computed age-standardized (world) rates (per 100 000 person-year) and provided an overview of trends since 1980 using joinpoint regression models. RESULTS: Cancer mortality from some common cancers (including colorectum and lung) is still comparatively low in Latin America, and decreasing trends continue for some cancer sites (including stomach, uterus, male lung cancers) in several countries. However, there were upward trends for colorectal cancer for both sexes, and for women lung and breast cancer mortality in most countries. During the last decade, lung cancer mortality in women rose by 1-3% per year in all Latin American countries except Mexico and Costa Rica, whereas rises of about 1% were registered for breast cancer in Brazil, Colombia and Venezuela. Moreover, high mortality from cancer of the cervix uteri was recorded in most countries, with rates over 13/100 000 women in Cuba and Venezuela. In men, upward trends were registered in prostate cancer mortality in Brazil and Colombia, but also in Cuba, where the rate in 2005-2009 was more than twice that in the USA (23.6 versus 10/100 000). CONCLUSIONS: Tobacco control, efficient screening programs, early cancer detection and widespread access to treatments continue to be a major priority for most Latin American countries.

Reversed shoulder arthroplasty baseplate fixed according to the major columns principle

Purpose Cadaveric study at our institution has demonstrated that optimal basaplate fixation of a reversed shoulder arthroplasty (RSA) could be achieved with screws in three major columns. Our aim was to review our early rate of aseptic glenoid loosening in a series of baseplate fixed according to this principle. Material and Methods Between 2005 and 2008, 48 RSA (Aequalis Reversed) were implanted in 48 patients with an average age of 74.4 years (range, 56 to 86 years). There were 37 women and 11 men. Twenty-seven primary RSAs were performed for cuff tear arthropathy, 3 after failed rotator cuff surgery, 6 for failed arthroplasties, 7 for acute fractures and 5 after failed ORIF. All baseplate fixation were done using a nonlocking posterior screw in the spine, a nonlocking anterior screw in the glenoid body, a locking superior screw in the coracoid and a locking inferior screw in the pillar. All patients were reviewed with standardized radiographs. The number of screws were reported. We measured the position of the screws in relation to the scapular spine and the coracoid process in two different views. We defined screw positions as totally, partially or out of the target. Finally we reported glenoid aseptic loosening which was defined as implant subsidence. Results Four patients were lost to follow-up. Thus, 44 shoulders could be reviewed after a mean follow-up of 13 months (range, 6 to 32 months). All baseplates were fixed with 4 screws. Thirty-seven (84%) screws were either partially or totally in the spine. Thus, 7 (16%) scapular spine screws were out of the target. No coracoid screw was out the target. Two (4.5%) patients had glenoid loosening. Both had a scapular spine and a coracoid screw partially in the bone. Conclusion Early aseptic glenoid loosening occurred before the two years follow-up and is most of time related to technical problems and/or insufficient bone stock and bone quality. Our study demonstrate that baseplate fixation according to the three columns principle is a reproducible technique and a valuable way to prevent early glenoid loosening.

Signifiant decrease in in-hospital mortality and major adverse cardiac events in Swiss STEMI patients between 2000 and December 2007

Rapport de synthèse : Objectifs : évaluer la survie intra-hospitalière des patients présentant un infarctus du myocarde avec sus-décalage du segment ST admis dans les hôpitaux suisses entre 2000 et 2007, et identifier les paramètres prédictifs de mortalité intra-hospitalière et d'événements cardio-vasculaires majeurs (infarctus, réinfarctus, attaque cérébrale). Méthode : utilisation des données du registre national suisse AMIS Plus (Acute Myocardial lnfarction and Unstable Angina in Switzerland). Tous les patients admis pour un infarctus du myocarde avec sus-décalage du segment ST ou bloc de branche gauche nouveau dans un hôpital suisse participant au registre entre janvier 2000 et décembre 2007 ont été inclus. Résultats: nous avons étudié 12 026 patients présentant un infarctus du myocarde avec sus-décalage du segment ST ou bloc de branche gauche nouveau admis dans 54 hôpitaux suisses différents. L'âge moyen est de 64+-13 ans et 73% des patients inclus sont des hommes. L'incidence de mortalité intra-hospitalière est de 7.6% en 2000 et de 6% en 2007. Le taux de réinfarctus diminue de 3.7% en 2000 à 0.9% en 2007. L'utilisation de médicaments thrombolytiques chute de 40.2% à 2% entre 2000 et 2007. Les paramètres prédictifs cliniques de mortalité sont : un âge> 65-ans, une classe Killips Ill ou IV, un diabète et un infarctus du myocarde avec onde Q (au moment de la présentation). Les patients traités par revascularisation coronarienne percutanée ont un taux inférieur de mortalité et de réinfarctus (3.9% versus 11.2% et 1.1% versus 3.1%, respectivement, p<0.001) sur la période de temps étudiée. Le nombre de patients traités par revascularisation coronarienne percutanée augmente de 43% en 2000 à 85% en 2007. Les patients admis dans les hôpitaux bénéficiant d'une salle de cathétérisme cardiaque ont un taux de mortalité plus bas que les patients hopitalisés dans les centres sans salle de cathétérisme cardiaque. Mais les caractéristiques démographiques de ces deux populations sont très différentes. La mortalité intra-hospitalière ainsi que le taux de réinfarctus diminuent significativement au cours y de la période étudiée, parallèlement à l'augmentation de |'utilisation de la revascularisation coronarienne percutanée. La revascularisation coronarienne percutanée est le paramètre prédictif de survie le plus important. Conclusion: la mortalité intra-hospitalière et le taux de réinfarctus du myocarde ont diminué de manière significative chez les patients souffrant d'un infarctus du myocarde avec sus-décalage du segment ST au cours de ces sept dernières années, parallèlement à l'augmentation significative de la revascularisation coronarienne percutanée en plus de la thérapie médicamenteuse. La survie n'est È pas liée au lieu d'hospitalisation mais à l'accès à une revascularisation coronarienne percutanée.

Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism.

BACKGROUND: The Outpatient Bleeding Risk Index (OBRI) and the Kuijer, RIETE and Kearon scores are clinical prognostic scores for bleeding in patients receiving oral anticoagulants for venous thromboembolism (VTE). We prospectively compared the performance of these scores in elderly patients with VTE. METHODS: In a prospective multicenter Swiss cohort study, we studied 663 patients aged ≥ 65 years with acute VTE. The outcome was a first major bleeding at 90 days. We classified patients into three categories of bleeding risk (low, intermediate and high) according to each score and dichotomized patients as high vs. low or intermediate risk. We calculated the area under the receiver-operating characteristic (ROC) curve, positive predictive values and likelihood ratios for each score. RESULTS: Overall, 28 out of 663 patients (4.2%, 95% confidence interval [CI] 2.8-6.0%) had a first major bleeding within 90 days. According to different scores, the rate of major bleeding varied from 1.9% to 2.1% in low-risk, from 4.2% to 5.0% in intermediate-risk and from 3.1% to 6.6% in high-risk patients. The discriminative power of the scores was poor to moderate, with areas under the ROC curve ranging from 0.49 to 0.60 (P = 0.21). The positive predictive values and positive likelihood ratios were low and varied from 3.1% to 6.6% and from 0.72 to 1.59, respectively. CONCLUSION: In elderly patients with VTE, existing bleeding risk scores do not have sufficient accuracy and power to discriminate between patients with VTE who are at a high risk of short-term major bleeding and those who are not.

Major, minor, trace element, Sm-Nd and Sr isotope compositions of mafic rocks from the earliest oceanic crust of the Alpine Tethys

Recent isotopic and biochronologic dating has demonstrated that the Gets nappe contains remnants of the oldest part of the oceanic crust of the Alpine Tethys. The ophiolites are associated with deep sea sediments, platform carbonates and continental crustal elements suggesting a transitional environment between continental and oceanic crust. Therefore, the ophiolites from the Gets nappe provide the opportunity to assess the nature of mantle source and the magma evolution during the final rifting stage of the European lithosphere. Trace clement analyses of mafic rocks can he divided into two sets: (1) P, Zr and Y contents are consistent with those of mid-ocean ridge basalts and REE patterns have a P-MORB affinity. (2) P,Zr Ti and Y contents are compatible with within-plate basalts and are characterized by REE spectra similar to that of T-MORB. Both have Nd isotopic compositions similar to those of synrift magma of the Red Sea and to the Rhine Graben. The model ages are in agreement with an LREE-enriched subcontinental mantle source derived from depleted mantle 800 to 900 Ma ago. Minor, trace element and Sm-Nd compositions suggest that these rocks are basaltic relies of an earliest stage of oceanic spreading i.e. an embryonic ocean. Comparison between REE patterns, Nd and Sr isotope compositions, isotopic and biochronologic ages from different Alpine Tethys ophiolites shows that samples with enriched LREE are from the older ophiolitic suites and are relies of the embryonic ocean floor. Later phases of ocean spreading are characterized by basalts that are depleted in LREE.

Effect of major hepatectomy on glucose and lactate metabolism.

BACKGROUND: The liver plays an important role in glucose and lactate metabolism. Major hepatectomy may therefore be suspected to cause alterations of glucose and lactate homeostasis. METHODS: Thirteen subjects were studied: six patients after major hepatectomy and seven healthy subjects who had fasted overnight. Glucose turnover was measured with 6,6(2)H glucose. Lactate metabolism was assessed using two complementary approaches: 13C-glucose synthesis and 13CO2 production from an exogenous 13C-labeled lactate load infused over 15 minutes were measured, then the plasma lactate concentrations observed over 185 minutes after lactate load were fitted using a biexponential model to calculate lactate clearance, endogenous production, and half-lives. RESULTS: Three to five liver segments were excised. Compared to healthy controls, the following results were observed in the patients: 1) normal endogenous glucose production; 2) unchanged 13C-lactate oxidation and transformation into glucose; 3) similar basal plasma lactate concentration, lactate clearance, and lactate endogenous production; 4) decreased plasma lactate half-life 1 and increased half-life 2. CONCLUSIONS: Glucose and lactate metabolism are well maintained in patients after major hepatectomy, demonstrating a large liver functional reserve. Reduction in the size of normal liver parenchyma does not lead to hyperlactatemia. The use of a pharmacokinetic model, however, allows the detection of subtle alterations of lactate metabolism.