Forum MГ©dical Suisse Forum Medico Svizzero Schweizerisches Medizin-Forum 17.5.2013 Supplementum 60 Online-Publikation auf www.medicalforum.ch Swiss Medical Forum 81. Jahresversammlung der Schweizerischen Gesellschaft fГјr Allgemeine Innere Medizin 81e AssemblГ©e annuelle de la SociГ©tГ© Suisse de MГ©decine Interne GГ©nГ©rale 81a Riunione annuale della SocietГ Svizzera di Medicina Interna Generale 81st Annual Meeting of the Swiss Society of General Internal Medicine Basel, 29.вЂ“31. Mai 2013 Editores Medicorum Helveticorum Offizielles Fortbildungsorgan der FMH www.medicalforum.ch Organe officiel de la FMH pour la formation continue www.medicalforum.ch Bollettino ufficiale per la formazione della FMH www.medicalforum.ch Inhalt / Sommaire FM 105 - FM 107 S. 5 - 7 Presidential Symposium SGH FM 222 вЂ“ FM 225 S. 8 - 10 Freie Mitteilungen SGIM - Infektiologie / Immunologie Communications libres SSMI - Infectiologie / Immunologie FM 226 вЂ“ FM 229 S. 11 - 13 Freie Mitteilungen SGIM - Allgemeine Innere Medizin 1 Communications libres SSMI - MГ©decine interne gГ©nГ©rale 1 FM 230 вЂ“ FM 233 S. 14 - 16 Freie Mitteilungen SGIM - Notfallmedizin Communications libres SSMI вЂ“ Urgences FM 234 вЂ“ FM 237 S. 17 - 19 Freie Mitteilungen SGIM - Communications libres SSMI 2 Allgemeine Innere Medizin - MГ©decine interne gГ©nГ©rale 2 FM 238вЂ“ FM 241 S. 20 - 22 Freie Mitteilungen SGIM - Communications libres SSMI Kardiologie / Pneumologie - Cardiologie / Pneumologie FM 242вЂ“ FM 245 S. 23 - 26 Freie Mitteilungen SGIM - Communications libres SSMI Allgemeine Innere Medizin 3 - MГ©decine interne gГ©nГ©rale 3 FM 246вЂ“ FM 248 S. 27 - 28 Freie Mitteilungen SGIM - Communications libres SSMI Bluthochdruck - Hypertension artГ©rielle FM 249вЂ“ FM 252 S. 29 - 31 Freie Mitteilungen SGIM - Communications libres SSMI Endokrinologie - Endocrinologie FM 253вЂ“ FM 258 S. 32 - 36 Freie Mitteilungen SGIM - Communications libres SSMI Beste Freie Mitteilungen вЂ“ Meilleur Communication libres 1 FM 259вЂ“ FM 262 S. 37 - 39 Freie Mitteilungen SGIM - Communications libres SSMI MultimorbiditГ¤t - MultimorbiditГ© FM 263вЂ“ FM 270 S. 40 - 44 Freie Mitteilungen SGH - Communications libres SSH Experimental Hematology - Experimental Hematology FM 271 - FM 278 S. 45 - 49 Freie Mitteilungen SFGG - Communications libres SPSG FM 279вЂ“ FM 284 S. 50 - 53 Freie Mitteilungen SGH - Communications libres SSH Hemostasis, Vascular Biology and Transfusion Medicine FM 285 вЂ“ FM 292 S. 54 - 62 Freie Mitteilungen SGH - Communications libres SSH Clinical Hematology P 293 вЂ“ P 302 S. 63 - 68 Beste 10 Poster SGIM вЂ“ Meilleur 10 posters SSMI P 303 вЂ“ P 310 S. 69 - 75 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 1 - MГ©decine interne gГ©nГ©rale 1 P 311 - P 318 S. 76 - 80 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 2 - MГ©decine interne gГ©nГ©rale 2 P 319 - P 326 S. 81 - 88 Postesession 1 - Session des posters 1 Allgemeine Innere medizin 3 - MГ©decine interne gГ©nГ©rale 3 P 327 - P 334 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 4 - MГ©decine interne gГ©nГ©rale 4 2 S. 89 - 96 P 335 - P 342 S. 97 - 104 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 5 - MГ©decine interne gГ©nГ©rale 5 P 343 - P 350 S. 105 - 109 Postesession 2 - Session des posters 2 Onkologie вЂ“ Notfallmedizin / Psychiatrie / Neurologie Oncologie - Urgences / Psychiatrie - Neurologie P 351 вЂ“ P 359 S. 110 - 116 Postesession 2 - Session des posters 2 Psychiatrie / Neurologie - Arterieller Bluthochdruck вЂ“ Endocrinologie - Diabetik Psychiatrie / Neurologie - NГ©phrologie / Hypertension artГ©rielle Endocrinologie - DiabГ©tologie P 360 вЂ“ P 367 S. 117 - 121 Postesession 2 - Session des posters 2 Infektiologie - Immunologie - Rheumatologie / Infectiologie - Immunologie - Rhumatologie P 368 вЂ“ P 375 S. 122 - 127 Postesession 2 - Session des posters 2 Allgemeine Innere Medizin - Infektiologie / Immunologie / Rheumatologie MГ©decine interne gГ©nГ©rale - Infectiologie/Immunologie/Rhumatologie P 376 вЂ“ P 384 S. 128 - 135 Postesession 2 - Session des posters 2 Kardiologie - Pneumologie - Gastroenterologie 1 / Cardiologie - Pneumologie - GastroentГ©rologie 1 P 385 вЂ“ P 392 S. 136 - 142 Postesession 2 - Session des posters 2 Kardiologie - Pneumologie - Gastroenterologie 2 / Cardiologie / Pneumologie / GastroentГ©rologie 2 P 393 вЂ“ P 394 S. 143 - 144 Postersession SFGG - Session des posters SPSG P 395 вЂ“ P 402 S. 145 - 153 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 6 - MГ©decine interne gГ©nГ©rale 6 3 P 403 вЂ“ P 410 S. 154 - 160 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 7 - MГ©decine interne gГ©nГ©rale 7 P 411 вЂ“ P 419 S. 161 - 165 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 8 - MГ©decine interne gГ©nГ©rale 8 P 420 вЂ“ P 428 S. 166 - 172 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 9 - MГ©decine interne gГ©nГ©rale 9 P 429 вЂ“ P 437 S. 173 - 178 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 10 - MГ©decine interne gГ©nГ©rale 10 P 438 вЂ“ P 443 S. 179 - 182 Postersession SGH - Session des posters SSH Hemostasis, Vascular Biology and Transfusion P 444 вЂ“ P 464 S. 183 - 197 Postersession SGH - Session des posters SSH Clinical Hematology Autorenliste / Liste des auteurs 4 S. 198 - 213 Presidential Symposium SGH Presidential Symposium SSH 105 Imetelstat rapidly induces and maintains substantial haematologic and molecular responses in patients with essential thrombocythaemia (ET) who are refractory or intolerant to prior therapy: preliminary phase II results Gabriela Baerlocher*, Elisabeth Oppliger Leibundgut, Christina Ayran, Martha Blaney, Bart Burington, Dianne Morfeld, Olatoyosi Odenike, Oliver Ottman, Anita Reddy, Alexander Roeth, Gary Spitzer, Monic Stuart, Srdan Verstovsek, David Snyder Hematology, University Hospital Bern (Bern, CH); Geron Corporation (Menlo Park, CA, US); University of Chicago (Chicago, IL, US); Hematology, University Hospital of Frankfurt (Frankfurt, DE); Hematology, University Hospital Essen (Essen, DE); Upstate Oncology Associates (Greenville, SC, US); University of Houston (Houston, TX, US); Hematology and HCT, City of Hope (Duarte, CA, US) Background: Myeloproliferative neoplasms (MPNs), such as essential thrombocythemia (ET), are driven by neoplastic progenitor cells (NPC). The JAK2 V617F mutation is detected in approx. 50% of patients (pts) with ET, and its burden can be used to measure the treatment-induced molecular response (MR). Telomerase is upregulated in NPC and sustains indefinite replication. Imetelstat (Imet) is a first in class, potent, specific inhibitor of telomerase which selectively distributes to bone marrow and inhibits thrombopoiesis. Methods: A phase II study enrolled pts with ET who had failed or were intolerant to at least one prior therapy, or who refused standard therapy. Pts were treated with Imet 7.5 mg/kg or 9.4 mg/kg IV weekly. After attainment of best platelet (plt) response in the induction phase, maintenance therapy (MT) with Imet was commenced with dosing based upon plt count. Primary endpoint was best overall hematologic response (HR) with complete response (CR) defined as plt count <400 x 10^3/Вµl maintained for at least 4 consecutive weeks in the absence of new thromboembolic events. A key secondary endpoint was rate of MR in pts with JAK2 V617F. JAK2 V617F allele burden was measured by allele-specific qRT-PCR. CFU-Meg growth and tolerability were also assessed. Results: As of October 10th, 2012, 14 pts were treated. Median (md) age was 60 yrs with a md of 2 prior treatments. Md years since initial diagnosis were 5.8 and md initial plt count was 788 x 10^3/Вµl. Best overall HR was 100%, with 13 of 14 pts achieving a confirmed CR after a md of 6.1 weeks. Thirteen of 14 pts remain on MT. Six pts have reached 1 year of therapy and continue to be treated with ongoing HR. Dosing frequency on MT was reduced with time. A substantial decrease in JAK2 V617F allele burden (mean allele burden reduction of 82%) was demonstrated in all 7 JAK2 V617Fpositive pts. A reduction in CFU-Meg was also observed. Common adverse events reported were mild to moderate gastrointestinal toxicities, reductions in neutrophil counts, and fatigue. Conclusions: Imet rapidly induces and maintains HR in pts with ET who have failed or are intolerant to conventional therapies. Importantly, substantial MR is observed in all JAK2 V617F-positive pts and inhibition of CFU-Meg is demonstrated. These results suggest that Imet has a relatively selective inhibitory effect on the growth of the neoplastic clone(s) which drive ET and has the potential to modify the underlying biology of MPNs. 106 Hereditary thrombocytosis caused by a novel germ-line mutation in the gelsolin gene Annalisa Pianta*, Pontus Lundberg, Kun Liu, Hui Hao-Shen, Renate Looser, Robert Kralovics, Takafumi Shimizu, Amy Shapiro, Radek Skoda Department of Biomedicine (Basel, CH); CeMM Research Center for Molecular Medicine (Vienna, AT); Indiana Hemophilia Thrombosis (Indianapolis, US) Introduction: Hereditary thrombocytosis (HT) is a familial myeloproliferative disorder characterized by an elevated platelet count in peripheral blood. Activating mutations in the thrombopoietin (THPO) gene and the gene for the THPO receptor, MPL, account for approximately 10% of HT. However, in about 90% of HT the disease-causing gene remains unknown. Here we study a large family with 12 affected family members in 5-generations with HT. Disease transmission is autosomal dominant with high penetrance. Methods: Mutations in MPL and THPO were excluded by capillary sequencing. Genome-wide linkage analysis was performed on DNA from 21 family members using microsatellites and single nucleotide 5 polymorphism arrays. All genes within the co-segregating region were sequenced by classical DNA sequencing and by Next Generation Sequencing. Computational analysis, platelet-biogenesis in vitro assay and transgenic mice were used to prove the function of the mutation. Results: Linkage analysis defined a single co-segregating region on chromosome 9 with a LOD score of 4.3 (a LOD score of >3.3 is considered proof for linkage). Sequencing of all exons and splice junctions within this chromosomal interval revealed a candidate mutation. The alteration, a C/T transversion resulting in a Gly to Cys amino acid change, was observed in the gene encoding for gelsolin. Computational predictions of the protein structure showed that this single amino acid change is very likely to affect protein function since the alteration is located at the interface where gelsolin interacts with actin. Platelet-biogenesis in vitro assays showed that the candidate alteration increased the release of platelets-like particles in DAMI cell line stably transfected with the mutant gelsolin. To study the in vivo role of the candidate mutation, transgenic mice expressing the human mutant gelsolin were generated. These mice developed thrombocytosis and increased numbers of megakaryocytes. Conclusion: We describe a familial isolated thrombocytosis caused by a mutation in gelsolin, a gene not previously linked to any hematological disorder. Transgenic mice expressing mutant gelsolin showed an increased platelet count and number of megakaryocytes, thus recapitulating the phenotype observed in the family. The exact mechanism of how this newly identified genetic alteration leads to increased megakaryocytopoiesis needs further investigation 107 Investigation into the role of protein S in platelets Sara Calzavarini*, Francois Saller, Laurent Burnier, Monica Azevedo, Debora Sanches Rodrigues, Anne Brisset, Jose Fernandez, John H Griffin, Anne Angelillo-Scherrer Centre Hospitalier Universitaire Vaudois (Lausanne, CH); AP-HP, HГґpital ParГ© (Paris, FR); Molecular and Experimental Medicine, The Scripps Research Institute, (La Jolla, US); DSM Nutritional Products Ltd Branch Pentapharm (Basel, CH) Background: Anticoagulant protein S (PS) is essential for maintaining the haemostatic balance. Our previous characterization of PS deficiency in mouse models has shown similarities with the human phenotypes: heterozygous PS-deficient mice had increased thrombotic risk whereas homozygous deficiency in PS was incompatible with life. Most of the PS in plasma is thought to be synthesized by hepatocytes, however the PS gene (ProS) is also expressed by several other cell types, including megakaryocytes (MK). In particular, about 2.5% of PS is stored in platelets and released upon platelet stimulation. So far, little is known about the functionality and importance of platelet PS (pltPS). Methods and Results: Mice carrying a conditional protein S knockout allele in MK lineage were established using the Pf4 promoter as Cre drivers (ProSLox/LoxPf4Cre+). ProSLox/Lox Pf4Cre+ mice did not have detectable PS levels in platelet lysates (n=5) but normal levels in plasma (88.9В±4.6%, n=19), as assessed by antigenic assays. Comparative analyses of complete blood counts established that these animals retained a normal blood cell profile. Platelets were tested for their functionality ex vivo by Platelet Function Analyzer-200 (PFA-200) and by light transmission aggregometry using 6 collagen and ADP as agonists, without showing any difference compared to ProSLox/Lox mice. Differently, tail clipping test showed a relevant decrease of bleeding time compared to ProSLox/Lox mice (P=0.021). When challenged in a tissue factor-induced thromboembolism model, ProSLox/Lox Pf4Cre+ (n=15) mice exhibited a notable thrombotic phenotype in vivo (survival rate 46.7% compared to 85.8%, ProSLox/Lox mice, n=14; P<0.05). Beside its role on activated protein C, PS acts as cofactor of tissue factor pathway inhibitor alpha (TFPI alpha) in the inhibition of factor Xa (FXa). The complete deletion of ProS gene in MK lineage did not affect TFPI alpha expression, as assessed by antigenic assay of platelet lysates. Preliminary data on PS cofactor activity toward TFPI alpha indicate that the absence of PS in platelet lysates abolish the capacity of TFPI alpha to inhibit FXa, as assessed by amidolytic activity assay. Conclusions: All together these data suggest that pltPS is delivered at the site of thrombosis to counterbalances procoagulant activities on platelets thus inhibiting thrombus growth. Upon release, pltPS may function as an anticoagulant protein enhancing the TFPI-dependent anticoagulant pathway. 7 Freie Mitteilungen SGIM - Communications libres SSMI Infektiologie / Immunologie - Infectiologie / Immunologie FM222 Increasing incidence and atypical presentation of tularaemia in Switzerland Urs Karrer*, Jan Amort, Silke Polsfuss, Paola Pilo, Jacques Gubler, Guido Bloemberg Cantonal Hospital of Winterthur (Winterthur, CH); University of Zurich (ZГјrich, CH); University of Bern (Bern, CH) Background: Tularemia has been a very rare disease in Switzerland with ~7 cases (range: 2-13) annually from 2004 to 2009 despite mandatory reporting since 2004. Most cases presented as typical arthropod bite associated (ulcero)glandular disease. The diagnosis was mainly confirmed by F. tularensis serology, by molecular diagnostics (i.e. PCR) and only rarely by culture of F. tularensis. In 2010/11 we have seen a moderate increase of tularemia to 14 and 13 annual cases, respectively. However, a total of 37 confirmed tularemia cases were reported to the national authorities in 2012. Methods: We performed a retrospective epidemiological and clinical analysis of all confirmed cases of tularemia in Switzerland between 2004 and 2012 (n=98). Detailed review of clinical data, molecular diagnostics and management was performed for ~50% of cases since 2010. Results: Incidence rates of tularemia have increased 10-fold between 2004 (0.04/100вЂ™000 inhabitants) and 2012 (0.46/100вЂ™000). Maximal rates of up to 1 case/100вЂ™000 were noted in the cantons of Zurich, Aargau and Lucerne. More detailed epidemiological analyses will be presented to indicate the establishment of true вЂ�hot spotsвЂ™. Overall, the clinical pattern of tularemia has not significantly changed over time: 55% of patients present with local (ulcero)glandular disease while 32% suffered from systemic disease, mostly pneumonia. During the past decade, one patient with tularemia died and 60% were hospitalised. In 2012, 4 of our 6 patients presented with unusual disease manifestations, namely severe sepsis with macrophage activation syndrome, empyema of a pneumonectomy cavity, perimyocarditis and local tularemia secondary to a bussard attack. Molecular diagnostics allowed the timely diagnosis and treatment of these patients. While a short course (5-10 days) of intravenous aminoglycoside combined with oral Doxycyclin (14-42 days) was successful in all patients with systemic disease oral therapy was usually sufficient for local disease. Nevertheless, surgical drainage was required in up to 50% of patients with lymphadenitis. Discussion: In certain areas of Switzerland, incidence of tularemia has increased to a level which is relevant to the general practitioner. Epidemiological data are best explained by a true increase in disease incidence and not just by a reporting bias. The broad clinical spectrum and appropriate management of the disease will be discussed in light of the changing epidemiology. FM223 Progressive proximal muscle weakness after cessation of statin use: a case of statin-triggered autoimmunity Laetitia Mauti*, Veronika Kana, Stephan Regenass, CГ¤cilia Reiner, Herbert Budka, Dominik Schaer, Irene Studer UniversitГ¤tsspital ZГјrich (ZГјrich, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Introduction: Statins are a widely used for the treatment of dyslipidemia and secondary prophylaxis after cardio-vascular events. While the major side effect of reversible statin-induced myopathy is well known, a new kind of statin-induced myopathy has recently been described, which persists after discontinuation of the drug. Case Report: We report the case of a 73-year-old woman with gradually progressive, painless, symmetrical proximal muscle weakness developing 3 years after the initiation of treatment with atorvastatin. The highly elevated creatinine-kinase levels did not decline nor did symptoms improve more than six weeks after discontinuation of the statin. MRI showed diffuse signal enhancement in all proximal muscle groups and muscle biopsy yielded histological findings compatible with statin-induced necrotizing auto-immune myopathy (NAM). ELISA for antibodies against HMGCR (3-Hydroxy-3Methylglutaryl-Coenzym-A-reductase) was positive. The patient was started on immunosuppressants and symptoms improved along with a rapid reduction of creatinine-kinase levels. Discussion: Recently, a new form of myopathy associated with statin use has been described. Statininduced necrotizing auto-immune myopathy is mediated by antibodies against HMGCR. This enzyme, 8 which is blocked by statins, seems to become up-regulated in regenerating muscle fibers after an initial - possibly statin-induced - minor lesion. This statin-triggered auto-immune disease persists upon discontinuation of statins and requires longtime immuno-suppressive treatment. FM224 Simple and fast prediction of Legionella species in community-acquired pneumonia. Validation of a prediction rule Sebastian Haubitz*, Fabienne Hitz, Lena Graedel, Marcus Batschwaroff, Timothy Lee Wiemken, Paula Peyrani Dicastelnuovo, Julio Ramirez, Christoph Fux, Beat Mueller, Philipp Schuetz Kantonsspital Aarau (Aarau, CH); UniversitГ¤t Basel (Basel, CH); University of Louisville (Louisville, US) Introduction: Ruling out Legionella sp. in patients presenting with community acquired pneumonia (CAP) besides the low prevalence is important due to differences in treatment regimens. Antigen tests as well as blood cultures have low sensitivity and ofthen there is an important time delay making empirical broad spectrum coverage necessary particularly in severe cases. Fiumefreddo et al. recently proposed a clinical score based on 6 clinical and laboratory variables (fever, cough, sodium, lactatedehydrogenase, C-reactive protein, platelet count) which allowed assessing the likelihood of Legionella[1]. Yet, this prediction tool needs validation in an independent patient cohort before implementation into clinical routine. Methods: We analyzed data from a large multinational database of patients with CAP (CAPO)[2] between 2001 and 2012, includiung 8278 patients at the time of analysis. Patients were excluded if less than 5 of the 6 variables were available. In the remaining 1046 patients we performed logistic regression analysis and area under the receiver operating characteristics (ROC) curve to study the association of these variables with the diagnosis of Legionella. Results: The propagated score using 6 dichotomized variables shows good diagnostic performance with an area under the ROC curve of 0.84. Performance increased markedly when the continuous variables were applied in the regression equation utilizing the original coefficients, area under ROC curve: 0.91. Conclusions: This analysis validates the Legionella score in an independent sample and shows high diagnostic accuracy. Interventional trials with adapted antibiotic regimes for non-inferiority in a real live population are warranted. References: [1] Fiumefreddo R, Zaborsky R, Haeuptle J, et al. Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department. BMC pulm medicine 2009; 9:4-4 [2] Ramirez JA. Fostering international multicenter collaborative research: the CAPO Project. Int J Tuberc Lung Dis 2007; 11:1062-1065 9 FM225 Measles vaccination in Switzerland: results of a population-based survey on vaccination coverage and determinants in 2012 Monica Wymann*, Mirjam MГ¤usezahl-Feuz Bundesamt fГјr Gesundheit (Bern, CH) Introduction: In December 2011 the Federal Council passed the National Strategy on Measles Elimination 2011вЂ“2015. One of the goals is that in accordance with WHO guidelines 95% of all children are vaccinated with 2 doses of measles vaccine by the age of 2. An essential factor for the evaluation of this goal is the knowledge of the vaccination coverage. Since 1999 national data is collected for 2-, 8- and 16-year-olds through the Swiss National Vaccination Coverage Survey (SNVCS). In addition in 2012 the Federal Office of Public Health (FOPH) conducted a measles baseline survey to collect vaccination coverage data, to assess reasons for and against vaccination and knowledge and attitude towards measles vaccination and elimination. Methods: Computer assisted telephone interviews were conducted with parents of 2 to16-year-olds and with young adults (20 to 29-year-olds) by a professional provider. Following the telephone interview, respondents were asked to send their or their childвЂ™s vaccination card to the FOPH. A total of 3237 interviews were conducted, 1814 with parents of children (N=1535 vaccination cards received) and 1423 with young adults (N=807 vaccination cards). Results: Vaccination coverage was 95% for 1 dose and 89% for 2 doses in 2-year-olds; 95% for 1 dose and 90% for 2 doses in 3 to 16-year-olds; and 93% for 1 dose and 77% for 2 doses in 20 to 29year-olds. Main reasons to vaccinate children on time were their parentsвЂ™ wish to protect them (58.5%) and recommendation by the pediatrician/general practitioner (GPs) (48.2%). Late vaccinations (first dose after 2nd birthday) had been in 20% of cases directly recommended by the pediatrician/GPs. 43% of the young unvaccinated adults and 34% of parents of unvaccinated children showed a willingness to vaccinate themselves or their child in order to help reach measles elimination. Knowledge about measles was, especially in young adults, marked by uncertainty. Conclusions: The results on point vaccination coverage in this survey are congruent with the SNVCS data. As in the SNVCS coverage with 2 doses in 2-year-olds is still clearly below the targeted 95%. Pediatricians and GPs play a key role as motivators for parents to vaccinate their children on time, but organizational problems as well as insufficient knowledge in the general public seem to be part of the problem as well. Unified efforts on the structural as well as communicational level are needed to reach the goal of measles elimination in Switzerland. 10 Freie Mitteilungen SGIM - Communications libres SSMI Allgemeine Innere Medizin 1 - MГ©decine interne gГ©nГ©rale 1 FM226 Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism Waltraud Leiss*, Marie MГ©an, Andreas Limacher, Marc Righini, Kurt Jaeger, Hans-JГјrg Beer, Joseph Osterwalder, Beat Frauchiger, Christian M. Matter, Nils Kucher, Anne Angelillo-Scherrer, Jacques Cornuz, Martin Banyai, Bernhard LГ¤mmle, Marc Husmann, Michael Egloff, Markus Aschwanden, Henri Bounameaux, Nicolas Rodondi, Drahomir Aujesky Bern University Hospital (Bern, CH); University of Bern (Bern, CH); Geneva University Hospital (GenГЁve, CH); Basel University Hospital (Basel, CH); Cantonal Hospital of Baden (Baden, CH); Cantonal Hospital of St. Gallen (St. Gallen, CH); Cantonal Hospital of Frauenfeld (Frauenfeld, CH); University of Zurich and Zurich University Hospital (ZГјrich, CH); Lausanne University Hospital (Lausanne, CH); University of Lausanne (Lausanne, CH); Cantonal Hospital of Lucerne (Luzern, CH); Zurich University Hospital and University of Zurich (ZГјrich, CH) Background: Venous thromboembolism (VTE) often affects multimorbid older patients who take multiple concomitant drugs (polypharmacy). Although drug interactions with vitamin K antagonists are a potential cause of excessive anticoagulation and bleeding, whether polypharmacy increases bleeding risk in elderly patients with VTE is uncertain. Methods: In a multicenter Swiss cohort study, we prospectively enrolled consecutive patients aged >=65 years who received vitamin K antagonists for acute VTE between September 2009 and March 2012. The presence of polypharmacy, defined as the use of more than 4 different drugs, was assessed at baseline. The outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin >=20 g/L or leading to the transfusion >=2 units of red blood cells. We assessed the association between polypharmacy and the time to a first major bleeding using Cox proportional hazard analysis, adjusting for known bleeding risk factors (age, gender, history of major bleeding, active cancer, chronic liver disease, chronic renal disease, cardiac disease, thrombocytopenia, cerebrovascular disease, diabetes mellitus, anemia, arterial hypertension, recent major surgery and presence of symptomatic pulmonary embolism). Results: Of 830 enrolled patients, 413 (49.8%) had polypharmacy. The mean +-SD follow-up duration was 17.8 +-9.3 months. The overall incidence of major bleeding was 6.4% per person-year. Patients with polypharmacy had a significantly higher incidence of major bleeding than patients without (9.0% vs. 4.1% per person-year; p=0.002). After multivariate adjustment, polypharmacy remained significantly associated with major bleeding (hazard ratio 2.1, 95% confidence interval 1.2-3.5; p=0.007). Patients with polypharmacy did not spend a higher percentage of time with an excessive international normalized ratio (>3.0) than patients without (17.7% vs. 16.0%; p=0.18). Conclusion: Polypharmacy is common in elderly patients receiving vitamin K antagonists for VTE, and is an independent predictor of major bleeding. Further studies need to explore by which mechanism polypharmacy increases the bleeding risk in elderly patients with VTE. FM227 PhysiciansвЂ™ response to control of cardiovascular risk factors in Switzerland: overtreatment, undertreatment or appropriate care? Stefan Weiler*, Armin Gemperli, Tinh-Hai Collet, Douglas Bauer, Lukas Zimmerli, Jacques Cornuz, Edouard Battegay, Jean-Michel Gaspoz, Eve Kerr, Drahomir Aujesky, Nicolas Rodondi Inselspital Bern (Bern, CH); CTU Bern (Bern, CH); University of Lausanne (Lausanne, CH); University of California (San Francisco, CH); University Hospital of Zurich (ZГјrich, CH); University Hospitals of Geneva (GenГЁve, CH); University of Michigan (Ann Arbor, CH) Background: Evaluating whether physicians respond appropriately to poor risk factor control better reflects quality of care than measuring proportions in control. New measures of potential overtreatment have been recently suggested. These quality measurements have mainly been examined in US integrated healthcare systems and not in settings without systematic quality monitoring. Methods: We performed a retrospective cohort study of 1,002 randomly selected patients aged 50-80 years from four university primary care settings in Switzerland, a country without quality monitoring. In regard to control of hypertension, dyslipidemia and diabetes, we assessed the proportion of patients in 11 poor control and defined вЂњappropriate careвЂќ as a therapy modification or return to control without therapy modification within 12 months. We also examined potential overtreatment of these conditions and defined it as intensive treatment among low-risk patients who already have low target values. Results: Within 12 months, 61% of patients experienced therapy modification for poor control of hypertension, 33% for dyslipidemia, and 85% for diabetes. Increases in number of drug classes (2851%) and in drug doses (10-61%) were most common. 0-5% of poorly controlled conditions returned to control without therapy modification. Patients with target organ damage and higher baseline values were more likely to receive appropriate care. We found potential overtreatment among 2% of patients for hypertension, 3% for diabetes and 4% for dyslipidemia. Conclusions: High rates of appropriate care were observed for poorly controlled diabetes mellitus and lower rates for hypertension and dyslipidemia. Overtreatment appears uncommon. Such measures may provide a better picture of the quality of care than relying only on simple measures of proportions in control. FM228 Suspicion of heparin-induced thrombocytopenia in internal medicine: how appropriate are anti-PF4 antibody tests? Yan Beauverd*, Elena Tessitore, FranГ§oise Boehlen, Eric Gerstel, Mathieu Nendaz, Arnaud Perrier, Jean-Luc Reny HГґpitaux Universitaires de GenГЁve (GenГЁve, CH) Objective: To describe the clinical management of patients suspected of HIT and evaluate to what extent the 4TвЂ™s score and the HEP score might safely decrease anti-PF4 antibodies testing in internal medicine patients clinically suspected of type II heparin induced thrombocytopenia (HIT). Methods: Internal medicine patients treated with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux in whom anti-PF4 were assayed were included. Non inclusion criteria were absence of thrombocytopenia or fall of platelets count and transfer from another hospital. Results: We included 74 patients over a 29-month period with a mean age of 68В±16 years. 25 (34%) were transferred from the intensive care Unit. 43 (58%) were treated with UFH, 31 (42%) with LMWH and none with fondaparinux. Indication was thromboprophylaxis in 45 (61%) and therapeutic in 29 (39%). 11 patients (15%) tested positive for antiPF4 and 4 (5.4%) had confirmed HIT. Clinicians documented the 4TвЂ™s score in only 10 (14%) patients and the HEP score was never used. The retrospectively calculated 4TвЂ™s score was < 4 in 54 patients (73%) who would not have needed antiPF4 testing (Table). HEP score was < 2 implying no antiPF4 testing was necessary in 34 patients (46%, p<0.0001 compared to 4TвЂ™s). Both scores had a sensitivity of 100% (no patient with a score below the cut-off had HIT). Specificity of 4Ts was 77% and that of HEP was 48%. Following anti-PF4 testing, clinicians stopped heparin in 48 patients (65%) among which 25 (34%) were switched to fondaparinux while the remaining had either a transient or definitive anticoagulant arrest. In 3 patients, a heparin-induced platelet aggregation (HIPA) test was performed (1 despite a 4TвЂ™s score <4). At three months of follow-up none of the patients were readmitted for a HIT-related condition. Conclusions: Validated and recommended scores for HIT were vastly underused in this internal medicine population while they could have avoided 73% of the requested antiPF4 tests (4TвЂ™s) or 46% (HEP) and have a high sensitivity and safety using the appropriate cut-offs. 12 FM229 International variation in GP treatment strategies for subclinical hypothyroidism in older adults Wendy P.J. den Elzen, Anne LefГЁbre - van de Fliert, Vanessa Virgini*, Simon P. Mooijaart, Patricia Kearney, Ngaire Kerse, Christian D. Mallen, Vera McCarthy, Christiane Muth, Peter Frey, Thomas Rosemann, Audrey Russell, Henk Schers, David J. Stott, Margot W.M. de Waal, Alex Warner, Rudi G.J. Westendorp, Nicolas Rodondi, Jacobijn Gussekloo Leiden University Medical Center (Leiden, NL); Inselspital Bern (Bern, CH); Institute for Evidencebased Medicine in Old age (Leiden, NL); University College Cork (Cork, IE); The University of Auckland (Auckland, NZ); Keele University (Keele, GB); Johann Wolfgang Goethe University (Frankfurt, DE); BIHAM, UniversitГ¤t Bern (Bern, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH); Radboud University Medical Center (Nijmegen, NL); University of Glasgow (Glasgow, GB); University College London (London, GB) Introduction: Since there is limited evidence about the impact of treatment of subclinical hypothyroidism on clinical outcomes, especially in older persons, international consensus on the management of subclinical hypothyroidism is lacking. We investigated the variation in treatment strategies of GPs for older patients with subclinical hypothyroidism depending on patient characteristics and country. Methods: We assessed the treatment strategy of GPs (treatment yes/no, starting dose of thyroxine) for eight cases presenting a woman with non-specific complaints and subclinical hypothyroidism. The 8 cases differed in patient characteristics age (70 vs 85 years), vitality status (vital vs. vulnerable) and TSH concentration (6 vs. 15 mU/L). The NetQuestionnaire survey was emailed to GP networks in the Netherlands, Germany, England, Ireland, Switzerland and New Zealand. Results: A total of 524 GPs participated to the survey; 129 from the Netherlands, Switzerland n=262, Germany n=61, England n=22, Ireland n=19, and New Zealand n=31. We found large variations across countries, with % starting therapy going from 35% in the Netherlands, 54% in Switzerland to 75% in Germany. Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old women (pooled OR, random effects model, 0.74 [95% CI 0.63-0.87]). Older women with TSH 15 mU/L were more likely to get treated than women with TSH 6 mU/L (pooled OR 9.4 [95% CI 5.8-15.4). Across countries, differences in treatment strategy were observed for each case, witth most pronounced when TSH was 6 mU/L. Discussion: GPs treatment strategies of older persons with subclinical hypothyroidism vary not only by patient characteristics but also largely by country. This large variation underlines the need for evidence about the effects of treatment of subclinical hypothyroidism by a good quality RCT targeting clinical outcomes. 13 Freie Mitteilungen SGIM - Communications libres SSMI Notfallmedizin - Urgences FM230 Frequent users of the emergency department in Switzerland: a prospective, controlled, cross-sectional study Patrick Bodenmann*, Fabrice Althaus, Stephanie Stucki, Corine Ansermet, Sophie Guyot, Katia Iglesias, Sophie Paroz, Lionel Trueb, Olivier Hugli, Jean-Bernard Daeppen Policlinique MГ©dicale Universitaire (Lausanne, CH); Centre Hospitalier Universitaire Vaudois (Lausanne, CH) Introduction: A heterogeneous subgroup of patients account for a substantial proportion of all emergency department (ED) visits. The aim of this study was to systematically describe frequent users of the ED in Switzerland. Methods: This prospective controlled cross-sectional study compared frequent users of the ED to nonfrequent users (control group), and was conducted from November 2009 to June 2010 at the University Hospital of Lausanne. Frequent users were defined as patients with five or more visits to the ED in the previous 12 months; they were compared to controls in terms of socio-demographic characteristics, medical indicators, and health care use. Outcome measures were obtained through a robust questionnaire using previously validated scales. Results: During the study period, 24,277 patients attended the ED and 351 met the definition of frequent user (1.4% of all ED patients). Frequent users made a total of 2,030 visits in the past year, which represented 6.3% of the 32,441 visits made by all ED users during the same period. A total of 226 frequent users and 173 controls were interviewed. In a multivariate analysis, adjusted odds ratio of being a frequent user was 23.2 (95% CI 9.1-59.2) for patients with three or more admissions to hospital, 8.4 (95% CI 2.1-32.7) for patients who do not have a primary care practitioner (PCP), 4.4 (95% CI 2.1-9.0) for patients living close to the ED (less than 5 km), 4.3 (95% CI 2.0-9.2) for patients with a household income lower than 3,000 Swiss Francs/month, 2.7 (95% CI 1.2-6.1) for patients who had attended other EDs, 2.6 (95% CI 1.1-5.9) for patients having a moderate to severe tobacco use, 2.3 (95% CI 1.2-4.7) for patients having at least one mental problem (panic, anxiety, or mood disorder), 1.2 (95% CI 1.1-1.4) with a change of one unit according to the Charlson Index (somatic comorbidities). The risk of being a frequent user was decreased by 74.8% (95% CI 0.1-0.5) for patients with no admission to hospital, 72.5% (95% CI 0.1-0.9) for people attending for injuries, and 68.1% (95% CI 0.1-0.7) for patients having a chronic somatic condition. Conclusions: Frequent users of the ED are a socially and medically vulnerable population. These results are helpful to better target the complex needs of frequent users of the ED: through better connection with a PCP, availability of ED-based case management teams, and as also by informing decisions about further services which should be provided to patients in the ED. FM231 Evolution of some quality indicators after the opening of a 'fast track way' (Notfallpraxis) in an emergency department Mattia Lepori*, Massimo Trobia, Mario Lazzaro, Adriana Degiorgi Ospedale Regionale (Bellinzona, CH); Ospedale Regionale (Lugano, CH) Background: there are many quality indicators to evaluate the performance of an ED; some of them are mainly addressed to the waiting times and the quickness of the take in charge of patients, often influenced by the EDвЂ™s overcrowding, and causing patientsвЂ™ dissatisfaction. Aim: to evaluate the evolution of some quality indicators, before and after the opening of a вЂњfast track wayвЂќ (FTW) in the ED of a regional hospital, for the least serious cases. Methodology: we studied the evolution of 4 quality indicators related to to the waiting times and the quickness of the take in charge of patients, comparing the data for two periods before (March-August 2011) and after (March-August 2012) the FTWвЂ™s opening. Results: during the two observed periods, the number of patients was very similar, being of 11148 (2011) vs 11678 (2012), (P=NS). The measurement of the following indicators showed a favourable evolution: вЂў Take in charge of patients in less than 30 minutes: 86.4% vs 74.3% (P < 0.05) вЂў Patients with waiting time higher than 90 minutes: : 4.4% vs 12.3% (P < 0.05) вЂў Number of written complaints due to long waiting time: 0.7/month vs 7/month (P < 0.05) 14 вЂў Percentage of patients who left the ED before being visited: 0.87% vs 1.78% (P < 0.01) Moreover, a survey (performed granting anonimity) among 500 FTWвЂ™s patients, showed a positive appraisal (92%) of the services performed by this new unit. Conclusion: the opening of a FTW for the least serious cases, improves the quality and the perception of satisfaction of the EDвЂ™s patients. FM232 Patient characteristics and patterns of intoxication: one-time and repeated use of emergency ambulance services in Zurich Nina Rosset, Barbara Holzer, Christoph Minder, Gabriela SchГ¤tti, Edouard Battegay, Stefan MГјller, Lukas Zimmerli* UniversitГ¤tsSpital ZГјrich (ZГјrich, CH); UniversitГ¤t ZГјrich (ZГјrich, CH); Schutz und Rettung ZГјrich (ZГјrich, CH) Objective: Intoxication, whether from alcohol, drugs, or alcohol and drugs in combination, remains a challenging burden on emergency services. The increasing alcohol consumption among adolescents and young adults, particularly heavy episodic drinking, and the resulting increase in the use of health care resources for alcohol intoxication has been a widely discussed topic. The aim of this study was to investigate the utilization of ambulance services due to alcohol and drug intoxication during 1 year in the greater metropolitan area of Zurich, Switzerland, with an emphasis on characteristic differences between patients with one-time or repeated use. Method: All ambulance services report forms filed in 2010 were systematically screened for ambulance services utilizations where alcohol intoxication or intoxication due to consumption of illicit or legal drugs was the chief complaint. Results: The majority of the intoxicated patients recorded (92%, n=2156), used ambulance services only once in 2010, whereas 8% of patients (n=185) were transported by ambulance services multiple times. Men made up approximately 65% of the study population, for both one-time and repeated users. Repeated users differed from persons with one-time use in their characteristics and patterns of intoxication. On average, patients with repeated ambulance use were almost 8 years older and had a different pattern of ambulance use over the course of the week with no clear peak on any specific day. More than half of the one-time utilizations (64.3%) occurred on the weekend (Friday to Sunday), with a clear peak on Saturday (Figure 1). The mean number of ambulance services in patients with repeated use was 2.8 (SD = 1.517) in the 1-year study period: Repeated-users were less likely to be injured than patients with one-time ambulance services use and more often showed aggression or uncooperative behavior towards paramedics. All cases of death associated with intoxication involved patients with one-time ambulance use. Conclusions: The ambulance services usersвЂ™ generally slight impairment of consciousness and the high proportion of intoxicated patients without any injuries bring up the question of how many of these patients could be adequately cared for in a sobering center. Sobering centers might relieve hospital emergency units of patients not requiring acute emergency care and, in addition, could provide intervention services to prevent relapses. 15 FM233 Unconsciousness, low oxygen saturation and myocardial infarction. Acute methemoglobinaemia: beware of poppers! Olivier Clerc*, Markus Schneemann, Hugo Kupferschmidt UniversitГ¤tsspital ZГјrich (ZГјrich, CH); Schweizerisches Toxikologisches Informationszentrum (ZГјrich, CH) Introduction: Acute methemoglobinemia following drug intoxication is an uncommon, but a challenging and life-threatening condition. Methods: Case report, pathophysiological and clinical discussion. Results: A 37 years old man with HIV-infection treated with tenofovir, emtricitabin and nevirapine presented to our emergency department after an unclear fall with unconsciousness, weakness, dyspnea, left chest pain and headache. Oxygen saturation was 74% on room air and 90% with 10 l/min oxygen. The clinical examination was otherwise normal. ECG showed transitory negative T waves in II, III, aVF and V2-6. Laboratory tests found increased troponin (0.028 ug/l) and prolactin (38.8 ug/l). A full body CT showed no traumatic lesion, normal lungs and no pulmonary embolism. The blood gas analysis under oxygen pointed out an oxygen partial pressure of 51 kPa (N 11-14), saturated hemoglobin 91% (N 95-99%), oxyhemoglobin 52% (N 94-99%) and methemoglobin 43% (N <1,5%)! It demonstrated an acute severe methemoglobinemia with typical symptoms. Methemoglobin has hemes with iron in the oxidized state (Fe3+), unable to carry oxygen and increasing the oxygen affinity of non-oxidized hemes. Both aspects cause tissue hypoxia, in our case myocardial infarction and unconfirmed seizures. Pulse oximetry is inaccurate and blood gas analysis with co-oximetry is necessary to diagnose this condition. The cause is rarely genetic and mostly drug-induced by nitrites (nitric oxide, nitroglycerine, amylnitrite), local anesthetics, metoclopramide, sulfonamides, dapsone, clofazimine, chloroquine, primaquine, paraquat, derivatives of benzene and aniline. If methemoglobinemia is >30%, intravenous methylene blue 1-2 mg/kg is indicated to activate NADPH methemoglobin reductase in red blood cells and restore hemoglobin. In severe cases, blood transfusion and hyperbaric oxygen can be helpful. Our patient finally admitted having sniffed poppers and injected ketamine. Nitrites such as amylnitrite and isobutylnitrite ("poppers") are vasodilators abused for their aphrodisiac effects and cause methemoglobinemia. They were used to treat angina pectoris, are cyanide antidotes, but now mostly recreational drugs. In the meantime, our patientвЂ™s methemoglobin and arterial oxygen had returned to acceptable levels. No specific therapy was needed. Conclusion: Methemoglobinemia >30% is a serious condition which clinicians should consider in medical and recreative drug users. Methylene blue is the treatment of choice. 16 Freie Mitteilungen SGIM - Communications libres SSMI Allgemeine Innere Medizin 2 - MГ©decine interne gГ©nГ©rale 2 FM234 REX: diagnostic radiation exposure of inpatients in a department of medicine over the past two years Markus F. RГјtti*, Petra Ferrari Pedrini, Stefan Zechmann, Stephan Scheidegger, Rahel Kubik, Jana Efe, JГјrg H. Beer Cantonal Hospital of Baden (Baden, CH); Zurich University of Applied Sciences (Winterthur, CH) Background: Routine application of imaging methods using ionizing radiation are a cornerstone of diagnostic medicine. Physicians are increasingly aware of both the effective doses applied and the risk estimates associated with radiological investigations. The aim of this study was the assessment of the number of diagnostic x-ray procedures as well as an average radiation exposure; at the same time, we obtained the number of diagnostic MRI over a period of two years in the internal medicine population at a Swiss teaching hospital. The data would then set the basis for an optimal diagnostic quality at the expense of a minimal radiation exposure and the evidence for teaching and further improvement. Methods: We assessed the annual number of conventional radiographies, CT scans, fluoroscopies and MRIs in 2011 and 2012. Using the ICRP (International Commisssion of Radiological Protection)60 and ICRP-103 data, we estimated the radiation exposure for each procedure and the average radiation exposure of the medical inpatients in 2011 and in 2012. Results: In 2011/2012 a total of 7490/7132 x-ray examinations were performed at the Department of Medicine, which translates into an average radiation exposure of 3.35/3.03 mSv per patient. The 2 consecutive years show a trend to less radiation exposure while the MRIs applied increased slightly (see table). Conclusions: An inverse trend of radiation exposure and MRI exams can be observed over the past 2 years. Many factors may account for this finding, among them the ALARA principle (as low as reasonably achievable) applied in many teaching sessions at both Departments of Medicine and Radiology. This practice may increase the quality of care. The use of modern equipment with ever lower radiation exposure helps to further enhance our goal of lowering the radiation dose applied per patient. Further Work will analyze the effective individual dose/patient and the exposure of the 10 years before to support the conclusion. 17 FM235 Patient and physician gender concordance in preventive care in university primary care settings Simone KrГ¤henmann-MГјller*, Vanessa Virgini, Manuel Blum, Bruno da Costa, Tinh-Hai Collet, Stefan Weiler, Yonas Martin, Jaques Cornuz, Edouard Battegay, Jean-Michel Gaspoz, Douglas Charles Bauer, Eve Kerr, Drahomir Aujesky, Nicolas Rodondi Inselspital Bern (Bern, CH); University of Bern (Bern, CH); University Hospital of Lausanne (Lausanne, CH); University Hospital of Zurich (Zurich, CH); University Hospital of Geneva (GenГЁve, CH); University of California (San Francisco, US); University of Michigan (Ann Arbor, US) Background: The proportion of female physicians working in primary care medicine has increased for several decades. Several studies have reported physician gender differences in preventive health care received by patients, especially for gender-specific preventive services. However, limited data exist on the role of patient and physician gender and gender concordance in the broad spectrum of preventive care. Therefore, we assessed the association between physician gender, patient-physician gender concordance, and the quality of preventive care in Swiss university primary care settings. Methods: We performed a retrospective cohort study of 1001 randomly selected patients aged 50-80 years from four Swiss university primary care settings. We used indicators derived from RANDвЂ™s Quality Assessment Tools indicators and calculated percentages of recommended preventive care (such as behavioral counseling and cancer screening) according to physician and patient gender. We used a hierarchical multivariate logistic regression, adjusting for patientsвЂ™ age and occupation, and for physiciansвЂ™ age, function and centre (both as random factors). Results: 1001 patients (mean age 63.5 years, 557 male) were followed by 189 physicians (mean age 34.2 years, 90 male, 94.7% residents). After multivariate adjustment, female patients received less recommended preventive care than male patients (88.4% vs. 91.3%, p<0.001). Female physicians provided significantly more preventive care than male physicians (p=0.04) to both female (88.8% vs. 87.7%) and male patients (91.6% vs. 90.7%). We found no evidence that preventive care differed among gender concordant and discordant patient-physician pairs (p for interaction = 0.78). Female physicians provided particularly more recommended cancer screening (colon cancer, breast cancer) than male physicians (81.2% vs. 75.3%, p=0.01). Conclusion: In Swiss primary care settings, female patients receive less preventive care than male patients. Furthermore, female physicians provide significantly more preventive care than their male colleagues, particularly for cancer screening. This study suggests that greater attention should be paid to female patients in preventive health care. Further studies are needed to understand why female physicians tend to provide better preventive care. FM236 Reporting of randomized controlled trials that were discontinued: an international multicentre empirical study Benjamin Kasenda*, Erik von Elm, Anette BlГјmle, Yuki Tomonaga, John You, Mihaela Stegert, Dominik Mertz, Theresa Bengough, Kelechi Kalu Olu, Matthias Briel on behalf of the DISCO-study group Background: Randomized controlled trials (RCTs) may be discontinued prematurely for reasons including unanticipated adverse effects, apparent benefit, futility, or slow accrual. Discontinued trials have ethical implications: (i) participants consent on the premise of contributing to new medical knowledge, (ii) limited resources for research are wasted, and (iii) bias might be introduced to metaanalyses if data are not available. Currently little is known about the epidemiology and publication history of discontinued RCTs. Objectives and Methods: Our aims were to determine: (i) the prevalence of RCT discontinuation for all reasons, (ii) differences between industry and investigator-initiated RCTs, (iii) risk factors for termination due to slow accrual, and (iv) the probability for publication of discontinued RCTs. We established a multicentre cohort of RCTs based on protocols approved by 6 research ethics committees (RECs) from 2000 to 2003 in Switzerland, Germany, and Canada. From all included RCT protocols we extracted data on trial characteristics (e.g. medical field, single- vs multicentre design, length of follow-up) and on planned recruitment (sample size calculations, period, etc.). We determined completion status and publications of trials by using information from REC files and publications identified through literature searches, or by surveying investigators. Results: We included 953 RCT protocols. Of these, 556 (58%) trials are known to be completed as planned, 271 (28%) were stopped early for any reason. Industry initiated trials (N=546 [57%]) were 18 completed in 69% whereas investigator-initiated trials (N=405, [43%]) were completed only in 44%. The completion status of 125 (13%) trials is still under evaluation. In total, 580 (61%) trials were published, 199 (21%) were definitely not. Industry-initiated trials were published in 66% whereas investigator-initiated trials were published in 54%. The publication status of 173 (18%) trials is still under evaluation. At the conference we will present final results of our study. Conclusions: Our study provides insights into the prevalence and reporting of discontinued RCTs. Empirical data on these aspects may help further emphasize the need for reporting data from discontinued trials in order to (i) meet the ethical obligations related to RCTs, (ii) prevent early RCT discontinuation due to slow accrual, (iii) reduce the waste of limited resources, and (iv) prevent potential bias in systematic reviews. FM237 Differential effect of Charlson index and its components on in-hospital mortality and health costs Marco Martinuz*, GГ©rard Waeber, Pedro Marques-Vidal CHUV (Lausanne, CH); IUMSP (Lausanne, CH) Introduction: The Charlson index (Charlson, 1987) is a commonly used comorbidity index in outcome studies. Still, the use of different weights makes its calculation cumbersome, while the sum of its components (comorbidities) is easier to compute. In this study, we assessed the effects of 1) the Charlson index adapted for the Swiss population and 2) the sum of its components (number of comorbidities, maximum 15) on a) in-hospital deaths and b) cost of hospitalization. Methods: Anonymous data was obtained from the administrative database of the department of internal medicine of the Lausanne University Hospital (CHUV). All hospitalizations of adult (>=18 years) patients occurring between 2003 and 2011 were included. For each hospitalization, the Charlson index and the number of comorbidities were calculated. Analyses were conducted using Stata. Results: Data from 32,741 hospitalizations occurring between 2003 and 2011 was analyzed. On bivariate analysis, both the Charlson index and the number of comorbidities were significantly and positively associated with in hospital death. Conversely, multivariate adjustment for age, gender and calendar year using Cox regression showed that the association was no longer significant for the number of comorbidities (table). On bivariate analysis, hospitalization costs increased both with Charlson index and with number of comorbidities, but the increase was much steeper for the number of comorbidities (figure). Robust regression after adjusting for age, gender, calendar year and duration of hospital stay showed that the increase in one comorbidity led to an average increase in hospital costs of 321 CHF (95% CI: 272 to 370), while the increase in one score point of the Charlson index led to a decrease in hospital costs of 49 CHF (95% CI: 31 to 67). Conclusion: Charlson index is better than the number of comorbidities in predicting in-hospital death. Conversely, the number of comorbidities significantly increases hospital costs. 19 Freie Mitteilungen SGIM - Communications libres SSMI Kardiologie / Pneumologie вЂ“ Cardiologie / Pneumologie FM238 Factors associated with exacerbation in the GP-based Swiss Chronic Obstructive Pulmonary Disease (COPD) cohort Nebal Abu Hussein*, Pierre-Olivier Bridevaux, Prashant Chhajed, Jean-William Fitting, Thomas Geiser, Ladina Joos Zellweger, Malcolm Kohler, Sabrina Maier, David Miedinger, Salome Schafroth TГ¶rГ¶k, Robert Thurnheer, Michael Tamm, JГ¶rg Daniel Leuppi UniversitГ¤tsspital Basel (Basel, CH); HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); Centre Hospitalier Universitaire Vaudois (Lausanne, CH); Inselspital Bern (Bern, CH); Claraspital (Basel, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH); Kantonsspital MГјnsterlingen (MГјnsterlingen, CH) Background: Patients with COPD often suffer from acute exacerbations, which can require hospitalization. Frequent COPD exacerbations are related with higher mortality. Our objective was to investigate predictors for exacerbation in a general practitionersвЂ™ (GPвЂ™s) based Swiss COPD cohort. Methods: In questionnaire-based cohort, COPD patients from 23 Swiss cantons were screened and enrolled into our cohort. Demographic data, medical treatment, spirometric parameters and exacerbation history were collected and recorded for 24 months. The patients with presumed mild to very severe COPD (GOLD stages I-IV) were seen by their GPs at least twice a year during the study period. Results: Among 139 GPs, 465 COPD patients (64% male, mean age 68 years) were analyzed. In the study period of two years, 239 exacerbations occurred (57 patients with > 3 exacerbations, 182 patients with 1-2 exacerbations and 235 patients with no exacerbation. Chronic cough (Hazarad Ratio HR 2.29, p =2.29), sputum production (HR 3.28, p =0) and severe to very severe dyspnea (HR 2.89, 3.96, p =0) were correlated with high exacerbationsвЂ™ risk. Cardiovascular diseases (HR 1.45 p =0.02), previous rehabilitation (HR 2.96, p =0), hospitalization (HR 1,709, p = 0.09) and a history of exacerbation at baseline (HR 7.66 p =0) were significantly associated with a future exacerbation. Conclusion: Exacerbations in the past and current severe symptoms such as sputum production, dyspnea and cough seem to be predictors for future exacerbation in patients with COPD treated in primaryвЂ“care settings. FM239 Predictive value of exhaled nitric oxide to predict exercise-induced bronchoconstriction Claudia Gregoriano*, Nebal Abu Hussein, Sabrina Maier, Stefanie Zogg, Daniela Margelli Hartmann, David Miedinger, JГ¶rg Daniel Leuppi UniversitГ¤tsspital Basel (Basel, CH) Background: In fire brigade environments, there are lots of asthma-triggering and вЂ“aggravating factors, which can lead to respiratory symptoms. Working with self-contained breathing apparatus (SCBA) might cause bronchoconstriction in asthmatic patients, because of the dry and cool air delivered by SCBA. Methods: A prospective study of fire-fighters assigned to work with SCBA was carried out. Participants completed self-administered questionnaires on respiratory symptoms. Fire-fighters of the University Hospital Basel were exercise challenged by climbing up 46 floors of the St. Chrischona radio tower wearing SCBA. Prior to the exercise, exhaled nitric oxide (FeNO) and forced expiratory volume in one second (FEV1) were measured. Upon arrival on the top, FEV1 was assessed every minute during a 10-minute period. Results: 18 fire-fighters aged 27 to 53 (89% male, age 42.7+/-7.1yrs) participated in this study. Complete data were available from 13 participants, who were finally analysed. 8 subjects (62%) were non-smoker and 3 (23%) had an established diagnosis of asthma. Mean measured FeNO was 13.9+/4.6ppb. No participant exceeded the limit value of 25ppb. Mean baseline FEV1 predicted was 3.8+/0.6l/min. 8 individuals (62%) showed a significant drop in FEV1 after this exercise challenge test: 5 individuals (39%) had a fall of >10%, 1 (8%) had a fall of >15% and 2 (15%) had a fall of >20% in FEV1 after exercise. Those with a significant drop had a mean FeNO of 16+/-5 vs. 12+/-3ppb (p=ns). All individual with a fall of >15% were current or ex-smoker. 2 out of 3 asthmatics had a significant drop in FEV1 after exercise. 20 Conclusion: In this population of active fire-fighters, we found a high prevalence of smokers, selfreported asthma diagnosis and exercise-induced bronchoconstriction. Those individuals, who admitted smoking or asthma, were more likely to have significant fall in FEV1 post exercise with SCBA. Individuals with significant fall in FEV1 tended to have higher FeNO values. FM240 Does EuroSCORE predict intensity of postoperative care and rehabilitation parameters? Volkhard GГ¶ber*, Uta FГ¤h, Dorothee Keller, Hugo Saner, Thierry Carrel, Lars Englberger Inselspital Bern (Bern, CH) Background: An increasing number of older and more multi-morbid patients undergo cardiac surgery which results in increased postoperative morbidity, prolonged ICU length of stay (LOS) and higher hospital costs. We aimed to evaluate the EuroSCORE model for the prediction of ICU LOS, hospital LOS, required nursing effort, and type of cardiac rehabilitation. Patients and methods: Prospective observational evaluation of 505 consecutive adult patients (mean age 65.1В±12.1 years, 25.7% female) who underwent cardiac and/or aortic thoracic surgery with cardiopulmonary bypass (CPB). Results: Median additive and logistic EuroSCORE was 5 (IQR 3-7) and 5.8 (IQR 2.6 - 14.1), respectively. In univariate analysis additive and logistic EuroSCORE were significantly associated with prolonged ICU LOS, prolonged hospital LOS, higher daily nursing effort, and type of rehabilitation (inpatient versus ambulant); p<0.001 for all correlations). Multivariate analysis including other clinically relevant variables (CPB time, type of operation, age, body mass index, urgency of surgery, left ventricular ejection fraction) showed higher additive EuroSCORE and higher logistic EuroSCORE independently associated with prolonged ICU LOS, prolonged hospital LOS, and higher daily nursing effort. However, EuroSCORE did not independently predict the type of rehabilitation. Conclusions: The EuroSCORE can be used to identify patients with elevated risk for prolonged ICU stay, prolonged hospital LOS and higher intensity of postoperative care. This information may support timely planning of ICU resources, hospital beds and postoperative nursing. FM241 Acute kidney injury and worsening kidney function predict outcomes of acute heart failure patients GrГ©gory Berra*, Nicolas Garin, Anne-Sophie Janot-Berthier, Arnaud Perrier, Pierre-Yves Martin, SГ©bastien Carballo HГґpitaux Universitaires de GenГЁve (GenГЁve, CH) Introduction: Renal function is a strong predictor of outcome in acute heart failure, but the prognostic implication of a deterioration of renal function during hospital management is debated. We aimed to test if worsening renal function during the first 7 days of hospital stay was independently associated with prognosis. Method: Retrospective cohort study of 646 heart failure inpatients followed until 365 days or death. The primary endpoint was the hazard ratio (HR) of death or readmission. Acute renal failure (ARF) was defined according to Acute Kidney Injury Network (AKIN). Worsening renal function (WRF) presenting during hospital stay was classified according to AKIN, using the difference between the first and the highest creatinine value during the first 7 days of hospital stay. We used Kaplan Meier survival analysis and Cox proportional hazard model to test the association between clinical and biological variables and the primary outcome. Results: ARF, WRF, hemoglobin and creatinine levels at admission and use of loop diuretics before admission were significantly associated with the primary outcome in univariate analysis (figure).Only ARF and WRF remained significantly associated with the outcome in a multivariate model, with HRs for death or readmission of 1.32 (95%CI 1.12-1.55, p=0.001) and 1.27 (95%CI 1.07-1.51, p=0.005) respectively. Conclusions: Worsening renal function during the first days of hospitalization is strongly associated with a poor outcome. Strict monitoring of renal function during hospital stay is therefore warranted. 21 22 Freie Mitteilungen SGIM - Communications libres SSMI Allgemeine Innere Medizin 3 - MГ©decine interne gГ©nГ©rale 3 FM242 LUFTIBUS study: how the Swiss get weaker with ageing. Epidemiology of muscle mass and strength Paolo M. Suter*, Tina Sander, Alexander Turk, Otto BrГ¤ndli USZ (ZГјrich, CH); Lunge Zurich (ZГјrich, CH) Introduction: The loss of muscle mass, i.e. the loss of the active metabolic tissue, is one of the most important risk factors for the development of the chronic diseases of aging. The epidemiology of the muscle mass and muscle strength at the population level in Switzerland is mostly unknown. Method: In the setting of the COPD-Roadshow of Lunge ZГјrich (www.lunge-zuerich.ch) we assessed from April 2010 to May 2012 at 42 locations in 9 different Swiss Cantons 8332 individuals (age range 7- 96 years, m/f=47.5/52.5%). The test battery included a standard pulmonary function test (spirometry), body weight (kg), body height (cm), grip strength measurements (Jamar hyraulic handdynamometer) at the dominant & non-dominant arm and body composition by bioimpedance measurements (Tanita BC-420MA; data on fat mass, muscle mass (MM)). Data from the preliminary analysis of the 20-89 year old participants will be presented. Results: The decline in MM with aging was significant in men and women (p < 0.0001). There was a significant relationship between MM and the grip strength in women and men (r=0.45, p < 0.0001). MM loss started early with an acceleration around the age of 40 years in men; in women the decline was more gradual and continuous without acceleration at a certain age. The relation between age and grip strength for the right arm in men and women are shown in Figure 1 (ANOVA for trend over age p < 0.0001 for men & women). Conclusion: The Luftibus Study is the first large scale study in Switzerland reporting the changes of MM and grip strength in a population of free living subjects. The loss of muscle mass is a central pathophysiologic drive for the development of most age related chronic diseases. In view of the large variability of the MM in all age groups with a large fraction of the population with low grip strength (proxy for low MM) preventive strategies to minimize muscle loss and maintain muscle function will be critical for the maintenance of health and a good functional status with aging. Strategies to achieve this will be discussed in the context of this unique epidemiologic data set. 23 FM243 Are biomarkers useful to identify heavy drinking among people with alcohol dependence? Nicolas Bertholet*, Michael Winter, Debbie Cheng, Jeffrey Samet, Richard Saitz Service d'alcoologie, Centre hospitalier universitaire vaudois (Lausanne, CH); Boston University (Boston, US) Background: Managing patients with alcohol dependence includes assessment for heavy drinking, often done by asking patients. Biomarkers have been recommended to detect heavy drinking but evidence of their accuracy is limited. Aim : We assessed the operating characteristics of disialo-Carbohydrate-Deficient Transferrin (%dCDT), gamma-glutamyltransferase (GGT), %dCDT and GGT together, and breath alcohol for identifying heavy drinking among people with dependence. Methods: We used cross-sectional data from 402 adults with alcohol dependence and current heavy drinking. Subjects were referred to primary care and assessed with biomarkers 6 months after enrollment. For %dCDT a cutoff point of >=1.7% defined a positive test; a positive GGT was >=66 U/L; the combination test was defined as positive if either individual test was positive; a positive breath alcohol test was >0. We assessed biomarker performance for detecting three heavy alcohol use levels over the past 30 days as determined using the Timeline Follow-back calendar method reference standard in confidential research interviews : 1) any heavy drinking (>=4 drinks in a day or >7 drinks/week for women, >=5 drinks in a day or >14 drinks/week for men), 2) recurrent heavy drinking (>=5 drinks in a day on at least 5 days) and 3) persistent heavy drinking (>=5 drinks in a day on at least 7 consecutive days). Results: By self-report reference standard, the prevalence of any heavy drinking, recurrent, and persistent heavy drinking was 54%, 34%, and 17% respectively. The Table displays the performance of each studied test (%dCDT, GGT, both, breath alcohol) for each of the three self-reported heavy alcohol use levels over the past 30 days. Conclusions: %dCDT alone yielded the best likelihood ratio positive for each alcohol use level, however it was not adequately sensitive to detect any, recurrent, or persistent heavy drinking. A noninvasive breath alcohol test was comparable to GGT but neither of these two was sufficiently sensitive 24 (both tests missed 70-80% of the cases). Although biomarkers may provide useful information, determination of their role and incremental value over self-report in clinical settings is needed. FM244 Are rehospitalisation rates a reliable quality marker? Adrian Bachofner*, Regina Classen, Werner Zimmerli Kantonsspital Liestal (Liestal, CH) Background. Rehospitalisation rates are proposed to be a marker of quality of care provided by hospitals. In Switzerland, the ANQ (Nationaler Verein fГјr QualitГ¤tsentwicklung in SpitГ¤lern) is generating such rates applying the patient classification software SQLape in order to detect вЂњpotentially avoidable readmissionsвЂќ. The SQLape algorithm is undisclosed to its end user. In this algorithm, each rehospitalisation within 30 days which is linked to a previously established condition, is classified as potentially avoidable. Objectives. To pinpoint the causes of early rehospitalisation in order to extract the fraction of potentially avoidable readmissions. To evaluate whether the ANQ algorithm can be used as reliable quality marker. Methods. According to the SQLape software (version 2011), 274 cases were identified as potentially avoidable readmission to the Medical University Clinic Liestal in 2010. We established a set of 3 main categories defining the reason for вЂњpotentially avoidable readmissionвЂќ: (1) patient care during index admission, (2) discharge planning, and (3) outpatient follow up. A 4th category included cases considered as misclassified. The 274 pairs of discharge reports (index admission and rehospitalisation) were analysed, in order to define the single leading cause of rehospitalisation. Results. 18 of 21 cases in category 1, 23/26 in category 2, 6/15 in category 3 and 0/212 in category 4 have to be considered as potentially avoidable readmission. This corresponds to only 17% of all 274 patients who have been classified by the ANQ algorithm. Examples for misclassification as вЂњpotentially avoidable readmissionвЂќ were the following situations: Category 1. Self-discharge against medical advice (n=3); category 2. Accurate instruction of an incompliant patient (n=3); category 3. Error in outpatient treatment (n=5), direct consulting of Emergency Room instead of primary care physician (n=4); and category 4. Transfer of patient to in-house geriatric ward (n=51) or readmission for chronic progressive condition, adequately diagnosed and treated during index stay (n=96). Conclusion. In only 17% (47/274) of the patients classified as вЂњpotentially avoidable readmissionsвЂќ by SQLape, readmission could have been avoided by providing a better quality. Thus, the classification software SQLape 2011 of the ANQ cannot be used as quality marker of hospital care. 25 FM245 Potentially avoidable readmissions within 30 days: a retrospective analysis of 11074 admissions in a division of general internal medicine Marc Uhlmann*, Olivier Lamy, Estelle LГ©cureux, Hong Dung Duong, GГ©rard Waeber, Anne-Claude Griesser CHUV (Lausanne, CH) Introduction: Hospital readmission (RA) rate within 30 days after discharge is an inpatient quality of care indicator highlighting too early discharge or suboptimal care and coordination. Some early RA are deemed potentially avoidable (RAPA) vs non-avoidable (RANA). In the context of the Swiss quality measures program launched by the National Quality Association (ANQ) it has become mandatory to evaluate the RAPA by mean of the SQLape computerized algorithm from routine administrative data. We aimed to analyze the patientsвЂ™ and staysвЂ™ characteristics within RAPA and RANA for a 3 years period in the division of general internal medicine (DGIM). Method: All hospitalizations between 1.1.2009 and 31.12.2011 in our 200 acute care beds DGIM were analyzed. We defined 5 groups of index stays: 1) ended by death 2) followed by no early RA 3) SQLape non-eligible, followed by early RA 4) SQLape eligible with RANA 5) SQLape-eligible with RAPA. Patients discharged to home directly from the emergency room were excluded. The SQLape definition of RAPA includes: not planned at discharge, caused by at least 1 active diagnosis present during the index hospitalization. Patients who died or were transferred are SQLape non-eligible. Results: 11вЂ™074 admissions were analyzed. 93% came from home or long-term care facility. Mean age 72.0 +/- 16.8y (23.7 % > 85y), 50.3% females, Charlson comorbidity score 2.3 В± 2.3, 41% with psychiatric and 20% with oncological comorbidities. The length of stay was 16 +/- 15 days, 49.7% had been admitted at least once within 12 months before the index admission. 8.4% died, 64.8% returned at home or long-term care facility, 26.8% were transferred to other hospitals. 77.4% were not early RA. Of the 1575 (14.2%) early RA, 385 (3.5%) were SQLape-non eligible and RA, 410 (3.7%) SQLape-eligible RANA and 780 (7.0%) SQLape-eligible RAPA. The median time from discharge to RA was 13 days for RAPA and 15.5 days for RANA. Pulmonary (incl. Cancer, RAPA 24%, RANA 25%), cardiovascular (RAPA 21%, RANA 27%) and digestive (incl. Cancer, RAPA 19%, RANA 15%) diseases account for two third of RA. Conclusion: We observed a 30 days RA rate of 14.2%. Half of the RA were deemed RAPA according to SQLape. Considering the burden and the cost of RA, 2 main measures are needed: 1) general preventive measures (e.g. medication review) and 2) identification of high risk patients to implement targeted preventive measures (e.g. discharge plan including the patient, family and caregivers). 26 Freie Mitteilungen SGIM - Communications libres SSMI Bluthochdruck - Hypertension artГ©rielle FM246 Relationship between copeptin and nocturnal blood pressure in young and healthy adults Tobias SchГ¶n*, Stefanie Aeschbacher, Stefanie Leib, Martin Risch, Lorenz Risch, David Conen UniversitГ¤tsspital - Innere Medizin (Basel, CH); Labormedizinisches Zentrum Dr Risch (Schaan, LI); Private UniversitГ¤t im FГјrstentum Liechtenstein (Triesen, LI) Purpose: Copeptin is a vasopressin related stress hormone. We investigated whether copeptin is associated with 24-hour ambulatory daytime and/or nighttime blood pressure levels in young and healthy adults. Method: The Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk Factors (GAPP) study is a population based cohort study of healthy adults aged 25-41 years in the Principality of Liechtenstein. Individuals with diabetes, BMI >35 kg/m^2 and prevalent cardiovascular disease were excluded. Copeptin was assayed using an immunoluminometric assay (BRAHMS GmbH). Ambulatory blood pressure monitoring was performed using a validated, fully automatic, noninvasive device (Schiller BR-102 plus). Results: Of 1443 individuals included in this study, 53% were female. The median age was 38 years, BMI was 24.2 kg/m^2, and 21% were active smokers. The median copeptin levels were 3.7 (interquartile range [IQR]: 2.5, 5.7) and 2.3 pmol/l (IQR: 1.6, 3.4) in men and women, respectively. In multivariable linear regression models, log-transformed Copeptin was significantly associated with systolic and diastolic blood pressure during sleep (systolic blood pressure: Beta= 0.84 (95% confidence interval [CI]: 0.03, 1.66), p=0.04; diastolic blood pressure: Beta= 1.23 (95% CI: 0.60, 1.87), p=0.0001), as shown in the Table. However, copeptin was not associated with daytime blood pressure levels (systolic blood pressure: Beta= -0.09 (CI: -0.85, 0.68, p=0.83), diastolic blood pressure: Beta= 0.45 (CI: -0.17, 1.08, p=0.15). The relationship between copeptin and nighttime blood pressure seemed to be stronger in men compared to women (p for interaction 0.005). Conclusion: In this large population based study of young and healthy adults, the stress hormone copeptin was significantly associated with elevated nighttime but not daytime blood pressure levels. Our data therefore suggest that stress may be involved in blood pressure elevations during sleep. 27 FM247 Comparison of a wrist device with position sensor and an arm device to measure blood pressure in elderly persons Celine Guggiari*, Christophe BГјla, Stephan Eyer, Katia Iglesias, Bernard Waeber CHUV (Epalinges, CH) Background: Home blood pressure (BP) monitoring is recommended by several clinical guidelines and has been shown feasible in older persons. Wrist manometers have been recently proposed for such home BP measurement, but their accuracy has not been previously assessed in older patients. Methods: Forty eight subjects (33 women and 15 men, mean age 81.3В±8.0 years) had their BP measured with a wrist device with position sensor and an arm device in random order in sitting position. Results: Average BP measures were systematically lower with wrist than arm device for systolic BP (120.1В±2.2 vs 130.5В±2.2 mmHg, p<.001) and diastolic BP (69.7В±1.3 vs 66.0В±1.3 mmHg, p<.001) (Figure). Moreover, a 10 mmHg or greater difference between arm and wrist device was observed in 54.2% and 18.8% of systolic and diastolic measures, respectively. Conclusions: Compared to arm device, wrist device with position sensor systematically underestimated systolic as well as diastolic BP. The magnitude of the difference is clinically significant and questions the use of wrist device to monitor BP in elderly persons. FM248 Effects of weight on blood pressure at rest and during exercise Andreas SchГ¶nenberger*, Renate Schoenenberger, Paolo Suter, Paul Erne Inselspital (Bern, CH); Luzerner Kantonsspital (Luzern, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Introduction: Body weight (BW) and blood pressure (BP) have a close relationship which has been accounted for by hormonal changes. No previous study evaluated the effect of wearing an external weight vest on BP to answer the question whether there is a simple mechanism between BW and BP. Methods: Seventeen healthy volunteers underwent weight reduction (WR) by caloric restriction. Before and after WR, BW, body fat percentage and BP at rest and during exercise were measured. Before and after WR, exercise testing was performed twice with random allocation of a weight vest (10 kg) to one of the tests. Linear regression was used to detect independent associations between BP and weight vest, BW or body fat percentage. Results: BW decreased from 89.4 В± 15.4 kg before to 79.1 В± 14.0 kg after WR (P<0.001). WR led to significant decreases of BP at rest (from 130.0/85.9 mmHg to 112.5/77.8 mmHg, P<0.001 for systolic and diastolic BP) and during exercise. The weight vest significantly increased BP at rest (to 136.1/90.7 mmHg before and 125.8/84.6 mmHg after WR) and during exercise. Linear regression revealed evidence for independent associations of weight vest with BP (P=0.006 for systolic and P=0.008 for diastolic BP at rest). Conclusion: This study shows that wearing of an external weight vest has immediate effects on BP at rest and during exercise independent of BW or body fat. More research is needed to understand the physiological mechanisms between weight and BP. 28 Freie Mitteilungen SGIM - Communications libres SSMI Endokrinologie - Endocrinologie FM249 Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomized controlled trials Viktoria Luise Gloy*, Matthias Briel, Deepak L. Bhatt, Sangeeta R. Kashyap, Philip R. Schauer, Geltrude Mingrone, Heiner C. Bucher, Alain J. Nordmann UniversitГ¤tsspital Basel (Basel, CH); Brigham and Women's Hospital, and Harvard Medical School (Boston, US); Cleveland Clinic (Cleveland, US); UniversitГ Cattolica S. Cuore (Rom, IT) Introduction: The overall effects of bariatric surgery compared to non-surgical treatment for obesity are unclear. We aimed at quantifying the effects of bariatric surgery compared to non-surgical treatment for obesity. Methods: We searched Medline, Embase, and the Cochrane Library from their inception to December 2012 regardless of language or publication status. Eligible studies were randomized controlled trials (>=1 year follow-up) which included individuals with a BMI greater 30 kg/m2, compared current bariatric surgery techniques to non-surgical treatment, and reported on body weight, cardiovascular risk factors, quality of life, and/or adverse events. Two investigators independently abstracted data and assessed risk of bias. Any disagreements were resolved by consensus. Results: The meta-analysis included 7 studies with 508 individuals (mean BMI: 34 to 48 kg/m2). Individuals allocated to bariatric surgery lost more body weight (mean difference [MD] -25 kg, 95% confidence interval [CI] -31 to -20 kg) compared to non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 11.9, 95% CI 2.1 to 66.7) and metabolic syndrome, greater improvements in quality of life and reductions in drug use (no pooled data). Triglycerides decreased more (MD -0.5, 95% CI -0.7 to -0.3 mmol/L) and HDL-cholesterol increased more (MD 0.16, 95% CI 0.1 to 0.2 mmol/L). Changes in blood pressure, total cholesterol or LDL were not different. Serious adverse events after bariatric surgery were relatively rare. Conclusions: Bariatric surgery improves body weight, cardiovascular risk factors, and quality of life more efficiently than non-surgical treatment. Results are limited because only 7 RCTs could be included and apply only to younger individuals with a BMI greater 35 kg/m2. FM250 Comparison of diabetes quality of care indicators as reported by patients and primary care physicians Tinh-Hai Collet, Patrick TaffГ©, Julie Bordet, Bernard Burnand, Isabelle Peytremann-Bridevaux* Policlinique MГ©dicale Universitaire & Service d'Endocrinologie, DiabГ©tologie et MГ©tabolisme (Lausanne, CH); Institut Universitaire de MГ©decine Sociale et PrГ©ventive (Lausanne, CH) Background: Patient self-report of care is pervasive in daily care and clinical research. We compared reliability and agreement parameters between patient and physician reports of diabetes-related processes and outcome of care. Methods: We used self-reported data from a community-based survey including non-institutionalized adults with diabetes living in the canton of Vaud. The following past 12 months diabetes processes of care were documented: HbA1c, lipids, microabuminuria, blood pressure, weight, feet and eye exams. Participants were also asked to provide current levels of HbA1c, height, weight, and blood pressure, if known; corresponding data were collected from treating physicians. For dichotomous variables, we assessed reliability by CohenвЂ™s kappa (discrimination of two dichotomous reports) and agreement by uniform kappa (measurement error and how close two reports are). For continuous measures, we used LinвЂ™s concordance correlation coefficient to evaluate reproducibility and Bland & AltmanвЂ™s 95% limits of agreement to assess measurement error. Results: Out of 406 patients included in the survey, 210 presented both self-reported and physicianreported data. Mean age was 65 years, 40% were women, 51% had diabetes for >10 years and 49% were treated with insulin. Agreement between patient and physician report was good for past 12 months routine processes of care, such as measurement of blood pressure (uniform kappa=0.94), HbA1c (0.93), weight (0.88), and lipid profile (0.78); it was less satisfactory for procedures such as urine analysis, foot and eye exam (all <0.50). CohenвЂ™s kappa values were all low (<0.25). Comparisons of patient and physician report of continuous variables showed high concordance correlation coefficients for height and weight (0.93 and 29 0.97, resp.) and smaller ones for HbA1c (0.72) and blood pressure (0.5-0.6). Limits of agreement were large in all cases (height В±6 cm, weight В±10 kg, HbA1C В±2% and blood pressure В±25 mmHg). Conclusions: Our results suggested good concordance between patient and physician reports of routine dichotomous processes of care, with decreasing concordance for procedures such as urine analysis, foot and eye exam, which may reflect difficulties for patients to figure out what these exams truly represent. Patient and physician reports of continuous outcomes yielded less good results. Evaluation of quality of care from self-reported indicators should be made cautiously. FM251 Gynecomastia in an obese man: not always an insignificant finding Lea Slahor*, Stefan Fischli, Christoph Henzen Luzerner Kantonsspital (Luzern, CH) Case report: A 48-year-old man was referred for surgical breast reduction, as the recent onset of bilateral breast enlargement had been considered to be due to obesity. In our out-patient clinic further medical history revealed sexual dysfunction. No medication, no co-morbidities. On physical examination body mass index was 31.8 kg/m^2, blood pressure 140/90 mmHg, pulse rate 78/min, palpable tender breast tissue (3 cm) beneath the areolae bilaterally, no galactorrhea, low-normal bilateral testes volume. Thyroid, renal and hepatic disease dysfunction were excluded with laboratory studies. Isolated hypogonadotropic (secondary) hypogonadism was confirmed (total serum testosterone 4.69 nmol/l, reference range 5.76-28.12 nmol/l and LH 2.9 U/l, reference range 1.7-8.6 U/l), caused by severe hyperprolactinemia (7561 ug/l, reference range 4.0-15.2 ug/l). MRI of the pituitary gland showed a 4.1 cm sellar mass, thus a macroprolactinoma was diagnosed. Suprasellar extension and optic chiasm compression led to visual field defects(bitemporal hemianopsia). Under dopamine agonist therapy (quinagolid, 225 ug daily) the prolactin level (31 ug/l) and tumor size (2.4 cm) decreased significantly within 3 months. Furthermore gonadal function was restored and gynecomastia reduced. Comment: Gynecomastia is caused by an androgen/estrogen imbalance, for instance as a result of increased aromatization of androgens to estrogens in adipose tissue in obese men. Even though a secondary hypogonadism is a common finding in obese men, a hyperprolactinemia has to be excluded. Prolactinomas (lactotroph adenomas) are the most common hormone-secreting pituitary tumors, whereat serum prolactin levels parallel tumor size. Conclusion: New-onset of postpubertal gynecomastia may be the single clinical sign of an underlying endocrine disorder. Even in obese men, exclusion of an androgen-deficiency is mandatory and in case of marked hypogonadotropic hypogonadism secondary cases as hyperprolactinemia should be evaluated. 30 FM252 Subclinical thyroid dysfunction and functional capacity among older adults: a prospective cohort study Vanessa Virgini*, Liselotte Wijsman, Nicolas Rodondi, Douglas Bauer, Jacobijn Gussekloo, Wendy den Elzen, Patricia Kearney, Wouter Jukema, Rudi Westendorp, Ian Ford, David Stott, Simon Mooijaart Inselspital, UniversitГ¤tspital Bern (Bern, CH); Leiden University Medical Center (Leiden, NL); San Francisco University Center (San Francisco, US); University College Cork (Cork, IE); University of Glasgow (Glasgow, GB); Institute for Evidence-Based Medicine in Old Age (Leiden, NL) Background: Subclinical thyroid dysfunction is common among older adults and has been associated with decreased functional capacity, but data are conflicting. Furthermore, there are no data on the association between persistent subclinical thyroid dysfunction and functional capacity. We investigated the association between subclinical thyroid dysfunction as well as persistent subclinical thyroid dysfunction and functional capacity in an elderly population. Methods: Men and women aged 70-82 years (n=5182) who participated to the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) were included. Self-reported functional capacity was examined using the Barthel Index (BI) and the Instrumental Activities of Daily Living (IADL) at baseline and over a mean 3.2-year follow-up period. Thyroid function was assessed at baseline and after six months. Participants were classified into three thyroid states groups: subclinical hyperthyroidism (TSH<=0.45mIU/L), subclinical hypothyroidism (TSH>=4.5mIU/L, both with normal free T4 levels) and euthyroidism (0.45-4.5mIU/L). Multivariate models were used to determine the relationship between thyroid function as well as persistent thyroid function and functional capacity. Results: At baseline, subclinical hyperthyroidism was present in 65 (1.3%) participants and subclinical hypothyroidism in 173 (3.3%) participants. Compared to euthyroid participants (mean BI 19.77+/(standard error) 0.01, mean IADL 13.62+/-0.02), there was no difference in functional capacity for participants with subclinical hyperthyroidism (mean BI 19.63+/-0.09, mean IADL 13.60+/-0.12, both pvalues>0.05) or subclinical hypothyroidism (mean BI 19.85+/-0.05, mean IADL 13.63+/-0.07, both pvalues>0.05) at baseline. Over a mean 3.2-year period, there was no association between thyroid function and annual decline of either BI or IADL (all p-values>0.05). No association was found between persistent subclinical thyroid dysfunction and functional capacity at baseline or during followup (all p-values>0.05). Conclusion: In a large population of generally well-functioning community-dwelling older persons, there is no evidence to support the relationship between subclinical thyroid dysfunction and selfreported functional capacity. These findings suggest that screening for subclinical thyroid dysfunction might not be indicated in older adults with decreased functional capacity. 31 Freie Mitteilungen SGIM - Communications libres SSMI Beste Freie Mitteilungen вЂ“ Meilleur Communication libres FM253 Is multimorbidity coming into conflict with quality of care? Sven Streit*, Stefan Weiler, Tinh-Hai Collet, Douglas Bauer, Lukas Zimmerli, Peter Frey, Jacques Cornuz, Jean-Michel Gaspoz, Edouard Battegay, Eve Kerr, Drahomir Aujesky, Nicolas Rodondi Insitute of General Practice BIHAM (Bern, CH); Bern University Hospital, Bern (Bern, CH); Lausanne University Hospital (Lausanne, CH); University of California San Francisco (California, US); University Hospital of Zurich (Zurich, CH); Berner Institut fГјr Hausarztmedizin BIHAM (Bern, CH); Lausanne University Hospital (Lausanne, CH); University Hospitals of Geneva, and Faculty of Medicine (GenГЁve, CH); University of Michigan (Ann Arbor Michigan, US) Introduction: Clinical trials often exclude patients with comorbidities, but caring for patients with multimorbidity is very common for general internists. Data on the impact of multimorbidity on quality of care are conflicting. We aimed to analyze the association of multimorbidity and quality of preventive care. Methods: In a random sample of 1002 patients attending four Swiss university primary care settings, we abstracted medical charts over 2 years to build a retrospective cohort. The inclusion criteria were patients aged between 50-80 years followed for >= 1 year. As published definitions of multimorbidity are inconsistent, we derived a new set of comorbidities based on previous studies and added comorbidities used for the Charlson index and psychiatric diseases as an important comorbidity, finally leading to 17 comorbidities. To evaluate the quality of preventive care and care for cardiovascular risk factors (CVRF), we searched medical charts for indicators from RAND's Quality Assessment Tool. We calculated the percentage of provided care as recommended care divided by patients who where eligible for each indicator. We calculated two aggregate scores of quality of preventive care and care for CVRF. Results: The mean age was 63.5 years, 44% were women. Participants had a mean of 2.6 (SD 1.9) comorbidities, while only 7.6% had no comorbidities. The mean Charlson index was 1.8 points (SD 1.9). Overall, participants received 69% of recommended preventive care and 84% received recommended care for CVRF. Quality of care remained stable with increasing number of comorbidities both for prevention (Figure 1) and for CVRF. Results were similar in analyses limited to Charlson index and after adjusting for age, gender, civil status, legal status, work, center and number of visits. Among subgroups of diseases (cardiovascular disease, psychiatric disorders, chronic pulmonary disease, cancer or depression), we found similar quality of care. Conclusions: In university primary care settings in Switzerland, multimorbidity was very common and less than 10% of participants had no comorbidities. Quality of care for preventive care as well as for CVRF was independent of increasing number of comorbidities. These findings confirm the high prevalence of patients with multimorbidity in primary care and demonstrate that a high level of preventive care is possible despite multimorbidity. 32 FM254 Suboptimal adherence to initial processes of care in elderly patients with acute venous thromboembolism Anna Stuck*, Marie MГ©an, Andreas Limacher, Marc Righini, Kurt JГ¤ger, Hans JГјrg Beer, Joseph Osterwalder, Beat Frauchiger, Christian Matter, Nils Kucher, Anne Angelillo-Scherrer, Jacques Cornuz, Martin Banyai, Bernhard LГ¤mmle, Marc Husmann, Michael Egloff, Markus Aschwanden, Henri Bounameaux, Nicolas Rodondi, Drahomir Aujesky Bern University Hospital and University of Bern (Bern, CH); University of Bern (Bern, CH); Geneva University Hospital (GenГЁve, CH); Basel University Hospital (Basel, CH); Cantonal Hospital of Baden (Baden, CH); Cantonal Hospital of St. Gallen (St. Gallen, CH); Cantonal Hospital of Frauenfeld (Frauenfeld, CH); ZГјrich University Hospital (ZГјrich, CH); Lausanne University Hospital (Lausanne, CH); University of Lausanne (Lausanne, CH); Cantonal Hospital of Lucerne (Luzern, CH); ZГјrich University Hospital and University of ZГјrich (ZГјrich, CH) Background: Although venous thromboembolism (VTE) is common in elderly persons, limited data exist on the quality of care in elderly patients with VTE, and it is unknown whether such patients receive recommended processes of care in the early phase of VTE. Methods: We prospectively studied consecutive in- and outpatients aged >=65 years with acute, symptomatic VTE from all five Swiss university- and four non-university hospitals between September 2009 and March 2011. We systematically assessed whether the following five processes of care, which are recommended by the American College of Chest Physicians, were performed in each patient: (1) duration of parenteral anticoagulation for >=5 days; (2) start of oral anticoagulation on the first treatment day; (3) continuation of parenteral anticoagulation until the international normalized ratio [INR] is >=2 for >=24 hours; (4) use of low-molecular-weight heparin monotherapy in patients with cancer; and (5) prescription of compression stockings in patients with symptomatic deep vein thrombosis. We used multivariable logistic models to identify patient and hospital factors independently associated with adherence to recommended processes of care. Results: Our cohort comprised 950 patients with VTE (median age 75 years). Of these, 86.0% (645/750) received parenteral anticoagulation for >=5 days, 46.7% (350/750) had oral anticoagulation started on the first treatment day, and 36.5% (274/750) had an INR >=2 for >=24 hours before parenteral anticoagulation was discontinued. Overall, 34.6% (53/153) of patients with cancer received low-molecular-weight heparin monotherapy and 71.9% (304/423) of patients with symptomatic deep vein thrombosis were prescribed compression stockings. In multivariable analysis, obesity (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.47-0.97), symptomatic pulmonary embolism (OR 0.61, 95% CI 0.43-0.86), and hospital-acquired VTE (OR 0.32, 95% CI, 0.19-0.54) were negatively associated with the initiation of oral anticoagulation on the first treatment day. Conclusion: The adherence to most recommended processes of care was suboptimal in elderly patients with VTE. Several patient characteristics were associated with lower rates of initiating oral anticoagulation on the first treatment day. Further efforts are needed to improve quality of care in elderly patients with VTE. FM255 A high risk of falls is associated with an increased risk of medically-relevant non-major bleeding in elderly patients receiving anticoagulants Marie MГ©an*, Andreas Limacher, Pascal KГ¤mpfen, Drahomir Aujesky Inselpital (Bern, CH) Introduction: We aimed to evaluate whether a high falls risk is associated with an increased risk of bleeding in elderly pts receiving anticoagulants for acute venous thromboembolism (VTE). Methods: In a multicenter prospective Swiss cohort, we prospectively enrolled consecutive pts aged >=65 years who received anticoagulants for acute VTE between 09/2009 and 03/2012. We assessed the falls risk by asking pt two validated questions: 1) "Did you fall during the last year? ", 2) "Did you notice any problems with gait, balance or mobility? ". If at least one of these questions was answered positively, the falls risk was considered high. The primary outcome was the occurrence of a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin >=;20 g/L or leading to the transfusion >=2 units of red blood cells. The secondary outcome was the occurrence of a first non-major bleeding requiring medical attention. To examine the association between falls risk and bleeding, we used a Cox proportional hazards model, adjusted for age, gender, history of major bleeding, anemia, thrombocytopenia, cardiac disease, diabetes mellitus, arterial hypertension, cancer, chronic liver disease, chronic renal disease, overt pulmonary embolism, 33 surgery in the last 3 months, polypharmacy, concomitant treatment with antiplatelet agents, and history of stroke or transient ischemic attack. Results: Of 991 enrolled pts, 458 (46.2%) had a high risk of falls. The mean В±SD follow-up duration was 17 В± 10 months. The overall incidence rate of major and medically-relevant non-major bleeding was 7.9 events and 12.0 events per 100 person-years, respectively. Pts with a high falls risk had a somewhat higher rate of major bleeding (9.6 vs. 6.6; p=0.06) and a significantly higher rate of medically-relevant non-major bleeding (16.7 vs. 8.3; p<0.001) than pts with a low falls risk (Fig.). After adjustment, a high falls risk was significantly associated with non-major bleeding (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.18-2.36; p=0.004) but not with major bleeding (HR 1.18, 95% CI 0.78 to 1.77; p=0.43). Discussion: In this prospective cohort of elderly pts with acute VTE, pts at high falls risk had a significantly increased risk of medically-relevant non-major bleeding. A high falls risk may be an argument against prolonging anticoagulation duration beyond 3 months in such pts. FM256 Vascular dysfunction and hypertension in offspring of RDP mice is associated with insulin resistance Agim Pireva*, Emrush Rexhaj, Stefano Rimoldi, Elise Bouillet, Claudio Sartori, Yves Allemann, Urs Scherrer Inselspital (Bern, CH); CHUV (Lausanne, CH) Background: Epidemiological and experimental studies in humans suggest that environmental influences acting early in life predispose to premature cardiovascular and metabolic disease. In line with these concept we recently found that children born after a pregnancy complicated by preeclampsia display vascular dysfunction. In mice restrictive diet during pregnancy (RDP, a model mimicking preeclampsia in humans) induce vascular dysfunction in the offspring involving decreased vascular nitric oxide bioavailability. There is abundant evidence that NO plays an important role in the regulation of insulin sensitivity in animals and humans. We speculated that offspring of RDP mice are insulin-resistant. 34 Methods: To test this hypothesis, we assessed insulin sensitivity (intraperitoneal glucose tolerance test (IPGTT) and euglycemic-hyperinsulinemic clamp studies) in offspring of RDP and control mice fed with high fat diet (HFD) for 8 wks. To test for the underlying mechanism we studied basal and insulin stimulated glucose uptake in isolated skeletal muscles. Results: The main new finding was that HFD induced more severe insulin resistance in offspring of RDP than in control mice, as evidenced by a markedly smaller glucose infusion rate to maintain euglycemia (77.4В±10.7 vs. 96.7В±12.2, P<.001) and a higher plasma glucose concentration during the IPGTT(ANOVA<.01) in offspring of RDP than in control mice. Insulin resistance appeared not to be related to an intrinsic defect of skeletal muscle because insulin stimulated glucose uptake was similar in RDP and control mice (34.8В±17.6 vs. 35.6В±12.4, P=0.91). Conclusion: We demonstrate for the first time that RDP causes insulin resistant in mice. In analogy to other NO-deficient states, this problem may be related to vascular dysfunction resulting in impaired insulin stimulation of blood flow and substrate delivery to skeletal muscle tissue. Preeclampsiainduced vascular dysfunction has also been found in humans. We speculate that preeclampsia represents a novel risk factor facilitating diet-induced insulin resistance in humans. Grant support: Swiss National Science Foundation and Swiss Society of Hypertension FM257 Association of peripheral neuropathy with circulating advanced glycation endproducts, soluble receptor for advanced glycation end-products and other risk factors in patients with type 2 diabetes Carole Aubert*, Pierre-Louis Michel, Philippe GillГ©ry, StГ©phane Jaisson, MichГЁle FonfrГЁde, Florence Morel, AgnГЁs Hartemann, Olivier Bourron HГґpital Cantonal de Fribourg (Fribourg, CH); HГґpital de la PitiГ©-SalpГЄtriГЁre (Paris, FR); HГґpital universitaire de Reims (Reims, FR) Introduction: Pathogenesis of diabetic peripheral neuropathy is not yet fully understood. Nonenzymatic glycation is one of the contributing mechanisms. The aim of this study was to assess, in a population of patients with type 2 diabetes, the respective relationship between glycation and peripheral neuropathy, compared with other identified risk factors for peripheral neuropathy. Methods: We included 198 patients with type 2 diabetes. Serum concentrations of 3 advanced glycation end products (carboxymethyllysine, methyl-glyoxal-hydroimidazolone-1 and pentosidine) and of their soluble receptor (sRAGE) were measured. Peripheral neuropathy was assessed by the neuropathy disability score and by the Semmes-Weinstein 10g-monofilament test. It was defined as either an abnormal monofilament test and/or a neuropathy disability score >=6. We performed multivariate regression analyses that we adjusted for potential confounding factors for neuropathy: age, gender, diabetes duration, current smoking, systolic blood pressure, waist, height, peripheral arterial occlusive disease, glycated haemoglobin and lipid profile. Results: The prevalence of peripheral neuropathy was 20.7% (n=41). Table 1 shows factors associated with neuropathy, in univariate and multivariate regression analyses. sRAGE was independently and positively associated with the severity and the presence of peripheral neuropathy. Carboxymethyllysine was independently and positively associated with an abnormal monofilament test. No significant association was found between peripheral neuropathy and methyl-glyoxalhydroimidazolone-1 or pentosidine. Waist, height, current smoking, glycated haemoglobin and peripheral arterial occlusive disease were independently associated with peripheral neuropathy. Conclusion: Carboxymethyllysine and sRAGE were independently associated with peripheral neuropathy. This study confirms the relationship between advanced glycation and peripheral neuropathy, independently of other known risk factors for peripheral neuropathy, in patients with type 2 diabetes. Our results may help assessing the impact of hyperglycemia in the pathogenesis of peripheral neuropathy, and have direct future therapeutic implications, as inhibition of advanced glycation may slow down progression of peripheral neuropathy. But further studies are needed to assess the cause-to-effect relationship between advanced glycation and peripheral neuropathy. 35 FM258 Post-traumatic stress disorder in relatives of patients with out-of-hospital cardiac arrest Marius Zimmerli*, Kai Tisljar, Gian-Marco Balestra, Wolf Langewitz, Stephan Marsch, Sabina Hunziker UniversitГ¤t Basel (Basel, CH) Introduction: Being a family member of an out of hospital cardiac arrest (OHCA) patient causes substantial psychological stress which may put them at increased risk for development of psychological and psychosomatic long-term consequences, such as post-traumatic stress disorder (PTSD). Yet, frequencies and risk factors for PTSD in this population are unknown. To answer this question, we performed a survey with relatives of OHCA patients hospitalized at the University Hospital in Basel between January 2007 and August 2012. Methods: This is a prospective observational study. Consecutive relatives of OHCA patients were contacted by phone interview using structured questionnaires, such as the revised Impact of Event Scale (IES-r) for assessing PTSD and the Family-Satisfaction with Care in the ICU (FS-ICU) instrument to assess risk factors associated with ICU care. Results: From a total of 101 included relatives (30% male, mean age 58 [SD В±12.1] years), 40 (39.6%) had PTSD-related symptoms. In multivariate logistic regression analysis [odds ratio, 95% confidence interval], several relative-related factors (female gender [3.3, 1.08-10.11], past history of depression [3.63, 1.02-12.96]), patient-related factors (hypothermia treatment [2.86, 0.96-8.48]) and factors associated with ICU care (long time-interval to receive prognostic information from ICU staff [2.11, 0.83-5.38], therapeutic measures not perceived as being sufficient [18.4, 1.52-224.22], conflict with ICU staff [3.61, 0.71-18.4]) were predictors for PTSD. A model including these factors showed high discrimination with an area under the curve of 0.77. Death of the patient was not associated with PTSD [OR 0.71, 95%CI 0.31-1.60, p=0.40] nor was it an effect modifier (p=ns). Conclusion: This is the first study systematically investigating long-term psychological burden of relatives from OHCA patients. PTSD was found in a high proportion of relatives and was associated with baseline factors, as well as relatives experience with initial ICU care and the interaction with the treating team including sharing of prognostic information. Further research is needed to develop preventive strategies in this population. 36 Freie Mitteilungen SGIM - Communications libres SSMI MultimorbiditГ¤t - MultimorbiditГ© FM259 Therapeutic conflicts in patients with multimorbidity: a retrospective analysis from an emergency department of a tertiary care hospital Stefan Markun*, Roksana Rodak, Vladimir Kaplan, Claudia Wagner, Barbara Holzer, Edouard Battegay, Lukas Zimmerli UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Objective: Multimorbidity, or multiple active conditions in one patient, is increasingly common, particularly among the elderly. However, the applicability and feasibility of clinical practice guidelines (CPGs) in multimorbid patients is unknown. The aim of the study was to identify and quantify potential therapeutic conflicts in patients with multimorbidity assuming stringent adherence to CPGs for each active condition. Methods: We reviewed the medical documentation of all patients >=18 years with at least two active conditions, admitted from the emergency department to the medical ward of the Division of Internal Medicine at the University Hospital Zurich during January 2009. In individual patients we assumed treatment as suggested by CPGs for each active condition and counted the number of therapeutic conflicts that arouse. Therapeutic conflicts were classified as major or minor according to clinical importance and severity. Absolutely contraindicated treatments were rated as major therapeutic conflicts, whereas treatments that were applicable under precautionary measures were defined as minor therapeutic conflicts. Results: We analyzed 166 patients with a mean age (В±SD) of 63 (В±19) years, and a mean number of active conditions (В±SD) of 6.6 (В±3.4). We found 239 therapeutic conflicts in 81 patients (49%). Major therapeutic conflicts were found in 48 patients (29%), with the most frequent conflict situation occurring in patients with an infectious disease and concurrent immunosuppressive therapy, mostly due to an organ transplant. Minor therapeutic conflicts occurred in 68 patients (41%), with the most frequent conflict situation consisting of use of diuretics, mainly due to heart failure, in severe acute or chronic renal failure. Conclusion: We found that therapeutic conflicts were common in multimorbid patients with one out of two having minor, and one out of three having major therapeutic conflicts. Thus, applicability of CPGs in these patients appears to be limited. Managing multimorbidity is a complex task for health care professionals as well as patients. Alternative strategies need to be developed. FM260 Prevalence of measured and self-reported multimorbidity in the Swiss-CoLaus population-based study Basile Pache*, Peter Vollenweider, GГ©rard Waeber, Pedro Marques-Vidal Centre Hospitalier Universitaire Vaudois (Lausanne, CH); The Swiss Institute of social epidemiology (Lausanne, CH) Introduction: The prevalence of multimorbidity (MM) in hospitalized patients is increasing and recognized as an important factor that may modify the strategies of treatment and increase the length of stay. Little is currently known about the prevalence of MM in the general population and if measured or self-reported diseases are different in the outpatient setting compared to hospitalized patients. The objective of the study was, therefore, to assess the prevalence of self-reported and measured MM in representative sample of the general population aged 35-75 years in Switzerland. Method: Data were obtained from the population based CoLaus Study: 3712 participants (1965 women, 50В±9 years). MM was defined as presenting >=2 morbidities according to a list of 27 items (either measured or self-reported data, according to Barret et al.) or a Functional Comorbidity Index (FCI) (18 items, measured only). Results: The prevalence of MM according to these three definitions is summarized in the table 1. For all definitions prevalence of MM was higher in women, elderly participants, those with lower education levels, Swiss nationals, former smokers and obese participants. The prevalence of MM when measured data were used was significantly higher than according to self-reported (p<0.001). Multivariate analysis confirmed most of these associations, except that no difference was found for educational level and for overweight participants. 37 Conclusion: The prevalence of MM is high in the general population, ranging from 13.8 and 50.3% even in the younger age group. The prevalence is higher in women, and increases with age and weight. The prevalence varies considerably according to the definition and is lower when using selfreported compared to measured data. References: 1. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet. 2012;380(9836):37-43. 2. Groll DL, To T, Bombardier C, Wright JG. The development of a comorbidity index with physical function as the outcome. J Clin Epidemiol. 2005;58(6):595-602. FM261 Living arrangements and informal care needs one-to-three years after stroke rehabilitation Heike Geschwindner*, Horst Rettke Pflegezentren der Stadt ZГјrich (ZГјrich, CH); UniversitГ¤tsspital ZГјrich, Zentrum Klinische Pflegewissenschaft (ZГјrich, CH) Introduction: Stroke is a major cause of persisting disabilities and long-lasting needs for daily care and assistance. Rehabilitation aims at restoring functioning and community reintegration. Goal setting and evaluation guides these processes. However, when being discharged an informal care setting has to be established to maintain daily care and assistance for an indefinite time period. Method: A cross-sectional study has been conducted with a sample (n=287) of first-ever stroke patients one to three years post-discharge from inpatient neurorehabilitation. Results: At discharge from rehabilitation, about 80% of all respondents (n=174) attained their shortterm goal set at admission. One to three years post-discharge they showed a lesser degree in attaining their long-term goals. However, the majority was living at home with help, and 14% were living in an institution. Most stroke survivors were limited in physical and cognitive functioning to some extent. Also problems concerning communication skills were stated. Then again, limitations were not necessarily related to the actual living arrangement. Even when assessed as living independently stroke patients may need assistance in вЂ�instrumental activities of daily livingвЂ™, e.g. household tasks. The results show that even three years post-discharge a considerable number of stroke survivors (17%) are in need of daily care and support. Informal care is frequently provided by partners or family members. Depending on a stroke survivorвЂ™s limitations in physical or cognitive functioning as well as in 38 socio-cultural activities more persons had been involved. If limitations require constant support, care is given by the partner and close family members. However, if care has to be provided only at specific points in time, home care services might be called in. While immediately after discharge the partner or a close family member is often the only caregiver, our study results point to a shift towards the involvement of more persons in informal caregiving in the long term. Conclusions: The high proportion of non-attainment of long-term goals, the often times enduring demand for personal support and care post-stroke and continuing involvement of informal caregivers require attention. Already during inpatient rehabilitation health care professionals should address long-term outcomes and consequences by carefully informing and educating of the individual stroke patient and family members. FM262 Polypharmacy in a division of general internal medicine: a retrospective study of the number and types of medications prescribed Marc Uhlmann*, Estelle LГ©cureux, Anne-Claude Griesser, Hong Dung Duong, Olivier Lamy CHUV (Lausanne, CH) Introduction: Adverse drug events (ADE) account for the majority of hospital-based adverse events and are a frequent cause of readmission. As the risk of ADE increases with the number of medications, polypharmacy is of major concern. This is particularly true for the majority of patients hospitalized in a division of general internal medicine (DGIM) mostly elderly and/or polymorbide. We retrospectively analyzed the amount and types of medications prescribed, the number of prescribers and treatment modifications over a 3 year period in our DGIM. Method: All hospitalizations between 1.1.2009 and 31.12.2011 in our tertiary DGIM (200 acute care beds) were analyzed. We extracted prescription data from the computerized physician order entry program (CPOE). The CPOE was unavailable for 409 patients. Patients discharged to home directly from the emergency room were excluded. Results: 11вЂ™074 admissions were analyzed. 93% came from home or long-term care facility. Mean age was 72.0 +/- 16.8y (52.8% > 75y, 23.7% > 85y), 50.3% were females, Charlson comorbidity score was 2.3 В± 2.3, 41% had psychiatric comorbidities. The length of stay was 16 +/- 15 days. During one hospital stay one patient had (mean) 16.5 different medications prescribed, 26 prescription interventions and 3.7 prescribers. The most frequent prescriptions were (% of patients): benzodiazepines (BZ 66.7%), anticoagulants (AC 59.5%), NSAID and anti-platelets (NAP 48.1%), opiates (OP 45.8%) diuretics (DI 44.0%), anti-depressants or neuroleptics (ADN 38.0%) and antidiabetics (AD 21.2%). At discharge (N=7вЂ™747) the mean number of medications prescribed was 7.7; 2вЂ™690 patients (34.7%) had > 10 different medications. The most frequent prescriptions were: NAP (39.2%), DI (38.5%), BZ (37.7%) ADN (22.6%), AC (21.2%), AD (18.0%), OP (16.5%) and systemic steroids (9.6%). Conclusion: As the definition of polypharmacy differs between вЂњmanyвЂќ and over 5-10, our observation of 34.7% patients being discharged with > 10 different medications is striking. The proportion of some high-risk medicines used is also source of concern as they have been associated with increased ADE. Balance between over- and underprescription is necessary but difficult to achieve. As a multifaceted approach seems increasingly necessary to reduce ADE, especially for the elderly during transition of care, a comprehensive medication review by the hospital prescribers is mandatory. 39 Freie Mitteilungen SGH - Communications libres SSH Experimental Hematology - Experimental Hematology FM263 Endothelial cells are essential to sense lipopolysaccharide (LPS) in a Myd88dependent manner and to subsequently induce emergency myelopoiesis Steffen BГ¶ttcher*, Ramin Radpour, Rahel Gerosa, Mathias HeikenwГ¤lder, Manfred Kopf, Markus Manz UniversitГ¤tsSpital ZГјrich (ZГјrich, CH); Technische UniversitГ¤t MГјnchen (MГјnchen, DE); EidgenГ¶ssische Technische Hochschule (ZГјrich, CH) Severe systemic infections evoke a well-characterized and tightly-regulated hematopoietic response program to enhance myeloid cell output, a condition which is referred to as emergency myelopoiesis. However, detailed information on the initial steps involving pathogen recognition and translation into accelerated bone marrow (BM) myelopoiesis are still lacking. We have recently demonstrated that LPS-induced emergency myelopoiesis depends on TLR4-expressing non-hematopoietic cells (Boettcher et al., J Immunol. 2012 Jun 15;188(12):5824-8.). However, the precise identity and localization of the non-hematopoietic cell type crucial for sensing gram negative infection-derived lipopolysaccharide (LPS) have remained elusive to date. We now have addressed this fundamental question using Cre-loxP recombination technology. In order to specifically delete TLR-downstream signaling in various non-hematopoietic cells including BM Nestin+ mesenchymal stem cells (MSCs) and their progeny, perivascular cells, endothelial cells, and hepatocytes, we generated Nes-Cre;Myd88fl/fl, Pdgfrb-Cre;Myd88fl/fl, Tek-Cre;Myd88fl/fl, and AlbCre;Myd88fl/fl mice, respectively. We observed a normal increase in the frequency of BM CD11b+Gr1low immature myeloid precursors accompanied by a decrease of BM CD11b+Gr-1high mature myeloid cells upon LPS stimulation characteristic for efficient emergency myelopoiesis in NesCre;Myd88fl/fl, Pdgfrb-Cre;Myd88fl/fl, and Alb-Cre;Myd88fl/fl mice as compared to control mice. Furthermore, we measured highly-elevated plasma G-CSF levels in these mouse strains upon LPS injection. Hence, intact TLR-signaling in mesenchymal stromal cells incl. Nestin+ MSCs, perivascular cells as well as hepatocytes is dispensable for induction of emergency myelopoiesis. Strikingly, TekCre;Myd88fl/fl mice were completely non-responsive towards LPS stimulation as assessed by the above-mentioned parameters. Furthermore, freshly isolated endothelial cells from various solid organs expressed Tlr2, Tlr4 and Myd88 transcripts at similar to even higher levels than cDCs and pDCs. Preliminary results showed the same effects when Tek-Cre;Myd88fl/fl mice were infected with E. coli. Our results thus demonstrate a fundamental and unanticipated role of the endothelium for sensing of systemically spread pathogens and subsequent stimulation of BM emergency myelopoiesis. FM264 Engineering a bone marrow stem cell niche through endochondrial ossification Hitoshi Takizawa*, Elia Piccinini, Celeste Scotti, Markus Manz, Ivan Martin Hematology, University Hospital Zurich (ZГјrich, CH); 2) Departments of Surgery and of Biomedicine, University Hospital Basel (Basel, CH); Departments of Surgery and of Biomedicine, University Hospital Basel (Basel, CH) Bone marrow (BM) is a primary hematopoietic organ where lifelong self-renewing and hematopoietic stem cells (HSCs) produce millions of all blood lineage cells every day. Robust regenerative potential of HSCs is maintained in a unique microenvironment, termed HSC niche that produces necessary and sufficient regulatory factors for HSC homeostasis. The structural and functional establishment of this privileged niche at the embryo stage critically depends on the developmental process of endochondral ossification. Through a вЂќdevelopmental engineeringвЂќ approach, we recapitulated the endochondral route by ex vivo culture of human adult mesenchymal stromal cells (hMSC) on a collagen sponge under chondrogenic and hypertrophic conditions. Implantation into C57BL/6 nude mice allowed the cartilaginous template to undergo extensive remodeling with CD31+ vessel ingrowth, TRAP+/MMP13+ osteoclast activity, and formation of mineralized bony tissue, thus defining an ectopic ossicle (EO). Flowcytometric analysis of the EO-derived cells after 6 month in vivo remodeling showed comparable frequencies of phenotypic mouse HSCs and progenitor cells to control native femurs. To test their in vivo functionality, total cells harvested from EOs were transplanted together with competitor BM cells into lethally irradiated congenic mice. Peripheral blood analysis showed that EO-derived cells 40 engrafted and reconstituted all blood lineages similar to control BM cells. BM analysis of recipients after 3.5 months confirmed the successful engraftment and maintenance of EO-derived HSCs, indicating a functional hematopoietic hierarchy reestablished by HSCs in EO. These findings demonstrate that during in vivo stromal tissue remodeling the engineered EO becomes capable of allowing endogenous HSCs to home and produce functional hematopoiesis, supporting its functional equivalence in HSC niche formation to control BM. The engineering of ectopic BM niches with hMSC could serve as a model to investigate physiology and pathophysiology of HSC maintenance and hematopoiesis. Moreover, understanding of niche mediated regulatory mechanisms of normal and pathologic HSCs will open the perspective towards improving clinical outcome of HSCbased regenerative medicine as well as cancer stem cell targeting therapies. FM265 Loss of STAT1 ameliorates the phenotype of essential thrombocytaemia and exacerbates erythropoiesis in in vivo models of JAK2V617F-driven MPN Adrian Duek*, Pontus Lundberg, Takafumi Shimizu, Jean Grisouard, Radek Skoda University of Basel (Basel, CH) Introduction. Myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic progenitors, and include chronic myeloid leukaemia (CML), polycythaemia vera PV), essential thrombocythaemia (ET) and others. In 2005, several independent groups identified a recurrent mutation (V617F) in the pseudokinase domain of JAK2 in most patients with PV, ET or PMF. Its presence has been shown responsible for cytokine hypersensitivity, aberrant regulation of its kinase activity by SOCS proteins, and downregulation of PRMT5 methyltransferase activity. However, the question is how a unique mutation might give rise to at least three different diseases. Recent publications have stressed the fact that STAT1 signaling is activated in ET but not in PV. STAT1 promotes megakaryopoiesis while inhibiting erythropoiesis and thus contributes to the ET phenotype. Methods. To test the hypothesis that STAT1 promotes megakaryopoiesis and represses erythropoiesis in the context of JAK2V617F-driven MPN, we used our transgenic mice expressing the human JAK2V617F gene activated by CRE-recombinase under the control of either Vav (ET mouse model) or the Scl promoter (PV mouse model), and crossed them with germline STAT1 knock out (STAT1-/-) mice. Results. JAK2V617F/VavCre/STAT1-/- mice showed attenuated ET phenotype in peripheral blood comparing to JAK2V617F/VavCre/STAT1+/+. However, the mice still displayed splenomegaly, evidence of myeloproliferation and fibrosis in both bone marrow and spleen. Analysis of megakaryopoiesis in hematopoietic tissues revealed arrest in megakaryocytic maturation and increase of pSTAT3 and pSTAT5 levels. JAK2V617F/SclCre/STAT1-/- line revealed similar attenuation in platelet counts along with an evident exacerbation of the PV phenotype in peripheral blood. Analysis of erythropoiesis demonstrated marked increase of erythroid precursors in spleen. The phenotype was reproducible in recipient animals upon bone marrow transplantation. Conclusion: We show that STAT1 plays a central role in determining the phenotypic presentation of JAK2V617F-driven MPN by promoting megakaryopoiesis and repressing erythropoiesis. Bone marrow transplantation showed that the changes observed in transgenic mice were cell autonomous and not due to the effect of STAT1 deficiency on the microenvironment. However, nullizygousity of STAT1 is not enough to totally abrogate the ET phenotype. 41 FM266 Engraftment and homing of human lymphoma B-cells are controlled by junctional adhesion molecule C Carmen DoГ±ate*, Christiane Ody, Beat A. Imhof, Thomas Matthes HГґpitaux Universitaire de GenГЁve (GenГЁve, CH); UniversitГ© de GenГЁve (GenГЁve, CH) Introduction: The junctional adhesion molecules (JAMs) are a subgroup of the Immunoglobulin superfamily. JAM members localize at endothelial tight junctions and have been involved in the formation and maintenance of interendothelial junctions and in leukocyte transmigration. JAM-C is also expressed in human B cells and this expression is tightly controlled during differentiation, allowing the classification of JAM-Cpos and JAM-Cneg B-cell lymphomas. In the current study, we investigated the role of JAM-C in the homing and engraftment of normal and malignant B cells. Methods: Human B cells were isolated from peripheral blood of healthy donors and lymphoma patients. To study the role of JAM-C in B cell migration, B cells were incubated with a polyclonal and six different monoclonal anti-JAM-C antibodies and injected i.v. into NOD/SCID mice. Homing of cells to lymphoid organs (bone marrow, spleen, lymph nodes) was analyzed one hour later by flow cytometry. To identify the interactions of JAM-C on B cells, binding, adhesion, immunofluorescence and surface plasmon resonance assays were performed. To investigate the role of JAM-C in lymphoma dissemination, the JAM-C positive B-cell line Jeko-1 was used for long-term engraftment assays. Jeko-1 cells were injected into NOD/SCID mice and animals were treated for three weeks with anti-JAM-C antibodies. Tumor burden was evaluated in lymphoid organs on day 26. Results: Treatment with the polyclonal and 2/6 monoclonal anti-JAM-C antibodies reduced the homing of normal and JAM-Cpos lymphoma B cells to lymph nodes, bone marrow and spleen by 50-60%. Adhesion and plasmon resonance studies identified JAM-B as the major ligand for JAM-C, and immunofluorescence analysis demonstrated the expression of JAM-B on murine and human lymphatic endothelial cells. Accordingly, anti-JAM-C antibodies reduced the adhesion of JAM-C expressing B cells to the ligand JAM-B by 50% and inhibited the binding of soluble JAM-B to JAM-Cpos B cells. Long-term administration of anti-JAM-C antibodies reduced significantly the engraftment of JAM-Cpos Jeko-1 cells in the bone marrow (21%), spleen (94%) and lymph nodes (93%) of NOD/SCID mice. Conclusions: Our results demonstrate a functional role of JAM-C in B cell homing and engraftment into lymphoid organs. Anti-JAM-C antibodies could thus represent a potential therapeutic approach preventing lymphoma B cells from reaching supportive lymphoid microenvironments in bone marrow, lymph nodes and spleen. FM267 Aberrant somatic hypermutation-dependent BCL2 mutations in B-cell lymphomas and their involvement in the evolution of follicular lymphoma Regula Burkhard*, Urban Novak UniversitГ¤t Bern (Bern, CH); Inselspital (Bern, CH) Somatic hypermutation (SHM) is active in germinal centers (GC) and randomly introduces mutations in immunoglobulin heavy chain genes (IgH) of B cells. Unlike normal B cells, 50% of diffuse large B cell lymphomas (DLBCL) have somatic mutations in several proto-oncogenes. The features of these mutations are consistent with an aberrant activity of the SHM (ASHM) mechanism on non-Ig loci. Recently, BCL2 was identified as a novel target of ASHM in DLBCL (Saito & Novak, 2009). In 90% of follicular lymphoma (FL) and 35% of GC-derived DLBCL, BCL2 expression is deregulated due to the translocation t(14;18) joining BCL2 to the Ig enhancer. Clinically, FL is characterized by an indolent course, but multiple relapses and transformation into DLBCL. To investigate if BCL2 is targeted by ASHM in B cell non-HodgkinвЂ™s lymphomas (B-NHLs) other than DLBCL, a panel of 104 primary BNHLs was screened for BCL2 mutations (promoter, exon 1 and 2, intron) by direct sequencing. Clonal BCL2 mutations with features similar to those reported for IgH were present in various t(14;18) positive and negative B-NHLs, which defines them as ASHM-depend. In comparison to DLBCL, BCL2 mutation frequency was lower in t(14;18) positive FL (0.77 vs. 0.31%) whereas it was higher in t(14;18) negative FL (0.08 vs. 0.03%). To determine the involvement of BCL2 mutations during the progression of FL, 10 matched pairs of FL relapsing to FL or DLBCL in the follow-up were investigated. The lymphomas were clonally related in 9/10 cases as assessed by IgH-fragment length analysis. Examination of BCL2 mutations in paired samples revealed two different patterns of a genomic evolution of FL: (i) A direct / linear evolution from the antecedent FL clone reflected by few novel clonal mutations in the DLBCL compared to the FL biopsy. (ii) The evolution from a common progenitor cell characterized by both shared and unique clonal mutations in the initial FL and the 42 relapsed or transformed FL counterpart. As expected, in the clonally unrelated samples from one patient, the sequential FL biopsies displayed no common BCL2 mutations, suggesting that the second FL clone reflects a novel tumor and not a relapse of the ancestral FL. In summary, ASHM-dependent BCL2 mutations are not restricted to DLBCL, indicating a critical involvement in B-NHL. BCL2 mutational analysis in serial biopsies of relapsing or transforming FL revealed contrasting patterns of genomic evolution mirroring the complexity of FL. FM268 Microtubule-associated protein 1S (MAP1S) is a novel PU.1 transcriptional target in neutrophil differentiation of acute promyelocytic cells Aladin Haimovici*, Martin Fey, Mario Tschan HГґpital de l'Ile (Bern, CH) The development of mature neutrophils is a complex process that is controlled by transcription factors such as the myeloid master regulator PU.1. Suppression of PU.1 by the oncogenic fusion protein PML-RARA in acute promyelocytic leukemia (APL) plays a major role in blocking differentiation of these leukemic cells. In addition to its role in myeloid development, PU.1 is implicated in cell survival and proliferation. The latter novel function of PU.1 has scarcely been studied. In this study we focused on PU.1 targets involved in autophagy, which is mainly considered as a cell survival mechanism. A first candidate gene possibly linking PU.1 to autophagy is the microtubule-associated protein 1S (MAP1S). Generally, microtubules are associated with autophagosomes, which will fuse with lysosomes for degradation of their contents. MAP1S has been implicated in microtubule dynamics, mitotic abnormalities and cell death. Absence of this protein may result in various neurodegenerative disorders, heart disease and cancer. We found that MAP1S is downregulated (mean delta Ct = 0,64) in primary AML patient samples (n=120) compared to mature myeloid cells of healthy donors (mean delta Ct = 3,45). Accordingly, MAP1S expression is upregulated in APL cell lines upon all-trans retinoic acid (ATRA)-induced neutrophil differentiation. Knocking down PU.1 in NB4 APL cells significantly impaired MAP1S upregulation during ATRA-induced differentiation. Moreover, PU.1 binding to the MAP1S promoter was shown by chromatin immunoprecipitation. Using lentiviral vectors expressing shRNAs targeting MAP1S, we observed significantly attenuated neutrophil differentiation in NB4 MAP1S knockdown as compared to control cells. Furthermore, knocking down MAP1S also attenuated ATRA-induced autophagy. Together, we identified MAP1S as novel transcriptional target of PU.1 with low expression in AML and a function in neutrophil development of APL cells. As hematopoietic cells undergo several changes in morphology, the cytoskeleton might play an important role in this process. Therefore a tight regulation of these cytoskeleton-associated compounds is needed. Overall, our data link PU.1 to the cytoskeleton indicate a novel function of this transcription factor. FM269 Mesenchymal stem cells inhibit T-lymphocytes after poly(I:C) stimulation JosГ© Maria Rincon Garriz, Marie Luce Piallat, Thomas Laumonier, Vincent Kindler* Geneva University Hospital (GenГЁve, CH); Geneva Medical University Center (GenГЁve, CH) Introduction: Lymph nodes are disseminated structures located in privileged regions of the body where they drain the afferent lymph. They play a key role in the maintenance of self tolerance in steady state conditions, and they restrain inflammation to specific sites during the ongoing of the immune response. They comprise cells from hematopoietic origin recognized as effectors of acquired immunity, and a stromal compartment, composed of various mesenchymal cell types including mesenchymal stem cells (MSC), follicular dendritic cells (FDC), and fibroblastic reticular cell (FRC) cells. Whereas MSC and FDC have been identified as key regulators of T and B lymphocytes, the function of FRC has been thought for a long time to be restricted to structural tasks. However recent investigations have demonstrated that FRC also participate to T and B lymphocyte control. We therefore investigated whether MSC derived from human bone marrow could differentiate in FRC in vitro. Methods: Human MSC were purified from femoral head remains and amplified in vitro. Their phenotype and their metabolic activity under various culture conditions were assessed by FACS and biochemical assays. Results: Human MSC amplified in vitro in the presence of platelet supernatant exhibited a phenotype resembling that of FRC (CD31-, CD54low, CD44+, CD146+, alpha SMA+) suggesting that they spontaneously differentiated toward this lineage. When incubated with poly IC in vitro they showed 43 similar phenotypic alterations than murine FRC exposed to poly IC in vivo, namely an increase in MHC-I, CD54 and B7-H1 expression. Moreover MSC incubated with poly IC or gamma-interferon actively depleted the culture medium in L-tryptophan indicating that the indolamine 2,3 deoxygenase was activated, and such media could not support T cell proliferation. Conclusion: These observations suggest that the systemic anti-inflammatory effect exerted by MSC when infused intravenously (as documented by their ability to control steroid-resistant graft versus host disease) may reflect the physiological regulation that MSCs, or their progeny differentiated in FRC exert in the lymph nodes when exposed to local inflammation. FM270 New function for Dicer1 in differentiation of acute promyelocytic leukaemia cells Julian Wampfler*, Maritn F. Fey, Mario P. Tschan Institute of Pathology, University of Bern (Bern, CH); Inselspital (Bern, CH) MicroRNAs (miRNAs) are globally downregulated in cancer and often impact on cellular differentiation programs. Dicer1, an RNAse III family member, plays a key role in miRNA maturation. Importantly, Dicer1 mutations correlate with adverse prognosis in many human cancers including ovarian cancer, lung carcinoma and malignant melanoma. We investigated if Dicer1 plays a role in the pathology of acute myeloid leukemia (AML) that is characterized by a block of myeloid differentiation at different stages. Firstly, we quantified Dicer1 mRNA expression in a large cohort of AML patient samples (n = 119). We found a significant downregulation of Dicer1 in AML blasts and normal CD34^+ progenitor cells as compared to mature neutrophils from healthy donors. In line with these findings, PML-RARA positive acute promyelocytic leukemia (APL) NB4 cells displayed a significant induction of Dicer1 mRNA expression upon all-trans retinoic acid (ATRA) induced neutrophil differentiation. Conversely, NB4-R2 ATRA-resistant cells showed no induction of Dicer1 expression indicating that Dicer1 upregulation is not due to an unspecific ATRA-response. Next, to address the function of Dicer1 in neutrophil differentiation, we generated two independent NB4 Dicer1 knockdown cell lines using lentiviral vectors expressing small harpin (sh) RNA targeting Dicer1. Of note, inhibiting Dicer1 will phenocopy a cancer-like low miRNA expression model based on its central role in miRNA maturation. Dicer1 knockdown resulted in a significantly reduced induction of the neutrophil-specific miR-223 during neutrophil differentiation showing functionality of the implemented Dicer1 knockdown. Generally, Dicer1 knockdown cells displayed attenuated neutrophil differentiation compared to control shRNA cells as assessed by CD11b and granulocyte colony-stimulating factor receptor expression as well as reduced autophagy activity as measured by LC3 dot formation on cytospin preparations. Autophagy, a bulk degeneration process, was recently linked to PML-RARA degradation in APL. Our results indicate that Dicer1 plays a significant new role in neutrophil differentiation and in autophagy of APL cells. We observed Dicer1 downregulation in a large cohort of clinical AML patient samples and CD34^+ progenitor cells indicating that low Dicer1 expression is associated with an immature myeloid phenotype. Dicer1 and thus miRNA deficiency leads to multiple alterations of pathways important for APL differentiation and autophagy. 44 Freie Mitteilungen SFGG - Communications libres SPSG FM271 Variations in population health status: results from a survey addressing inequalities in ageing in Switzerland Christophe Luthy*, Catherine Ludwig, Christine Cedraschi, Anne-francoise Allaz, Francois Herrmann hГґpitaux universitaires de genГЁve (GenГЁve, CH) Objectives: The present cross-sectional, nation-wide survey aims to describe Health Related Quality of Life (HRQOL) of elderly people in Switzerland. Data focusing on these aspects are scarce. However, the conceptualization and assessment of HRQOL are crucial to health policy and evaluation research in this population. Methods: Stratified random samples representative of the general population aged >65 (65-69, 70-74, 75-79, 80-84, 85-80, > 90), living in the community (N=2907). The survey was conducted in the 3 linguistic areas. The EQ-5D was used to assess HRQOL. This self-reported questionnaire investigates 5 dimensions: Mobility (MO), Self-Care (SC), Usual Activities (UA), Pain/Discomfort (PD), and Anxiety/Depression (AD). Each dimension is subdivided into three categories (no problem, moderate problem, extreme problem) and provides a global score (Visual Analogue Scale ranging from 0 to 100). Socio-demographic variables included gender and education, besides age and linguistic area. Regression analyses were carried out on the scores of each 5 dimensions. Results: Mean EQ-5D global score was 75 (SD=20) for the total sample, and decreased with age, ranging from 79 (SD=19) in the younger group to 71 (SD=22) in the oldest. Twenty-five percent of the sample reported difficulties in MO, ranging from 9% in the younger group to 59% in the oldest; 7% reported difficulties in SC (from 1% to 26%); 14% reported difficulties in UA (6% to 40%); 51% reported PD (42% to 62%); and 21% reported AD (18% to 23%). Interestingly, the evaluation of the severity, i.e. 'moderate' or 'extreme' problem, of each dimension had an impact on the global VAS score for PD and AD only; as for the functional items, i.e. MO, SC and UA, only the presence or absence of problems played a role. Regression analyses showed that the effect of age was significant on all measures, except AD. Besides, age explained more than 10% of the variance, but in the functional dimensions only. Linguistic areas, gender and education had a significant effect although they explained only a marginal part of the variance (<5%). Discussion: HRQOL in the elderly is overall good although it decreases with age. Interestingly, functional dimensions are more affected by age than pain and emotional problems. There is a similar trend for the global score. Taken together, these results suggest that functional dimensions play a major role in determining self-reported HRQOL in the aging population. FM272 Prevalence of polypharmacy and potentially inappropriate medication in the older, community-dwelling population in Switzerland Eva Blozik*, Roland Rapold, Jan von Overbeck, Oliver Reich Schweizer Zentrum fГјr Telemedizin Medgate (Basel, CH); Helsana (ZГјrich, CH); Helsana (ZГјrich, CH) Introduction: Polypharmacy and potentially inappropriate medication (PIM) are associated with adverse outcomes such as hospitalisation, loss of productivity, and death. This study evaluates the prevalence of polypharmacy and PIM in the older, community-dwelling population in Switzerland. Methods: The analysis is done based on claims data of community-dwelling persons aged older than 65 years insured with the Helsana health insurance group (>3 million person years in the years 20082010). We calculated the number of medications submitted for reimbursement, the proportion of persons with polypharmacy, and the proportion of persons receiving PIM according to the updated BeerвЂ™s criteria and the PRISCUS list. Additionally, we estimated cost for medications and PIM, and identified the most prevalent groups of PIM according to the Anatomical Therapeutic Chemical Classification System (ATC). Results: Forty-one percent of the older population in Switzerland received 5 or more medications which is one of the common definitions of polypharmacy, and over 23% had a PIM according to Beers criteria or the PRISCUS list. The most prevalent PIM were psycholeptics, sex hormons, antiinflammatory drugs, and psychoanaleptics. 45 Conclusion: The prevalence of polypharmacy and PIM in Switzerland seems to be alarmingly high and is associated with considerable cost. A broad spectrum of interventions on the individual level as well as on the population level is urgently needed. FM273 PatientsвЂ™ characteristics associated with opiate prescription at discharge in post-acute rehabilitation: a pilot study Simona Mateiciuc*, MГ©lanie Theodoloz, NoГ©mie Marcoz, Rebecca Dreher Ensemble Hospitalier de la CГґte (Gilly, CH) Objective: To investigate patientsвЂ™ characteristics associated with opiate prescription at discharge in post- acute rehabilitation. Opiates were defined using WHO criteria. Method: Over 12 months, opiate prescription at discharge was recorded prospectively in 392 patients ( mean age 82.9 В± 6.4 years; 71.9 % women; 63% living alone) consecutively admitted to post acute rehabilitation. Data on demographics, medical and functional status were collected upon admission using standardised instruments. Results: Overall 23,2% (91/392) of patients had opiates prescribed at discharge. Compared to persons without opiates, those with opiates at discharge, had no statistically significant difference regarding age (mean 81.4 В±6.2 vs 83.3 В±6.4 years; p= .53), sex (80.2% women vs 69.4% women, p=.061); living alone (70.3% vs 60.8% , p=.23), functional status at discharge (Barthel score 74.3 В±25 vs 76.3 В±23.3 p=.53) . In multivariate analysis age (being younger) (p=.001) and living alone (p=.04) were independent predictors for having opiates prescribed at discharge. Concomitant laxative prescription occurred in 83.3% of cases. Conclusions: In these real world conditions, opiate prescription was high, with nearly a quarter of these elderly, frail persons being discharged from a post- acute rehabilitation with an opiate. Interestingly, age and living alone were the only independent characteristics associated with opiate prescription. Further, larger studies need to be undertaken to better determine further characteristics. FM274 Predictors of revascularisation after acute coronary syndrome in elderly patients Christophe Graf*, Anne Auckenthaler, Francois Sarasin, Gabriel Gold, Francois Herrmann, Thierry Chevalley HГґpital des Trois ChГЄne (Thonex, CH); HГґpitaux Universitaires de GenГЁve (GenГЁve, CH) Acute coronary syndrome (ACS) is a major health problem and leads to a high rate of mortality. Therapeutic strategies include either conservative or invasive treatment like percutaneous coronary intervention or coronary artery bypass grafting. Invasive treatment is superior to control symptoms. However, as older patients are often excluded from randomized controlled trials, its benefit in this population is not established. The choice of treatment is based on a risk-stratification using for instance the TIMI score, but does not take into account the comorbidities or the functional status. This study aims at evaluating whether the comorbidities or the functional status influence the choice of treatment in older patients with ACS. We performed a cross-sectional study at the Geneva University hospitals. Patients over 70 years admitted to the emergency department for ACS were included over a 6 month period. Exclusion criteria were dementia, terminal illness or cardiac intervention in the previous 6 months. Functional status was assessed by the Barthel index. Active comorbidities, cardio-vascular risk factors (CVRF), TIMI scores and biological measurement like creatinemia were collected. 103 patients were included (mean age (В±SD) 83.4В±5.9 years, 54% of females). 57 patients (55%) underwent a revascularization. According to the Barthel index, 7 (7%) patients were severely dependent, 56 (54%) moderately dependent, and 40 (39%) independent. The number of active comorbidities were (median (В±IQR)) 3В±2, of CVRF 2В±1, and TIMI scores 3В±1. Mean creatinemia was 114В±49 Вµmol/l. In univariate logistic regression models, age and creatinemia were associated with a decreased rate of revascularization with odds ratio (OR) and 95% confident interval [95% CI] of 0.79 [0.72-0.87] and 0.98 [0.97-0.99], respectively. On the other hand, Barthel index was positively associated with a higher rate of invasive procedure of 1.05 [1.01-1.09]. Sex, number of CVRF, number of comorbidities, and TIMI scores were not associated with the choice of treatment. In the multiple regression analysis, age, creatinemia, number of CVRF, and number of comorbidities explained 30% of the model's variance. 46 After an ACS, the choice between conservative or invasive treatment is clearly influenced by the patients' age. Nevertheless, our results suggest that the number of comorbidities as well as the functional status have to be taken into account for this decision. FM275 The Liverpool Care Pathway (LCP) in the Geriatrische Klinik St. Gallen. Yesterday, today, tomorrow Bozana Popovic Sesartic*, Gabriela Bischofberger, Thomas MГјnzer Geriatrische Klinik (St. Gallen, CH) The Liverpool Care Pathway (LCP) is a standardised instrument for symptom control in palliative care, used to support dying patients and their families during the period of dying and beyond death. It was introduced in 2006 as a pilot project in the Geriatric Clinic St. Gallen (GC) and is established there since 2007. A project group responsible for the introduction of LCP developed new forms and conducted intensive training with the medical staff. Between 2007 and 2012, 126 women and 98 men with an average age of 84.5 years were induced in the LCP. The main reasons for inclusion were: cancer, stroke, heart failure and pneumonia. The average treatment time was 4 days. A statistical analysis of symptoms during the last days and hours before death (pain, agitation, bronchial secretions, nausea/vomiting, dyspnoea) helped to improve the concept. Until now there was a lack of experience with LCP in geriatrics. The question when an old person is dying, remains still unanswered. Therefore the project вЂњdiagnosing dyingвЂќ was initiated. вЂњDiagnosing dyingвЂќ is a prospective multicenter observational study with the goal to develop and validate an instrument for the improvement of care and the detection of indicators for dying during the last days and hours of life. It is a part of the OPCARE9 project, which is funded by the FP7 programme of the European Commission started in October 2012. Based on our retrospective data analysis the LCP has become a very useful palliative care tool in acute geriatrics. The structured approach leads to a transparent and optimized process for all involved, thus reducing the psychological pressure on the medical team and the patientвЂ™s relatives. The self-determination of the patient and his or her autonomy is guaranteed, the relatives are more involved and therefore happier and relieved. The excellent experience with LCP in GC has led to the decision to extend the LCP procedure to the long term care unit of the вЂњCompetence Centre for Health and AgingвЂќ in St. Gallen. FM276 Patients admitted to post-acute rehabilitation following a hip fracture: outcomes and related factors Sylvain Frascarolo*, Christophe BГјla, Laurence Seematter-Bagnoud Centre Hospitalier Universitaire Vaudois (Lausanne, CH) Introduction: Hospital admissions following hip fracture increase due to the growing number of oldestold persons. Information regarding the profile and outcome of older patients admitted to post-acute rehabilitation after a hip fracture is still fragmentary. This study aimed to describe the characteristics of these patients, as well as functional recovery and other outcomes at discharge. Methods: Subjects were community-dwelling patients (N=665) aged 65+ years admitted to the university rehabilitation center following a hip fracture. Within 48 hours of admission, each patient was systematically evaluated by rehabilitation team members who collected information on sociodemographics, medical, functional, affective, and cognitive status. Outcomes were functional gain on the Barthel scale, length of stay, and discharge destination. Results: Patients were aged 84.1В±7.0 years, 77.4% were female. Prior to hospitalization, 65.8% lived alone, and 50.6% received formal home care. At admission, 33.3% of the subjects had cognitive impairment and 16.1% had depressive symptoms, 7.7 % having both. Overall, mean Barthel score increased from 52.1В±18.0 at admission to 75.4В±20.6 at discharge (mean gain 23.3). Functional performance at discharge was strongly associated with cognitive and affective status at admission and decreased gradually from patients cognitively intact without depressive symptoms to those with both cognitive and depressive problems, who achieved the lowest functional gain (See Figure). Mean length of stay varied according to patientsвЂ™ cognitive status, ranging from 25.7В±13.5 days in those cognitively intact to 29.7В±13.8 days among cognitively impaired ones (p<.001). In contrast, length of stay was similar among patients without and with depressive symptoms (26.9В±13.5 vs 26.7В±14.9, p=.855). 47 Overall, most patients were discharged back home (70.8%). However, this proportion gradually decreased from 82.8% among cognitively intact patients without depressive symptoms to only 45.6% in patients with both cognitive and depressive problems. In parallel, the proportion admitted to long term care increased. Conclusion: Overall, older persons admitted to post-acute rehabilitation following hip fracture show significant recovery during their stay. However, patients with cognitive and/or depressive problems show significantly poorer rehabilitation outcomes, suggesting that they might benefit from specific, longer, or more intensive rehabilitation interventions. FM277 Complications during inpatient geriatric rehabilitation following proximal femoral fractures and rehabilitation outcome Matthias Frank*, Annika Lanz, Christian Ritter, Norbert Suhm, Eveline Nonnenmacher, Yvonne Zysset, Martin Conzelmann Felix Platter Spital (Basel, CH); UniversitГ¤tsspital (Basel, CH) Background: Proximal femoral fractures (PFF) are the most common fractures above the age of 80 years. Medical and surgical complications are often observed during inpatient geriatric rehabilitation. Methods: We retrospectively studied all patients entering geriatric inpatient rehabilitation following surgery for a PFF (pertrochanteric or femoral neck) between January 2011 and May 2012. Data on medical and surgical complications were extracted from the medical records. Baseline data included sociodemographic variables and the results of the geratric assessment on admission. Complications were classified according to a consensus paper on outcome parameters in orthogeriatric management (Liem et al., submitted) Results: 109 patients were identified. There were 57 pertrochanteric and 52 femoral neck fractures. 69 patients (63%) suffered from at least one complication. Urinary (29%) and cardiac (17%) complications were observed most frequently. Surgical complications were less common (11%). 39 (35%) patients had more than one complication. On admission, patients with complications were significantly older, showed weaker hand grip, were more dependent (Barthel Index 41.4В±16.8 vs 53.9В±14.9) and scored lower on the MMSE. During rehabilitation, gain in Barthel index was similar in both groups (25.8В±18.6 vs 27.7В±14.2), but patients suffering from complications had a longer length of stay (36.0В±18.9 vs. 26.1В±11.5 days) and were less likely to be discharged to their own home directly (59.4% vs. 85.0%). 48 Conclusion: Geriatric rehabilitation in PFF is complicated by medical or - to a much lesser extent вЂ“ surgical problems in more than half of patients. Geriatric assessment on admission can identify patients at higher risk for complications. Rehabilitation length of stay is prolonged considerably in patients suffering from complications. FM278 Teaching functional assessment to medical students: why not play games? Philippe Huber*, Abdelmalek Saber, Yves Schnellmann, Gabriel Gold Service de gГ©riatrie (GenГЁve, CH) Introduction: Nowadays, most physicians take care of a growing aging population suffering from multiple chronic diseases and disabilities. Therefore, a good knowledge of functional assessment is required, and this topic should be addressed in the pregraduate medical curriculum. Method: We report our 10-year experience with a seminar on functional assessment using an "aging game" as a pedagogic vector. This seminar is organized by geriatricians, occupational therapists and physiotherapists. First, medical students are exposed to various situations where they experiment disabilities and try to elaborate compensatory strategies. Then, they reflect on a challenging discharge project by analyzing a written clinical case. This written case gives the opportunity to reflect on functional assessment, on the importance of a multidisciplinary approach, and on the implication of various actors of the health care system in the community. Finally, students are introduced to the use of validated functional assessment instruments. Results: Evaluation indicated that this pedagogical approach is much valuated by the students and foster the acquisition of knowledge in functional assessment. Conclusion: This seminar shows a good efficacy in introducing medical students to the difficult concept of functional assessment. Moreover, this seminar can easily be adapted to the training of other health care professionals. 49 Freie Mitteilungen SGH - Communications libres SSH Hemostasis, Vascular Biology and Transfusion Medicine - Hemostasis, Vascular Biology and Transfusion Medicine FM279 Dietary alpha-linolenic acid reduces platelet clearance in spleen and liver inducing an increased platelet count in ApoE-/- mice Simona Stivala*, Christine Lohmann, Thomas LГјscher, Christian Matter, Hans JГјrg Beer Kantonsspital Baden (Baden, CH); Physiology Institute, University of Zurich (Zurich, CH); University Hospital (Zurich, CH) Introduction: We recently showed that the plant-derived n-3 fatty acid alpha-linolenic acid (ALA) has cardioprotective effects by reducing experimental atherosclerosis and platelet-dependent thrombosis in mice. We hypothesized that ALA might lead to a prolonged platelet survival in the circulation due to a reduced platelet activation. Methods: 8-week-old male ApoE-/- mice were fed a 0,21g% cholesterol diet containing either a high (7,3g%) or low (0,03g%) ALA content for 16 weeks. Platelet counts were assessed monthly. Platelet production was analyzed by reticulated platelet staining and megakaryocyte-CFU. Platelet turnover was assessed by plasma glycocalicin (GC) concentration (ELISA), normalized to the platelet count (the GC-Index). Platelet clearance in spleen and liver was determined by immunofluorescence staining on frozen sections. GPIbalpha cleavage upon thrombin stimulation was assessed by flow cytometry. Results: After 16 weeks mice in the high-ALA group had significantly higher platelet counts compared to the low-ALA group (1591В±650x103/ Вµ l vs 1053В±323x103 Вµ l, n=30, p=0.0002), without showing different tail bleeding times (285В±83 high-ALA vs 221В±56 sec low-ALA, n=5, p=n.s.). Platelet production was not different between the two groups as assessed by the reticulated platelet count (72В±34 x103/ Вµ l in the low ALA vs 55В±47 x103/ Вµ l in the high ALA group, n=15, p=n.s.), and number of megakaryocyte-CFU from bone marrow (12В±4 vs 11В±4, n=3). Plasma GC was significantly lower in the high ALA group (25В±15 vs 53В±27 Вµ g/ml, n=17, p=0.0007), and the GC-Index was 6,6В±3 vs 15В±5, n=17, p<0.0001. Platelet clearance in spleen and liver was significantly reduced in the high ALA group (spleen CD41+ area: 143,482 um2 vs 94,724 um2, n=3, p=0.0049; liver: 54,095 um2 vs 33,224, n=3, p=0.033). GPIbalpha cleavage upon thrombin stimulation was significantly reduced in platelets from the high ALA mice (mean fluorescence intensity vs resting state: 64 В±5% high ALA vs 52 В±8% low ALA, n= 6, p=0.01). Conclusions: A diet rich in ALA increases the platelet count by reducing platelet clearance. Mechanisms may include the inhibition of MAP kinase p38 phosphorylation and therefore reduced platelet activation and a reduced GPIbalpha cleavage. The finding might be of clinical importance in transfusion medicine. 50 FM280 Genotype and phenotype of a large series of patients with congenital dysfibrinogenaemia Alessandro Casini*, FranГ§oise Boehlen, Marguerite Neerman-Arbez, Philippe de Moerloose HUG (GenГЁve, CH); CMU (GenГЁve, CH) Introduction: Congenital dysfibrinogenemias (CD) are characterized by biosynthesis of a structurally abnormal fibrinogen molecule that exhibits reduced functional properties compared to level of fibrinogen antigen. To date a large number of mutations have been identified in patients with CD, although few are predictive of the clinical phenotype. In order to better understand the clinical complications in relation to the genotypes, we report a survey of 65 CD diagnosed in our laboratory. Method: Biological and clinical characteristics were recorded at reception of samples using a standardized case report. After isolation of genomic DNA, exons and intron-exon junctions of the fibrinogen genes were amplified by polymerase chain reaction (PCR) and sequenced. Results: Between 2005 and 2012 we diagnosed 65 CD. Samples were sent to our laboratory principally to perform a familial screening (n=23, 36%), before surgery (n=14, 21%), following thrombosis (n=8, 12%) and for investigation of bleeding (n=7, 11%). The median age at time of DNA analysis was 36 years (range 1 вЂ“ 76 years). The median fibrinogen activity (Clauss method) was 0.66 g/l (range 0.1 вЂ“ 2.3) and the median antigen fibrinogen was 3.5 g/l (range 1.4 вЂ“ 5.3). Mutations were identified in the coding sequences of fibrinogen genes in all 54/54 (100%) probands. Heterozygous missense mutations in residues Arg35(Arg19) of FGA in exon 2, Arg301(Arg275) of FGG exon 8 and surrounding residues accounted for almost 75% of CD (Table 1). Twenty-three patients (35%) had mild bleeding episodes, easy bruising, epistaxis and menorrhagia being the most frequent. Thirteen (20%) and 3 (5%) patients experienced at least one venous or arterial thrombosis, respectively. A total of 30 pregnancies were reported, including 6 (20%) miscarriages. Deliveries were not associated with bleeding complications. Conclusions: Mutations in exon 2 of FGA and in exon 8 of FGG are the most frequent causes of CD. At the time of diagnosis half of patients experienced mild bleeding or thrombotic events. CD is associated with miscarriage. An ongoing trial is evaluating the long term follow-up of these patients in order to better define the true incidence of bleeding complications and/or thrombotic events during the course of disease. 51 FM281 Clinical outcome of haemophilia patients undergoing major orthopaedic surgery without pharmacological thromboprophylaxis Stefan Rinderknecht Graf*, Bernhard Gerber, Peter P. Koch, Brigitte Brand Spital BГјlach (BГјlach, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH); UniversitГ¤tsklinik Balgrist (ZГјrich, CH) Background: Hemophilia patients are generally considered at low risk for venous thromboembolism. However, orthopedic surgery for hemophilic arthropathy exposes them to well established major risk factors for venous thrombosis due to the procedure itself, long immobilization, and factor replacement therapy. In contrast to non-hemophilia patients, pharmacological prevention of thromboembolism for hemophilia patients is not well studied nor standardized and largely depends on local practice. A multicenter European survey reported that 50% of centers are using anticoagulant prophylaxis. At our center, in agreement between orthopedic surgeon and hematologist, no pharmacological prevention of thromboembolism is given to patients undergoing orthopedic surgery. Aim: The present study analyzes the safety and feasibility of this approach. Methods: Retrospective analysis of all orthopedic operations performed in hemophilia patients of our center between 1978 and 2012. Results: A total of 166 major orthopedic operations were performed in 47 patients. 43 (91.5 %) had hemophilia A and 4 (8.5%) hemophilia B. 31 (66%) patients suffered from severe, 14 (29.8%) from moderate and 2 (4.3%) from mild disease, respectively. One patient (2.1%) had a combined FVIII/Factor V deficiency. Median age was 44.9 years (IQR 34.9-55.0). Orthopedic interventions were divided into surgery of the lower extremity (n=138, 83.1%%) and the upper extremity (n=21, 12.7%), for 7 (4.2%) data are missing. Follow-up information 9 weeks after surgery could be obtained for 124 operations (74.7%). No clinical signs of venous thromboembolism were observed in all cases. One (0.6 %) intervention in a mild hemophiliac was complicated by a life-threatening perioperative myocardial infarction. Data on factor consumption was available for 101 interventions (60.3%) with a total dose per hospitalization of 45вЂ™000 IU (IQR 33вЂ™250-60вЂ™250) given to patients (mean body weight of 71.3 kg). Transfusions of red blood cells were needed in 12.3% of all interventions. Conclusions: In this cohort of hemophilia patients undergoing orthopedic surgery without pharmacological prevention of thromboembolism followed over an overall period of 34 years, no symptomatic deep venous thrombosis or pulmonary embolism was observed. Prospective trials incorporating a systematic assessment for thrombosis are needed to confirm these encouraging data. FM282 Insights into the role of protein S/growth arrest-specific gene 6 pathway in the pathophysiology of purpura fulminans Raja Prince*, Sara Calzavarini, FranГ§ois Saller, Monica Azevedo, Michael Racine, Anne AngelilloScherrer Centre Hospitalier Universitaire Vaudois (Lausanne, CH) Background: Currently, purpura fulminans (PF) pathophysiology involves a complete blood flow blockade in dermal and subcutaneous vasculature, the blockade being of thrombotic or infectious origin. Both protein S (ProS) and growth arrest-specific gene 6 (Gas6) product are vitamin K-dependent proteins. ProS is a natural anticoagulant. Its physiological importance is evident in PF and other lifethreatening thrombotic disorders typical of ProS deficient patients. ProS deficiency in mice has shown similarities with the human phenotypes. In contrast to ProS, Gas6 displays a procoagulant effect, amplifying platelet activation and upregulating tissue factor in the vasculature. In tissues, ProS and Gas6 exert cellular functions by binding to and activating tyrosine kinase receptors of the Tyro3 family (TAM) on the cell surface. Methods and results: Mice with complete Gas6 or partial ProS deficiency did not develop spontaneous PF. To study further the role of ProS, Gas6 and TAM receptors in PF pathophysiology, we generated a model mimicking this disorder by exposing mice to warfarin, a vitamin K antagonist. Wild-type (WT) mice, or mice deficient in ProS, Gas6 or in either one of the TAM receptors received warfarin for 5 days. Most of Gas6-/- mice and Gas-/-/ProS+/- mice succumbed to this challenge whereas most WT mice survived (mortality rate: 85% in Gas6-/- and 87% in Gas6-/-/ProS+/- compared to 5% in WT mice, p<0.05). Some mice deficient in TAM receptors also died during warfarin challenge. On warfarin, part of the mice with ProS/Gas6 pathway deficiency developed skin lesions compatible with PF 52 involving ears, extremities and genital areas. Such lesions were never observed in WT. Early lesions were erythematous with highly visible ear skin vessels, necrosis appearing in advanced lesions. Ear skin histology of mice with PF showed vascular engorgement, intradermal edema and only rare thrombosis in early lesions, whereas massive red blood cell extravasation, intra-epidermal hemorrhagic blisters and necrosis were found in advanced lesions. Conclusions: There was a prominent vascular involvement in PF lesions when the ProS/Gas6 pathway was deficient. Lack of Gas6 or TAM receptors being antithrombotic, the thrombotic process might be less central in PF pathophysiology than currently admitted. Thus, the vasculature might constitute the main target during PF development and the ProS/Gas6 pathway through the TAM receptors in the endothelium appeared to be involved in the process. FM283 Anti-idiotypic DARPin molecules: potential new treatment tools for acquired thrombotic thrombocytopenic purpura (aTTP)? Monica Schaller*, Sabine Hiltbrunner, Irmela Sulzer, Monique Vogel, Karim Kentouche, Bernhard LГ¤mmle, Johanna Kremer Hovinga Inselspital Bern (Bern, CH); Friedrich Schiller UniversitГ¤t (Jena, DE) Aim: The hallmark of aTTP is a severe ADAMTS13 deficiency resulting from autoantibodies (Abs) neutralizing and/or accelerating ADAMTS13 clearance. Despite the success of plasma exchange the risk of relapse is ~ 40%. A therapy using small molecules capable to neutralize inhibitory antiADAMTS13 Abs and to eliminate anti-ADAMTS13 specific memory B- and plasma cells would be highly desirable. Method: Two small protein libraries of Designed-Ankyrin-Repeat-Protein (DARPins, Molecular Partners AG, Switzerland) coding for 2 (N2C, diversity of 1015) or 3 (N3C, 1023) randomized ankyrin repeat modules were screened against an equimolar pool of 3 previously generated spleen-derived inhibitory monoclonal anti-ADAMTS13 Abs holding 1 of 4 CDR3 motifs shared by two acquired TTP patients (pat) using Ribosomal display. DNA sequence of selected anti-idiotypic single DARPin clones from the fourth panning round were analyzed and DARPins purified to test their specificity and neutralization potential towards the selecting and additional inhibitory Abs (n=5) holding the same CDR3 motif by ELISA or FRETS assay. Furthermore the binding capacity of an equimolar pool of the selected DARPins towards anti-ADAMTS13 Abs in plasma of 37 different aTTP Pat were tested by ELISA. Results: Nine unique, as revealed by their DNA sequence, anti-idiotypic DARPins were highly specific for their targets. Preincubation with spleen-derived inhibitory anti-ADAMTS13 Abs (equimolar mAbs pool) with a 10- fold molar excess of four 4 anti-idiotypic DARPins restored ADAMTS13 activity in plasma in a dose-dependent manner as assessed by FRETS assay. Moreover, the four anti-idiotypic DARPins bound anti-ADAMTS13 antibodies from plasma of 27/37 additional aTTP Pat and reduced binding to immobilized recombinant ADAMTS13 by 70-95% when pre-incubated with Pat plasma (n=5). Conclusions: Using inhibitory anti-ADAMTS13 Abs of one Pat we were able to select 4 different highly specific anti-idiotypic DARPins that not only bind to anti-ADAMTS13 Abs holding a similar CDR3 motif than the selecting Abs, but also to a substantial proportion of anti-ADAMTS13 Abs in plasma of randomly selected aaTTP Pat. Our results are promising and hint at a limited number of different antiidiotypic molecules necessary to neutralize inhibitory anti-ADAMTS13 Abs as a therapy. Affinity and neutralizing analysis of all 9 selected anti-idiotypic DARPins are underway. FM284 Acute coronary syndrome in persons with haemophilia Philippe de Moerloose*, Peter Staritz, Roger Schutgens, G. Dolan on behalf of the Advance Working Group Introduction. As life expectancy in persons with hemophilia (PWH) increases, cardiovascular disease management becomes more important. Currently, evidence based guidelines for antithrombotic management in PWH are lacking. ADVANCE is an expert panel of European hemophilia centers supported by an educational grant from Bayer Healthcare. Methods. Using structured communication techniques and a 35 point questionnaire to establish consensus, 15 ADVANCE members reviewed recent ESC guidelines for STEMI, NSTEMI and myocardial revascularization with regard to hemophilia. 53 Results. Questions are shown with percentage of agreement in parenthesis. A hemophilia expert should be consulted as soon as PWH present with an acute coronary syndrome (ACS) (100%). PWH should be managed according to the ESC "high bleeding risk" patient category (100%). Treatment of an ACS should be started immediately (33%) or delayed until replacement therapy is available based on known factor levels (66%). Fibrinolysis is justified in replaced PWH when early PCI is not available (100%). Target factor level should be >=30 (100%), >=50 (78%), >=80 (53%). Target peak level for early PCI should be >=30 (100%), >=50 (93%), >=80 (80%). Bare metal stents are preferred over drug eluting (93%). All patients should receive dual antiplatelet therapy (87%). Anticoagulants are not advisable in non-replaced PWH (80%), but are acceptable in replaced PWH (100%) with a preference for unfractionated heparin and enoxaparin. The trough level for PWH undergoing long term dual antiplatelet therapy should be >=1% (100%); >=5% (87%); >=10% (40%); >=30% (33%). Conclusions. In ACS and myocardial revascularization, hemophilia treaters have to deal with controversial therapeutic aims such as clotting factor replacement and therapeutic standards, including anticoagulation and antiplatelet therapy which is normally contraindicated in PWH. Complete consensus was not achieved especially concerning dosage of clotting factors. Risks and benefits have to be assessed for every situation. The results of our process could aid decision making when tailoring therapy for each PWH and setting. 54 Freie Mitteilungen SGH - Communications libres SSH Clinical Hematology - Clinical Hematology FM285 Very early onset of autoimmune thrombotic thrombocytopenic purpura in five children of Polynesian origin, in four cases combined with immunodeficiency Magnus Mansouri Taleghani*, Peter Bradbeer, Nyree Cole, George Chan, Bernhard LГ¤mmle, Johanna A. Kremer Hovinga Bern University Hospital and the University of Bern (Bern, CH); Starship Children's Hospital (Auckland, NZ); Auckland City Hospital (Auckland, NZ) Background Autoimmune thrombotic thrombocytopenic purpura (aTTP) is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia with schistocytes on the peripheral blood smear and a variable degree of endorgan ischemia. The high mortality if left untreated (80-90%) and a relapsing course in 44% of survivors underline the seriousness of this disease. Underlying is a severe ADAMTS13 deficiency (<5% of the normal) due to inhibitory autoantibodies preventing normal processing of unusually large Von Willebrand factor multimers. First episodes of aTTP typically occur in women between 20-40 years of age and are rarely seen in children. Observation Strikingly, over the last 7 years we observed frequently relapsing aTTP with severe acquired ADAMTS13 deficiency and inhibitory autoantibodies in 5 children (aged 1-11 years) of Polynesian origin. At least 4 of the 5 cases have additional signs and symptoms indicative of a common variable immune deficiency (CVID). Results Case 1,2 and 3 have hypogammaglobulinaemia requiring regular intravenous immunoglobulin infusions (IvIg) for at least 5 years now. While in case 1 hypogammaglobulinaemia and other symptoms indicative of immunological dysregulation (eosinophilic colitis, asthma, excemaвЂ¦) had been documented prior to the first aTTP episode, in cases 2 and 3 (siblings) this was noted after Rituximab treatment for relapsing aTTP. A poor response to single vaccinations (Diphtheria and Tetanus, Pneumococcus) was documented in case 1 and 2, a negative pneumococcal serology in case 4, as well as recurrent invasive infections including pneumococcal pneumonia, meningitis and otitis media in cases 1 and 3. Flowcytometry was done in 2 children revealing low CD4 (Case 1) and decreased switched- and memory B-cell levels (case 3), respectively. Conclusions Although cytopenias such as idiopathic thrombocytopenia or EvansвЂ™ syndrome, both differential diagnoses of aTTP, and various other autoimmune diseases have been reported in CVID, the association with aTTP is novel (or underreported). The common Polynesian ethnicity and the shared clinical phenotype with the unusual early onset of aTTP hints at a new genetic underlying mechanism. Further detailed diagnostics to confirm CVID or similar according to standard criteria (www.esid.com), family studies and the search for common underlying genetic aberrations are underway. FM286 A novel disease entity characterised by idiopathic generalised seizures and Lferritin deficiency Jeroen Goede*, Anna Cozzi, Paolo Santambrogio, Daniela Privitera, Vania Broccoli, Ida Luisa Rotundo, Barbara Garavaglia, Rudolf Benz, Martina Muckenthaler, Sonia Levi UniversitГ¤tsSpital ZГјrich (ZГјrich, CH); San Raffaele Scientific Institute (Milano, IT); Vita-Salute San Raffaele University (Milano, IT); IRCCS Foundation Neurological Institute "C. Besta" (Milano, IT); Kantonsspital MГјnsterlingen (MГјnsterlingen, CH); University of Heidelberg (Heidelberg, DE) Introduction: Genetic ablation of the H-ferritin gene in animal models reveals its critical importance for development, while the role of the L-ferritin gene in vertebrates has not been addressed. Here we describe a case of a 23-year old female patient affected by a homozygous loss of function mutation in the L-ferritin gene and idiopathic generalized seizures during infancy. The patient is hallmarked by a up to now unpublished homozygous nucleotide substitution (G310T) in exon 3 of the L-ferritin gene, which results in a stop codon at amino acid 104 (E104X), generating a peptide unable to fold in a ferritin full cage. 55 Methods: We characterized parameters of iron homeostasis and oxidative status in primary fibroblasts that were derived from a patientвЂ™s skin biopsy, as well as in dopaminergic neurons from reprogrammed fibroblasts. Results: We show that the L-chain ferritin in E104X fibroblasts is undetectable and that the ferritin molecule is composed only of H-chains. In accordance with the enhanced capacity of the H-ferritin homopolymer to incorporate iron, the labile iron pool is decreased (~ 4 fold), which may have caused increased cellular iron uptake (~1.5 fold) via transferrin receptor 1 (~1.4 fold increase). Moreover reduced iron availability caused cytosolic scavengers of reactive oxygen species (catalase and SOD1 protein were reduced by ~ 4 and ~ 2.5 fold, respectively). Despite cytosolic iron starvation, reactive oxygen species (ROS) production was enhanced and higher levels of oxidized proteins were detected. Furthermore, ferritin showed an accelerated degradation rate in E104X cells (half-life was ~ 5 h compared to ~18 h in controls). The increase in reactive oxygen species and transferrin receptor 1 protein levels was further confirmed in reprogrammed dopaminergic neurons from E104X fibroblasts that were obtained with an efficiency of about 10%. Conclusion: Our results highlight for the first time the pathophysiological consequences of human Lferritin deficiency and contribute to the definition of a new disease entity characterized by the absence of L-peptide in ferritin and idiopathic generalized seizure. FM287 Anaemia in the elderly: a component of polymorbidity or quite a normal finding when slight? Corina Risch*, Pedro Medina, Martin Risch, Jean-FranГ§ois Lambert, Urs Nydegger, Lorenz Risch UniversitГ¤t Triesen (Triesen, LI); labormedizinisches zentrum Dr. Risch (Liebefeld, CH); Zentrallabor Kantonsspital GraubГјnden (Chur, CH); Service d'HГ©matologie, CHUV (Lausanne, CH) The World Health Organization defines cut-offs at 120 g/L (women) and 130 g/L (men). 56 As yet, clinical experience points to slightly below WHO standard hemoglobin levels as a normal consequence of aging, current laboratory cut-offs not accounting for the elderly. The prevalence of clinically overt anemia in the elderly has been stratified into one-third to nutritional deficiency, another-third to iron/hepcidin dysbalance and a last-third to inflammation. All by searching for age-adapted reference intervals (RI) in our regional healthy elderly in Switzerland, we also wanted to gain insights on an array of laboratory analytes possibly associated with hemoglobin levels. The Seniorlabor study has so far recruited over 1600 subjectively healthy Caucasian inhabitants >60 yrs of age. Venous blood samples were drawn after an overnight fasting period. Hemoglobin was assessed using an XE-5000 hematology analyzer (Sysmex-Digitana, Switzerland). RIs were assessed according to the CLSI-guideline C28-A3. Here we report on the results from 557 men and 722 women. Men had significantly higher median hemoglobin levels than women (149 vs. 137 g/L; p<0.001), and there was a significant Spearman rank correlation between age and hemoglobin level (r=-0.113; p<0.001). Thus RIs were stratified according to age and gender. Double-sided 95% reference intervals for men were: 129-168 g/L (age 60-69), 125 вЂ“ 168 g/L (age 70-79) and 118-169 g/L (age >80). The respective RIs for females were: 120-157 g/L (age 60-69), 116 вЂ“ 156 g/L (age 70-79), 115-164 g/L (age >80). A linear regression model incorporating age, female gender, testosterone, ferritin, CRP, ALAT, cholinesterase, and total bilirubin as significant predictors (all p<0.01) of hemoglobin concentrations accounted for 37.4% of hemoglobin concentration variance. Interestingly, in this model, we could not observe a significant association between hemoglobin and kidney function (CKD-EPI eGFR), folate concentrations, Holo-Transcobalamin concentrations, and T4 concentrations. With progressive age, there is a considerable decline of the lower limits of hemoglobin concentrations., which is more pronounced in men than in women and seems to converge above age 80. The WHO cut-offs seem to be valid at age 60, but tend to get too restrictive at older age. This may cause overdiagnosis of anemia, and consequently, may perturbate an elderly personsвЂ™ wellbeing and lead to unnecessary and costly follow-up investigations. FM288 Is less chemotherapy detrimental in adults with Philadelphia chromosome (Ph)positive acute lymphoblastic leukaemia (ALL) treated with high-dose imatinib? Results of the prospective, randomized GRAAPH-2005 study Yves Chalandon*, Xavier Thomas, Sandrine Hayette, Jean-Michel Cayuela, Claire Abbal, FranГ§oise Huguet, Emmanuel Raffoux, Thibault Leguay, Stephane Lepretre, Martine Escoffre-Barbe, Sebastien Maury, CГ©line Berthon, Emmanuelle Tavernier, Jean-FranГ§ois Lambert, Marina Lafage, VГ©ronique LhГ©ritier, Sylvie Chevret, Norbert Ifrah, HervГ© Dombret GRAALL group (Group for Research on Adult Acute Lymphoblastic Leukemia) Aim: To compare a less intensive regimen based on high-dose imatinib (IM) to an intensive IM/HyperCVAD regimen in adults with Ph+ ALL, in terms of early response and outcome after stem cell transplantation (SCT). Methods: Patients (pts) aged 18-60 years with previously untreated Ph+ ALL were eligible. After a steroid prephase, cycle 1 differed between randomization arms. In arm A (IM-based), IM was given at 800 mg on d1-28, combined with vincristine-dexamethasone. In arm B (IM/HyperCVAD), IM was given at 800 mg on d1-14, combined with adriamycin, cyclophosphamide, vincristine, dexamethasone. All pts received a cycle 2 combining high-dose methotrexate and AraC with IM at 800 mg on d1-14, whatever their response. Minimal residual disease (MRD) was done by quantitative RQ-PCR after cycle 1 (MRD1) and cycle 2 (MRD2). Major MRD response was defined as BCR-ABL/ABL ratio <0.1%. Then, all pts were to receive alloSCT using related or unrelated matched donor SC or autoSCT if no donor and a major MRD2 response. IM/chemotherapy maintenance was planned after autoSCT. In the absence of SCT, pts received alternating cycles 1 (as in arm B) and cycles 2 followed by maintenance. The primary objective was non-inferiority of arm A in term of major MRD2 response. Results: 268/270 pts were evaluable for this analysis (135 arm A, 133 arm B; median age, 47 yrs; median fup, 40 mths). Main pt characteristics were well-balanced. Due to higher induction mortality in arm B (9 vs 1 deaths; P=0.01), CR rate was higher in the less intensive arm A (98% vs 91%; P=0.006). The rates of pts reaching major MRD2 response was 65% (66% arm A, 64% arm B; P=0.79, non-inferiority primary endpoint thus demonstrated, P= 0.004). EFS at 3 yrs was 41% (95% CI, 35-48) and OS 52% (95% CI, 45-58, Fig. 1) and no difference between both arms. 160 pts received alloSCT and 34 autoSCT in CR1. Allo TRM was similar in both arms (29% vs 21% at 3 years; P=0.46). MRD2 did not significantly influence post-allotransplant EFS and OS. When restricting the comparison to pts achieving major MRD2 response, there was no difference after auto as compared to alloSCT (Fig. 2). 57 Conclusions: We demonstrated here that chemotherapy intensity may be safely reduced when associated with high-dose IM. Similar outcome after auto and alloSCT observed in MRD responders validates MRD as an important early surrogate endpoint for treatment stratification and new drug investigation in this disease. 58 FM289 Impact of mutated NPM1 reduction upon chemotherapy on overall survival in acute myeloid leukaemia (AML) patients Judit Bencze*, Stefan Balabanov, Kornelius Arn, Markus Manz, Jeroen Goede UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Introduction: During the last years moleculargenetic alterations are increasingly recognized in their important predictive role for outcome of AML patients with normal karyotype at diagnosis. Approximately 50% of AML-patients with normal karyotype harbor a mutation of the nucleophosmingene (NPM1), which in absence of a FLT3-ITD-mutation indicates a favorable risk group regarding relapse free and overall survival. However about 40% of NPM1-mutated AML patients carry a FLT3ITD mutation that worsens prognosis. Recently a study published by KrГ¶nke et al. demonstrated an important prognostic value of quantitative PCR NPM1 mutation analysis during therapy. Methods: We retrospectively analyzed the data of 78 AML patients with an NPM1 mutation (Type A or B) at our division since the year 2007. 58 of these patients were treated with intensive chemotherapy. Samples of bone marrow and/or peripheral blood from patients at diagnosis and at different follow-up times were examined by sensitive RQ-PCR assays for NPM1. The follow-up time points were regeneration after the first and the second induction chemotherapy cycle and after consolidation. Consolidation consisted of a conventional third chemotherapy cycle (n=25), allogeneic hematopoietic stem cell transplantation (allo-HSCT; n=18) or high dose chemotherapy with autologous stem cell transplantation (n=1). Results: From the 58 curatively treated AML-patients with a NPM1 mutation 35% (20) showed coexistence of a FLT3-ITD mutation. In patients not treated with allogeneic stem cell transplantation the presence of the FLT3-ITD mutation caused a significant decrease in overall survival. This significant difference in patient survival is not visible if we include the patients that were treated with allo-HSCT, namely 11 (29%) of the group with isolated NPM1 mutations and 10 (50%) of the FLT3ITD-group. In addition, patients with NPM1 mutations who achieved a >4 log reduction in NPM1 values after 2 induction therapies (n=16 with isolated NPM1 mutation and n=8 with additional FLT3ITD) had a significantly longer overall survival in contrast to those achieving <4 log reduction (n=9 with isolated NPM1 mutation and n=5 with additional FLT3-ITD). Conclusion: Our results confirm that the kinetics of clearance of NPM1 mutated cells has an important impact on overall survival in NPM1-AML patients and should be used as prognostic tool regarding the indication of allogeneic bone marrow transplantation in NPM1 mutated leukemias. 59 FM290 Effect of anti-fungal and anti-bacterial prophylaxis in intensive acute myeloid leukaemia (AML) therapy: a single centre experience Bernhard Gerber*, Jan KГ¶ppel, Michaela Paul, Gayathri Nair, Thi Dan Linh Ngyuen-Kim, Thomas Frauenfelder, Urs Schanz, Markus G. Manz UniversitГ¤tsSpital ZГјrich (ZГјrich, CH); UniversitГ¤t (ZГјrich, CH) Background: Infections remain a concern in AML and the optimal strategy to reduce infection related morbidity and mortality is a matter of debate. The efficacy might depend on local settings. At our institution we did not use prophylaxis until March 2010, when an anti-infective chemoprophylaxis with posaconazole, levofloxacin and trimethroprim/sulfamethoxazole was introduced to accompany intensive chemotherapy. Aims: To assess the impact of the newly introduced primary prophylaxis scheme on the incidence of invasive fungal disease (IFD) and bacteremia. Methods: Retrospective single-center study performed at the leukemia ward (normal ventilation) and hematopoietic stem cell transplantation unit (air filtration and positive-pressure) of the University Hospital Zurich between 2009 and 2011. All Patients >18 years with AML or high-risk MDS (IPSS >1.5) receiving intensive chemotherapy were included. Statistical analysis compared the patient cohorts before and after introduction of the prophylaxis scheme. IFDs were classified according to the EORTC/MSG 2008 guidelines. Results: The study comprised 88 patients receiving a total of 203 chemotherapy cycles. Baseline characteristics were similar in the non-prophylaxis and the prophylaxis cohort and other treatment regimens or locations were not changed during the study time. Median age of the study population was 51.3 years (IQR 20.7), 45 (51%) were male. Five and 7 patients in the non-prophylaxis and prophylaxis cohort were diagnosed with IFD before the start of chemotherapy and excluded from the analysis. Adherence to the prophylaxis scheme was 81.7% for posaconazole and 69.5% for levofloxacin. Overall survival at 100 days was 88.4% in the non-prophylaxis and 84.4% in the prophylaxis period. IFD were more common in the non-prophylaxis period than in the prophylaxis period (88.9% and 55.3%; p = 0.0032). In both groups IFD were classified as 'possible' (EORTC/MSG) in the vast majority of all cases (93.5% and 81%). In multivariate analysis chemoprophylaxis a well as treatment in the hematopoietic stem cell transplantation unit (n=39) both led to a reduction in IFD (p<0.0001 and p = 0.0021, respectively). The incidence of bacteremia was not significantly different in the non-prophylaxis and the prophylaxis group (32.6% vs. 34.6%). Conclusions: Combined antifungal and antibacterial primary prophylaxis with posaconazole resulted in a significant reduction of possible IFD but did not reduce the incidence of bacteremia. 60 FM291 Importance of microarray analysis as a prognostic clinical tool in chronic lymphocytic leukaemia Nolwen Prie*, Sandrine Bougeon, Naomi Esther Kramer, Laurence Etter, Ornella Bruzzese, Delphine Ernst, Sarah Porter, Dominique Muehlematter, Jacqueline Schoumans CHUV (Lausanne, CH) Introduction: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy with a highly variable clinical course. In addition to the mutational status of the immunoglobulin heavy chain, recurrent genomic abnormalities are among the strongest prognostic markers. Specific aberrations of prognostic significance are usually detected by interphase fluorescence in situ hybridization (iFISH). Array-based genomic technologies allow genome-wide screening for genomic alterations. They have proved to be effective in the detection of copy number abnormalities (CNA) and copy-neutral loss of heterozygosity (CN-LOH) and have consequently enabled the identification of new recurrent abnormalities of clinical relevance. The aim of this study was to assess the usefulness of array based comparative genomic hybridization (CGH)+single nucleotide polymorphism (SNP) array as an alternative to iFISH for the detection of genomic abnormalities in routine clinical use. Methods: Peripheral blood samples of 70 CLL patients were analysed both by iFISH and CGH+SNP arrays. Results: Genomic abnormalities were detected by iFISH in 51 patients (72.8 %) and by array in 52 patients (74.3 %). A high degree of concordance was observed (97 %) between both methods. A discrepancy was observed in two patients with low proportions of abnormal cells (< 10 %) that were only detected by iFISH. Conversely, by array, additional acquired genomic abnormalities not included in the FISH panel were detected in 25 patients. Some were recurrent abnormalities such as loss of 1q, 8p, 9p, 10q, 12p, 15q, 18p and gain of 2p, 4q, 8q, 17q which appear to be of prognostic significance. Large stretches >10 Mb of CNLOH were detected in 6% of the cases and accurate size mapping of clinically relevant genomic markers was obtained in 69% of abnormal cases by array analysis. Overall, array analysis provided additional clinical relevant genomic data in 88% of abnormal cases. In addition, allowing the precise identification of breakpoints, aCGH can determine deleted regions of prognostic significance and identify candidate genes implicated in CLL of potential clinical relevance. Conclusion: CGH+SNP array analysis is a robust, high resolution and sensitive screening method for routine clinical use in CLL and is able to reliably detect abnormalities only present in 10% of the cells. Array analysis shows clearly a higher diagnostic yield than iFISH. FM292 Is there a difference in the disease risk index for outcome of patients undergoing allogeneic haematopoietic stem cell transplantation after T-cell depletion? Yan Beauverd*, Eddy Roosnek, Yordanka Tirefort, Monika Nagy-Hulliger, Michael Bernimoulin, Olga Tsopra, Vincent Kindler, Marc Ansari, Carole Dantin, Alessandro Casini, Anne-Pascale Grandjean, Ekaterina Chigrinova, Stavroula Masouridi-Levrat, Yves Chalandon HГґpitaux Universitaires de GenГЁve (GenГЁve, CH) Objective: We have investigated if the disease risk index, previously published by Armand et al. (Blood 2012;120:905-13), which is predictive of the outcome after allogeneic HSCT is also valid in our center, where 63% of patients are transplanted with T-cell depleted grafts (TDEP). Methods: We have analyzed 416 patients with various hematological malignancies transplanted between January 1998 and October 2012. Patient characteristics are described in the table. GVHD prophylaxis consisted mostly of calcineurin inhibitors (CSA) В± MTX (MAC) or MMF (RIC). Results: Overall survival (OS) and disease free survival at 4 years were 50.2В±5% and 40.6В±5% respectively. Incidence of relapse, relapse death and treatment related mortality (TRM) were 37.2В±5%, 34.7В±5% and 23.2В±5%. OS at 4 years for low, intermediate, high and very high overall risk was 82.1В±12%, 51.6В±7%, 31В±10% and 33.7В±30% respectively (p<0.0001). 4-year relapse incidence for low, intermediate, high and very high risk was 11.5В±10%, 35.3В±6%, 49.2В±10% and 59.7В±30% respectively (p<0.0001). For TDEP transplant patients, 4-year OS for low, intermediate and high overall risk was 88.3В±11%, 51В±8% and 42.6В±15% respectively (p<0.001) (very high risk patients were too few to be taken in account into the analysis). 4-year TRM and relapse incidence for low, intermediate and high overall risk were 8.6В±10%, 23.4В±7%, 20.4В±14%, (p=0.048) and 8.6В±10%, 37В±8%, 55.8В±14% (p<0.0001) respectively. In univariate analysis, there was a significant impact of 61 TDEP on the low and high overall risk group regarding OS (better OS p=0.011 (low risk) and p=0.038 (high risk)), but there was no impact on TRM, relapse incidence or relapse death. This was confirmed in multivariate analysis with a HR=0.68 (0.50-0.92) for TDEP (p=0.015). Other factors that impacted OS in multivariate analysis were disease risk and type of donor (p<0001). Patients who received TDEP displayed a lower acute GvHD grade 2-4 incidence (21 vs 43%, p<0.0001) and severe chronic GvHD was 11% vs 17%,p=0.22. Conclusions: Our study confirms the prognostic value of the disease risk index as previously shown by Armand et al. Interestingly, we found a significant impact of TDEP on OS. However results should be taken with caution due to the low number of patients in the low risk and very high risk groups and to the retrospective nature of the study. The disease risk index is an easy and feasible prognostic score for HSCT and may help identify patients that would benefit from TDEP. 62 Beste 10 Poster SGIM вЂ“ Meilleur 10 posters SSMI P293 Interpretation in the medical setting: between translation and mediation Marina Sleptsova* UniversitГ¤tsspital Basel (Basel, CH) Background: Errors in translation may have a significant impact upon health care. There is no uniform understanding of the role that a professional medical interpreter should adhere to. Models range from the interpreter as a conduit that transfers meaning from one language to the other to the interpreter as a cultural broker who helps establish a helpful relationship. Aim: We tried to assess role understanding of interpreters in a cohort of health care providers (hcp; N=387) and professional interpreters (N=365) from Switzerland. Methods: We used the German version of the IPRI questionnaire (C. Angelelli, 2004; overall Cronbach alpha: .70/.68 for hcp and interpreters, respectively) that lists 38 statements on the role of interpreters that are responded to from completely disagree to completely agree on a 6 point Likert scale (dividing line between 3: donвЂ™t agree and 4: agree). After removal of non-distinctive items it contains four subscales that describe different functions of the interpreter (Trust: 8 items, Cronbach alpha .67/.70; Align: 6 items, Cronbach alpha .71/.73; culture: 6 items, Cronbach alpha .70/.65; Affect, 8 items, Cronbach alpha .72/.65 in hcpвЂ™s/interpreters, respectively). Results: The establishment of a trustful relationship is seen as not important by both groups; both strongly do not agree that it is the primary task of the interpreter to form a close alliance with the patient: (1.80 В± 0.74 vs. 1.84 В± 0.66; p= n.s.). Interpreters rather support the importance of a culturally sensitive interpretation (3.83 В± 0.84 vs. 3.60 В± 0.83 in hcp; p<0.001). Both groups agree that the interpreter should not help express patient emotions beyond the correct translation of emotional utterances (2.77 В± 0.77 vs. 2.78 В± 0.78; p= n.s.). Conclusion: In both groups the idea that interpreters should serve as patientsвЂ™ advocate is not supported, establishing a trustful relationship and supporting the expression of emotions is also not seen as a primary task of interpretation. This speaks in favour of a neutral role that more closely resembles the conduit model of interpretation. P294 Sepsis due to Candidatus neoehrlichia mikurensis: (still) rare in humans, but not in ticks! Daniela Bircher*, Florian P. Maurer, Guido V. Bloemberg, Urs Karrer, Jacques Gubler Medizinische Poliklinik Kantonsspital Winterthur (Winterthur, CH); Institut fГјr Medizinische Mikrobiologie UniversitГ¤t ZГјrich (ZГјrich, CH) Case: In January 2012, a 58 year old patient was referred to our outpatient clinic because of a 3 month-history of recurrent fever up to 40В°C, chills, night sweats and weight loss of 5 kg. Six months earlier, he had finished six cycles of R-CHOP chemotherapy (Rituximab, Cyclophosphamide, Doxorubicin, Vincristin, Prednisolon) for a stage IV follicular lymphoma achieving complete remission. At time of referral he was treated with Rituximab every 3 months. Multiple blood cultures and HIV-, EBV- and CMV-serologies had excluded active infection. A PET-CT scan showed no signs of recurrent lymphoma. The general condition of the patient was markedly reduced. He was underweight (BMI 19 kg/m2), had a low blood pressure (95/60 mmHg) and tachycardia (100/min) but no fever (36.7 В°C). Otherwise, the physical exam was completely unremarkable. Lab results: hemoglobin 93 g/l, platelets 199 G/l, leucocytes 6.2 G/l, lymphocytes 0.22 G/l, ESR 94 mm/h, CRP 92 mg/l, normal liver and renal parameters. Bone marrow biopsy indicated unspecific inflammation without lymphoma. Broad-range 16S rRNA gene PCR of bone marrow and peripheral blood was positive and sequencing of the amplicons identified the presence of Candidatus Neoehrlichia mikurensis. Oral antibiotic therapy with doxycycline was initiated and fever subsided within days. After 2 weeks, 16S PCR from blood was negative and the patient had gained 6 kg. Oral doxycycline was continued for 6 weeks and the patient made a full recovery. Discussion: Neoehrlichiosis caused by Ca. Neoehrlichia mikurensis is an emerging tick-borne disease. Ca. Neoehrlichia mikurensis is a novel bacterial species belonging to the family of Anaplasmatacea and was recently isolated in a surprisingly high proportion of ticks from the greater Zurich area (up to 8%). Since 2008, eight human cases of neoehrlichiosis have been described in Europe, three of them in Switzerland, mostly affecting immunocompromised patients. The disease is associated with severe systemic inflammation with fever, malaise and weight-loss. Ca. Neoehrlichia mikurensis -specific or 63 broad range 16S rRNA gene PCR of blood or lymphoid organs is the preferred diagnostic method since successful culture methods or serological tests are not available. The treatment of choice for neoehrlichiosis is oral doxycyclin for six weeks. Neoehrlichiosis should be considered in immunocompromised patients with inflammatory syndromes not responding to conventional antimicrobial (beta-lactam) therapy. P295 Beef it up: severe hypercalcaemia caused by parenteral self-administration of a veterinary drug containing high dose vitamin A, D, and E Henriette Heinrich*, Rahel Schwotzer, Dominik Schneider, Daniel Franzen UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Introduction: Fixation of modern society on physical appereances has led to increasing abuse of performance enhancing substances as well as injection of muscle augmenting substances not only among professional body builders. The side effects are widely known. Here, we present a case of intoxication due to self-administration of a parenteral veterinary drug containing vitamin A, D, and E. Case report: A previously healthy 19-year-old man was referred because of recurrent vomiting, nausea and weight loss of 15 kg within the last 3 months. The patientвЂ™s history revealed dysthymia but was otherwise noncontributory. Alcohol or ilicit drug abuse was denied. Three months ago, he had moved from Brasil to Switzerland, where his father runs a gym. In Brasil, he was doing resistance training, but had not achieved satisfying results from his personal point of view. For this reason, he weekly self-administered a veterinary drug containing high dose vitamin A, D, and E over 3 months into brachial, pectoral, and deltoid muscles. Normally, the applied veterinary compound (ADE LabovetВ®) is applied in cattle production for vitamin supplementation. Clinical examination was uneventful, but biceps, pectoral and deltoid muscles were palpably and asymmetrically prominent. Laboratory studies revealed a raised total albumin-corrected calcium serum level of 3.66mmol/l and phosphate level of 0.76mmol/l. TSH serum level, chest X-ray, and abdominal ultrasound were normal. PTH serum levels were low ruling out hyperparathyroidism. Hence, vitamin D intoxication was presumed. During the treatment with hydration, furosemide and zolendronat, his calcium serum levels returned to normal values. Depressive symptoms did not recur. Discussion: The assumed cumulative dose of self-injected substance was 400ml, whereas 100ml contains 20000000 U vitamin A, 500000U vitamin D3 and 6800 U vitamin E. A quantity toxic to humans remains undisputable. Intramuscular injection of high dose vitamins A, D, and E leads to muscular pseudohypertrophy imitating a silicon like effect by causing muscle edema. But a synergistic effect of absorbed vitamin A and D leads to the clinical picture of hypervitaminosis A and D with vomiting, anorexia, weight loss and psychiatric abnomalities. The treatment is analogous to the one of hypercalemia. There are only a few case reports originating from South America, which describe this entity in amateur body builders. Once again, a proper patientвЂ�s history is crucial! P296 Antigen-specific functionality of anti-FAP re-directed CD8+ T-cells Christoph Renner, Petra Schuberth, Christian Hagedorn, Alex Soltermann, Sandra Tomaszek, Rolf Stahel, Walter Weder, Ulf Petrausch* UniversitГ¤tsSpital Basel (Basel, CH); UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Introduction: T cells can be re-directed by retro-viral transfer of chimeric antigen receptors (CAR) that recognize tumor-associated antigens (TAA). Adoptive T cell therapy (ACT) with CAR re-directed T cells represents a new branch of immunotherapy and has recently shown clinical responses in CLL. However, in solid organ cancers ACT has to be intensively investigated since the efficacy of ACT has not conclusively been shown so far. Malignant pleural mesothelioma (MPM) is considered an incurable disease where new treatment options like ACT could be evaluated. Fibroblast activation protein (FAP) is predominantly expressed on the surface of tumor-associated fibroblasts and on particular cancer types. FAP is a promising target for ACT because of its expression in a wide spectrum of malignant lesions. Methods: Immunohistochemistry (IHC) was performed with the monoclonal antibody F19 in MPM and healthy tissue. IFN gamma ELISA and cytotoxicity assays were performed to demonstrate in vitro functionality. Immunodeficient mice (NSG) were co-injected with FAP positive tumor cells and redirected T cells to demonstrate protection against a tumor challenge in vivo. The model system allowed in vivo imaging by measuring the bioluminescence of luceferin, because the tumor cells were modified to express luciferase. 64 Results: We demonstrated expression of FAP by IHC in epitheloid, sarcomatoid and bi-phasic MPM. We evaluated FAP expression in healthy tissue, to estimate off-tissue/on-target toxicity of FAP-specific T cells. By IHC significant FAP expression could be found in pancreatic tissue. FAP-specific redirected T cells were successfully generated by retro-viral transduction of an anti-FAP-F19CD28/CD3-CAR. Expression of the CAR was observed in 35-55% of CD8+ T cells. FAP-specific redirected T cells lysed FAP positive mesothelioma cells and inflammatory fibroblasts in an antigenspecific manner in vitro. In the mouse model FAP-specific re-directed T cells inhibited the growth of xenografted FAP positive human tumor cells in the peritoneal cavity. Conclusion: Our data indicate the functionality of anti-FAP re-directed CD8+ T cells. Because of the FAP expression in MPM we will start a phase I ACT trial for patients with MPM (Figure 1A&B) in 2013. Re-directed T cells will be transfered in the malignant effusion (Figure 1C) of patients with MPM not accessible for surgery at the time point of screening. P297 Delayed positivity of Legionella urinary antigen: apropos of two cases Thierry Gigandet*, Robert Escher, Gabriel Waldegg, Markus Riederer, Martin Egger Regionalspital Emmental AG (Burgdorf, CH) Introduction: Legionella pneumophila urinary antigen test (LUAT) is a useful tool for rapid diagnosis of Legionella pneumonia: Urine samples are easy to obtain, the analysis is simple to perform, and the test has a short turnaround time. It has a high specificity (98-99%) but limited sensitivity (70-85%) depending on the type of assay, Legionella serogroup, and the clinical situation. Whereas prolonged positivity of the LUAT is well described, there is little information in the literature concerning delayed positivity. Case description: Case 1: A 67 year-old man with chronic lymphocytic leukemia, diagnosed 11 years ago and untreated so far, presented with a 3-day history of fever up to 40В°C, dry cough and moderate headache. The chest X-ray showed a pulmonary infiltrate in the right lower lobe. LUAT was negative and treatment with ceftriaxone was started. After clinical worsening necessitating intensive care a LUAT on day 5 was positive. Legionella pneumonia was confirmed by PCR in bronchoalveolar lavage fluid. Case 2: After a 4-day history of chills and increasing dyspnea a 50 year-old smoker with chronic obstructive pulmonary disease (COPD) GOLD III, presented with severe dyspnea, a temperature of 65 37.7В°C and atrial flutter. The chest X-ray showed a pulmonary infiltrate in the lingula. LUAT was negative. Treatment with amoxicillin/clavulanic acid was started. After 3 days of clinical and radiographic worsening with increasing C-reactive protein a repeat LUAT was positive. A positive Legionella PCR from pleural fluid confirmed the diagnosis. Both patients were treated with levofloxacin and left the hospital in good condition. Discussion: Our cases illustrate that LUAT may turn positive only a few days into the clinical manifestation of Legionella pneumonia. This observation pertains to the BinaxNOWTM Legionella test used in our hospital and may not be applicable to other brands. Such cases may contribute to the false negatives responsible for the limited sensitivity reported for LUAT. The observation has implications for the empiric coverage for Legionella in treatment of community acquired pneumonia. Chronic lymphocytic leukemia and severe COPD, respectively, could have cautioned to provide coverage for Legionella in our patients despite negative LUAT. Conclusion: Repeated testing for LUAT may be warranted before withholding or stopping antibiotics against Legionella in moderately severe to severe community-acquired pneumonia. P298 Pitfalls in the microbiological diagnosis of pneumococci: clinical relevance Nadine Lippuner*, Reinhard Zbinden, Christlieb Haller UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Case Report: A previously healthy 82 year old woman presented with a 9 day history of respiratory tract infection, non-productive cough, fever and a respiratory rate of 22/min. Further investigation revealed leucocytosis, a markedly increased concentration of C-reactive protein and a right upper lobe infiltrate on the chest x-ray. The patient was hospitalized and treated empirically for communityacquired lobar pneumonia with intravenous amoxicillin/clavulanate. The clinical impression of pneumococcal pneumonia was supported by gram-positive cocci in 4 of 4 blood culture bottles and a positive pneumococcal antigen agglutination test directly from the blood cultures. The pneumococcal antigen test in the urin however was negative. Eventually a streptococcus mitis group isolate was reported in the blood cultures. This unexpected result prompted a thorough investigation of potential foci of S. mitis bacteremia including a dental evaluation and echocardiography. The discharge from the hospital was delayed for 2 days despite the rapid clinical response with resolution of the fever within 24 hours. The patient was instructed to monitor her temperature, continue oral antibiotic treatment and follow up as an outpatient. Two weeks later the initial clinical diagnosis of pneumococcal bacteremia was confirmed by recA gene sequencing, which definitively identified the isolated bacteria as pneumococci. The technically challenging distinction between S. mitis and S. pneumoniae had caused some difficulty in the interpretation of the results with further confusion because of the term вЂњS. mitis groupвЂќ. Discussion: The differentiation between S. mitis and S. pneumoniae - both members of the S. mitis group - with conventional methods can be challenging if colony morphology is not typical and bile solubility is not clearly positive. Evidently this difficulty also exists for state of the art techniques like MALDI-TOF fingerprinting, 16S PCR and Vitek2. In this patient the routine microbiology results led to unnecessary tests, prolonged hospital stay and caused considerable anxiety to the patient. Conclusion: Clinicians need to be aware of the pitfalls in the differentiation between some streptococci within the S. mitis group (namely S. mitis and S. pneumoniae) even with modern laboratory methods. In case of discrepancies between clinical and laboratory findings the direct communication between laboratory and clinical physicians remains essential for optimal patient management. P299 Introduction and outcome analysis of systematic semi-automated alerts regarding metformin dose-adjustment in patients with renal impairment in a Swiss university hospital Regina Krattinger*, Guido Bucklar, Ludwig Perger, Gerd Kullak-Ublick, Edouard Battegay, Stefan Russmann UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Background: Lack of dose-adjustment in response to impaired renal function is an important and avoidable cause of adverse drug reactions and additional costs in hospitalized patients. Today, electronic drug prescription provides new opportunities for the identification and prevention of prescribing errors, including those that involve wrong dosing. This study introduced and evaluated 66 automated electronic surveillance of metformin therapy in patients with impaired renal function, followed by manual expert dosing recommendations. Methods: We developed an algorithm that automatically identified patients of a Swiss University Hospital with an estimated glomerular filtration rate (eGFR) below 60 ml/min and prescriptions for metformin. Real-time automated alerts were displayed to clinical pharmacologists, who then reviewed electronic medical records and provided dosing recommendations to prescribing physicians based on locally customized guidelines published by Lipska et al. (Diabetes Care 2011;34,1431-7). Results: During the calendar year 2012 we identified 436 cases with an eGFR <60 ml/min and current metformin therapy. Among those, guideline-based dose reduction or stop of therapy was recommended in 123 cases. In 88 (92.6%) out of 95 cases with known follow-up, our recommendations led to an according change of therapy. We did not observe consistent changes in the number of necessary recommendations per month over time. Furthermore, we identified 2 patients with lactic acidosis under metformin therapy that had not been adjusted for impaired renal function. Conclusions: Automated detection followed by manual expert recommendations (вЂњsemi-automated alertsвЂќ) was highly efficient and detected a considerable absolute number of metformin dosing errors. Their clinical relevance was underlined by 2 cases of lactic acidosis, which is a possible adverse effect of metformin therapy. Our specific semi-automated alerts achieved compliance above 90% among physicians, which compares to a typical compliance of less than 5% for unspecific automated alerts. There was no evidence for a lasting educative effect of alerts on metformin prescribing behaviour. Our findings indicate that, along with other preventive measures, continued semi-automated alerts can play an important role for the efficient and effective prevention of clinically and economically relevant medication errors. P300 Accuracy of four cardiovascular risk scores in a Swiss population-based cohort Julien Vaucher*, Pedro Marques-Vidal, FranГ§ois Bastardot, Didier Locca, Olivier Muller, Patrik Michel, GГ©rard Waeber, Peter Vollenweider CoLaus Study Purpose: To assess the global cardiovascular (CV) risk of an individual, several scores have been developed. However, their accuracy and comparability need to be evaluated in populations others from which they were derived. The aim of this study was to compare the predictive accuracy of 4 CV risk scores using data of a large population-based cohort. Methods: Prospective cohort study including 4980 participants (2698 women, mean ageВ± SD: 52.7В±10.8 years) in Lausanne, Switzerland followed for an average of 5.5 years (range 0.2 - 8.5). Two end points were assessed: 1) coronary heart disease (CHD), and 2) CV diseases (CVD). Four risk scores were compared: original and recalibrated Framingham coronary heart disease scores (1998 and 2001); original PROCAM score (2002) and its recalibrated version for Switzerland (IAS-AGLA); Reynolds risk score. Discrimination was assessed using Harrell's C statistics, model fitness using Akaike's information criterion (AIC) and calibration using pseudo Hosmer-Lemeshow test. The sensitivity, specificity and corresponding 95% confidence intervals were assessed for each risk score using the highest risk category ([20+ % at 10 years) as the "positive" test. Results: Recalibrated and original 1998 and original 2001 Framingham scores show better discrimination (>0.720) and model fitness (low AIC) for CHD and CVD. All 4 scores are correctly calibrated (Chi2<20). The recalibrated Framingham 1998 score has the best sensitivities, 37.8% and 40.4%, for CHD and CVD, respectively. All scores present specificities >90%. Framingham 1998, PROCAM and IAS-AGLA scores include the greatest proportion of subjects (>200) in the high risk category whereas recalibrated Framingham 2001 and Reynolds include <=44 subjects. Conclusion: In this cohort, we see variations of accuracy between risk scores, the original Framingham 2001 score demonstrating the best compromise between its accuracy and its limited selection of subjects in the highest risk category. We advocate that national guidelines, based on independently validated data, take into account calibrated CV risk scores for their respective countries. P301 Allergy to chlorhexidine: rare but not to be ignored Ewa Degenhardt*, Manuel Bubenhofer, Arthur Helbling, Ulrich Weber-Mani, M Fricker UniversitГ¤tsspital Bern (Bern, CH); Stadthofpraxis (Thun, CH); Zieglerspital (Bern, CH) Background: The broad spectrum antimicrobial agent chlorhexidine (CHX) is widely used in medicine for disinfection of skin and mucosal tissue, e.g., in dental hygiene, surgical procedures, central venous 67 catheterization and urethral catheterization. It is part of daily health care and a component of cosmetics. Allergic reactions to CHX have been reported only occasionally. Objectives: The purpose of this study was to elucidate the circumstances of the occurrence of allergy in subjects with a proven allergy to CHX. Methods: The clinical records from the years 2005-2010 from both allergy units in Bern (Division of Clinical Immunology and Allergology of University Hospital Bern and Allergy Unit of Clinic of Internal Medicine, Zieglerspital, Spital Netz Bern) were searched for patients with CHX allergy. Allergy work up including accurate history, skin tests, serological tests (e.g. ImmunoCAP, BAT), and eventually a follow up by telephone was carried out in 20 patients (16 m, 4 w; mean age of 46 years (11-76y)) with a history of CHX allergy. Results: Of the 20 patients with CHX allergy, 16 (80%) had an IgE-mediated, and 4 a delayed type reaction after exposure to CHX. Immediate type allergic reactions - all systemic - occurred during dental/mouth cleaning (3), at the dentist office (4), during urological procedures (5), perioperatively (3) and after topic use (1). Specific IgE was detected in 11/16 patients, ranging from 0.78-13.0 kU/l (RAST classes 2-3). Two patients had a positive basophilic activation test. The 4 patients with eczematous skin lesions used topical products such as Merfen. As concluded from the patient's history, they most probably became sensitized to CHX by a previous invasive procedure. 6 patients had a coexisting atopic constitution. Conclusion: In this study, the majority of patients with an allergy to CHX showed an immediate type reaction (IgE-mediated) following CHX contact. Allergic reactions to CHX are indeed rare, but may have a life-threatening potential. Allergy to CHX can occur anywhere, where CHX is used. In the Swiss Drug Compendium 55 products are listed, and 88 commonly known cosmetic brands on the Swiss market contain CHX. Therefore, CHX is an ubiquitous substance and may be a cause for anaphylaxis in hospitals, in dentist's surgery, or even at home. P302 Chronology of extraintestinal manifestations relative to inflammatory bowel disease (IBD) diagnosis in the Swiss Inflammatory Bowel Disease cohort Stephan Vavricka*, Gerhard Rogler, Ekaterina Safroneeva, Alain Schoepfer Stadtspital Triemli (ZГјrich, CH); UniversitГ¤tsspital (ZГјrich, CH); CHUV (Lausanne, CH) Background: Data on the frequency of extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are scarce. There is especially a paucity of data evaluating the chronology between IBD diagnosis and the occurrence of the EIM. Aim: To assess the type and frequency of EIM in IBD patients and to evaluate their chronologic behavior. Methods: Analysis of data from the Swiss Inflammatory Bowel Disease Cohort (SIBDCS) which collects data since 2005 on a large sample of IBD patients from hospitals and private practices across Switzerland. Parametric data are demonstrated as mean В± SD, non-parametric data as median + interquartile range (IQR). Results: At total of 1,143 patients were analyzed (572 (50%) female, mean age 42.1 В± 14.4 years), 629 with CrohnвЂ™s disease (CD), 501 with ulcerative colitis (UC), and 13 with indeterminate colitis (IC). Of these, 374 (32.7%) presented one to five EIM (65% with CD, 33% with UC, 2% with IC). Of those patients suffering from EIM, 41.7% presented two, 12.4% three, 5.3% four, and 3.2% five EIM during lifetime. The initial EIM presented with the following frequencies: peripheral arthritis (PA) 63.4%, ankylosing spondylitis (AS) 8.1%, primary sclerosing cholangitis (PSC) 6%, uveitis 5.7%, oral aphthosis 5.7%, erythema nodosum (EN) 5%, other 3.6%, pyoderma gangrenosum 1.8%, psoriasis 0.7%. In only 7.1% of cases, the EIM manifested before IBD diagnosis was made (median time 28 months before IBD diagnosis, IQR 7-60 months), in 92.9% EIM manifested after established IBD diagnosis (median 72 months, IQR 9-147 months). When looking at all EIM occurring during lifetime in IBD patients, the frequencies were as follows (total exceeds 100 due to potential presence of multiple EIM): peripheral arthritis 69.3%, oral aphthosis 23%, ankylosing spondylitis 19.4%, uveitis 15.5%, erythema nodosum 14.5%, PSC 7.8%, pyoderma gangrenosum 6%, psoriasis 2.8%. Conclusion: EIMs are a frequent problem in IBD patients. The vast majority of EIM manifest after IBD diagnosis is established. Peripheral arthritis, ankylosing spondylitis, and PSC represent the most frequent first manifestations of an EIM. Peripheral arthritis, oral aphthosis, and ankylosing spondylitis represent the most frequent EIM during lifetime of an IBD patient. 68 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 1 - MГ©decine interne gГ©nГ©rale 1 P303 Recurrent falls: no pitfall Raphael Butsch*, Markus Schneemann UniversitГ¤tsspital ZГјrich (ZГјrich, CH) A 56-year-old Swiss woman was in hospital in june 2012 for strumectomy. Our clinic was involved due to mild hypertension during the hospital stay. Her past medical history revealed recurrent falling on her knees once to four times a year for the lastfour years. She reported no stumbling, no prodromal signs and no loss of consciousness. Personal history was remarkable for hypertension, well controlled GravesвЂ™ disease, depression and obesity. Her medication consisted of candesartan 4 mg and carbimazole 5 - 10 mg daily. Clinical examination was unremarkable with exception of the knees. ECG, laboratory findings and an orthostatic test were normal. How should we call this patientвЂ™s condition? It is neither a syncope nor a seizure. Rather, it might be called a вЂњdrop attackвЂќ. Patients with drop attacks are rare and the differential diagnosis is limited. Drop attacks are mentioned in patients with narcolepsy, atonic seizures, vertebrobasilar insufficiency and in patients with thyroid hypofunction. Neither of these disorders was suspected in this woman. , D. L. Stevens and W. B. Matthews wrote an article in the British Medical Journal about such a disturbance in 1973 (1). They called it вЂњcryptogenic drop attackвЂќ. In French it is referred to as вЂњMaladie des genoux bleusвЂќ, the reason is obvious (see figure of our patient). Initially, they collected 54 patients complaining about drop attacks, thereof 51 were women. Cases with an underlying disease promoting falls were excluded. Amongst these, all three men were out. Subsequently, they started a deliberate search for women with similar complaints attending the gynecological clinic. This process resulted in a total of 40 female patients complaining about falls without warning, without vertigo or other cephalic sensations, without evidence of any malfunction of the lower limbs and not induced by change of posture or head movements. In 28 women follow up was successful. Their mean age was 45 years. 26 out of 28 only fell forward, 27 only while walking, all of them suffered injuries of their knees, some as well of injuries of wrists, nose, face or chest. 10 were aware of falling, 16 at least of crashing to the ground. 2 did not recall falling but stood up quickly and resumed walking. And most important: In all of these cases it was impossible to find a causal factor. They are cryptogenic drop attacks - to this date! Acknowledgment of this fact - and one look at the patientвЂ™s knees - may prevent extensive investigations. 69 P304 Pharmacologic treatment of persistent hiccup after brain stem ischaemia David Muggli*, Florian Furrer, Anne Brausch, Simon Andreas MГјggler Stadtspital Waid - Medizinische Klinik (ZГјrich, CH) Introduction: Persistent hiccup (singultus) can be caused by neurological disease, such as brain stem ischemia. Quality of life is frequently impaired in these patients. No evidence-based therapy is currently available, therefore pharmacological treatment is empiric. Case presention: A 46-year old man was admitted with vertigo, slurred speech, gait ataxy, nausea and vomiting. Neurological examination showed dysarthria and hoarseness, dysphagia, spontaneous nystagmus, discrete left-sided HornerвЂ™s syndrome, palate deviation to the right side and impaired pain and temperature sensation of the right arm, consistent with WallenbergвЂ™s syndrome. CT and MRI scan of the brain showed acute ischemia of the left-sided posterolateral medulla oblongata. Fiber endoscopic evaluation of swallowing showed paresis of the left hypopharynx, with aspiration of fluid. Despite improvement of the dysarthria after a few days, the patient complained about persistent hiccup lasting for several days, disturbing him at night and impeding oral nutrition. A percutaneous endoscopic gastrostomy was performed to provide nutrition. Therapy of the hiccup by physical maneuvers and empiric medical treatment with metoclopramide and inhalative lidocaine brought no relief. An attempt with haloperidol led at last to full regression of the afflicting hiccup within two days. Conclusion: Persistent hiccup is defined as hiccup continuing longer than 48 hours and less than one month. The exact mechanism of hiccup remains unclear. Several neural pathways make up the putative hiccup reflex arc (Figure 1). The central connections for hiccups seem to involve an interaction among the medulla oblongata and reticular formation of the brain stem, phrenic nerve nuclei, and the hypothalamus. Dopamine and gamma-aminobutyric acid (GABA) are supposed to be involved as neurotransmitters. Any physical and chemical irritants, inflammatory and neoplastic conditions involving the hiccup reflex arc may cause hiccup. Treatment of an underlying condition should be the first step in treatment of hiccup. Due to the lack of controlled trials, pharmacologic treatment of hiccup is still empiric and mainly targets the neurotransmitters dopamine and GABA. Table 1 shows empiric therapies of hiccup. Chlorpromazine, a dopamine-receptor-blocker, is often used to treat hiccup and is the only approved drug by the US Food and Drug Administration, but not available in Switzerland. 70 71 P305 Screening for latent tuberculosis: confusion between skin test (Mantouxв„ў) and BCG vaccine Jean-Philippe Aegerter*, Jean-Pierre Zellweger, Laurent Christin Service de MГ©decine (Nyon, CH); Ligue Pulmonaire Vaudoise (Lausanne, CH) A 34 year old female consults our emergency department (ED) 4 days after receiving a tuberculosis (TB) screening skin test at her primary care physicianвЂ™s office. She works as a kindergarten teacher and is a bout to start a new job; a TB screening skin test is part of a standard pre-enrollment check up. She is known for severe Crohn disease which has been very well controlled with inFLIXimab injections. She received the BCG vaccine in 1981. A TB skin test (Mantouxв„ў) is recorded as negative in her vaccination record in 2004, just before initiating inFLIXimab treatment. She comes to the ED complaining of severe pain at the site of injection. It is hot and red, firm, tender, without lymphadenitis. The ED physician considers this as a booster effect and prescribes a topical NSAID. She returns to the ER 48 hours later because of persisting pain and redness. The lesion is very tender and fluctuant. An incision brings out purulent fluid. A ZiehlвЂ“Neelsen stain reveals acid-fast bacilli; a PCR returns positive for Mycobacterium tuberculosis complex. A chest x-ray is normal. A Quantiferonв„ў test returns negative. Our investigations reveal that her physicianвЂ™s assistant injected her with BCG vaccine instead of Mantouxв„ў test. Since inFLIXimab treatment could not be interrupted, we decided to put the patient on rifampicin and isoniazid for 6 months. Her Crohn disease has remained well controlled. The lesion has completely healed, leaving a frank scar. Comment: decrease in use of TB screening skin tests favors the confusion between products (i.e. Mantoux vs BCG), even more so that their packaging is quite similar. Since skin test has very poor specificity for Mycobacterium tuberculosis and given this high risk of confusion, specific immunologic blood tests to detect latent tuberculosis should be our first choice in such situations. P306 The border of reproductive control: undocumented immigration as a risk factor for unintended pregnancy in Geneva Alejandra Casillas*, Patrick Bodenmann, Manuella Epiney, Laurent GГ©taz, Olivier Irion, Hans Wolff Hopitaux Universitaires de GenГЁve (GenГЁve, CH); Centre Hospitalier de Vaud, PMU (Lausanne, CH) Background: Unintended pregnancies reflect health disparities, and an unmet need for family planning. Using the only Swiss database to inquire about pregnancy intention, this study examined the relationship between immigrant documentation and unintended pregnancy. Methods: We used questionnaire data from pregnant women presenting to the public hospital in Geneva from February 2005-October 2006; women were asked if their pregnancy was intended. Using Chi-square tests, we compared unintended pregnancies between documented and undocumented women. We used logistic regression to examine whether undocumented status was associated with unintended pregnancy after adjusting for socio-demographics, family interaction/presence, health-services utilization, reproductive history, drug use, violence exposure, and psychological trauma. We present odds ratios with 95% confidence intervals of the adjusted analyses, significant at the p<=0.05 level. Results: 409 women were invited to participate and 394 accepted (96%). 161 were undocumented, uninsured immigrants of which 84% were Latina. More undocumented women were younger, employed, lived in a one-room apartment, used contraception at conception (including "insecure" methods: condom-only, calendar, retraction) and never had a Pap smear. Less were married, had a stable relationship with the baby's father, had family or children in Geneva, had knowledge of emergency contraception, used medications, and ever used tobacco or any other substance. Undocumented women had more unintended pregnancies (75.2% vs. 20.6%, p<0.001). Undocumented status was associated with unintended pregnancy after adjustment (OR 6.2, 1.8-21.2), as was a history of psychological problems (OR 4.1, 1.3-12.7). Stable relationship with baby's father (OR 0.10, 0.02-0.60), history of abortion (OR 0.35, 0.12-0.997), and current psychiatric treatment (OR 0.03, 0.004-0.04) decreased odds. Contraception non-use was notably associated with lower odds of unintended pregnancy (OR 0.013, 0.004-0.04). Conclusions: Undocumented status increased the odds of unintended pregnancy. Factors linked to domestic stability and health treatment were protective. Contraception non-use decreased odds of unintended pregnancy-- likely reflecting a desire for pregnancy in this group. However, this also 72 distributes some focus to the need for teaching of effective and correctly-utilized methods, among all women, given the use of insecure contraception observed in the study. P307 Validation of a French version of a low back pain questionnaire Michel Kossovsky*, Christophe Luthy, TimothГ© Fontolliet, Christine Cedraschi, Anne-FranГ§oise Allaz HГґpitaux Universitaires de GenГЁve (GenГЁve, CH) Introduction: Annual prevalence of low back pain (LBP) in Switzerland is estimated to reach 20 to 30%. A standardized definition of LBP is therefore important in terms of comparison between studies. This was the goal of the DELPHI DOLBaPP (DD) questionnaire, developed in English by a committee of 28 experts from 12 countries following a Delphi method. This seven-question self-administered questionnaire explores different domains related to LBP such as localization, associated limitations, irradiation, frequency, duration and severity. This questionnaire was translated in French by a team from Montreal, Quebec, Canada. Our purpose was to test whether this version was readily applicable to a French-speaking Swiss population. Method: The questionnaire was administered to 40 subjects suffering LBP. The comprehension of each item of the DD was assessed on a 7-point scale, ranging from вЂ�incomprehensibleвЂ™ to вЂ�very understandableвЂ™. Then, each item was reformulated by the subjects in their own words. A semistructured interview guide helped investigators to identify words or expressions that could be associated with comprehension problems. Three other validated questionnaires testing severity and consequences of pain (Brief Pain Inventory; BPI), quality of life (EuroQol-5D) and disability (Oswestry Disability Index; ODI) were administered in order to verify further construct validity. Results: Only 1 DD item concerning the duration of LBP did not reach a comprehension level considered as satisfactory: only 40% of the subjects succeeded in properly reformulating it. The same item was significantly less understood on the 7-point scale than the other 6 (5.3 SD 1.9 vs. 6.9 SD 0.3; p<0.001). The response to other questionnaires did reinforce the construct validity of the DD questionnaire. Subjects who mentioned limitations on the DD questionnaire had a significantly higher incapacity level according to the ODI questionnaire (56.1 % SD 17.4 vs. 37.3% SD 17.5; p= 0.004). There was a strong correlation (0.73, p<0.001) between the pain intensity scale in the DD questionnaire and the average pain level assessed by the BPI questionnaire. Conclusion: The French version of the DD questionnaire can be used for studies in the French speaking part of Switzerland. A reformulation of one of the 7 questions could improve its comprehension among subjects with LBP. P308 Head-to-head comparison of 'fee-for-service' and 'diagnosis-related groups' hospitals in Switzerland: an observational study Noemi Weissenberger*, DГ©sirГ©e Thommen, Philipp Schuetz, Beat MГјller, Christoph Reemts, Thomas Holler, JГјrg Schifferli, Martin Gerber, Balthasar Hug UniversitГ¤tsspital Basel (Basel, CH); UniversitГ¤tsspital Aarau (Aarau, CH) Background: Reimbursement for inpatient treatment in Switzerland differed until 2012 among states (cantons). Some hospitals used Diagnosis Related Groups (DRG) based reimbursement and others fee-for-service (FFS). We compare length of hospital stay (LOS), patient satisfaction and quality of life between the two systems before a nation- wide implementation of DRG. Aim: To investigate differences in patient and hospital relevant outcomes between an AP-DRG and a FFS hospital in Switzerland, as baseline before a nation-wide adaption of the DRG system. Methods: In a prospective, two-center observational cohort study we identified from January to June 2011 all patients with a main diagnosis of either community-acquired pneumonia, exacerbation of chronic pulmonary obstructive disease, acute heart failure or total prosthesis of the hip and performed a systematic questionnaire survey 2-4 months after hospital discharge investigating the differences between the two hospitals. Endpoints: The primary endpoint of this study was LOS defined as hospital admission until discharge. Secondary endpoints were hospital readmission rates and patientsвЂ™ satisfaction with the discharge procedure and quality of life. Results: Of 1,093 hospitalized patients 450 were included (175 AP-DRG, 275 FFS). The median age was 77 years (48% male). Patients in the FFS hospital were older (median age 78 vs. 74 years; p<0.001) and suffered from more co-morbidities. 73 Mean LOS was 9 days and shorter in the AP-DRG hospital (mean 8.2 vs 9.5 days, p=0.04) in an unadjusted analysis. After multivariate adjustment, no significant difference in LOS was found (p=0.24). More patients from the FFS hospital were re-hospitalized for any reason (35% vs. 17.5%; p=0.01), re-admitted to acute-care institutions (11.7% vs. 5.2%; p=0.014), not satisfied with the discharge process (15.3% vs. 9.7%; p=0.02), had problems with self-care (93.8% vs. 88%; p=0.03) and with usual activities (79.3% vs. 76%; p=0.02) 90 days after enrollment. Discussion: Our data suggest that the AP-DRG hospital shows a higher patient satisfaction regarding discharge, lower rehospitalization rates and shorter LOS, which, however, is partly explained by a higher burden of comorbidities and disease severity in the FFS hospital. This study provides a solid baseline for comparison after nation-wide DRG implementation. Correspondence: PD Dr. B. Hug, MBA, MPH, Division of Internal Medicine, University Hospital Basel, E-Mail: [email protected] P309 Diagnosis and treatment of iron deficiency in medical inpatients in a Swiss tertiary university referral hospital Balthasar Hug*, AndrГ© Tichelli, Pascal Benkert, Guido Stirnimann, JГјrg Schifferli UniversitГ¤tsspital Basel (Basel, CH) Background: Iron deficiency anemia is common; a European study found iron deficiency (ID) in about every fifth young female (17-38 years)(1). The prevalence of ID in hospitalized patients is not well known and may be significantly higher among patients with severe or chronic illness. Aim: To evaluate the prevalence and the current diagnostic and treatment of iron deficiency (ID) in hospitalized patients at the division of internal medicine in a Swiss tertiary university referral center. Methods: Design: single center, retrospective observational cohort study including all consecutive inpatients of the division of internal medicine at a tertiary referral university hospital in northwestern Switzerland. Study duration: from July1st to December 31st 2011. Definitions: ID either ferritin <15 Вµg/L or ferritin <50 Вµg/L and transferrin saturation <20%. Anemia: males <130 g/L, females <120 g/L. Results: Within the observation period 2,251 unique patients (2,781 hospitalization cases) were enrolled; 55.5% were male and mean age was 66.4 years. Of these 2,267 cases (81.5 %) had their blood drawn; in 329 cases (14.5%) iron parameters (IP) were determined and 45 (13.7%, CI : [10.2% 17,8%]) cases/unique patients with ID were detected. In statistical estimation 103 cases (69.6%) with ID were not diagnosed. In ID the most prevalent diagnosis was heart failure (I50.01; 24,4 %) of which 72.7% had hemorrhage facilitating drugs (aspirin, phenprocoumon, heparins) on hospital admission or discharge. Two thirds of patients with laboratory proven iron deficiency received iron substitution (IS) of any kind (66.6%). Of the 30 patients receiving IS, 80% received it by i.v. route, 16.6% orally and one patient combined i.v. and p. os. ID was coded correctly in 60%. Conclusion: Iron deficiency (ID) is common in internal medicine and up to two thirds of concerned cases may not be diagnosed. Every seventh patient who had his iron parameters (IPs) analyzed was iron deficient and two thirds of patients with ID were treated with intravenous iron. Based on these results further studies using a prospective design in order to optimize diagnosis and treatment of patients with ID are warranted. Literature 1)Grondin MA, Ruivard M, Perreve A, et al. Prevalence of iron deficiency and health-related quality of life among female students. J Am Coll Nutr 2008; 27(2): 337-41. Correspondence: PD Dr. B. Hug, Division of Internal Medicine, University Hospital, Basel . E-Mail: [email protected] P310 Cholesterol pilot study Claude Rothen*, Theodor Kaufmann Rothen Medizinische Laboratorien (Basel, CH); Praxis BГјndnerhof (Basel, CH) Introduction and Background: Dyslipidemia requiring treatment is common. Often patients ask for an alternative treatment instead of the established statin therapy, mostly due to the occurrence of unpleasant side effects of this treatment. Some patients report considerable decrease of the cholesterol concentration with a red yeast rice treatment. Red yeast rice contains Monacolin a substance known to inhibit the HMG CoA reductase. Monacolin K is also the active substance in the HMG CoA reductase inhibitor Iovastatin. 74 The aim of this study is to answer the following question: Are there alternative therapies to the statin treatment with comparable main effects on the lipid profiles, potentially reduced side effects and at lower costs? Method: We asked 14 test persons to take over eight weeks 2X2 capsules of red yeast rice daily (2.4 gram) At baseline, after eight weeks, and after sixteen weeks blood samples were taken for total cholesterol, triglycerides, HDL, LDL, and the ratio Chol/HDL. Drug: We used capsules with red yeast with a defined content of monacolin K by 4% Analysis: The analysis were measured using a Beckman Coulter DxC To document the costs, we compared the daily costs of a common therapy with standard therapeutic drugs Results: From baseline to eight weeks we found in all patients a significant decrease of cholesterol from 6.26 mmol/l to 5.22 mmol/l (p=0.0012), for LDL from 3.97 mmol/l to 3.03 mmol/l (p=0.0016) and for the ratio from 4.03 to3.32 (p=0.001). After another eight weeks there was again an increase in the concentrations of cholesterol, LDL and the ratio observed. (Fig 1) Occasional side effects were reported The comparison of the costs shows that the cost of the natural treatment are about the same as the conventional treatment. Conclusions: Our small study showed a significant reduction of total cholesterol and LDL levels when taking red yeast rice for about eight weeks. In comparison to the statins, the competitive price and the low incidence of side effects indicate a possible alternative to the existing statin treatment. 75 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 2 - MГ©decine interne gГ©nГ©rale 2 P311 Interprofessional collaboration between residents and nurses on a simulated general internal medicine ward: behaviours enhancing teamwork quality Virginie Muller-Juge*, StГ©phane Cullati, Katherine Blondon, Patricia Hudelson, Fabienne MaГ®tre, Nu Vu, Geroges Savoldelli, Mathieu Nendaz University of Geneva (GenГЁve, CH); University Hospitals of Geneva (GenГЁve, CH) Introduction: Studies have shown that effective teamwork is necessary for optimal patient care. However, there is insufficient understanding of interactions between physicians and nurses on Internal Medicine wards as compared to intensive-care or reanimation settings. The aim of our study was to describe residentsвЂ™ and nursesвЂ™ behaviors that contribute to teamwork quality. Methodology: A volunteer sample of 14 residents and 14 nurses was recruited from the General Internal Medicine Division at the University Hospitals of Geneva, Switzerland. Resident-nurse pairs were asked to manage one non-urgent and one urgent clinical case in a simulated Internal Medicine ward, using a high-fidelity mannequin. After the simulation, participants attended a stimulated-recall session during which they viewed the videotape of the simulation and explained their actions and perceptions. All simulations were transcribed, coded, and analyzed, using a qualitative method (template analysis). During previous interviews with the study participants, we identified behaviors important to observe during the simulations, which then constituted the basis for our codebook, as well as items of published scales. A team of 3 researchers (consisting of an educationalist, a physician, and alternately one of the following: nurse, anthropologist, sociologist, or medical education specialist) first coded the videos independently and then compared and discussed coding differences until consensus was reached. Overall quality of teamwork during the simulations was scored based on patient management efficiency, shared management goals, and the general tone or atmosphere of the interaction. Results: Analyses were ongoing at the time of the abstract submission. Preliminary results suggest that, more than individual performance, the ability of the pair members to compensate for each otherвЂ™s weaknesses (such as lack of experience or autonomy) was associated with enhanced teamwork quality. Individual decision-making without dialogue, coordination, and communication was associated with diminished teamwork quality. The clinical case (urgent versus non-urgent) also seemed to influence participantsвЂ™ teamwork behaviors. Conclusion: Certain behaviors, similar to those observed in multimember reanimation teams, appear to enhance resident-nurse pair teamwork and may also compensate for some individual weaknesses. Such behaviors should be addressed in interprofessional training at the pre- and post-graduate levels. P312 Hepatitis B and prison officer perceptions: health beliefs about HBV transmission Alejandra Casillas*, Maria Pfefferle, Hans Wolff, Laurent GГ©taz Hopitaux Universitaires de GenГЁve (GenГЁve, CH) Background: It is important to examine the health beliefs of those in close contact with populations at high risk of infectious diseases, as is the case with prison officers. Incorrect beliefs among prison officers may affect the efficacy of risk reduction programs for all individuals. The goal of this study was to assess officersвЂ™ perceptions about hepatitis B (HBV) in the prison setting. Methods: This descriptive study included five prisons in western Switzerland. OfficersвЂ™ demographics, specific fears and knowledge regarding various infectious diseases were collected by anonymous questionnaire in 2012. Focusing on questions addressing HBV, we present descriptive analyses about transmission knowledge and protective behaviours, and the associations between fear of HBV infection and incorrect health beliefs. Results: 170 prison officers (96% participated) completed the survey: 88% male and 56% based at a pre-trial prison. While the majority (85%) recognized that contaminated needles could spread HBV, a lower proportion was aware of the risks from tattooing (72%), unprotected sexual intercourse (62%), sharing razors (69%) and toothbrushes (49%. Handshaking, food, and coughing were recognized as false modes by 70%, 36% and 30% of the prison officers, respectively. 76 In terms of HBV protection, 43% of participants stated that they used gloves when intervening in a fight. But only 46% of participants said they were vaccinated, 16% were unsure, while 38% definitely did not know their HBV vaccine status. Sterile needles and condoms were identified as prevention measures by 82% and 67% of prison officers, respectively. Regarding perceived fear, 44% had a moderate/great fear of HBV infection. There were significantly higher rates of false beliefs among prison officers with moderate/great fear of contracting HBV (ref: little/no fear) when asked about handshaking (RR 2.2, 95%CI 1.3-3.6), coughing (RR 1.3, 95%CI 1.031.5), and sharing food (RR 1.4, 95%CI 1.1-1.8) as possible transmission risks. Discussion: HBV knowledge and protection strategies are suboptimal among prison officers. As well, fear of HBV infection is associated with incorrect health beliefs. Improving health beliefs can decrease fears, and lead to useful health behaviours, like vaccination and glove use. As prison physicians rely on staff for ancillary support, it is increasingly important to address and improve their knowledge, for the benefit of vulnerable patients residing in the prison setting. P313 Syphilis and HSV2: prevalence study in a Swiss prison Alejandra Casillas*, Hans Wolff, Javier Barro, Laurent GГ©taz Hopitaux Universitaires de GenГЁve (GenГЁve, CH) Background : Latent syphilis infection and recurrence of Herpes Type-2 (HSV2) may lead to systemic patient complications, and predisposal for other STDвЂ™s, respectively. However, prevalence data in correctional settings (where patients may be at higher risk given behavioral history and SES) are lacking. This study aimed to estimate the prevalence of syphilis and HSV2 and associated risk factors, among male inmates in SwitzerlandвЂ™s largest pre-trial prison, Champ-Dollon, in Geneva. Methods: This cross-sectional study analyzed serological markers for syphilis and HSV2 in a representative sample of detainees. Screening for syphilis (ELISA) was offered in 2009 and 2011; confirmation and disease activity tests (TPHA and VDRL) were applied to positive cases. HSV2-IgG screening was only offered to participants recruited in 2011. Using a standardized questionnaire, we obtained socio-demographic characteristics and patient-recall of genital ulcer history. Results: 270/278 detainees were included for the syphilis screen (participation rate: 97.2%). Syphilis screening was positive among four patients (1.5%, 95%CI 0.5-3.5): one had a history of ulcer. Three had a positive TPHA-- with one positive and two inconclusive VDRL tests. 156/164 detainees participated in the HSV2 screen (participation rate: 95.1%). HSV2-IgG was positive among 35 participants (22.4%, 95%CI 16.1-29.8%). Among HSV2+, 15% (5/35) had recurrent genital ulcers in their history. Inmates from sub-Saharan African or Latin America had a higher risk of infection versus those from other origins (RR 2.3, 95%CI 1.3-4.1). Inmates with a primary school education or less had a higher risk versus those with more education (RR 2.2, 95% CI 1.14-4.1). History of sexual intercourse with prostitutes, number of sexual partners, and frequency of condom use were not associated with infection. Conclusions: Even though the observed syphilis prevalence among prisoners was higher than in the general population, studies are needed to define the cost-benefit of systematic screening given such rates, in this vulnerable population. HSV2 prevalence in this setting was more than two times higher than the Swiss general population among men of similar age. Interestingly, factors related to sexual risk history did not efficiently discriminate HSV2-infected inmates. Overall, we recommend strengthening preventive strategies in correctional settings, especially among low-educated inmates originating from countries known for HSV2 endemics. P314 The SPAM Network of family physicians: towards a better understanding of primary care in Switzerland Nicolas Senn*, Pakize Palan, Roland Fischer, Jacques Cornuz Policlinique MГ©dicale Universitaire (Lausanne, CH) Introduction: Primary care (PC) is evolving in Switzerland like elsewhere. In this context, it is important to have an accurate understanding of the functioning of PC. Recent works have identified an important lack of data in Switzerland, particularly with regard to the access, quality of care, satisfaction and services provided. The SPAM program (Swiss Primary Health Care Active Monitoring) aims to fill these gaps by creating a prospective monitoring tool. As no systematic data collection exists in Switzerland, it is essential to identify representative general internistsвЂ™ (GI) practices able to provide 77 first hand information on the performances of the PC system. Our objective is to describe the representativeness of the SPAM Network of 200 GIвЂ™s. Method: A random pre-selection of 2027 GI was drawn from more than 7000 members of the combined lists of the Swiss Family Physicians and Paediatricians Association (MFE) & Swiss General Internal Medicine Society (SSMI). The draws were stratified by canton. Afterwards, physicians for who general internal medicine was not the main clinical activity were removed. To investigate the representativeness, we draw for comparison a random sample of 200 GIвЂ™s from the same list of 2027 members (comparative group). The age was not available; therefore the date of birth was estimated from the FMH database by subtracting 25 years to the year of the federal diploma. Results: 200 GI accepted to join the Network (response rate = 9.9%). 62% speak German, 35% French and 4% Italian. In the comparative group, the prevalence rates were 76%, 23% and 1% respectively (p=0.02). 23% are female in the SPAM Network compared to 21% in the comparative group (p=0.63). Mean age in 2012 is 53.8 years (estimated age based on year of diploma) in the SPAM group compared to 53.4 in the comparative (p=0.68). For 4 cantons the recruitment target was reached (29 GPвЂ™s), 7 cantons contribute too much (88 GPвЂ™s, expected 52) and 12 cantons not enough (83 GPвЂ™s, expected 119). Conclusion: Based on these data, the SPAM network of general internists appears to be representative of Swiss general internists at a national level and will provide a solid basis to investigate performances of the PC system. During the meeting, further survey results will be presented on the activities of Swiss family physicians. P315 Improvement of adherence to daily oral vitamin D supplementation in a rheumatologic population: a pre/post-study Delphine Stoll*, Olivier Lamy, Didier Hans, Pascal Zufferey, Alexander So, Marc-Antoine Krieg, BГ©rengГЁre Aubry-Rozier CHUV (Lausanne, CH) Introduction: Vitamin D (Vit.D) reduces the risk of falls and fractures. Some experts recommend that serum Vit.D levels should be >30ng/ml (75nmol/l) for high-risk patients. Low Vit.D (<30ng/ml) was highly prevalent in our outpatient population (86% in 20091). Subsequent to Vit.D informational campaign to both our physicians and their patients we have evaluated the Vit.D status in a similar population 2 years later. Method: it.D levels were measured in November 20091 and 2011 in all outpatients who attended our clinic. 25-OH Vit.D level was categorized as deficient (<10Вµg/l), insufficient (10-30Вµg/l) or normal (>30Вµg/l). Patients who had received a high dose of Vit.D3 (>200вЂ™000IU) 6 months before each screening period were excluded. Patients not regularly seen at our clinic were also excluded. Results: In 2011, 239 patients were included (230 in 2009). The mean Vit.D level was 23.8 Вµg/l (4-53) (20.8ng/ml in 2009, p=0.0001). 4% had deficiency (8% in 2009), 68% insufficiency (79% in 2009), 28% normal levels (13% in 2009). The same percentage of patients was on daily oral Vit.D in 2009 and 2011 (38%). Of these supplemented patients 51% had normal results in 2011 compared to 25% in 2009 (p<0.01). Among the non-Vit.D users, 13 % had normal results in 2011 compared to 6% in 2009 (p=0.04). If we used the limit of 20ng/ml rather than 30ng/ml as recommended by many experts, 52% patients had Vit.D levels >20 ng/ml in 2009 and 66% in 2011 (p=0.001). During the two years of the study the number of 25-OH Vit.D testings (4875 in 2009 and 6896 in 2011) and the prescription of high doses of Vit.D3 (116 in 2009 and 253 in 2011) increased substantially in our hospital. These improvements could also be related to the increasing number of publications and grand round sessions about Vit.D between 2009 and 2011 in Switzerland. Conclusion: The prevalence of low Vit.D decreased in two years from 86% to 72%. These results were mainly due to the higher number of normal 25-OH Vit.D levels observed in patients taking oral daily Vit.D (increasing from 25% to 51%). These results may be explained by: 1) better adherence to oral daily Vit.D in the supplemented patients; 2) better information of physicians about hypovitaminosis D; 3) more frequent screening of Vit.D level and 4) higher prescription of high doses of Vit.D if this is deemed needed. 1. Stoll, D., et al., High prevalence of hypovitaminosis D in a Swiss rheumatology outpatient population. Swiss medical weekly, 2011. 141: p. w13196. 78 P316 Training clinical supervisors in how to teach communication skills: an exploration of factors affecting transfer to practice Noelle Junod Perron*, StГ©phane Cullati, Patricia Hudelson, Mathieu Nendaz, Diana Dolmans, Cees Van der Vleuten HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); Maastricht University (Maastricht, NL) Introduction: A faculty development program was designed to increase supervisorsвЂ™ ability to give feedback on junior doctorsвЂ™ communication skills (CS) in clinical practice. The program combined CS and teaching skills training. The aim of this study was to explore supervisorsвЂ™ perceptions of factors that facilitated skills transfer post-training. Methods: 28 clinical supervisors from two medical settings took part in the program at the Geneva University Hospitals, Switzerland. Skills transfer was explored through a short pre-post survey and semi-structured interviews. Interviews were audio taped, transcribed verbatim and analyzed thematically. Results: Transfer was reported by supervisors for both communication and teaching skills. Work characteristics that facilitated transfer of teaching skills included having opportunities to practice new skills, being involved in structured teaching activities, and the existence of supportive institutional policies. In addition, the combination of communication skills and teaching skills training in the same training program, a mixture of practice and reflective work, and a positive learning climate were found to be beneficial. Participants who reported teaching communication skills in practice were generally involved in structured communication skills teaching and expressed increased confidence and motivation post-training. Discussion: Opportunities to practice and systematic involvement of supervisors in communication skills structured teaching activities may increase transfer of communication skills teaching, probably because it reinforces practice, maintains motivation. It also helps supervisors join a community of teachers where exchange of ideas and insights can take place. P317 Does training improve clinical supervisorsвЂ™ ability to identify residentsвЂ™ communication skills and teach them interactively in clinical practice? Noelle Junod Perron*, Mathieu Nendaz, Johanna Sommer, Martine Louis-Simonet, Anne Gut, Cees Van der Vleuten, Diana Dolmans HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); FacultГ© de mГ©decine (GenГЁve, CH); Maastricht University (Maastricht, NL) Introduction: Observation of residentsвЂ™ communication skills followed by feedback by clinical supervisors is a key element of communication skills teaching in clinical practice. However, clinical supervisors may not be competent in identifying and addressing communication skills effectively. The aim of this study was to measure the impact of a training program in teaching communication skills on clinical supervisorsвЂ™ ability to identify residentsвЂ™ good and poor communication skills and their ability to address them in an interactive way during feedback sessions. Method: We conducted a pre-post controlled study in a hospital based and an outpatient setting at the Geneva University Hospitals. Clinical supervisors participated in a training program (9 hours in total) on how to teach communication skills in clinical practice over a period of 6-9 months. Outcome measures were the number and the type of communication skills identified by participants on three videotaped resident-patient encounters and the number of communication skills discussed in an interactive way during three feedback sessions made before and after intervention. Results : 48 clinical supervisors (28 in the intervention and 20 in the control group) participated. Trained participants did not identify a higher number of residentsвЂ™ communication skills on videotaped clinical encounters after the training. However, they taught a significantly higher number of communication issues in an interactive way during the feedback sessions after the training (effect sizes 1.36-1.77). Discussion : The training program did not increase the number of poor or good communication skills recognized by supervisors but was effective in increasing the number of communication issues discussed in an interactive way. Further research is needed to explore the respective weight of accurate identification of communication skills or effective teaching skills to make communication skills teaching more effective in clinical practice. 79 P318 Needle and syringe exchange programmes: acceptability and safety of retractable syringes for intravenous drug users in the largest pre-trial prison in Switzerland Hans Wolff*, Javier Barro, Alejandra Casillas, Thierry Favrod-Coune, Anne FranГ§ois, Jean-Pierre Rieder, Mariem Baroudi, Laurent GГ©taz, Barbara Broers Geneva University Hospitals (GenГЁve, CH) Background: Needle and Syringe Exchange Programs (NSP) are efficient to prevent infectious diseases in prison settings, but less than 1% of prisons worldwide have NSP. One identified barrier is organizational concern for needle stick injuries and use of soiled syringes as weapons among inmates. We evaluated 1) incarcerated drug usersвЂ™ experiences with retractable syringes in an NSP, and 2) beliefs and knowledge about NSP among prison officers (PO) and healthcare staff (HS) in prison. Method: In 2010, we replaced usual (insulin-type) syringes with retractable needle devices as part of the NSP in the prison of Champ-Dollon, Geneva; Switzerland. We examined the demographics, clinical profiles for and NSP use among NSP participants, and asked about the ease and safety of the retractable needle device use, in face-to-face interviews. We distributed 98 questionnaires to prison officers and to healthcare staff (HS), surveying individuals on their knowledge and opinions regarding drug use and harm reduction measures. Results: 284 retractable syringes were distributed to 28 inmates, with a return rate of 70%. Twenty-six of them accepted to participate in the study. Thirteen were selected for interview and 10 interviews were completed. Most participants were male (96.4%); mean age was 32 years (SD 4.8). They had a median of 2 previous incarcerations (range 1-45) with a median duration of 70.7 days (range 5-690). Median duration of IV drug use was 54 months (0-324). Seropravelence of HIV was 3%, HBV 7.1% and HCV 60.7%. The majority of participants expressed that retractable syringes were acceptable alternatives, but complained about difficulties due to the weight of the syringe and needle quality, as well as the difficulty to install and use the syringe filter. Of the 98 questionnaires distributed to PO and HS, 70% of PO and 100% of the HS estimated harm reduction policies as an effective means to reduce the risk of transmission of blood-borne infections. However, 90.3% of PO and 9.6 % of HS were still concerned about the use of syringes as weapons. Conclusion: This is the first study evaluating experiences with retractable syringes for NSP in a correctional setting. NSP was perceived as an acceptable alternative for incarcerated IV drug users. Acceptance may be increased by improving the quality and ease of use of the retractable device as suggested by prisoners. Addressing PO and HS safety concerns are an important step towards more disseminated NSP implementation. 80 Postesession 1 - Session des posters 1 Allgemeine Innere medizin 3 - MГ©decine interne gГ©nГ©rale 3 P319 Comparing perceived cross-cultural skillfulness between physicians and nurses at Lausanne University Hospital: does provider role make a difference? Alejandra Casillas*, Sophie Paroz, Alexander Green, Hans Wolff, Patrick Bodenmann Policlinique Medicale Universitaire, CHUV (Lausanne, CH); Policlinique Medical Universitaire, CHUV (Lausanne, CH); Harvard Medical School (Boston, US); Hopitaux Universitaires de Geneve (GenГЁve, CH) Background: As the diversity of the local population evolves, measuring providers' cultural competency and understanding what contextual factors may influence this skillfulness is necessary. Given a lack of information on provider role, this question is increasingly important, as Swiss nurse practitioners begin to assume clinical responsibilities for vulnerable patients. We compared perceived skillfulness and explanatory predictors between physicians and nurses working at a university hospital. Methods: A 64-item questionnaire on cross-cultural care, including translated/back-translated items from a validated American survey was mailed in November 2010 to residents, chief residents and nurses. Using Student's t-tests, we compared physicians' and nurses' mean composite scores for the nine perceived skillfulness items (4-point Likert-scale), and proportion of "3-good/4-very good" responses using Chi-square tests. We used linear regression to examine how provider role (physician vs. nurse) was associated with composite scores, adjusting for demographics (gender, non-French dominant language), workplace (time at institution, work-unit "sensitized" to cultural-care), items on reported cultural-competence training, and on cross-cultural care problem-awareness. We present results significant at the p=0.05 level. Results: Of 885 questionnaires, 371 (41.2%) returned the survey: 123 (33.6%) physicians and 239 (66.4%) nurses, reflecting institutional distribution of providers. Physicians had better mean composite scores for perceived skillfulness than nurses (2.7 vs. 2.5, p=.0005), and significantly higher proportion of "good/very good" responses for 4/9 items. After adjusting for explanatory variables, physicians remained more likely to have higher skillfulness (beta = 0.13, p=.049). Among all, higher skillfulness was associated with perception/awareness of problems in the following areas: inadequate crosscultural training (beta = 0.14, p=.012) and lack of practical experience caring for diverse populations (beta = 0.11, p=.040). Conclusions: Overall, perceived cross-cultural skillfulness among providers was low. Physicians had higher skillfulness than nurses. However, problem-awareness about cross-cultural care was positively associated with skillfulness among both groups. Thus, attuning providers' awareness to the surrounding problems in cross-cultural patient-care, can improve skillfulness- especially among nurses with rising responsibilities. P320 Predictors of cross-cultural care preparedness among physicians and nurses in Lausanne, Switzerland Alejandra Casillas*, Sophie Paroz, Alexander Green, Hans Wolff, Patrick Bodenmann Policlinique MГ©dicale Universitaire, CHUV (Lausanne, CH); Harvard Medical School (Boston, US); Hopitaux Universitaires de GenГЁve (GenГЁve, CH) Background: The changing influx of migrant and at-risk patients into the safety net represents a challenge for health providers. We evaluated health provider cross-cultural preparedness for commonly encountered vulnerable patient profiles. Methods: A 64-item questionnaire on cross-cultural care, including translated/back-translated items from a validated American survey was mailed in November 2010 to residents, chief residents and nurses. Preparedness items asked "How prepared do you feel to care forвЂ¦?" referring to patientprofiles, such as "patients with distrust of the health care system" on an ascending 5-point Likert scale. We examined proportions of "4-well/5-very well prepared," and the mean composite score for the eight items. We used simple and multivariate linear regression to examine the effect of the following variables on the composite: demographics (gender, non-French dominant language), work context (provider role, institution time, unit "sensitized" to cultural-care), and items on reported culturalcompetence training, and cross-cultural care problem-awareness. We present results significant at the p=0.05 level. 81 Results: Of 885 questionnaires, 371 (41.2%) returned the survey: 123 (33.6%) physicians and 239 (66.4%) nurses, reflecting the distribution of providers. The mean composite score was 3.30 (SD 0.70) with the highest proportion of "well/very well-prepared" responses for the item referring to patients with "cultures different from your own" (67.2%) and the lowest for "whose religious beliefs affect treatment" (21.9%). After multivariate adjustment, having a non-French dominant language (beta = 0.25, p=.012), nurse provider role (beta = 0.221, p=.03), working in a sensitized department (beta;= 0.21, p=.007), and having received training on the history/culture of a specific group (beta = 0.25, p=.03) remained significantly associated with higher preparedness; as was problem-awareness about the lack of practical experience caring for diverse populations (beta = 0.25, p=.004) and about inadequate crosscultural training (beta = 0.18, p=.04). Conclusions: Preparedness among providers leaves room for improvement. However, we found specific factors that can be incorporated into organizational strategies aimed at cross-cultural preparedness. The findings emphasize the institution's role in creating a diverse and culturallysensitive work environment towards increasing health provider preparedness-- thus improving crosscultural care. P321 Critical assessment of anticoagulant and antiplatelet agent prescription pattern in the polymorbid rehabilitation population after stroke and hip or knee surgery (CASAC Study) Helen Schmidt*, Helen Schmidt, Felix Angst, Andreas Gantenbein, Susanne Lehmann, Andre Aeschlimann, Hans JГјrg Beer RehaClinic Zurzach (Zurzach, CH); KSB (Baden, CH) Background: The prescription pattern of anticoagulant (AC) and antiplatelet therapy (APT) is changing rapidly with the advent of new oral anticoagulants (NOACs) and new antiplatelet agents (NAPAs). Dual or triple anticoagulation therapy (ACT) carries a high bleeding risk and its indication and duration requires careful assessment. Aim of the study: To critically appraise the indication and duration of AC and APT in the vulnerable population of a rehabilitation clinic after stroke and major orthopaedic surgery. Methods: 118 consecutive patients on NOACs, low molecular weight heparin (LMWH), Vitamin K antagonists (VKA) and/or APT were evaluated from March to October 2012 in this retrospective cohort study. Inclusion criterion was hospitalization after knee or hip surgery or stroke with the indication for AC. Demographics, diagnoses esp. renal function, atrial fibrillation (AF), co-medication, HAS-BLEDand CHA2DS2-VASc scores were obtained. Indications were critically reviewed according to the ACCP-guidelines (American College of Chest Physicians 2012) by a group of independent experts not involved in the treatment of the patients. Results: Mean age was 82 (В±4.5) years, 63% were female. Diagnostic categories were stroke in 22%, hip replacement in 48% and knee replacement in 30%. Creatinine Clearance <50ml/min occurred in 30% of the cases. The table shows the distribution of the use of AC, heparin and APT alone and in combination. Combinations of APT and VKA/NOAC or LMWH were found in 38% (45/118), 62% of these patients on this dual therapy (28/45) received PPIs. A HAS-BLED score of >=3 was found in 80% (94/118) from whom 49% (46/94) were on dual anticoagulation therapy. Conclusions: Our study shows that a) NOACs are prescribed at a high frequency and b) in more than one third as dual ACT in the daily practice of a frail rehabilitation patient population with a large number of comorbidities including renal failure. c) A prophylactic treatment with PPIs is lacking in a substantial proportion on dual ACT. To reduce the high bleeding risk, it is necessary to critically assess indication and duration of dual ACT. 82 P322 Traditional medicine travels too: a rare cause of lead poisoning Halima MГњLLER*, Simon Regard, Nicole Petriccioli, Omar Kherad La Tour Hospital (GenГЁve, CH) Introduction: Lead poisoning is a multisystemic organ disease which can present with non-specific symptoms such as fatigue, anorexia, arthralgia, myalgia, neurological disorders, anemia abdominal pain and encephalopathy. The diagnosis may represent a pitfall and is based on clinician consideration to order appropriate blood lead level and erythrocitic protoporphyrins. Methods: We report the case of a 42-year old man from Bhutan, who was admitted to the emergency departement of La Tour Hospital, with a 5-day history of abdominal pain, nausea and vomiting. Examination revealed pain on palpation of the right upper abdominal quadrant with no sign of peritonism. The patient resides in Geneva and frequently travels to his home country. Results: Blood tests revealed a cholestatic liver abnormality and a hemolytic anemia with hemoglobin level at 90 g/l. An abdominal ultrasound and a thoraco-abdominal CT scan proved normal. Serologies for HIV, CMV, EBV and hepatitis A,B,C were negative. A blood smear was performed and showed basophilic stippling highly evocative of a heavy metal poisoning. Blood and urinary lead levels were high at 80.8 mcg/dl and 208.8 mcg/g of creatinine respectively. An increase in urinary coproporphyrin III level up to 155.9 nmol/mmol was also noted. It was discovered that the origin of the intoxication was due to the patient taking Bhutanese traditional medicines to treat a resolutive BellвЂ™s palsy a few months earlier. These medicines were made of paper with ink writings, hair of a deceased local priest and an additional unidentified substance (cf figure 1). The analysis showed the presence of high level of lead. Conclusion: Lead exposure and poisoning is still a major health issue in developing countries. It has been estimated as responsible of 8вЂ™955вЂ™000 disability-adjusted life years (DALY) in 2004. Complementary and alternative medicines (CAM) have become more frequent causes of lead poisoning in the past few decades even in Western countries as they become more popular and easily available on Internet. Enhancing public awareness about potential harmful effect of CAM is a major objective of health care prevention. Meanwhile, it remains the responsibility of physician to obtain a detailed history of medications use, even in developed countries where lead exposure and poisoning are also reported. 83 P323 Quality of life after pulmonary embolism: validation of the French version of the PEmb-QoL questionnaire Mathilde Rochat*, Marie MГ©an, Olivier Hugli, Andreas Limacher, Drahomir Aujesky CHUV (Lausanne, CH); Inselspital (Berne, CH) Introduction: The PEmb-QoL is a validated 38-item questionnaire to quantify health-related quality of life in patients having experienced pulmonary embolism (PE). It includes 6 health dimensions: frequency of complaints, activities of daily living limitations, work-related problems, social limitations, intensity of complaints, and emotional complaints. Originally developed in English, we sought to prospectively validate the psychometric properties of a French version of the PEmb-QoL. Methods: We performed a forward and backward translation of the English version of PEmb-QoL into French. We screened all consecutive patients aged >18 years with an acute objectively confirmed PE admitted at the emergency department of the Lausanne university hospital from August 1, 2009 to September 30, 2011 using an electronic patient tracking system. We telephonically invited all screened patients who survived the PE episode for study participation. Patients who refused to participate or who had insufficient spoken language ability in French were excluded. Enrolled patients received per mail a baseline PEmb-QoL and SF-36 questionnaire. Patients were asked to complete and return both questionnaires using a stamped return envelope. In order to assess the reproducibility of the PEmb-QoL, participants were mailed a second PEmb-QoL and SF-36 questionnaire 10 days after the baseline evaluation. We assessed internal consistency, test-retest reliability, convergent validity, and construct validity of the French PEmb-QoL. Results: Of 242 patients screened, 102 (42.1%) fulfilled all eligibility criteria and were enrolled in the study. Internal consistency (CronbachвЂ™s alpha 0.7-0.95) and test- retest reliability (intra-class correlation coefficients 0.85-0.96) were adequate. Assessment of correlations between the dimensions of the PEmb-QoL questionnaire and other clinical measures (age, gender, obesity, cancer, central PE, history of PE, cardiovascular comorbidities) supported the construct validity of the questionnaire. 84 Correlations between the dimensions of the PEmb-QoL- and SF-36 questionnaires also supported convergent validity. Conclusion: We successfully validated the French version of the PEmb-QoL questionnaire in patients with PE. Our results show that the PEmb-QoL is a valuable tool for assessing health-related quality of life after PE in French speaking patients. P324 Impact of diuretic therapy-associated electrolyte disorders present on admission to the emergency department: a cross-sectional analysis Spyridon Arampatzis, Georg Funk, Alexander Leichtle, Georg Fiedler, Christoph Schwarz, Heinz Zimmermann, Aristomenis Exadaktylos, Gregor Lindner* Inselspital (Bern, CH); Otto Wagner Spital (Wien, AT); Medizinische UniversitГ¤t Graz (Graz, AT) Background: Diuretics are among the most commonly prescribed medications and, due to their mechanisms of action, electrolyte disorders are common side effects of their use. We investigated the associations between diuretics being taken and the prevalence of electrolyte disorders on admission as well as the impact of electrolyte disorders on patient outcome. Methods: In this cross sectional analysis, all patients presenting between 1 January 2010 and 31 December 2011 to the Emergency Department of the Inselspital, University Hospital Bern, Switzerland were included. Data on diuretic medication, baseline characteristics and laboratory data including electrolytes and renal function parameters were obtained from all patients. A multivariable logistic regression model was performed to assess the impact of factors on electrolyte disorders and patient outcome. Results: 8.5% of patients presenting to the ER used one diuretic, 2.5% two, and 0.4% three or four. 4% had hyponatraemia on admission and 12% hypernatraemia. Hypokalaemia was present in 11% and hyperkalaemia in 4%. All forms of dysnatraemia and dyskalaemia were more common in patients taking diuretics. Loop diuretics were an independent risk factor for hypernatraemia and hypokalaemia, while thiazide diuretics were associated with the presence of hyponatraemia and hypokalaemia. In the Cox regression model, all forms of dysnatraemia and dyskalaemia were independent risk factors for in hospital mortality. Conclusions: Existing diuretic treatment on admission to the ER was associated with an increased prevalence of electrolyte disorders. Diuretic therapy itself and disorders of serum sodium and potassium were risk factors for an adverse outcome. 85 P325 Etiology and symptoms of severe hypokalaemia in emergency department patients Grischa Marti, Christoph Schwarz, Alexander Leichtle, Georg Leichtle, Spyridon Arampatzis, Aristomenis Exadaktylos, Gregor Lindner* Inselspital (Bern, CH); Medizinische UniversitГ¤t Graz (Graz, AT) Purpose: To investigate the prevalence, etiology and symptoms of severe hypokalemia in patients presenting to the ED. Materials & Methods: In this retrospective, cross-sectional analysis we included all patients who received measurement of serum potassium between April 2008 and 31 March 2011 at the ED in order to calculate the prevalence rate for hypokalemia. Of all patients with a serum potassium below 2.6 mmol/L (severe hypokalemia) we performed a detailed review of the patients' charts from the ED and the chart of the following hospitalization. We identified ECG changes attributable to hypokalemia from the ECGs performed in the ED. Main findings: During the study period a total of 43.805 measurements of serum potassium were performed. 11% of patients had hypokalemia (potassium <= 3.5 mmol/L) at presentation. 53 patients with severe hypokalemia could be identified. 49% were symptomatic with weakness and muscle pain being the most common symptoms. 69% of patients had ECG changes with presence of a U wave followed by ST segment depression and ventricular extrasystoles. Malnutrition and use of diuretics were the main causes of severe hypokalemia. Conclusions: Hypokalemia is common in the ED. Severe hypokalemia is often symptomatic and more than two-third of patients have ECG changes. 86 87 P326 Hyperkalaemia in the emergency department: etiology, symptoms and outcome of a life-threatening electrolyte disorder Carmen PfortmГјller*, Christoph Schwarz, Alexander Leichtle, Georg Fiedler, Spyridon Arampatzis, Aristomenis Exadaktylos, Gregor Lindner Inselspital (Bern, CH); Medizinische UniversitГ¤t Graz (Graz, AT) Aims: To determine the prevalence, symptoms, etiology and outcome of severe hyperkalemia in the ED of a large university hospital. Methods: In this retrospective analysis patients admitted to our ED between 01 January 2009 and 31 December 2010 with measurement of serum potassium were included. Dyskalemias and dysnatremias were defined according to the reference range of our laboratory (normal range, potassium 3.5-4.5 mmol/L; sodium 135-145 mmol/L). Of all patients with severe hyperkalemia, (>= 6.0 mmol/L) patient charts were reviewed for information on the symptoms and etiology of hyperkalemia. Results: Of a total of 29.250 potassium measurements, 2.585 patients (8.8%) had hyperkalemia, and 3.252 (11%) had hypokalemia. 88 patients (3.4% and 0.3% of all patients) had severe hyperkalemia. Age of patients was 65 years (SD 17) with 20 patients (23%) being female and 68 male (77%). Potassium was 6.4 mmol/L (6.1-6.8) with a maximum of 10.9 mmol/L and creatinine was 192 umol/L (124-360). 36 patients (41%) had concurrent hyponatremia and 1 patient (1%) hypernatremia. Hyponatremia was significantly more common in patients with severe hyperkalemia than in normokalemic patients (36 vs. 9%, p<0.0001). In the venous blood gas analysis pH was 7.25 (7.037.34), pCO2 38 mmHg (28-46), bicarbonate 15.8 mmol/L (9.7-19.7) and lactate 2.0 mmol/L (1.4-7.2). 30 patients (34%) had metabolic acidemia, 5 (6%) respiratory acidosis and 1 patient had respiratory alkalosis, combined metabolic and respiratory acidosis or metabolic acidosis acidosis and respiratory alkalosis, respectively. 26 patients (30%) had symptoms attributable to hyperkalemia. 17 patients (65% of symptomatic and 19% of all) presented with arrhythmias as objectivated by ECG. General muscular weakness was present in 9 patients (34%/10%). 28 patients (64%) had ECG changes attributable to hyperkalemia. Renal insufficiency (40%), end-stage renal disease (23%), CPR (11%) and metabolic acidosis (6%) were the leading causes of severe hyperkalemia. Conclusion: Disorders of serum potassium are common in the ED with 1 in 5 patients presenting with it. Renal failure and cardiopulmonary resuscitation were the most common causes of hyperkalemia in our patients. 88 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 4 - MГ©decine interne gГ©nГ©rale 4 P327 Communication by official statements of Swiss Health organisations during debate of the federal smoking ban 2008-2012 Rainer Kaelin* Initiativkomitee Schutz vor Pasivrauchen Background: The Swiss legislative process towards a national smoking ban in public places started in 2004 by the signature of the WHO framework convention on Tobacco control and the initiative of MP F. Gutzwiller MD. By 10/2008 it had resulted in a federal Alibi вЂњGastro-boro- LawвЂќ, elaborated under heavy pressure by lobbying, failing to meet WHO standards. Therefore the Swiss Lung League (SLL; federation of cantonal lung leagues) launched a popular initiative aiming better legislation. The initiative was backed by a large alliance of health organizations. Despite 120 000 signatures collected by 2010, the law project was refused by national vote 9/2012, after heavy campaigning. Aim/Method: Since media reporting on the subject was poor (only 10 % of articles on smoking bans between 11/2009-02/2010 were in favour), the present work analyses official statements of health organizations in order to detect communication flaws, that may have contributed to insufficient information of media and public. Results: A. The federation of Swiss physicians (FMH) first declined the initiative (letter 03/09), arguing that backing of the prevention law debated in parliament was more important, but finally endorsed it (01/10) after a vote of their delegates. B. The internists societyвЂ™s president declined official public positioning on passive smoke protection at the 2008 congress arguing that the congress wasnвЂ™t smoke free and sponsors should be consulted first. The members assembly though endorsed the initiative 2010, but nevertheless no official public statement was issued. C: The SLL urged cantonal lung leagues to collect signatures, but some did not (ZH, VD). The president of the Vaud League disapproved the launch of the initiative (letter to SLL 12/08), but finally backed it by vote of the committee 2010. D. The national tobacco-fighting organization AT, member of the initiativeвЂ™s alliance, proposed its withdrawal 6 month before the popular vote, based on a committee decision. Conclusion: The refusal of the initiativeвЂ™s law proposal for a federal smoking ban cannot be attributed only to the influence of the tobacco lobby on media. Lack of coherent communication strategy of health organizations contributed to disinformation of the public P328 Progressive sporotrichoid and disseminated fish tank granuloma by Mycobacterium marinum in an HIV-infected patient Florian Kuss*, Jan Amort, Julia Sproedt, Urs Karrer, Jacques Gubler Kantonsspital Winterthur (Winterthur, CH) Case: In May 2012, a 45-year-old patient presented to our surgery department with a purulent ulcer under the right thumb nail and multiple satellite lesions along the extensor muscles. Prompt secondary healing was noted after surgical debridement of the lesions without the need for systemic antimicrobial therapy. Surprisingly, microbiology was only positive for Candida ssp. Two months later, progressive phlegmonous infection of the thumb involving the metacarpo-phalangeal joint had occurred. Moreover, distant abscesses had formed at the left arm and leg. Meanwhile, the patientsвЂ™ GP had diagnosed advanced HIV-infection with Candida esophagitis and wasting syndrome and had initiated antiretroviral therapy (ART) with Efavirenz, Emtricitabin and Tenofovir (AtriplaВ®) in June 2012. Considering the profound immunodeficiency of this fish tank owner, we suspected disseminated nontuberculous mycobacterial infection. Indeed, examination of material from several distant abscesses revealed acid fast bacilli in high density, later identified as Mycobacterium marinum. We introduced antimycobacterial therapy with Ethambutol, Rifampicin and Azithromycin and added adjunctive Prednisolone due to clinical evidence for immune reconstitution inflammatory syndrome (IRIS) involving several joints. Dosing of the antiretroviral therapy was adapted to the pharmacokinetic interaction with Rifampicin. While the patient swiftly recovered concerning his general condition, weight and immune status, the course of wound healing was protracted over months. In December 2012, Rifampicin and Prednisolone were stopped and Ethambutol and Azithromycine will be continued at least until February 2013. Discussion: This patient is a typical example of a вЂ�late-presenterвЂ™ negating his substantial risk of HIVinfection and obvious signs of deteriorating health. A HIV-Test was ordered only after endoscopy, 89 performed for evaluation of dysphagia and massive weight loss of ~15kg, had demonstrated Candida esophagitis. Insufficient communication between different health care providers further delayed appropriate management by 2-3 months leading to progressive sporotrichoid and disseminated M. marinum infection including IRIS. Concomittant antimycobacterial and antiretroviral therapy must take into consideration the potentially serious pharmacologic interactions. P329 Natriuretic peptides for early prediction of acute kidney injury in communityacquired pneumonia Albina Nowak*, Tobias Breidthardt, Sarah Dejung, Mirjam Christ-Crain, Roland Bingisser, Beatrice Drexler, Christophe Meune, David Marono, Tamina Mosimann, Beat MГјller, Christian MГјller UniversitГ¤tsspital ZГјrich (ZГјrich, CH); UniversitГ¤tsspital Basel (Basel, CH); Kantonsspital Aarau (Aarau, CH) Background: Community-acquired pneumonia (CAP) is common and associated with a considerable risk of acute kidney injury (AKI). Methods. We prospectively enrolled 341 patients presenting to the emergency department with CAP (mean age 72, male 61%). Blinded measurements of three natriuretic peptides (NT-proBNP, MRproANP and BNP) were performed upon presentation. The primary endpoint was the accuracy of the natriuretic peptides to predict AKI within 48 hours. Results. AKI occurred in 24 patients (7.6%) within the first 48 hours. NPs and creatinine were significantly higher in AKI compared with patients without AKI (NT-proBNP 9517 [2042-26792] vs 1177 [280-4167] pg/ml; MR-proANP 641 [196-1075] vs 182 [99-352] pmol/l; BNP 592 [230-1630] vs 160 [64-463] pg/ml; creatinine 166 [131-289] versus 100 [78-134] Вµmol/L, P<0.001 for each). Predictive accuracy as quantified by the area under the receiver operating characteristics curve was moderate to high: NT-proBNP 0.79 (95%CI 0.70-0.88), MR-proANP 0.78 (95%CI 0.67-0.88), BNP 0.74 (95%CI 0.63-0.85), creatinine 0.77 (95%CI 0.66-0.88). In multivariate logistic regression analysis, NPs remained the only independent AKI predictors: NT-proBNP (increase of 200 pg/ml) OR=1.01, 95%CI 1.00-1.01, P=0.009; MR-proANP (increase of 100 pg/ml) OR=1.23, 95%CI 1.09-1.39, P=0.001; BNP (increase of 100 pg/ml) OR=1.08, 95%CI 1.03-1.14, P=0.002. Conclusions. NP levels are significantly elevated in CAP-patients experiencing early AKI. Their potential to predict early AKI is comparable to serum creatinine and might be useful in cases of diagnostic uncertainty. 90 P330 Postgraduate competency-based (CB) curriculum in internal medicine (IM): pilot study of cliniciansвЂ™ definitions and perceptions of CanMEDS roles and physiciansвЂ™ competencies Matteo Monti*, Raphael Bonvin, Nu Viet Vu CHUV (Lausanne, CH); School of medicine and UDREM (GenГЁve, CH) CB education in the health profession has emerged as a priority for curriculum planners to align with societal needs. Switzerland has introduced for the pre- and postgraduate training a new curriculum largely inspired from the Canadian вЂњCanMEDS frameworkвЂќ. Since controversy exists regarding transferability of general competencies in different social and political settings, we undertook to determine, in the Swiss French IM in-patient hospital setting, 1) how front-line clinicians define competencies expected of residents at the end of their postgraduate training , 2) how they perceive the different roles defined in the CanMEDS. Methods: We conducted a mixed qualitative and quantitative study, among a purposive sample of faculty, chief residents, and residents at two large urban IM departments in Switzerland. 33 physicians (8 faculty, 10 chief residents and 15 residents) volunteered to participate in six semi-structured focus groups. The groups were guided by a protocol which included unstructured time for comments, a guided discussion and time to complete a questionnaire. All the activities were carried out to gather insights regarding the participantsвЂ™ definition of competence and views of the five different taxonomic levels of the Canadian framework. Focus groups discussions were tape-recorded and transcribed. Verbatim transcriptions were coded by two independent researchers and classifications are based on the consensus between the two researchers. We used for the analysis a вЂњGrounded theoryвЂќ approach. Descriptive statistics were used to analyse the questionnaires. FisherвЂ™s exact test was used to compare responses from the three categories of participants. Results: In all 6 focus groups, participantsвЂ™ definition of competence included statements amenable to all seven CanMEDS roles. Nevertheless the вЂњMedical Expert, Communicator, Collaborator, Professional and ScholarвЂќ roles were seen as most relevant to an in-patient IM rotation. Conversely the вЂњManagerвЂќ and вЂњHealth AdvocateвЂќ roles were judged as least relevant. Those findings were consistent with both the qualitative and quantitative analyses, independently from the physician status. Conclusions: Implementation in the Swiss context of a CB curriculum based on the seven CanMEDS roles is feasible and appropriate. Nevertheless adjustments are needed in the description of some 91 roles and competencies in order to make them acceptable and understandable for both the trainees and the clinical supervisors P331 Electrocardiographic manifestations in moderate to severe hyperkalaemia NoГ©mie Rapin*, Katia Iglesias-Rutishauser, Etienne Pruvot, Gerard Waeber, Matteo Monti FacultГ© de biologie et mГ©decine (Lausanne, CH); Centre de Recherche clinique, DГ©partement de formation et Recherche, FBM (Lausanne, CH); CHUV (Lausanne, CH) Hyperkalaemia is a serious electrolyte disturbance, which in extreme cases can lead to death. Classical ECG changes are: QT-shortening, tenting of T-waves, lengthening of the PR interval, onset conduction disturbances (BB- or AV- block), disappearance of P wave, QRS widening and finally asystole. While studies on healthy volunteers conducted in the '40s had suggested a good correlation between the level of potassium and ECG changes, more recently, several studies have found that in mild hyperkalaemia (< 7mmol/l) potassium levels did not correlate with the severity of ECG changes. The aim of our study was to determine which factors are associated to the development of ECG modifications in patients with moderate to severe hyperkalaemia. Secondary outcome was the estimation of mortality. Methods: We undertook a retrospective analysis of all cases of moderate to severe hyperkalaemia (K=>7,0mmol/l) in adults, hospitalised at our institution between 2009 and 2010. Patients were included if an ECG was available at the same time of the hyperkalaemic episode. ECG analysis were performed by two investigators, according to heart rate, QRS and QTc duration, T and RS amplitude and the presence of a conduction disturbance (brunch bundle- or AV-block and arrhythmia). Univariate and multivariate analysis were performed to look for associations between ECG characteristics, chemistry (K, Na, Ca, pH, HCO3, pO2, SatO2), co-morbidities and demographics. Results: Of the 913 patients screened, 82 were eligible for analysis. Mean age was 69y, 20,7% had ESRD, 23,1% an acute renal injury and 33,7% CKD. Mean K 7,46mmol/l (7,0 to 9,0). Mean pH 7,23 (6,71-7,46). No correlation was found between K levels and ECG changes or mortality. Conversely, the severity of acidosis was the only element capable of predicting the development of вЂњtypicalвЂќ ECG changes as well as the probability of cardiac arrest (CA) or death. CA/mortality rate was 30,5% during the hospitalisation, but only 8,5% could be directly attributable to hyperkalaemia. Conclusions: ECG is not a reliable tool for estimating the degree of hyperkalaemia or to select patients at risk of complications or death. In hyperkalaemic patients however the severity of metabolic acidosis is clearly associated with an increase in the QRS duration, the development of conduction disturbances and also with an increased mortality. People with a pH <7.2 concomitant to severe hyperkalaemia has to be considered particularly at risk. 92 P332 Complete hydatid mole in a perimenopausal women with a subsequent thyroid storm Maya Rutishauser*, Tobias Gonzenbach Spital BГјlach (BГјlach, CH); Spital Buelach (BГјlach, CH) Introduction: GTD are a rare complication of a normal pregnancy and occur often at the beginning or the end of the reproductive period. Most have an excellent prognosis, occasionally if the disease persists chemotherapy is required. A rare complication of gestational trophoblastic disease (GTD) is the development of a secondary hyperthyroidism, often disappearing after curettage. The underlying cause are structural and receptor analogies between humanic chorionic gonadotropin (HCG) and thyreotropic hormone (TSH). High HCG values as observed in GTD can induce a secondary hyperthyroidism. Case report: A 51-year-old perimenopausal patient (IV Gravida, III Para) presented to the emergency department with vomiting, nausea, diarrhea and vaginal bleeding for 2 months. Clinical examination showed a palpable mass in the abdomen. A CT scan demonstrated a 14x13x12cm non-invasive tumor of the uterus without abdominothoracic metastasis. Following a positive pregnancy test in the urine bHCG in the blood was analyzed, with a highly elevated value of 1618600 IU/L, leading to the assumption of a gestational trophoblastic disease. Further laboratory studies revealed a distinct hyperthyroidism (TSH < 0.008mU/L, fT4 87.7pmol/L, fT3 28.2pmol/L). During the hospital stay the patient developed a congestive heart failure (multifocal atrial tachycardia, dilated jugular veins, bilateral pretibial edema, pulmonary congestion), interpreted as a clinical manifestation of hyperthyroidism. Treatment with diuretics and ACE-Inhibitor, as well as Neomercazol and Propanolol was started, under which the clinical condition stabilized. The patient underwent a suction curettage. In the macroscopical, histological and immunhistochemical findings a complete hydatid mole was confirmed. During the follow-up with serological controls every 2 week initially a decrease of the HCG values was observed, followed by a sudden increase after 6 weeks. Abdominothoracic CT scan was repeated and multiple pulmonary nodules restrained to the left lung, consistent with metastatic disease were found. Chemotherapy with Methotrexat was started. Conclusion: The coincidence of a gestational trophoblastic disease and hyperthyroidism, sometimes devolving into a lifethreatening thyroid storm has been described in several papers; frequency varies between 7-10%. An early measurement of thyroid function, particularly before operations or CT scans with iodinated contrast is highly important. 93 P333 A legion appears sometimes not alone Isabel Morales*, Markus Eichelberger Inselspital Bern (Bern, CH) Case A 25-year-old otherwise healthy man was hospitalized due to dyspnea, cough, fever and gastrointestinal symptoms. Clinical examination revealed a tachypneic patient with fever. Radiography 94 showed infiltrates in the middle and right lower lobe. Urinary antigen test was positive for L. pneumophila. Under treatment with Levofloxacin the patient was discharged. 3 days later he was again admitted with sudden onset of right-sided chest pain, hemoptysis and painful swelling of the right leg. A chest CT scan showed multiple segmental bilateral pulmonary embolism. A totally thrombosed proximal Vena femoralis of the right leg was detected by ultrasound. Localized lysis was abandoned because of hemoptysis with risk of fatal bleeding. In absence of previous VTE and negative family history for VTE tumour screening was performed which was negative. Anticoagulation was started and antibiotic treatment with Levofloxacin was continued. In presence of extensive VTE screening for inherited thrombophilia was done and the result showed a heterozygous Factor V mutation. Discussion L. pneumophila is an aerobic gram-negative bacteria and causes LegionnairesвЂ™ disease as a syndrome of community-acquired pneumonia and gastrointestinal symptoms. The incidence depends upon the degree of water reservoir contamination, the intensity of exposure to that water, and the susceptibility of the host. Different serogroups exist and most of the cases belong to the L. pneumophila serogroup 1. Urinary antigen testing for L. pneumophila serogroup 1 is the diagnostic method of choice due to the fast availability of the result and the persistence of positive results after administration of the antibiotic therapy. Effective antibiotics are quinolones and macrolides. VTE may occur because of activation of tissue factor, a glycoprotein of the subendothelial component of the vessel wall. Tissue factor is activated because it comes into contact with blood during septicaemia; therefore the coagulation cascade is activated. Because of extensive manifestation of VTE despite of initial low-risk, screening for inherited thrombophilia was done and revealed heterozygous Factor V mutation. Retrospectively important risk factors of VTE was immobilization, heterozygous Factor V mutation and probably L. pneumophila itself. The length of anticoagulation was defined for 3 months; prophylactic anticoagulation is commonly recommended in potential high-risk situations. 95 P334 Attitudes towards morphine use among Swiss nurses and physicians Maria Ferreira, Henk Verloo, Margarida Vieira, Pedro Marques-Vidal* Hopital de Sion (Sion, CH); University of Applied Sciences, Nursing, La Source (Lausanne, CH); Universidade CatГіlica (Lissabon, PT); IUMSP (Lausanne, CH) Background: There is little information regarding risk perception and attitudes on morphine use in Switzerland. Objectives: We aimed at assessing such attitudes in a sample of health professionals in the Frenchspeaking part of Switzerland. Study design: Cross-sectional study. Setting: five non-university hospitals of the French-speaking canton of Valais, Switzerland. Methods: 431 nurses and 40 physicians (age range: 20-63). Risk perception and attitudes towards morphine use were assessed using a validated questionnaire. Results: Over half of participants showed a negative attitude regarding most adverse events related to morphine, while less than one third showed a similar attitude regarding other statements. On bivariate analyses, participants working in geriatrics showed a more negative attitude towards use of morphine than participants working in medicine and surgery. Non-Swiss participants also showed a more negative attitude than Swiss regarding use of morphine. Conversely, no differences were found between genders, profession (nurses or physicians), years of experience (<=14 and >14) and religion (catholic vs. others/no religion). These findings were further confirmed by multivariate adjustment. Limitations: possible selection bias due to responders only. Results limited to French speaking participants. Conclusion: Attitudes regarding morphine uses are mainly driven by its potential adverse effects and vary according to specialty and nationality. Educational measures directed at health professionals working in geriatrics or coming from abroad might reduce the high morphinophobia levels observed in these groups. 96 Postesession 1 - Session des posters 1 Allgemeine Innere Medizin 5 - MГ©decine interne gГ©nГ©rale 5 P335 Contribution of multimorbidity to overall mortality in the population-based CoLaus study Basile Pache*, Peter Vollenweider, Martin Preisig, Pedro Marques-Vidal, GГ©rard Waeber Centre Hospitalier Universitaire Vaudois (Lausanne, CH); The Swiss Institute of social epidemiology (Lausanne, CH) Introduction: Multimorbidity (MM) is currently a major health concern for hospitalized patients but little is known about the relative importance of MM in the general population. Accordingly we assessed whether MM could be a good predictor of overall mortality. Method: Data from the population based CoLaus Study: 3239 participants (1731 women, mean age 50+/-9 years) followed for a median time of 5.4 years (range 0.4 to 8.5 years). MM was defined as presenting >=2 morbidities according to Barnett et al. (27 items, measured data). Survival analysis was conducted using Cox regression. Results: During follow-up, 53 (1.6%) participants died. Participants who died had a higher number of morbidities (2.4 +/- 1.6 vs. 1.9 +/- 1.5, p<0.05) and had a higher prevalence of MM (69.8% vs. 55.9%, p<0.05). On bivariate analysis, presence of MM (defined as a yes/no variable) was significantly related with overall mortality: relative risk (RR) of 1.84, 95% confidence interval [1.02; 3.31], p<0.05 (see figure), but this association became non-significant after adjusting for age, gender and smoking: RR=1.68 [0.93; 3.04], p=0.09. Similar results were obtained when using the number of morbidities: RR for an extra morbidity 1.22 [1.05; 1.44], p<0.02; after adjusting for age, gender and smoking, RR=1.16 [0.99; 1.37], p=0.07. Conclusion: During a short 5 year observation period, measured MM in the general population is associated with overall mortality. This association becomes borderline significant after multivariate adjustment. These observations will have to be confirmed during a longer follow-up period. This increased mortality in MM patients may require developing specific strategies of screening and prevention. Reference: 1. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet. 2012;380(9836):37-43. 97 P336 Severe vitamin D deficiency and fatigue in a patient from Africa Katarzyna Keller*, Albina Nowak UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Case history: A 39 years old otherwise healthy patient, born in Ethiopia, complained about fatigue and weakness for several months. Findings: The clinical examination of this slim patient was uneventful. The laboratory findings revealed a 25-hydroxy vitamin D under the detection level, a severe hypophosphatemia and an elevated parathyroid hormone serum level (Table 1). Diagnosis: Severe vitamin D deficiency with secondary hyperparathyroidism due to lack of sun exposure and dark skin pigmentation. Therapy and results After vitamin D supplementation 15 000 units as drops once per week, the fatigue improved, the patient felt stronger. The clinical improvement correlated with the increase of serum vitamin D and phosphate levels along with decrease of serum parathyroid hormone levels after 4 and 6 weeks of supplementation (Table 1). Discussion: As food contains insufficient amounts of vitamin D, its synthesis in the skin is the most important source. Black people have a reduced synthesis capacity of vitamin D in the skin due to pigmentation. Furthermore, there is an evidence of increased vitamin D degradation in the dark skin. These phenomena function as a protection against vitamin D excess in areas with high sunlight exposure. However, in the northern hemisphere, especially during the winter, this mechanism can be a risk factor for vitamin D deficiency. Conclusion: Dark-skinned persons with insufficient sun exposure are at high risk for vitamin D deficiency. In such situations, the Vitamin D level should be measured, the Vitamin D deficiency should be treated. 98 P337 Prevalence of prediabetes in healthy adults using HbA1c versus fasting plasma glucose: the GAPP study Jonas Blum*, Stefanie Aeschbacher, Tobias Schoen, Katrin Pumpol, Martin Risch, Lorenz Risch, David Conen UniversitГ¤tsspital Basel (Basel, CH); Labormedizinisches Zentrum Dr Risch (Schaan, LI) Introduction: According to current guidelines, both hemoglobin A1c (HbA1c) (5.7-6.4%) and fasting plasma glucose (FPG, 5.6-6.9mmol/l) can be used as a screening tool for prediabetes. However, the correlation between HbA1c and FPG for the diagnosis of prediabetes or diabetes is not well studied, especially among young and healthy adults. Methods: The Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk Factors (GAPP) study is a population based cohort of healthy adults aged 25-41 years in the Principality of Liechtenstein. Main exclusion criteria are a prevalent cardiovascular disease, a prior diagnosis of diabetes mellitus and a body mass index (BMI) >35 kg/m2. FPG and HbA1c were assayed using a Roche Cobas 6000 (F.Hoffmann вЂ“ La Roche, Switzerland) and high-performance liquid chromatography (Bio-Rad D-10), respectively. Prediabetes was defined according to the current guidelines as FPG between 5.6 and 6.9 mmol/l and/or HbA1c between 5.7 and 6.4%. Results: Of 1568 subjects who completed the baseline examination, 839 (53.5%) were women, mean age was 36.4 +- 4.9 years and the mean BMI was 24.7 +- 3.7 kg/m2. Obesity (BMI >=30kg/m2) was present in 156 (9.9%) participants. The correlation coefficient between HbA1c and FPG was 0.25 (p<0.0001). Overall, 476 (30.4%) had prediabetes (36.6% among men, 25.2% among women, p<0.0001). A diagnosis of prediabetes was present in 427 (27.2%) by HbA1c criteria only, 98 (6.3%) by FPG criteria only and 49 (3.1%) by both criteria. This difference in prevalence was greater in women than in men (p<0.0001), as shown in the Table. Conclusion: The prevalence of prediabetes among young and healthy adults is highly dependent on the test used and is significantly higher using HbA1c criterion. This is especially true among women. If confirmed, our findings will have important implications for screening recommendation in the population. 99 P338 Where is the fever ? Erwin GrГјter*, Hans-Ruedi RГ¤z Kantonsspital Baden (Baden, CH) A 45 year old woman with dizziness, headache and a blood pressure of 180/120 mmHg was hospitalized. Her history revealed a known untreated hypertension grad 1 and dysmenorrhea with regular intake of ibuprofen, a non steroidal anti-inflammatory agent (NSAIA). 2006 she had a gastroscopy (because of epigastric pain) without any pathological findings. Clinical examination showed no relevant pathologic findings. There was no specific family history. Surprisingly laboratory evaluation revealed severe renal failure with an eGFR of 25ml/min/1.73m2 according to the CKD-Epi-Formula. Proteinuria was 4g/day, sodium, potassium, calcium, phosphate, cholesterol and triglycerides where in the normal range, albumin was low, 30g/l. ANA, anti-ds-DNA, ANCA, C3,C4, circulating immune complexes and rheumatoid factor, they all were in the normal range. Clinically, edema was completely absent. Ultrasound showed a hyperechogenic kidney parenchyma, with normal length, a smooth kidney surface and no pyelo-urethral dilatation. Only the spleen was slightly enlarged. A kidney biopsy was performed. The unexpected result was an AAamyloidosis of the kidney. The rheumatologic and cardiologic workup showed no pathologic results: an osteoarthritis of the ankles was explained by the history of intensive and competitive ice-skating in her youth. The myocardium was normal and showed no signs of amyloidosis. Gastroscopy was normal, but histology proved presence of AA-amyloid in the submucosal vessels. To find the reason for deposition of AA-amyloid, we once more turned to the personal history of the patient. She originated from Georgia, so we considered the possible presence of Familial Mediterranean Fever (FMF), although fever episodes and signs of inflammation (CRP 7mg/l) were absent. A genetic examination revealed a compound heterozygotia for the MEFV- (= Mediterranean fever) gene. Therefore, in this 45 year old lady without fever, we could confirm the presence of double heterozygous mutation of MEFV with severe chronic kidney disease stage IV A3 because of AAamyloidosis. Conclusions: FMF can cause AA-amyloidosis without fever or inflammation. A genetic testing of FMF should be undertaken in any case of unexplained AA-amyloidosis P339 Psychological adjustment in cancer patients hospitalised in a supportive care unit Christophe Luthy*, Angela Pugliesi, Christine Cedraschi, Elisa Rapiti, Anne-francoise Allaz hГґpitaux universitaires de genГЁve (GenГЁve, CH); registre genevois du cancer (GenГЁve, CH) Aim: Cancer patients develop various cognitive and emotional reactions in their attempts to adjust to disease and illness. An active adjustment may be associated with less distress. We investigated the association between their mental adjustment and the psychological impact of the disease. Methods: 164 consecutive patients hospitalized in a supportive care unit responded to a questionnaire including psychological dimensions investigated by the Hospital Anxiety and Depression Scale 100 (HADS), the Distress Thermometer (DT) a graphic scale rated from 0-10, and the Mental Adjustment to Cancer index (MAC). Socio-demographic and clinical characteristics were also recorded, along with functional aspects (Performance Status), and the Physician Global Clinical Impression (PGCI) a numerical scale rated from 0-10 assessing the estimated survival prognosis at the admission. Results: 67% of the patients were men; mean age was 65 years (SD=14). Median time since diagnosis was 1.8 years (range=0.1-12.5 years). A wide range of cancer diagnoses were represented; 26% had primary local diseases, 41% had local recurrences, and 33% had metastatic diseases. Anxiety and depression rating scores were moderate to high (mean HADS: 10.5В±0.5 and 10В±0.5, respectively; mean DT score: 4.7В±0.2). The results of linear correlation tests showed a statistically strong and inverse association between the dimension referring to fighting spirit in the MAC and anxiety and depression as measured by the HADS (p<0.001), by the DT (p<0.001), and by specific subscales of the MAC (p<0.001). Fighting spirit was also significantly associated with a better evaluation of patientвЂ™s Performance Status (p<0.01) as well as with a better PGCI (p<0.01). Conversely, hopelessness/helplessness was associated with a worse PGI (p<0.05). Conclusions: Cancer patients experienced a high impact of the disease in terms of anxiety and depression. Mental adjustment seemed to play a buffering role as mental adjustment strategies allowing for a sense of control was related to a better psychological well-being. Patients endorsing such strategies also elicited better clinical prognostic evaluations in the physicians. P340 Sweet syndrome: an association with acute calcific tendinitis? Matthias Zellweger*, Sergio Compagnoni, Raphael Jeker Kantonsspital GraubГјnden (Chur, CH) Case report: A 69-year-old woman was presented with a history of neck stiffness and neck pain, weakness of the arms since the day before. Furthermore she had pain and swelling in the left wrist. No headaches, no pain when chewing, no fever. There was no history of trauma, upper respiratory infection, or dental problems. The flexion of the neck was restricted, and the posterolateral portion of the neck was tender at palpation. The examination of the oro- and nasopharynx was normal and the neurological status was also normal. In 2008, there was reported a non-traumatic desinsertion of the hip abductors. Laboratoy findings showed a highly increased c-reactive protein (386 mg/l). Erythrocyte sedimentation rate was 56 mm/h. Determination of anti nuclear-antibodies were slightly elevated (1:160), the anti citrullin and anti neutrophil antibodies were not elevated. The radiography of the hand releaved signs of a crystal arthropathy. A cervical and thoracic magnetic reonance tomography showed markedly increased signal intensity corresponding to an inflammation of the soft tissue anterior and posterior of the vertebral column. Without suspicion of a bacterial infection we treated with corticosteroids (100 mg methylprednisolon iv) and diclofenac. A rapid improvement of symptoms and a decrease of the inflammatory markers were registered and the corticosteroids were reduced to 40 mg orally. One week later, the patient presented with fever (39В° Celsius), weakness, and an palpable exanthema. Skin biopsy releaved a neutrophilic dermatosis. The neutrophil count in the blood releaved 36 000 granulocytes/ml. We diagnosed a Sweet-Syndrome and we treated with methylprednisolone. The dermatosis disappeared and the patient had a good evaluation in the next 7 days. Discussion: This case report is impressive for us because of two reasons. First the presentation of a crystal arthropathy with such clinical and radiological signs. This presentation could be misdiagnosed with retropharyngeal abscess, meningitis and infectious spondylitis. Second reason: The appearance of a Sweet-Syndrome under the treatment with 40 mg of prednisolon and the crystal arthropathy as the trigger disease for the Sweet-Syndrome. As a trigger for the SweetSyndrome we discuss also the treatment with diclofenac, which is known as a trigger. 101 P341 An unusual case of sarcoidosis Emily Pollock*, Irene Studer, Valentin Gisler, Panagiotis Samaras UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Introduction: Sarcoidosis is an inflammatory granulomatous disease of unknown aetiology capable of involving any organ, with a typical histological finding of non-caseating granulomas. The clinical outcome is extremely variable: sarcoidosis may resolve within months or be chronic, requiring systemic therapy. Annual follow-up is recommended. Case report: A 42-year-old male patient with sarcoidosis, hepatitis C, COPD and previous substance abuse attended routine follow-up at our clinic in May 2011. Sarcoidosis had been diagnosed in 2002 based on a clinical picture of weakness, relapsing fever, generalized lymphadenopathy, dyspnoea and myalgia together with a lymph node biopsy showing typical granulomas. Tuberculosis had been excluded. Previously, in March 2010, the disease had been stable with stationary findings of hilar lymphadenopathy and reduced diffusion capacity. At follow-up, the patient felt well but reported mild neck and shoulder pain for the past two months and a new skin lesion on the left lateral chest wall. Chest x-ray showed numerous additional lesions up to 1.5 cm in diameter (figure 1). Computerised tomography confirmed multiple pulmonary nodules which were consistent with, but not typical for, sarcoidosis. Two weeks later the patient developed intense neck pain and mild tetraparesis. MRI showed a spaceoccupying lesion with destruction of the C2 vertebra and spinal cord compression (figure 2). Biopsy revealed a diffuse large B-cell non-HodgkinвЂ™s lymphoma stage IV AE, IPI risk score 3 (highintermediate). Following surgical decompression and six cycles of R-CHOP chemotherapy, the weakness resolved and the patient remains lymphoma recurrence free one year later. His sarcoidosis has never required treatment. Conclusion: вЂў Our patient with long-standing sarcoidosis developed a new diagnosis of diffuse large B-cell lymphoma. вЂў Sarcoidosis has previously been associated with a range of malignancies, above all HodgkinвЂ™s and non-HodgkinвЂ™s lymophoma, but also several solid organ tumours [1, 2]. This predisposition is thought to occur through immune dysregulation [1]. вЂў It has also been suggested that lymphoma acts as a predisposing factor for sarcoidosis [3]. вЂў It may be particularly difficult to recognize the coexistence of sarcoidosis and lymphoma because both are fluorodeoxyglucose-avid and show an uptake in PET imaging [3]. вЂў Our case emphasizes the importance of obtaining a second tissue diagnosis when the clinical course is unusual in either condition. 102 P342 Challenges to patient-centred care in a general internal medicine context: findings from an exploratory study David Gachoud*, Mathieu Albert, Scott Reeves Service de mГ©decine interne, Centre Hospitalier Universitaire Vaudois & UnitГ© pГ©dagogique, FacultГ© de Biologie et MГ©decine, UniversitГ© de Lausanne (Lausanne, CH); University of Toronto (Toronto, CA); University of California (San Francisco, US) Introduction: If we are to promote more patient-centred approaches in care delivery, we have to better characterize the situations in which being patient-centred is difficult to achieve. Data from professionals in health and social care are important because they are the people charged with operationalizing patient-centred care (PCC) in their daily practice. However, empirical accounts from frontline care providers are still lacking, and it is important to gather experiences not only from doctors but also from the other care providers. Indeed, experiences from different professions can help inform our understanding of patient care, which is expected to be both patient-centred and collaborative. Methods: This study was based on the following research question: What factors make the provision of PCC difficult to achieve? Sample and setting A purposeful sampling technique was used, allowing for a series of choices about the participants and their professional affiliation. Because patient-centredness is the focus, 3 professions appeared to be of special interest: general internists, nurses and social workers. The study was undertaken in the General Internal Medicine Division of a teaching hospital located in a North American context. Data Collection: To answer the research question, a methodological approach based on a theory called phenomenology was chosen. Accordingly, semi-structured interviews were used since they generate understanding of the meanings different individuals have of their lived world. Interviews with 8 physicians, 10 nurses and 10 social workers were eventually conducted. Data analysis An inductive thematic analysis was employed to make sense of the interview data. Results: The thematic analysis allowed identifying various types of challenges to PCC. Although most of the challenges were perceived by all three groups of professionals, they were perceived to a different degree across the professions, which likely reflected the scope of practice of each profession. The challenges and their distribution across the professions are illustrated in Table 1. Examples of challenges are provided in Table 2. Discussion: There is a tension between what is supposed to be done вЂ“ what stands in the philosophy of patient -centredness вЂ“ and what is currently done вЂ“ the real life with all the challenges to PCC. According to some participantsвЂ™ accounts, PCC clearly risks becoming a mere illusion for health care professionals on which too great pressures are imposed. 103 104 Postesession 2 - Session des posters 2 Onkologie вЂ“ Notfallmedizin / Psychiatrie / Neurologie Oncologie - Urgences / Psychiatrie - Neurologie P343 VerlГ¤ngerung der PSA-Kontrollintervalle bei MГ¤nnern mit Initialem PSA-Wert von 0-1.99 Marco Randazzo*, Daniel Seiler, Andreas Huber, Rainer Grobholz, Martin Baumgartner, Franz Recker, Maciej Kwiatkowski Kantonsspital Aarau (Aarau, CH) Einleitung: PSA ist ein Risikostratifizierer fГјr die zukГјnftige Entwicklung eines Prostatakarzinoms (PCa). In der Screening-Kohorte des Kantons Aargau hatte ein Grossteil der MГ¤nner (75%) in der ersten Runde PSA-Werte zwischen 0 - 1.99ng/ml. Die Kontrollintervalle in diesem Bereich sind jedoch noch nicht definiert. Ziel unserer Studie war deswegen die Adaptation der PSA-Kontrollintervalle. Patienten und Methoden: Von 08/1998 - 08/2003 wurden 10.311 MГ¤nner 1:1 in die Screening Gruppe bzw. in die Kontrollgruppe randomisiert. Ab einem PSA-Wert von 3.0ng/ml sowie zwischen 1.0 und 3.0ng/ml und einer PSA-Ratio < 20% (nur wГ¤hrend der 1. Runde) wurde die Indikation zur Biopsie gestellt. Im Abstand von 4 Jahren erfolgten bis anhin 3 Screening-Runden. Im PSA-Bereich 0 - 1.99 wurde die Inzidenz aggressiver Prostatakarzinom-Inzidenz (Gleason >= 7a) detektiert. Resultate: Insgesamt wurden in der 1. Runde n=4932 MГ¤nner dem PSA-Screening unterzogen, was einer 96.1%igen Compliance rate entspricht. Innerhalb von 3 Screening-Runden wurden kumulativ n=482 PCa detektiert. Das mediane Follow-up betrug 9.6 Jahre. Im Bereich 0 - 1.99 lagen n = 3745 MГ¤nner. Das mediane Alter der Patient betrug 60.0 (PSA 0 - 0.99) bzw. 61.1 (1.0 - 1.99) Jahre. Bei n = 2308 betrug der PSA-Wert 0 - 0.99ng/ml und bei n = 1437 MГ¤nnern 1 - 1.99ng/ml. An signifikanten PCa (Gleason >= 7a) wurden im Bereich 0 - 0.99 gesamthaft 0.3% sowie im Bereich 1 - 1.99 0.53% detektiert. Schlussfolgerung: Anhand der geringen Inzidenz an signifikanten Prostatakarzinomen Гјber fast 10 Jahre ist eine VerlГ¤ngerung des PSA-Kontrollintervalls auf 6 - 8 fГјr PSA-Werte von 0 - 0.99 vorstellbar. DemgegenГјber erachten wir ein Kontrollintervall fГјr 4 Jahre fГјr den Bereich von 1 - 1.99 fГјr durchaus gerechtfertigt. P344 Acquired angioedema! Acquired angioedema? Raphael Butsch*, Karla Chaloupka, Verena Niggemeier, Dominik Schaer, Daniel Franzen UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) A 31-year-old male was referred with sudden onset of rapidly progressive and painful facial oedema beginning a few hours earlier in connection with fever, chills, nausea and vomiting. He denied itching or exanthema. There was no history of allergy or (hereditary) angioedema. Aside from immunosuppressive drugs (ciclosporine, mycophenolate mofetil and prednisone because of renal transplantation due kidney aplasia), he only took bisoprolol and calcitriol, but no ACE-inhibitor. Clinical examination revealed severe angioedema of both periorbital regions with firm consistence, which was painful on palpation. The swelling of his eyelids precluded proper eye opening. The tongue and throat were unremarkable. His vital signs and his breath sound were completely normal. Laboratory results were significant for raised inflammatory markers and acute-on-chronic renal failure (leucocytes 14.1 G/l with the eosinophil count within the normal range, C-reactive protein 81 mg/l, glomerular filtration rate 23 ml/min). Assuming a first episode of acquired angioedema, the patient was treated with a plasma-derived C1 esterase inhibitor (BerinertВ®), tranexamic acid (CyklokapronВ®) and fresh-frozen plasma, after the initial treatment with corticosteroids and histamine 1- and 2-blockers were unsuccessful. Simultaneously, an antibiotic medication with piperacillin/tazobactam (TazobacВ®) for suspected infection of unknown site was instituted. Since then, the angioedema was not progressive, and the pain was slightly improving. However, the initial diagnosis was wrong! Two days after, his C-reactive protein value began to rise significantly to 408 mg/l, while the leucocytes count was falling. Blood cultures grew group A Streptococci. In the MRI of his head, the diagnosis of periorbital necrotizing fasciitis was confirmed. His treatment was subsequently changed to clindamycin and ceftriaxone and the patient recovered slowly. Delayed surgical debridement of his eye lids was carried out in the course, and he could be discharged from hospital after 21 days. 105 Facial (or periorbital) fasciitis is are rare and potentially lethal differential diagnosis of acute angioedema, in particular if accompanied by severe pain and/or fever. Knowledge on the appearance of this disorder cannot be overemphasized, as only early recognition and immediate initiation of highdose antibiotics combined with tissue debridement help to decrease the mortality. P345 Rheumatoid arthritis and malignant pleural mesothelioma: curse or blessing? A case report Peter Moosmann* Kantonsspital (Aarau, CH) Introduction: Inhibitors of pro-inflammatory cytokines have greatly changed rheumatoid arthritis (RA) outcomes. They could also be beneficial in malignant pleural mesothelioma (MPM) since a cytokineinduced chronic inflammatory response apparently favors mesothelial cell transformation. Case Report: A 55 year-old man with RA was treated with methotrexate from 2003-2006 (stopped due to possible lung toxicity). Sulfasalazine was installed thereafter (till Oct вЂ�09). 2007 вЂ“ 2009 he received etanercept and leflunomide (from Dec вЂ�08). Only the start of tocilizumab (TCZ) in Jun вЂ�09 led to a significant clinical improvement. TCZ was paused in Mar вЂ�10, when a right-sided pleural effusion developed. Repeated diagnostic procedures were unsuccessful. The patient received rituximab twice in Aug вЂ�10 (no improvement). Finally, epithelial MPM was diagnosed in Oct вЂ�10 (possible asbestos exposure). A trimodality therapy was started with platin-pemetrexed combination chemotherapy. However, the disease was progressive after 3 cycles. Because of side effects and a flare-up of the RA the patient refused further antineoplastic treatment. When TCZ was resumed in Apr вЂ�11 symptoms disappeared and the patientвЂ™s performance status (PS) returned to normal. A CT scan in Dec вЂ™12 showed progressive disease. Discussion: MPM remains an incurable disease even in patients with good PS and early stage disease. The median survival time in treated pts is <12 months. First-line chemotherapy was ineffective and surgical intervention not feasible in the reported case. Anti IL-6R directed therapy improved RA-related symptoms. Tumor growth appears rather slow: the patient is alive and under treatment 27 months after diagnosis. Did he profit from an antitumor effect of the IL-6R inhibitor? Indeed, there is evidence that pro-inflammatory cytokines contribute to MPM pathogenesis and might be rewarding targets for novel therapies. IL-6 induces cell growth in MPM cell lines that can be suppressed by IL-6 blockage. Although tumor progression appears unusually slow in this patient, there 106 are long-term survivors in MPM, especially among patients with low-risk features. No neat tumor response was documented in this case. It remains unclear whether TCZ was able to influence the primary course of the malignancy, therefore. Perhaps, the progressive MPM simply secreted IL-6 facilitating the RA flare-up, and TCZ controlled the latter. Conclusion: The case of a patient with RA and MPM is presented and put up for discussion. P346 Do we overdose erlotinib in patients with non-small-cell lung cancer and activating epidermal growth factor receptor mutation? Sophie Bauer*, Marc Kueng, Luc Burdet, David Chabanel, Daniel Betticher HFR Fribourg (Fribourg, CH); HIB Payerne (Payerne, CH) Introduction: Tyrosine kinase inhibitors are today standard first line treatments for patients suffering from stage IV non-small-cell lung cancer (NSCLC) with activating epidermal growth factor (EGFR) mutation. Side effects in particular skin reactions and diarrhea are frequently responsible for therapy interruption and/or dose reduction. The established erlotinib dose of 150 mg/day has been defined as the maximal tolerated dose limited by toxicity. A retrospective study in 7 patients receiving erlotinib at 25 mg/day described response rates in 71% and a progression free survival of 17 months (6-35 months), (Yeo W et al. J Thorac Oncol. 2010, 5, 1048-1053). Toxicities were minimal with only two patients suffering from rash and none experiencing diarrhea. We report here on a patient who had erlotinib dose reduction at 25 mg/day after skin rash and has a high benefit from therapy. Case presentation: 70-years old woman suffering from an adenocarcinoma in the upper right lung lobe, stage II. She underwent lobectomy and mediastinal lymphadenectomy and received adjuvant chemotherapy. Sixteen months later, relapse was diagnosed with pulmonary metastases. Since an EGFR mutation, exon 19 deletions, was detected, we started erlotinib 100mg/day. Treatment was stopped after 32 days because of grade 3 thoracic and cervical exanthema. Under 25mg/day, erlotinib was well tolerated and led to a complete remission with disappearance of all lung metastases; remission duration is presently 10 months. Treatment is ongoing. Discussion: To our knowledge, this is the first presentation of a complete remission in a patient with NSCLC stage IV disease on erlotinib at a 25 mg/day dose. We have today no data allowing us to define the optimal dose of erlotinib in order to obtain best tumor response and lowest toxicity incidence. Trials investigating different dose levels of erlotinib (25-100 mg/day) in patients with EGFR mutated lung cancer are warranted. Conclusion: This patient presentation together with previously reported cases indicate that lower dose of erlotinib may be sufficient for patients with NSCLC harboring the activating EGFR mutation, thus allowing to diminish erlotinib side effects. P347 Complete remission of Castleman's disease and Kaposi's sarcoma in an HIVpositive patient: the importance of combined therapy VГ©rГЁne Dougoud-Chauvin*, Christian Chuard, Daniel Betticher, Marc KГјng HFR-Fribourg (Fribourg, CH) Introduction: The multicentric CastlemanвЂ™s disease (MCD) is a lymphoproliferative disorder associated with HIV and human herpesvirus 8 (HHV-8). It is characterised by generalized lymphadenopathy, multi organ involvement and systemic features. The prognosis of HHV-8 associated MCD is poor. Chemotherapy such as CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) as well as the anti-CD20 antibody Rituximab (R) have significant activity in the treatment of this rare disease. KaposiвЂ�s sarcoma (KS) is a low-grade vascular tumor associated with infection with HHV-8 and HIV. The primary treatment of HIV-associated KS is highly active antiretroviral therapy (HAART). Poor response to local treatment and symptomatic visceral involvement are indications for systemic chemotherapy such as liposomal anthracyclines. Case presentation: We present here the follow-up at 5 years of a 51 years old black patient from Congo who has been diagnosed HIV positive stage C3 in February 2007. A few months later a MCD was diagnosed on an axillary biopsy performed because of fever, generalized lymphadenopathy, splenomegaly and poor performance status. Because of a low CD4 count (177 cells/mm3) and a high viral load (379'000 copies/ml) a HAART was initiated. Immunochemotherapy with R-CHOP resulted in a very good partial response on the lymphadenopathy and the splenomegaly but KS lesions confirmed by biopsy on the extremities and the tongue appeared. The chemotherapy was changed for liposomal doxorubicin (PLD) and the KS improved after 3 cycles. After restart of R with chemotherapy we noted 107 a progression of the KS. PLD as monotherapy was given from December 2007 until March 2008 but stopped because of fall of the CD4 count. After radiotherapy of some skin lesions, another 15 cycles of PLD monthly from June 2008 until September 2009 led to a complete remission of the KS and of the MCD that is still maintained until 2013. Under HAART the HIV disease is still under control with undetectable viral load. Conclusion: Both multicentric CastlemanвЂ™s disease and KaposiвЂ™s sarcoma in this patient were responsive to PLD, the treatment of choice for KS. R was highly effective in controlling MCD in this HIV positive patient but it appeared to exacerbate concomitant KS. The inhibition of HIV replication by HAART leads to an immune reconstitution and a better control of the KS and the MCD. P348 Intoxication with acetaminophen: a time-consuming story with happy end Cyrill Buehlmann*, Marcus Laube Spitalzentrum Biel (Biel, CH) A 16-year-old patient was referred to our emergency room by the family doctor because of dehydration owing to recurrent vomiting and decreased fluid intake for a week. He reported having eaten freshly picked mushrooms a week ago. He was in a reduced general condition, afebrile (37.3 В°C) and with normal hemodynamic values (BP 128/85 mmHg, pulse 87/min). The abdominal examination was unremarkable, except a light epigastric tenderness. The lab results are revealing an liver failure (Table). The story seemed odd and further exploration was done. Only after repeated questioning, the patient admitted to have ingested 39g of acetaminophen a week ago in a suicide attempt prompted by family problems. A therapy with acetylcysteine was initiated accordingly PrescottвЂ™s treatment-scheme and silibinin (LegalonВ®) was administered transiently. The patient was transferred to the intensive care unit and monitored according the King's College criteria with regard to a possible livertransplantation. In this context there was an emergency psychiatric case conference done to evaluate latent suicidality. Although that the serum acetaminophen level was below the limit of detection (<6.6 pmol/l) the acetylcysteine was given for 5 days (intravenous and peroral). Silibilin treatment was stopped after recapitulating the case history with the patientвЂ™s father. The patient recovered and left the hospital after 7 days for home. In our patient, repeated history by three physicians and the finding of empty blister packs by the father, suggested delayed an intoxication with acetaminophen to be the cause of the liver failure. Without a healthy suspiciousness and insistency a livesaving treatment would have been omitted in our patient. Even without hundert per cent certitude it is crucial in an emergency situation to include other causes dangerous to life and to start treatment for those affection as rapidly as possible. Afterwards meticulous medical procedures has to be carried out including a recapitulation of the case history with the patient and the relatives. P349 Sweet syndrome in a patient with myelodysplastic syndrome (MDS) after treatment with azacitidine Linda RГјegg*, Andreas Erdmann, Paul Scheidegger, Gad Singer, AndrГЁe Friedl, Clemens Caspar Kantonsspital Baden (Baden, CH); Allergie- und Hautpraxis Brugg (Brugg, CH) Here we report a 84 year old female with newly diagnosed Myelodysplastic Syndrome (MDS) who developed fever, malaise and papular skin lesions after antineoplastic treatment with azacitidine. The patient was admitted to our hospital three weeks after start of the chemotherapy, she felt extremely weak, CRP values were markedly elevated. Initially a pulmonary infection was suspected radiologically and antibiotic therapy was started. However, the clinical condition did not improve and fevers persisted. Further infectiological evaluations did not show evidence of any infectious focus; in addition serological exams for Herpes simplex and Varizella zoster as well as Leishmania turned out to be negative, we did not find any proof of the presence of atypical mycobacteria. A few days after hospitalization multiple papular, nodular skin lesions appeared rather quickly at the neck, both arms and in the face, measuring from 0.5cm to 3cm in diameter, without any itching. An acute neutrophilic dermatosis (Sweet syndrome) was suspected and could be confirmed by histological evaluation. The symptoms and skin lesions resolved rapidly, after initiating high-dose steroid therapy. The appearance of Sweet syndrome has been described in the context of MDS and other malignancies, but only single cases after exposure to azacitidine are reported in the literature. Since the bone marrow aspirate 108 showed improvement of the MDS, we decided to rexpose the patient to azactidine. After two weeks the patient developed the same symptoms, without the skin lesions though, and the symptoms resolved again with steroids. Hence, we postulate a azacitidine induced systemic inflammatory response presenting as a Sweet syndrome P350 Severe neurotoxicity after body packing Christiane Buschbeck*, Heike Juch, Bernhard Zoller, Christoph A. Meier, Simon Ritter Stadtspital Triemli ZГјrich (ZГјrich, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Background: Cocaine toxicity usually causes agitation, tachycardia, hypertension and occasionally self-limited seizures. We report a fatal case of unintentional cocaine overdose associated with prolonged epileptic activity and refractory shock. Case Report: A 28-year old man was admitted after successful resuscitation following a generalized seizure and a subsequent short-period cardiac arrest. He presented unconscious with bilateral mydriasis, a blood pressure of 78/27 mmHg, heart rate of 74/min, and temperature of 36.6В°C. Arterial blood gas analysis revealed lactic acidosis (pH 6.46, lactate 27 mmol/L) with a methemoglobin of 3.4%. Antidotes for possible cyanide poisoning were administered (hydroxocobalamin, sodium thiosulfate) and hemodynamic instability improved thereafter. Computed tomography (CT) scan of the head was normal and a CT scan of the abdomen showed six foreign bodies in the distal sigma and rectum. All packets, of which one was damaged with visible leakage, were safely removed by endoscopy shortly after admission. However, the patient remained in coma, while cocaine was detected in the urine. Electroencephalography demonstrated a non convulsive status epilepticus (Figure: Intermittent generalized spike-wave discharges and amplitude depression). Despite antiepileptic therapy and total colectomy for ischemic colitis, the patient developed combined septic and circulatory shock with multiple organ failure, including liver failure and severe rhabdomyolysis (serum myoglobin >30вЂ™000 mcg/L). He died thirty-eight hours after presentation. Discussion: Cocaine acts via blockade of the presynaptic reuptake of biogenic amines, leading to both adrenergic crisis and pro convulsive effects. Internal concealment used by drug dealers to smuggle cocaine can therefore be life-threatening in case of package leakage. However, accidental overdose death following body packing is a rare condition. Systemic drug toxicity from a ruptured packet can lead to severe neurotoxicity, such as ischemic stroke, or intracranial hemorrhage. Status epilepticus in a body packer may result from prolonged cocaine release within the gastrointestinal tract. Immediate removal of the packets is recommended, generally by surgery. Conclusions: Smuggling illicit drugs by use of body packing can result in acute drug intoxication and subsequent death due to rupture of the packages. Body packing and cocaine intoxication should be considered in patients with unexplained coma and sustained seizures. 109 Postesession 2 - Session des posters 2 Psychiatrie / Neurologie - Arterieller Bluthochdruck вЂ“ Endocrinologie - Diabetik Psychiatrie / Neurologie - NГ©phrologie / Hypertension artГ©rielle Endocrinologie - DiabГ©tologie P351 Hirnstamminfarkt, Infektion oder Neuropathie? Jens Alexander Petersen*, Konstantin Burgmann, Ludwig Theodor Heuss Spital Zollikerberg (Zollikerberg, CH) Einleitung: Das Miller-Fisher-Syndrom (MFS) ist eine entzГјndliche Neuropathie mit typischer Trias aus Ophthalmoplegie, Ataxie und Areflexie. Die Abgrenzung vom Hirnstamminfarkt Schwierigkeiten kann bereiten. Fallbeschreibung: Ein 66jГ¤hriger Mann prГ¤sentierte sich mit neu aufgetretener GehunfГ¤higkeit. Er klagte Гјber diffuse GefГјhlsstГ¶rungen, es fielen eine Ophthalmoparese sowie eine ausgeprГ¤gte Dysarthrophonie auf. Im MRI konnte eine akute zerebrale IschГ¤mie ausgeschlossen werden, die Symptome waren jedoch progredient. VitB12, Folat, ANA und ANCA waren normal, die Suche nach HIV, Borrelien, FSME und Porphyrie negativ. Bei positivem Lues-Suchtest wurde eine Lumbalpunktion durchgefГјhrt, die den Verdacht auf Neurolues nicht bestГ¤tigte. Bei mГ¶glichem paraneoplastischen Geschehen erfolgte eine Tumorsuche per CT und Proteinelektrophorese, die ohne pathologischen Befund blieb. SchlieГџlich wurde aufgrund positiver GQ1b-AntikГ¶rper im Serum die Diagnose eines Miller-Fisher-Syndroms gestellt. Nach 14 Tagen besserten sich die Symptome spontan, der Patient konnte praktisch beschwerdefrei nach Hause entlassen werden. Bei bisher unbehandelter Lues erhielt er eine antibiotische Therapie. Diskussion: Das MFS ist eine seltene, akut entzГјndliche, vorwiegend sensible und axonale Polyradikuloneuropathie. Es ist Teil eines Spektrums entzГјndlicher Erkrankungen, das auch das Guillain-BarrГ©-Syndrom und die Bickerstaff-Hirnstammenzephalitis umfasst. Bei bis zu 90% der Patienten werden GQ1b-AK im Serum nachgewiesen. Wahrscheinlich wird das MFS durch virale Infekte getriggert (вЂћmolecular mimikryвЂњ). Unser Patient berichtete von einer вЂћLebensmittelvergiftungвЂњ wenige Tage vor Auftreten der Symptome, die retrospektiv eher als virale Gastroenteritis beurteilt wurde. Der Verlauf ist monophasisch und selbstlimitierend. Nach max. 4wГ¶chiger Progredienz bilden sich die Symptome zurГјck вЂ“ nach 1 Jahr sind bei 80% der Patienten keine Residuen mehr vorhanden. Komplikationen sind respiratorische Insuffizienz und autonome (kardiovaskulГ¤re) Dysregulationen. IntravenГ¶se Immunglobuline oder Phlasmapheresen stellen die einzigen Therapieoptionen dar. Schlussfolgerung: Bei Patienten mit Hirnstammsymptomen und GangstГ¶rung sollte nach Ausschluss akut behandlungsbedГјrftiger Erkrankungen (wie zerebraler IschГ¤mie, HГ¤morrhagie und Infektionen) das MFS differentialdiagnostisch in ErwГ¤gung gezogen werden. P352 Remission of anti-PLA2R-positive membranous nephropathy after transplantation: a case report Inge Maria Schudel*, Andreas Pasch Inselspital Bern (Bern, CH) Introduction: Membranous nephropathy is a major cause of nephrotic syndrome in adults. The M-type phospholipase A2 receptor (PLA2R) has been identified as the major antigen in this disease, and recent data indicate a causal role of anti-PLA2R autoantibodies. Current data indicate, that early recurrences of membranous nephropathy may occur after transplantation in anti-PLA2R-positive patients. However, the impact of post-transplantation immunosuppression on PLA2R serum titers is currently not known. Methods: We report a successful living donor kidney transplantation of a patient with end-stage renal disease due to anti-PLA2R autoantibody positive idiopathic membranous nephropathy. Results: Biopsy-proven membranous nephropathy was diagnosed in 1990 in a 53-year-old female patient. Upon progression to end-stage renal disease, she received a renal allograft from a living donor in 2012. Proteinuria before transplantation was 4.5 g/day. Upon transplantation, the patient received an induction therapy with basiliximab. Postoperative immunosuppression consisted of cyclosporine, mycophenolate mofetil, and glucocorticoids. The anti-PLA2R autoantibody titer was 1:80 3 weeks before transplantation, but returned to negative 6 weeks post transplantation. Consecutively, 110 and consistent with membranous nephropathy undergoing remission, proteinuria completely disappeared 3 weeks post transplantation. Conclusion: Renal transplantation may favorably influence disease activity and anti-PLA2R autoantibody titers in membranous nephropathy. Elevated anti-PLA2R autoantibody titers should not delay kidney transplantation. P353 Posterior reversible encephalopathy syndrome after postinfectious glomerulonephritis Ayla Yalamanoglu*, Alexander Imhof, Thomas KГјnzi SRO AG, Spital Langenthal (Langenthal, CH) Introduction: Posterior reversible encephalopathy syndrome (PRES) is characterized by clinical symptoms as headache, seizures, decreased level of consciousness, visual disturbances and focal neurologic deficits. Sometimes, diagnosis is made by radiologic findings on MRI, especially cerebral white matter edema of both occipital lobes. Mostly, PRES occurs in patients with high blood pressure, e. g. due to renal diseases. But the development of PRES has also been contributed to vasculitis, eclampsia, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome and HenochSchГ¶nlein purpura. Case: A 16-year-old male was admitted to our hospital because of acute history of headache and seizures. 14 days ago, a treatment with clarithromycin because of respiratory tract infection was started. At admission, the blood pressure was 180/100mmHg and the serum creatinine level was 128 umol/L. Furthermore, proteinuria (urine proteine/creatinine 5825 mg/g) and erythrocyturia (>40 erythrocytes/hpf) were found. The MRI revealed edema of the posterior cerebral white matter. The kidney biopsy showed an exsudative and membrano-proliferative glomerulonephritis with deposits of IgG and C3c, a finding consistent with the diagnosis of postinfectious glomerulonephritis (PGN). The diagnosis of a PRES due to hypertension because of PGN was made. A treatment with phenytoin for one month and lisinopril plus amlodipine was initiated. There were no further seizures reported. Discussion: The main cause of PRES may be a leakage of cerebral capillaries related to elevations of blood pressure exceeding the autoregulatory capacity of the vasculature. This results in focal fluid extravasation producing vasogenic edema. Alternatively, endothelial dysfunction may play a role in patients with autoimmune disorders. The predilection of the changes in the posterior cerebral region is probably due to the relative lack of sympathetic innervation of the vertebro-basilar circulation. The treatment consists of blood pressure lowering, usually leading to rapid resolution of clinical and radiologic manifestations without progression to chronic epilepsy. Conclusion: We want to point out, that in young adults presenting with headache, seizures and hypertension, PRES should be considered and underlying etiological factors should be analyzed. Early recognition and appropriate treatment result mostly in complete clinical and radiological remission. P354 A seizure after meditation Till Hauffe*, Claudine Meindl-Fridez, Paolo M. Suter, Urs Schwarz, Markus Schneemann UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) A 48 year old formerly healthy patient was admitted to the emergency room following a first time tonicclonic seizure after participating in a meditational event. The patient was disoriented and had a highly elevated blood pressure up to 230/130 mmHg. Otherwise, the physical examination and vital signs were normal. The ECG showed ST-Segment depressions and a positive Sokolow-Lyon Index. The laboratory studies showed a slightly elevated hs-Troponin and creatinine of 182 umol/l (GFR 37ml/min) combined with a proteinuria and a serum hypokalemia of 2.8mmol/l. Serum-glucose was elevated with 12.0mmol/l. Tentative diagnoses of an acute coronary syndrome, acute renal failure, diabetes mellitus, and a firsttime epileptic seizure were made. A head CT scan revealed several smaller hypodensities bilaterally in the occipital lobes and in the cerebellum. An additional MRI showed increased signal intensities in the T2-weighted and in the FLAIR image sequences (Fig. 1) corresponding to the abnormalities in the CT-Scan. 111 To rule out meningoencephalitis or subarachnoid hemorrhage, a lumbar puncture was performed (1 cell/uL, glucose 10 mmol/L, lactate 3.6 mmol/L, protein 0.7 g/L). Altogether, the diagnosis of a Posterior Reversible Encephalopathy Syndrome (PRES) due to malignant hypertension was made. Further investigations to rule out causes for secondary hypertension were done and a suspicious laboratory constellation with elevated methoxytyramine was found (see poster by C. Meindl-Fridez et al). Summary: PRES is a neurological disorder with distinct neuroradiological findings: 1.) In T2- and FLAIR-weighted MR image sequences, areas of vasogenic edema are typically seen bilaterally in the parietal and occipital lobes. 2.) The white-matter is always involved, yet additional cortical lesions are also frequent. 3.) Isolated lesions, e.g. in the brainstem or the cerebellum, are rare. If the underlying cause is treated promptly, those lesions are mostly fully reversible. Amongst many others, typical risk factors are hypertension, pregnancy, and calcineurin inhibitors. The pathophysiology is not fully understood; failures in the regulation of cerebral blood flow and/or endothelial dysfunction are discussed. P355 Downstream hormonal changes in the kidneys after unilateral renal denervation in the rat JГјrgen Bohlender*, FrГ©dГ©ric BirkhГ¤user, JГјrg Nussberger, Eric Grouzmann, George Thalmann, Hans Imboden HГґpital cantonal fribourgeois (Fribourg, CH); UniversitГ¤t Bern (Bern, CH); Centre Hospitalier Universitaire Vaudois (Lausanne, CH) Objective: Catheter-based renal denervation provides an effective treatment for some patients with resistant hypertension. It decreases also chronically blood pressure (BP) in animal models with experimental hypertension or even normotension which is partially explained by increased natriuresis and urinary volume. This effect may involve yet unknown downstream hormonal mechanisms 112 including the renin-angiotensin and kallikrein-kinin systems which may independently contribute to the resetting of the kidneys' pressure-natriuresis relationship. Methods: Left kidneys of 8 WKY rats were surgically denervated and 8 rats sham-operated. Six days thereafter, kidney concentrations of bradykinin (BK), kallikrein (K), renin (R), angiotensin (Ang) I and II, Ang(2-8), Ang(3-8), Ang(4-8), norepinephrine (NE), epinephrine (E), dopamine (D), and plasma R concentration (PRC) were determined by HPLC, biochemically or by radioimmunoassays. The renal innervation was studied immunohistologically using antibodies against tyrosine hydroxylase and calcitonin-gene related peptide. mRNA expression was quantified by RT-PCR. Results: PRC values showed no differences between treatment groups (p=NS). Catecholaminergic or sensory nerve fibers were no longer detected in denervated kidneys. Left denervated kidneys showed lower AngI (39.5%), AngII (35.1%, p=NS), R (30.2%), NE (99.2%), D (-30.4%) and BK (30.4%) concentrations (p<0.05) vs. sham left kidneys; K, Ang fragments, and E were comparable (p=NS). Right kidneys had lower BK (26.6%, p=NS), AngI (41.2%, p=NS), AngII (22.5%, p<0.05) and higher E (46.4%, p<0.05) levels vs. sham right kidneys without differences for K, R, Ang fragments, NE or DA. Intraindividually, left denervated kidneys had lower R (23.5%), Ang(2-8) (45.9%), D (28.6%), and NE (99.2%) levels vs. right kidneys (p<0.05). mRNA levels of D-decarboxylase (DDC), D-betahydroxylase, eNO-synthase (eNOS) and transforming growth-factor beta (TGFb) were higher (2259%) in denervated vs. right (p=NS) or sham kidneys (eNOS, p<0.05; DDC, TGFb, p=NS); Angsubstrate and converting enzyme were unchanged (p=NS). Conclusion: Unilateral renal denervation decreases ipsilateral kidney NE and bilateral AII and BK levels by side-dependent mechanisms documenting the importance of downstream hormonal adaptations that contribute to or modify the post-denervation natriuretic and blood-pressure lowering effects. P356 Diabetic patients who report receiving processes of diabetic care do not express a better quality of life Alejandra Casillas*, Katia Iglesias, Bernard Burnand, Isabelle Peytremann-Bridevaux IUMSP (Lausanne, CH) Background: Chronic disease management initiatives emphasize patient-centered care, and quality of life (QoL) is increasingly considered a representative outcome in that context. In this study we evaluated the association between receipt of processes of diabetic care and QoL. Methods: This cross-sectional population-based study (2011) used self-reported data from noninstitutionalized, adult diabetics, recruited from randomly selected community pharmacies in Vaud. Outcomes included the physical and mental composites of the SF-36 (PCS, MCS) and the diseasespecific Audit of Diabetes-Dependent QoL (ADDQoL). Main exposure variables were receipt of six diabetes processes-of care in the past 12 months. We also evaluated whether the association between care received and QoL was congruent with the chronic care model, when assessed by the Patient Assessment of Chronic Illness Care (PACIC). We used linear regressions to examine the association between process measures and the three composites of health-related QoL. Analyses were adjusted for age, gender, socioeconomic status, living companion, BMI, alcohol, smoking, physical activity, co-morbidities and diabetes mellitus (DM) characteristics (type, insulin use, complications, duration). Results: Mean age of the 406 diabetic patients was 64.4 years (SD 11.4), 58% were male and 72% had a living companion; 87% reported type 2 DM, half of respondents required insulin treatment, 47% had at least one DM complication, and about 50% had DM over 10 years. Crude overall mean QoL scores were PCS: 44.0 (SD 10.3), MCS: 47.1 (SD 11.2) and ADDQoL: -1.60 (SD 1.7). There were no significant PCS, MCS or ADDQoL differences among all process indicators, when comparing those who did/did not receive each individual process in bivariate analyses. After adjustment in models including all processes, receipt of influenza vaccine was associated with ADDQoL (?= -0.45, p=.01); there were no other associations between process indicators and QoL composites. Findings were similar even when more processes were reported with combined measures of processes of care. PACIC score was associated only with the MCS (?= 1.38, p=.03). Conclusions: Process indicators for diabetes care did not show an association with QoL. This may represent an effect lag time between time of process received and quality of life; or that treatment may be related with inconvenience and patient worry. Further research is needed to explore these unexpected findings. 113 P357 An unusual case of diabetes Yann Coattrenec*, Andreas Ebneter, VГ©rГЁne Dougoud-Chauvin, Enzo Fontana HFR (Fribourg, CH) Introduction: Type 2 diabetes represents the most frequent etiology of diabetes, followed by type 1. Secondary forms of diabetes, mainly in hospital, can exist and result from pancreatic pathologies. Other hormones excess can also be part of the origin of a diabetes manifestation. Case report: We report on the case of a 57-year-old man not known for metabolic disease and in particular without diabetes. He presented 2 months ago with small cell lung cancer (SCLC), extensive disease with multiple liver metastases, for which a dose-adapted chemotherapy was started (Cisplatin and Etopophos, half dose). During this treatment, he was admitted to the hospital because of generalized weakness, asthenia, weight loss, polydipsia and polyuria. Potassium was 2.8 mmol/l, and glucose was found at 24, 4 mmol/l and creatinin at 59 Вµmol/l. Liver function was severely impared. Blood pressure was 145/90 mmHg and general appearance was much reduced and the skin appeared gray-brown. The following work-up showed a high plasma cortisol up to 2751 nmol/l and an ACTH resulting very elevated to 252 ng/L . Insulin treatment was started and the oncological treatment was stopped because of the severe liver dysfunction. Two weeks later the patient died of his progressive cancer disease Discussion: The case here presents an extreme condition of diabetes secondary to a Cushing syndrome caused by an ectopic source of ACTH due to a SCLC. This paraneoplasic syndrom often presents with a metabolic alkalosis and hypokalemia and hyperglycemia consecutively of the important adrenal cortisol production following a very elevated ACTH. Insulin and potassium are mandatory in the supplied therapy with chemotherapy for the cancer. Conclusion: In non-obese oncological patient, it is important to search a possible cause of diabetes particularly an immunologic cause or other secondary origin. Indeed the therapy will be adapted according to the etiology and the efficacy. P358 Diagnose der subakuten Thyreoiditis Till Hauffe*, Christina Gold, Kemal Budak UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Einleitung: Eine subakute Thyreoiditis prГ¤sentiert sich praktisch immer mit einer schmerzhaften SchilddrГјse. Da eine klinisch manifeste Hyperthyreose nur in rund der HГ¤lfte der FГ¤lle auftritt, kann die Diagnosestellung erschwert sein. Die farbkodierte Duplexsonographie kann dem Grundversorger auch ohne profunde Ultraschallkenntnis bei der Diagnose helfen. Fallbericht: Eine 46 Jahre alte Patientin prГ¤sentierte sich mit MГјdigkeit, Herzrasen und Diarrhoe. 4 Wochen zuvor trat eine Episode mit antibiotikaresistenten Halsschmerzen auf. In der klinischen Untersuchung zeigten sich eine druckschmerzhafte SchilddrГјse sowie ein feinschlГ¤giger Tremor. AuswГ¤rtig wurde laborchemisch eine Hyperthyreose festgestellt und eine thyreostatische Therapie (Carbimazol) begonnen. Bei Erstkonsultation bei uns lag eine Hyperthyreose mit TSH 0.01mmol/l und fT3 23pmol/l und fT4 >100pmol/l vor. Bis auf leicht erhГ¶hte EntzГјndungsparameter (CRP 21mg/l) und einer leichten AnГ¤mie (Hb 10.9g/l) war das Labor unauffГ¤llig. In der farbkodierten Duplexsonographie zeigte sich keine gesteigerte Perfusion (s. Abb. A). Zusammen mit der Infektanamnese und der zervikalen Druckdolenz, liess dieser Befund an eine subakute Thyreoiditis denken. Es wurde eine symptomatische Therapie mit NSAR begonnen und die thyreostatische Therapie bei fehlender Indikation abgesetzt. Angesichts der ausgeprГ¤gten MГјdigkeit wurde auf eine Betablockertherapie verzichtet. Die TSH-RezeptorAntikГ¶rper (TRAK) fielen negativ aus, die SchilddrГјsenszintigraphie zeigte keine Anreicherung. Verlauf: Im Verlauf der nГ¤chsten Wochen erholte sich die Patientin, die EntzГјndungswerte normalisierten sich und laborchemisch zeigte sich eine subklinische Hypothyreose. Schlussfolgerung: Die ErschГ¶pfung wird hГ¤ufig mit der Hypothyreose assoziiert, kann allerdings auch bei Hyperthyreose auftreten. V. a. protrahiert verlaufende Halsschmerzen sollten an die Differentialdiagnose der subakuten Thyreoiditis denken lassen. Die Diagnose der subakuten Thyreoiditis wird klinisch gestellt, am wichtigsten sind Anamnese und Klinik. ErgГ¤nzend kann die Sonographie helfen, die Differentialdiagnosen einzugrenzen (Abb. 2, Morbus Basedow) und mittels Labor zu verifizieren. Eine Biopsie ist meist nicht notwendig. 114 Aufgrund der destruktiven EntzГјndungsreaktion treten SchilddrГјsenhormone unkontrolliert aus den Follikeln. Da es sich nicht um eine vermehrte Hormonproduktion handelt, therapiert man mit entzГјndungshemmenden Medikamenten und nicht mit Thyreostatika. 115 P359 How to use 24-hour ambulatory blood pressure measurement (ABPM) for smoking cessation Fabian Aigner*, Paolo Suter UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Introduction: Smoking is one of the most important risk factors in the modern world. Physicians are aware of the chronic effect of smoking in promoting lung cancer and arteriosclerosis. However, the immediate noxious effects of smoking on sympathetic nervous stimulation and overactivity in the setting of daily practice with consecutive immediate effects on blood pressure (BP), heart rate and myocardial contractility is ignored in the follow-up and control of patients. Here we report a case to raise awareness of the importance to consider exact smoking history and behavior before the measurement of office BP. Case: A 33-year-old man with primary hypertension (office BP 140/99 mmHg on perindopril 8 mg, bisoprolol 5 mg and HCTZ 12.5 mg) without target organ damage showed in regular BP consultation a very variable office BP ranging from (high-) normal to hypertensive grade I. Non-compliance was suspected. The same pattern was observed by the patient in his BP self-measurements. The patient reported that he observed a correlation between smoking (> 20 cigarettes/d) in relation to his BP selfmeasurement and the variability of the blood pressure values. The information of the patient was so convincing that we performed two 24-hour ABPM on two days (with/without smoking but with identical work, physical activity schedule and sleeping/rest schedule). Figure 1 shows the profiles with a mean decrease due to smoking cessation in systolic/diastolic BP of 11/7 mmHg during daytime and of 7/7 mmHg during the night. These convincing data motivated the patient to stop smoking. Conclusion: Smoking behavior is an important modulator for short and long term BP. Not only usual smoking habits but also short term smoking behavior should be addressed when measuring BP in the office and also for BP self-measurements. Further BP effects of smoking should be used to motivate for smoking cessation. Figure 1: 24-hour ABPM measurement on the smoking day (A) and the non-smoking day (B) 1. Omvik P. How smoking affects blood pressure. Blood Press 1996;5: 71-77. 2. Mann SJ, James GD, Wang RS, Pickering TG. Elevation of ambulatory systolic blood pressure in hypertensive smokers. A. Jama 1991;265: 2226-2228. 3. Groppelli A, Giorgi DM, Omboni S, Parati G, Mancia G. Persistent blood pressure increase induced by heavy smoking. J Hypertens 1992;10: 495-499. 116 Postesession 2 - Session des posters 2 Infektiologie - Immunologie - Rheumatologie / Infectiologie - Immunologie - Rhumatologie P360 Low numbers of community-acquired extended-spectrum beta-lactamases (ESBL) in a district in central Switzerland Rein Jan Piso*, Cornelia Haldemann, Jeanine Rotzetter, Ines Griesshammer, Stefano Bassetti Kantonsspital (Olten, CH) Objective: The prevalence of ESBL positive bacteria is increasing in most countries in Europe and elsewhere. Reasons for this increase are not well understood. A rise in community acquired ESBL is often proclaimed for the situation. We retrospectively analysed the medical history of 75 patients one year before the first detection of ESBL producing bacteria. Methods: Medical records of 75 consecutive patients with first detection of ESBL producing bacteria from 11/09 till 11/12 where studied. The detection was based on clinical specimen; we did not perform routine testing. We especially were interested in hospitalisation, antibiotic treatment and urinary catheters in the year prior to the first detection of ESBL. In cases of uncertainty, the family doctor of the patient was also questioned. Results: ESBL positive bacteria were detected in 54/75 patients in urine (72 В± 10.16%), 9/75 (12 В± 7.3%) in blood cultures, 8/75 (11 В± 7.1%) in wounds and in 11/75 (14.7 В± 8%)in other specimen. 53/75 (71В± 10.3 %) of our patients had been hospitalized in the year prior first detection of ESBL, 33/75 (41 В± 11 %) in medical department, 26/75 (35В±10.8%) in surgical, 7/75 (9 В±6.5%) on urological and 14/75 (19 В± 8.9%) in a rehabilitation clinic. 21/75 (28 В± 10.2 %) had been in the ICU, and 13/75 (17 В± 8.5 %) were urological patients. 13/75 (17 В± 8.5%) of the patients had received urinary catheter, and 47/75 (63 В± 11 %) had received antibiotic treatment in the year prior first detection of ESBL. Only in 15/75 (20В±9%) of our patients, no risk factor could be detected in the year prior first detection of ESBL. Conclusion: We found only a low number of true community acquired ESBL. Most patients had been hospitalized, and almost 2/3 has received antibiotic treatment in the year prior first detection of ESBL. P361 Pneumococcal spondylodiscitis and psoas abscess in a patient with bronchial carcinoma and poststenotic pneumonia Ines Griesshammer*, Rein Jan Piso, Stefano Bassetti, Markus Zuber, Tobias SchГјtz, Seiichi ErnГ©, David William Crook Kantonsspital Olten (Olten, CH) Introduction: S.pneumoniae is a common pathogen with high morbidity and mortality in humans in case of invasive infection. Usually it causes pneumonia, otitis media, sinusitis and meningitis. Disease patterns like spondylodiscitis and psoas abscess are uncommonly caused by S. pneumoniae. Case report: A 60 year old patient was admitted with lumboradicular pain that had not responded to his usual pain pills. He received palliative chemotherapy for a bronchial carcinoma with osseous metastases one week before admission. Fever, increased coughing or sputum were denied. Clinical examination revealed in- and exspiratory wheezing and pronounced lumbar back pain. CRP was elevated (284 mg/l), leucocyte count was 6.4 G/l with a left shift of 20%. Conventional x-ray and MRI showed evidence of new bone metastasis and initially no signs of spondylodiscitis. On day 3 the lower back pain worsened and signs of a sepsis occurred. Blood cultures showed Streptococcus pneumoniae. We postulated a pneumococcal pneumonia and changed antibiotic treatment to Penicillin G 4 x 5 Mio units/d. The patientsвЂ™ condition improved slightly but CRP remained high. The thoracoabdominal CT-scan exposed the poststenotic pneumonia plus a psoas abscess formation. Abscess drainage was performed which reduced both symptoms and inflammatory parameters. S. pneumonia was also detected in the psoas abscess. The control CT-scan 10 days later though showed a recrudescence of the left psoas abscess, but new abscess collection in the right psoas and now signs of a spondylodiscitis. A second surgery was accomplished. Discussion: Various bacteria, including S. aureus and Streptococci have been reported as pathogens of psoas abscess and spondylodiscitis. S. pneumoniae is a rare cause of spondylodiscitis. Prompt diagnosis is difficult since symptoms are often non-specific. In this case, we propose that the primary focus was a bacteremic pneumonia that caused spondylodiscitis which carried along the psoas 117 abscess, even if the spondylodicitis was not visible in the primary MRI. In general, the prognosis of pneumococcal psoas abscess is good when treated with immediate surgery and adequate antibiotic treatment but can have disastrous outcomes without treatment. Therefore psoas abscess and spondylodiscitis must be excluded in patients with pneumococcal bacteremia and suspicious focal symptoms, even if primary focus has been determined. P362 The "feverish granny syndrome": severe primary cytomegalovirus (CMV) infection in an elderly woman Julia SteinrГјcken*, Sylvia Mayr, Peter Graber Kantonsspital Liestal (Liestal, CH) Background: CMV is a common virus in humans with a highly variable seroprevalence, depending on age and socioeconomic factors. Primary CMV infection is usually mild or even asymptomatic in children or adolescents. However, CMV may cause severe disease in immunocompromized patients either by reactivation or primary infection. Primary CMV infection is a cause of high fever in the immunocompetent elderly without evident focus. Case description: A 60-year-old previously healthy woman presented with a 3-day history of fever, chills, myalgia, and weakness. On admission, fever (39.0В°C), hemorrhagic conjunctivitis, aphthous stomatitis, and a few abdominal skin blisters were present. Leukocyte counts were normal with 26% bands and lymphocytosis (3.5 x 109 /l, 55%) with atypical forms. In addition, thrombocytopenia (66 x 109 /l) and elevated CRP (239 mg/l), procalcitonin (1.25 Вµg/l), transaminases (ASAT 94 U/l, ASAT 75 U/l), and LDH (936 U/l) were detected. Thoracoabdominal CT was normal. At day 5 of illness, antibodies to CMV, HIV, Brucella and Q-fever were negative. Hematologic malignancy was excluded by bone marrow aspiration. After one week, the patientвЂ™s condition slowly improved, and inflammatory parameters decreased. On day 9, CMV serology was repeated, showing seroconversion with positive IgM and low avidity IgG antibodies. CMV PCR in blood was negative. However, CMV PCR from a stored serum sample taken on the 2nd day of hospitalization and from skin blister fluid were both positive, confirming the diagnosis of CMV infection. After 10 days, the patient could be discharged. Careful exposure history revealed that her daughter-in-law and her 8-month-old grandchild had suffered from a mild viral illness during the same time period, which turned out to be acute CMV infection after serologic testing. Clinical relevance: Primary CMV may cause severe symptoms in the elderly. Seronegative seniors are at risk to be infected by their grandchildren, causing the вЂњfeverish granny syndromeвЂќ. Unexplained fevers and atypical lymphocytes should raise the suspicion of primary CMV infection in seronegative elderly persons. Detection of CMV in blood or urine should be attempted by PCR to avoid unnecessary and costly diagnostic procedures. CMV serology may not be helpful in the early phase of illness, but is still important to establish the final diagnosis of acute CMV infection. P363 Fluctuating headache with changes in personality: cerebral vasculitis Beatrice MГјller*, Stefano Bassetti, Susanna Frigerio Kantonsspital Olten (Olten, CH) Background / Case presentation: Isolated cerebral vasculitis may present neurological symptoms with headache, cognitive deficits and invariably psychiatric signs without any other clinical manifestation. We present a 63-year-old patient with new onset and severe holocephal headache. In personal history a marginal zone B-cell non-Hodgkin lymphoma in 2009 is known, currently in complete remission. Physical examination showed reduced general condition with hypertensive blood pressure (183/95 mmHg). Behavioural neurologic examination presented an agitated and disinhibited patient. Initial Results: Laboratory results showed normal Leucocytes (9.6 G/L), C-reactive protein (1.9 mg/l) and almost regular sedimentation rate (12 mm/h). Cerebrospinal puncture exhibited a discrete increase of total protein to 0.57 g/l (standard 0.15-0.45), but no lymphocytic pleocytosis in CSF or other pathology, especially cytological analysis revealed no suspicious malignant cells. Native cranial CT exposed bihemispheric subcortical hypodensities. Due to progressive restlessness and increasing fluctuating headache accompanied by qualitative disturbance of consciousness with changes in personality the transfer to our ICU was necessary. Clinical Course: Non convulsive Status epilepticus could be excluded by EEG showing bilateral generalized slowing with frontal intermittent rhythmic delta activity (FIRDA). Anticonvulsant therapy with levetiracetam was installed with 1000 mg BID. Cerebral MRI scans showed bihemispheric 118 subcortical leucencephalopathy with subacute ischemic lesions in the left hippocampus and in the right parietal lobe. MR angiography revealed impressing irregularity of vessel calibre in several intracranial arteries. Our estimated diagnosis of cerebral vasculitis was confirmed by the cerebral angiography (Inselspital Bern) that showed the typical picture with significant irregularities of calibre of the intracerebral arteries. During treatment with high-dose corticosteroid therapy, monthly EndoxanВ® pulse therapy as well as anticonvulsant therapy qualitative disorders of consciousness regressed and the patient was almost completely free of headache. Conclusion: Our case report supports that normal serum inflammation markers do not rule out cerebral vasculitis and that constellation of headache accompanied with fluctuating changes in personality should prompt the search for cerebral vasculitis as an important differential diagnosis of secondary headache. P364 Wolf and dog: first manifestation of systemic lupus erythematosus combined with Capnocytophaga sepsis Marco Etter*, Agnes KneubГјhl, Christian Steffen Spital Lachen (Lachen, CH) Introduction: Systemic lupus erythematosus (SLE) and its treatment may alter immunologic response. Infection may induce SLE or trigger relapse. Capnocytophaga spp. is a gram-negative rod found in normal oral flora of dogs. Systemic infection in immune competent individuals is rare. Fatal sepsis may occur especially in asplenic individuals or persons with hepatic disease. Case Report: An 18-year-old patient was referred to our emergency department because of fever and chills and polyarthralgia for two weeks. He had a skin rash and neutropenia was documented. On admission he was in mild distress and febrile (39.2В°C). Vital signs where within normal range. Previous history was unremarkable. He lives with his parents and his brother, is an office employee, has a pet dog without reported bites and no recent travel history. Clinical examination showed a maculopapular scaling rash on the trunk, thighs and arms. On the second day of hospitalization a malar rash developed. He had generalized arthralgia without signs of arthritis. Laboratory testing revealed pancytopenia, elevated C-reactive protein and Creatinin. In addition complement factors C3 and C4 were low and antibodies against double-stranded DNA were elevated. One blood culture grew Capnocytophaga spp.. Urin investigation showed haematuria without casts and mild proteinuria. Treatment with co-amoxicillin was initiated. Later the Patient developed Libman Sachs endocarditis. Hence prednison and plaquenil were started. Renal biopsy showed lupus nephritis class III (World Health Organisation). After two months of treatment echo-cardiographic findings and renal function were normal. Azathioprin was added and Prednison gradually tapered. After 16 months, the patient is doing well. Discussion: We diagnosed SLE with Libman Sachs endocarditis and concomittant Capnocytophaga sepsis in this patient. It remains unclear, whether SLEвЂ™s associated immunodepression allowed systemic Capnocytophaga infection or if the latter induced SLE. Conclusion: Even if OccamвЂ™s razor may lead to a conclusive diagnosis such as SLE, in a febrile patient searching for bacterial infection is still necessary. P365 Life-threatening sepsis due to typhoidal tularaemia during infliximab therapy Nina Lutz* Kantonsspital Winterthur (Winterthur, CH) Case: In august 2012, a 31-year-old warehouse clerk was referred to our hospital due to fever and coughing since three days. For CrohnвЂ™s disease he was under treatment with the TNF-antagonist infliximab. The patient is of Turkish descent but grew up mostly in Winterthur. On presentation the patient was febrile without any localising signs or symptoms. Chest-X-Ray and CT scan revealed a large mediastinal (10x5cm) and several pleural masses (max. 5x5cm). Routine blood tests were normal beside an elevated CRP (86 mg/l). Pleural biopsy demonstrated malignant thymoma type B3. The PET-CT showed low intensity FDG-accumulation in thymus and pleural metastases. Moreover, very intense FDG-uptake was noted in tonsils, in multiple cervical, mediastinal and abdominal lymphnodes and in the enlarged spleen and liver raising the strong suspicion of additional disease. Meanwhile, the patient had developed severe systemic inflammation, progressive respiratory failure and cholestatic hepatitis with the following lab results: leucocytes 23x109/L, neutrophils 15.6x109/L, 119 CRP 483 mg/l, Procalcitonin 0.11 ng/ml, Ferritin 10вЂ™044 ug/L, Bilirubin 117 umol/l, ALAT 170 U/L, AP 323 U/L, LDH 1138 U/L. Biopsies of bone marrow, tonsil and mediastinal lymph node revealed necrotising lymphadenitis with atypical granulomas and severe inflammation without overt hemophagocytosis or lymphoma. Empirical treatment was started including high dose methylprednisolone and tuberculostatic therapy with Rifampicin, Isoniazid, Pyrazinamid and Moxifloxacin. The latter was included to treat possible alternative bacterial infections. Within days, the patientвЂ™s condition and lab results markedly improved. Surprisingly, broad spectrum bacterial PCR from the lymph node was positive for Francisella tularensis leading to the diagnosis of typhoidal tularemia with severe sepsis. Treatment was changed to Tobramycin i.v. for 5 days and Doxycyclin orally for 14 days and the patient made a full infectious recovery. Unfortunately, metastatic thymoma was unresponsive to chemotherapy and the patient was transferred to thoracic surgery in December 2012. Discussion: This patient developed life-threatening sepsis due to systemic infection with F. tularensis (subspecies holarctica). His disease course was extraordinarily fulminant and most likely triggered by anti-TNF therapy known to cause very inefficient Francisella control in mice. This case highlights the infectious risk of anti-TNF therapy beyond tuberculosis. P366 Rabbit fever Christina Lyko*, Christian Chuard HГґpital Cantonal Fribourg (Fribourg, CH) Introduction : Tularemia, also called rabbit fever, is an infection caused by Francisella tularensis, a zoonose transmitted to humans by contacts with infected animals or by vectors such as ticks. This disease is rare in Switzerland, where approximately 7 cases are recorded each year since the introduction of the mandatory declaration in 2004, but its incidence has recently increased. Cases report : 1) A 51-year-old woman, owner of an equestrian center, was sent to hospital in June 2012 after a 4-week therapy with beta-lactams for a cutaneous umbilical ulceration following tick bite with bilateral inguinal lymphadenopathy and malaise. The ulceration improved but the lymphadenopathy grew up and became fluctuant. Tularemia was suspected and confirmed serologically at the 21st day of illness. Doxycycline was administered for 3 weeks with clinical improvement reached on the 2nd day of therapy and complete resolution after 4 weeks of therapy. 2) A 58-year-old butcher presented in October 2012 with a skin lesion, flulike symptoms and weight loss. Physical examination revealed a painless 7-cm red plaque with a suppurative central ulceration on the upper chest wall. A tender, fluctuant, 3-cm lymph node was palpable in the ispilateral axillary region. Despite treatment with oral beta-lactams, the symptoms did not improve. Because a tick bite was possible, tularemia was suspected and a therapy with doxycycline was started. The clinical condition improved, but the serology for tularemia made on the 7th day of illness was negative. It was repeated 3 weeks later and finally confirmed the diagnosis. Discussion and conclusion: Clinical manifestations of tularemia are diverse, but the ulceroglandular disease is the most common form. Diagnosis is based on serology with antibody titer rise approximately 2 weeks after the onset of illness. When the suspicion is high, the serology should be repeated if necessary. Although this infection is rare, it should be part of the differential diagnosis in front of a clinical setting of lymphadenopathy with cutaneous ulceration, especially when it follows a tick bite or if a therapy with beta-lactams is not effective. P367 Penicillium marneffei sepsis: first manifestation of HIV infection Victor Speidel*, Stefanie Nicolaus, Madeleine Rothen Spitalzentrum Biel (Biel, CH) Introduction: Though rarely seen in immunocompetent patients, P. marneffei is one of the most common HIV-associated opportunistic infections in Southeast Asia. The dimorphic fungus is endemic in Southeast Asia, but only few imported cases have been reported in Switzerland. Clinical findings in patients with systemic infection are unspecific and may include fever (93%), skin lesions (83%), weight loss (59%), cough (50%), lymphadenopathy (40%) and diarrhea (27%). Case: A 52-year-old Swiss man consulted his family doctor for loss of appetite, nausea, dysphagia, fever, diarrhea and a weight loss of 10kg in 6 weeks. He had smoked about 40 packyears and had no 120 medical history apart from a dengue fever and treated syphilis about 20 years ago. Living in Switzerland, he had spent five months each year in Thailand for the last 20 years. Clinical examination showed cachexia, hypotension, fever, oral candidiasis, generalized lymphadenopathy and a non-pruritic papular rash on the head and trunk. Following a positive HIV-antibody test, further testing revealed a high viral load of 1.2mio cop/ml and a CD4 count of 26/Вµl. Blood cultures turned out positive for P. marneffei and antifungal therapy with itraconazole was initiated four days after start of antiretroviral therapy. During the first few weeks of treatment the skin lesions became more severe before disappearing after 2 months of therapy with resolution of all clinical symptoms, while the CD4 count rose to > 400/mm^3 and viral load decreased steeply. Conclusion: Late presentation of HIV-infection may vary and is not uncommon even in Switzerland. Although there are no endemic P. marneffei infections in western countries, they have to be thought of due to travelling and migration. Treatment recommendations include amphotericin B for 2 weeks, followed by 10 weeks of oral itraconazole, but alternatively itraconazole alone can be given for 12 weeks. Secondary prophylaxis needs to be continued until immune reconstitution is achieved to prevent relapse. Symptoms of P. marneffei infection may only present or worsen upon treatment with antiretrovirals due to immune restoration. The unmasking effect of improved cellular immunity is known as immune reconstitution inflammatory syndrome (IRIS). 121 Postesession 2 - Session des posters 2 Allgemeine Innere Medizin - Infektiologie / Immunologie / Rheumatologie MГ©decine interne gГ©nГ©rale - Infectiologie/Immunologie/Rhumatologie P368 Raubvogelangriff mit Folgen: TularГ¤mie (Hasenpest) Maria Trachsel*, Reinhard Imoberdorf, Jacques Gubler, Urs Karrer Kantonsspital Winterthur (Winterthur, CH) Fall: Ein 43- jГ¤hriger Patient wurde uns wegen persistierendem Fieber mit SchГјttelfrost sowie zervikaler und nuchaler Lymphknotenschwellung zugewiesen. 14 Tage zuvor wurde er beim Joggen von einem Raubvogel attackiert und erlitt am Kopf diverse Kratz- und Schnabelverletzungen. Eine orale antibiotische Therapie mit Amoxicillin/ClavulansГ¤ure hatte keine Besserung gebracht. Die Wunde am Kopf war klinisch nicht entzГјndet, nuchal und zervikal bestand eine ausgeprГ¤gte druckdolente Lymphknotenschwellung ohne RГ¶tung oder Fluktuation. Im Lymphknotenpunktat konnte mittels bakterieller Breitspektrum-PCR und kulturell Francisella tularensis nachgewiesen werden. Die Therapie mit Tobramycin intravenГ¶s (5 Tage), gefolgt von Doxycyclin peroral fГјr 2 Wochen resultierte in einer raschen Besserung mit Regredienz des Fiebers und der Lymphknotenschwellung. Diskussion: Die TularГ¤mie ist eine in der Schweiz bisher seltene meldepflichtige bakterielle Zoonose. 2012 wurde mit insgesamt 37 bestГ¤tigten FГ¤llen ein deutlicher Anstieg der Erkrankungen festgestellt. Die Гњbertragung erfolgt durch blutsaugende Arthropoden (insb. Zecken), Haut- oder Schleimhautkontakte mit infektiГ¶sem Tiermaterial, kontaminiertes Fleisch und Wasser oder durch Inhalation von infektiГ¶sem Material. Eine Гњbertragung von Mensch zu Mensch ist unbekannt. F. tularensis ist hochinfektiГ¶s, bereits 10 bis 50 Bakterien kГ¶nnen zur Infektion fГјhren. Die Krankheit beginnt nach kurzer Inkubationszeit von 3-5 Tagen (1-21 Tage) mit Allgemeinsymptomen gefolgt von lokalen Lymphknotenschwellungen. Am hГ¤ufigsten ist die ulcero-glandulГ¤re oder glandulГ¤re Manifestation, je nach Eintrittspforte kommen seltener auch oropharyngeale, thyphoidale oder pulmonale Formen vor. Diagnostisch ist die Kultur von F. tularensis anspruchsvoll und wird zunehmend durch die PCR aus Gewebe (ev. Blut) ersetzt. Die Serologie ist zuverlГ¤ssig, wird aber erst in der 2. Krankheitswoche positiv. Therapeutisch sollten Aminoglykoside, Tetrazykline oder Chinolone verwendet werden, denn Beta-Lactame sind unwirksam. Bei unserem Patienten lag eine ulzero-glandulГ¤re TularГ¤mie mit hГ¶chst ungewГ¶hnlicher Ansteckungsart vor. Wir gehen davon aus, dass der Raubvogel vor kurzem ein infiziertes Nagetier gerissen hatte und so die Bakterien auf unseren Patienten Гјbertragen konnte. WГ¤hrend Raubvogelattacken auf Jogger gerade in der Brutzeit regelmГ¤ssig vorkommen, ist in der Literatur lediglich ein Fall einer TularГ¤mie nach Raubvogelkontakt beschrieben. P369 Value of 18F-FDG-PET-CT in diagnosis of large vessel vasculitis with aortic arch involvement: two cases with impressive findings Daniel Portmann*, Jacques Gubler Kantonsspital Winterthur (Winterthur, CH) Introduction: Large vessel vasculitis (LVV) with involvement of the arotic arch is potentially life threatening and early detection can be crucial. Clinical signs and symptoms of LVV are nonspecific, making diagnosis and differentiation from polymyalgia rheumatica (PM) or Giant Cell Arteriitis (GCA) difficult. We report two cases of LVV where early diagnosis was made by PET-CT. Case 1: A 61-year-old woman was admitted to our outpatient clinic with a two month history of fever, drenching night sweats and weight loss of 5kg. Laboratory investigations suggested systemic inflammation with an erythrocyte sedimentation rate of >110 mm/hour, a C-reactive Protein of 239mg/l and normocytic anemia. An extensive diagnostic evaluation was performed to exclude an unknown primary tumor or an infectious cause. Finally, a PET-CT revealed LVV affecting aorta, subclavian, proximal brachial, common carotid and femoral arteries bilaterally (Fig 1). Case 2: A 57-year-old woman presented with a history of proximal muscle weakness, general fatigue and drenching night sweets. Her ESR was >100mm/h, her CRP 122mg/l. PET-CT revealed LVV affecting the whole aorta, the supraaortal arterial branches and popliteal arteries bilaterally (Fig 2).A temporal artery biopsy showed no signs GCA. Both patients had no signs of ischemia, notably no arm or leg claudication.Treatment with prednisolon and methotrexate (MTX)led to a rapid resolution of clinical symptoms and normalization of laboratory 122 parameters.Recovery in both patients took more time than one might expect from classical PM or GCA. Discussion: In patients with a clinical presentation of PM or GCA and extensive systemic complaints, the possibility of LVV should be evaluated. Beck et al. noted a different clinical pattern for patients LVV. While headache, jaw claudicatio and visual changes were rare, arm claudicatio is seen more often in patients with LVV compared to classical GCA (38% vs. 0%). Surprisingly, they found no difference in the rate of systemic symptoms. Inflammatory cell infiltration (revealed by PET) is likely to precede the development of edema of the vessel wall (depicted by MRI), making PET-CT the investigation of choice for LVV, with a sensitivity of 77-92% and specificity of 89-100%. Because of the potentially life threatening complications of LVV, an early diagnosis is crucial. While therapy of PM and GCA initially use steroids alone, patients with LVV may need an additional immunosuppresive agent, with MTX as first choice. 123 P370 Malta fever from South America Silvan Meier*, Thomas Bregenzer Spital Lachen AG (Lachen, CH) Introduction: Brucellosis is the worldвЂ™s most common bacterial zoonosis with more than half a million new cases annually. The mortality rate is about 2 %, mainly due to endocarditis. If untreated, osteoarticular and genitourinary complications may lead to severe sequelae. Only five to ten cases are reported in Switzerland annually, mainly imported from the Mediterranean region. After an incubation period of up to 60 days, undulating malaria-like fever is the most common symptom. Brucella is an intracellular pathogen with world wide occurrence. Many farm animals are reservoirs. It is mainly transmitted through breaks in the skin or ingestion of dairy products. Case Report: A 62-year-old patient suffered from fever, night-sweat, weight loss and fatigue for two months. He was referred by his general practitioner who excluded malaria. His previous history was unremarkable. There was evidence of past EBV-infection and hepatitis A. He was preparing his retirement and planned to relocate to a rural region in Brazil where his wife already emigrated to. She is farming there sheep and goats. He was exhausted, anorectic and complained in particular about a periodical, undulating fever up to 38В° C mainly in the evening. Clinical examination was without pathological findings, an infectious focus could not be identified. The laboratory results showed increased inflammation parameters and elevated liver enzymes. Abdominal sonography revealed splenomegaly with 13.9 x 4.6 cm, chest X-ray was normal. Serologic investigation was positive for brucella spp. All blood cultures grew brucella melitensis. Combination therapy with doxycycline and gentamicin for two weeks and doxycycline monotherapy for another four weeks was initiated. Clinical improvement and declining signs of inflammation were documented within one week of treatment. The patient is asymptomatic and doing well six months after treatment. Discussion: Brucellosis is rare in Switzerland and usually associated with a travel history in the Mediterranean region. However, B. melitensis occurs worldwide. Our patient may have acquired the infection when he visited his wife in Brazil. The recommended treatment is doxycycline combined with gentamicin although quinolones may yield similar efficacy. Conclusion: In patients with prolonged fever and constitutional symptoms, Malta fever should 124 P371 White Islands...Fever Islands... Philipp Jent*, Simon Steiner, Drahomir Aujesky, Daniel Vogel Division of General Internal Medicine, University Hospital Bern (Bern, CH); Division of Infectious Diseases, University Hospital Bern (Bern, CH) Introduction: Dengue is a self-limited systemic viral infection transmitted between humans by mosquitoes (A. aegypti and A. albopictus). Due to an increase in travel and global mobility a growing number of cases are also seen in Europe. This case report is an example showing the features of this infection with a huge global burden. Method: Case Report: A 42-year-old woman returned from a two month holiday trip to Peru, followed by 10 days in CuraГ§ao (Caribbean). She was admitted to our emergency room with fever, retro-orbital headache, heavy myalgia and joint pain with an onset 3 days after returning home. The clinical examination showed no specific infectious focus, the laboratory findings included leukopenia (1,5G/L) and thrombocytopenia (31G/L). The CRP was 3mg/L and malaria tests negative. Further evaluations, including blood and stool cultures as well as serology for viral hepatitis, also remained negative. 5 Days after onset of symptoms a bright red confluent macular rash of the lower limbs with вЂћislands of whiteвЂњ (unaffected skin) appeared (Fig. 1). In parallel, an increase of serum aminotransferase levels to 12 x the upper normal level was observed, peaking 9 days after symptom onset and declining thereafter (Fig. 2). The suspected diagnosis of dengue fever could be confirmed serologically. After 5 days the fever and pain stopped spontaneously. Hematocrit stayed stable and there were no signs of capillary leakage, severe bleeding or severe organ involment. Thrombocytes and leukocytes returned to normal. Key Points / Discussion - Consider dengue in patients returning from Southeast Asia, South Central Asia, the Caribbean and South America with fever, muscle and joint pain (вЂљbreak bone feverвЂ™) and headache. - Approximately 50% of the patients show a characteristic rash (вЂљislands of white in a sea of redвЂ™) predominantly of the lower limb. - Typical laboratory findings include thrombocytopenia and leukopenia. Aminotransfase level elevations are common; in less then 5% > 10 x the upper norm, as in our case. - In the period of defervescence (days 4-7) signs indicating severe dengue such as capillary leakage, bleeding (decreasing thrombocytes and hematocrit), increasing aminotransferase levels and neurological impairment must be monitored closely. P372 A rare cause of chronic diarrhoea Gabriela Keller*, Urs Karrer, Reinhard Imoberdorf, Stephan Bosshard Kantonsspital Winterthur (Winterthur, CH) Case: A 61 year old patient was admitted to our clinic due to chronic diarrhea and weight loss of 10 kg since 1 year. He did not report any fever, chills or sweating. His body mass index was 15 kg/m2. Stool examination only showed evidence of intestinal spirochetes and blastocystis hominis. Endoscopic, histologic and serologic investigations ruled out WhippleвЂ™s disease, coeliac disease, inflammatory bowel disease and other causes of chronic diarrhea combined with malnutrition. Thoraco-abdominal CT scan with subsequent biopsy showed a 6x7 cm thymoma without metastases of a mixed histologic type (AB). Total immunoglobulin levels in the serum (IgA, IgG and IgM) were substantially reduced indicating thymoma associated Good syndrome. With the presumptive diagnosis of opportunistic infectious diarrhea antimicrobial therapy against spirochetes and blastocystis was initiated leading to 125 prompt cessation of watery diarrhea. Hypogammaglobulinemia was substituted with intravenous immunoglobulin. In the short-term follow up the patient could maintain his body weight and was clinically without an infection. Diagnosis: Good syndrome is a rare cause of acquired immunodeficiency that occurs in association with thymomas. Due to hypogammaglobulinemia affected patients may suffer from severe opportunistic and recurrent bacterial infections. Discussion: Thymoma associated with hypogammaglobulinemia and profound susceptibility to recurrent and serious infections was first reported by Robert Good in 1954. Chronic diarrhea associated with thymoma is mostly seen in patients with hypogammaglobulinemia. However, chronic diarrhea may also occur with normal immunoglobulin levels. Our case illustrates that paraneoplastic disorders associated with thymoma may lead to progressive illness with wasting syndrome. In this setting, malnutrition which is crucial for the overall outcome may become self-perpetuating even in absence of detectable opportunistic infection. Survival of patients with Good syndrome is mainly limited by infection, autoimmune disease and hematologic complications. Complete surgical resection of the thymoma is the preferred treatment approach for these patients. However, despite thymectomy hypogammaglobulinemia may persist mandating the life long substitution of immunoglobulins. P373 Bilateral parotid swelling caused by? It`s written in the stars! Katja StГјrzebecher*, Kirsten Mertz, Franz BГјttner, Elke Ullmer Kantonsspital Baselland/ Liestal (Liestal, CH) Background: Sarcoidosis (SD) is a multisystem disorder affecting the respiratory system in >90% of patients. Extrapulmonary organs frequently involved are peripheral lymph nodes, skin, eyes, liver, heart, and central nervous system. Parotid gland involvement is rare (<6%). Case: A 24-year-old woman was admitted with non-tender swellings at both angles of the jaw. She denied cough, dyspnea, nightsweats or fever. Sonography revealed bulky, inhomogeneous parotid glands. Cervical lymph nodes were not enlarged. Laboratory findings were not conclusive. CT scan showed mediastinal and hilar lymphadenopathy. Additionally, round and irregular marginated masses were visible in the superior segment of both lower lobes. In 2002, Nakatsu et al. first described these coalescent granulomatous lesions as sarcoid "GALAXY SIGN". Bronchoscopy showed endobronchial cobblestone pattern, histologically containing non-caseating granulomas. BAL revealed lymphocytic alveolitis and CD4/ CD8 ratio was augmented. Infectious agents could not be detected. SD stage II with lung and parotid gland involvement was diagnosed. Systemic steroids were started (1mg/kg KG) and tapered over 6 months. Discussion: Bilateral parotid swelling may be caused by viral or bacterial infections, sialolithiasis, tumors or autoimmune disorders, mainly SjГ¶gren`s syndrome and SD. Parotid swelling due to SD, combined with uveitis, fever, and bell`s palsy is called Heerfordt`s syndrome. Bihilar lymphadenopathy is the most common radiological finding in patients with SD. Although small nodules along the bronchovascular bundles, interlobular septa, and major fissures or in the subpleural regions are frequently observed, large parenchymal nodules are less common, but also pathognomonic for SD. Coalescent nodules in the center form larger, more dense nodules than the peripheral satellite-like micronodules resembling a GALAXY. Histologically, these nodules correspond to interstitial granulomas. Peribronchial arrangement may result in an air bronchogram mimicking alveolar infiltration. Central cavitation may occur. Conclusion: Bilateral parotid swelling may be the first manifestation of SD. Bihilar lymphadenopathy and diffuse small nodules with perilymphatic distribution are typical radiological manifestations. In about 15% of patients, large, irregular marginated nodules occur. This вЂћGALAXY-SIGNвЂќ should raise suspicion for thoracic SD. Tbc is the most important differential diagnosis and has to be ruled out. P374 Immunomodulatory effects of low dose immunoglobulin replacement in patients with primary antibody disorders Peter Jandus*, Camilla Jandus, Lukas JГ¶rg, Daniel Yerly, Werner Pichler, Arthur Helbling Service d'Allergologei et d'Immunologie, HГґpitaux Univeristaires de GenГЁve (GenГЁve, CH); Ludwig Center for Cancer Research, UNIL (Lausanne, CH); Departement Rheumatologie, Klinical Immunologie und Allergologie, Allergische-Immunologische Poliklinik, Inselspital (Bern, CH); Departement Rheumatologie, Klinical Immunologie und Allergologie, Allergische-Immunologische Poliklinik, Inselspital (Bern, CH); CDepartement Rheumatologie, Klinical Immunologie und Allergologie, Allergische-Immunologische Poliklinik, Inselspital (Bern, CH) 126 Introduction: Understanding the mechanisms of action of high-dose intravenous immunoglobulins (IVIg) in autoimmune and inflammatory disorders has kept investigators busy over the past 3 decades. A number of mechanisms for immune modulationsand anti-inflammatory actions of high-dose IVIg have been described. In contrast, the mechanisms of action of low-dose IVIg in primary antibody disorders have not yet been thoroughly investigated. Aim of the study: a) Assess the effect of low-dose IVIg on immunological parameters in patients with primary antibody disorders, longitudinally during IVIg replacement. b) Identify correlations between favorable effects on clinical symptoms and modulation of immunological parameters during low-dose IVIg substitution. Methods: Eight patients with primary antibody disorders (CVID, subclass deficiency) with recurrent infections requiring immunoglobulin substitution were included in the study. Blood was withdrawn before the first IVIg replacement, at 3-4, at 6 and at 10-12 months of treatment. PBMCs were isolated and serum was collected stored at 80В°C. Quantification of pro- and anti-inflammatory cytokines in the serum is performed by ELISA, phenotypic and functional analyses of lymphocyte subsets and dendritic cells are assessed by multi-color flow cytometry and in vitro assays. Results: In preliminary experiments, we observed a significant increase in the concentration of a large number of cytokines in all 8 patients tested during low-dose IVIg, albeit with different kinetics. While IL2, IL-4, IL-10, IL-13, IL-1 beta, INF-gamma levels already were significantly higher 3-4 months after initiation of the replacement therapy than before, IL-5, IL-12p70, IL-17 showed a more delayed, yet sustained increase over the treatment period. Conclusion: Taken together, these preliminary analyses suggest a modulation of action of low-dose IVIg on the immune system supporting the hypothesis that a beneficial effect of low-dose IVIg in patients with primary antibody disorders cannot be explained only by the reconstitution of normal circulating immunoglobulin levels upon treatment. P375 Trends in the main diseases in an internal medicine ward, 2003-2011 Marco Martinuz*, GГ©rard Waeber, Pedro Marques-Vidal CHUV (Lausanne, CH) Introduction: Population aging leads to a considerable increase in the prevalence of specific diseases. We aimed to assess if those changes were already reflected in an Internal Medicine ward. Methods: Anonymous data was obtained from the administrative database of the department of internal medicine of the Lausanne University Hospital (CHUV). All hospitalizations of adult (>=18 years) patients occurring between 2003 and 2011 were included. Infections, cancers and diseases according to body system (heart, lungвЂ¦) were defined by the first letter of the ICD-10 code for the main cause of hospitalization. Specific diseases (myocardial infarction, heart failureвЂ¦) were defined by the first three letters of the ICD-10 codes for the main cause of hospitalization. Results: Data from 32,741 hospitalizations occurring between 2003 and 2011 was analyzed. Cardiovascular (ICD-10 code I) and respiratory (ICD-10 code J) diseases ranked first and second, respectively, and their ranks did not change during the study period (figure). Digestive and endocrine diseases decreased while psychiatric diseases increased from rank 9 in 2003 to rank 6 in 2011 (figure). Among specific diseases, pneumonia (organism unspecified, code J18) ranked first in 2003 and second in 2011. Acute myocardial infarction (code I21) ranked second in 2003 and third in 2011. Chronic obstructive pulmonary disease with acute lower respiratory infection (code J44) ranked third in 2003 and decreased to rank 8 in 2011. Conversely, heart failure (code I50) increased from rank 8 in 2003 to rank 1 in 2011 and delirium (not induced by alcohol and other psychoactive substances, code F05) increased from below rank 20 in 2003 to rank 4 in 2011. For more details, see table. Conclusion: In less than 10 years, considerable changes occurred in the presentation of patients attending an Internal Medicine ward. The changes in diseases call for adaptations in hospital staff and logistics. 127 Postesession 2 - Session des posters 2 Kardiologie - Pneumologie - Gastroenterologie 1 / Cardiologie - Pneumologie - GastroentГ©rologie 1 P376 Right cardiac obstruction in a healthy 76-year-old lady Tobias Г–ttl*, Daniel Jauslin, Pirmin HГ¤uptle, Marc Gutmann, Andreas Lohri Kantonsspital Baselland, Liestal (Liestal, CH) A 76-year-old woman was admitted because of orthopnea. She reported mild effort intolerance (NYHA II) over the past 6 months, but had continued her usual active lifestyle. Shortness of breath started to deteriorate 4 weeks earlier. She had a history of untreated hypertension and no immunosuppressive therapy. On admission, her heart rate was 100/min, peripheral oxygen saturation was 80%. Physical examination showed jugular venous distension and suspected bibasilar pleural effusions. Laboratory findings included a NT-proBNP level of 1100ng/l (normal value <125ng/l) and a LDH of 496 U/l (normal value <250 U/l), a chest X-ray confirmed bilateral pleural effusions. Cardiologic work-up included an initial transesophageal echocardiogram (TEE) that showed a circular pericardial effusion of 3cm, no valvular dysfunction and a normal systolic function. Unexpectedly, a large mass of 6.4x4.4cm was seen in the right ventricle that led to a high pressure in the right atrium with a right-to-left shunting through a patent foramen ovale (figure 1). Further imaging consisted of a thoracic and abdominal CT scan without signs of malignant lymphadenopathy or primary tumor. Neither diagnostic pericardiocentesis nor thoracentesis showed malignant cells. After intense discussions, the definite diagnostic was obtained by endomyocardial biopsy. Histologically, a myocardial infiltration by a diffuse large B-cell lymphoma (DLBCL) was found. For further staging, a bone marrow exam and a PET scan was performed. It confirmed the large tumor in the right heart and some activity in a single adjacent lymph node. Testing for HIV was negative. Symptoms started to improve after initiation of steroids and rituximab, a monoclonal anti-CD20 antibody . Treatment was continued with a modified R-CHOP regimen containing cyclophosphamide, mitoxantrone, vincristine and prednisone. An early CT scan of the heart showed a tremendous regression of the cardiac mass (figure 2), which was confirmed by a TEE four weeks later. After a total of 6 cycles of chemotherapy, the patient's condition was stable and she was oligosymptomatic. Primary malignant cardiac lymphoma are extremely rare in non-immunocompromised patients. They occur less frequently than sarcoma and respond favourably to chemotherapy. Nevertheless, few patients are desribed who obtain durable complete remissions. 128 129 P377 Association of ECG abnormalities and incident heart failure events Baris Gencer*, Javed Butler, Douglas Bauer, Reto Auer, Andreas Kalogeropoulos, Perdro MarquesVidal, William Applegate, Suzanne Satterfield, Tamara Harris, Anne Newman, Eric Vittinghoff, Nicolas Rodondi Geneva University Hospital (GenГЁve, CH); Emory University (Atlanta, US); University of California (San Francisco, US); Lausanne University Hospital (Lausanne, CH); Wake Forest University Baptist Medical Center (Winston Salem, US); University of Tennessee Health Science Center (Memphis, US); National Institute on Aging (Bethesda, US); University of Pittsburgh (Pittsburgh, US); Bern University Hospital (Bern, CH) Background: With the aging of the population, the heart failure (HF) incidence and prevalence trends are expected to significantly worsen unless concentrated prevention efforts are undertaken. ECG abnormalities are common in the elderly but data are limited for their association with HF risk. Objective: To assess whether baseline ECG abnormalities or dynamic changes are associated with an increased risk of HF. Method: A prospective cohort study of 2915 participants aged 70 to 79 years without a preexisting HF followed for a median period of 11.4 (IQR 7.0-11.7) years from the Health Aging and Body Composition study. The Minnesota Code was used to define major and minor ECG abnormalities at baseline and at 4-year. Main outcome measure was adjudicated incident HF events. Using Cox models, the (1) the association between ECG abnormalities and incident HF and (2) incremental value of adding ECG to the Health ABC HF Risk Score, was assessed. Results: At baseline, 380 participants (13.0%) had minor and 620 (21.3%) had major ECG abnormalities. During follow-up, 485 (16.6%) participants developed incident HF. After adjusting for the eight clinical variables in the Health ABC HF Risk Score, the hazard ratio (HR) was 1.27 (95% confidence interval [CI] 0.96-1.68) for minor and 1.99 (CI 1.61-2.44) for major ECG abnormalities (P for trend <0.001) compared to no ECG abnormalities. The association did not change according to presence of baseline CHD. At 4-year, 263 participants developed new and 549 had persistent abnormalities and both were associated with increased HF risk (HR = 1.94, CI 1.38-2.72 for new and HR=2.35, CI 1.82-3.02 for persistent compared to no ECG abnormalities). Baseline ECG correctly reclassified 10.6% of overall participants across the categories of the Health ABC HF Risk Score. Conclusion: Among older adults, baseline ECG abnormalities and changes in them over time are common; both are associated with an increased risk of HF. Whether ECG should be incorporated in routine screening of older adults should be evaluated in randomized controlled trials. 130 P378 Development of an aorto-left atrial fistula in a patient with ankylosing spondylitis Vera KГ¶nig*, Raphael Jeker, Felix SchГ¶nrath, Walter H. Reinhart, Piero O. Bonetti Kantonsspital GraubГјnden (Chur, CH); UniversitГ¤tsspital (ZГјrich, CH) Introduction: Ankylosing spondylitis (M. Bechterew) is a chronic inflammatory disease involving the spine, but also other organs such as the heart, lungs, eyes, kidneys and aortic root (aortitis). Involvement of the aortic root may lead to a thickening and dilation of the aortic wall and thickening and retraction of the aortic cusps with subsequent aortic regurgitation. We report on a patient with ankylosing spondylitis, who developed a fistula from the aortic root to the left atrium. Case report: A 49-year-old man with advanced ankylosing spondylitis was admitted for an echocardiographic control 18 months after mechanical aortic valve replacement and mitral valve reconstruction for severe aortic regurgitation and moderate mitral regurgitation, respectively, which were thought to be due to inflammation associated with ankylosing spondylitis. The patient reported a worsening of his condition with increasing weakness. Transthoracal/transesophageal echocardiography was suggestive for a supravalvular abscess on the posterior part of the aortic root with an aorto-atrial fistula between the sinus valsalvae and the left atrium. Assuming infective endocarditis, an empiric antibiotic treatment with rifampicin, gentamycin and vancomycin was started. Blood cultures withdrawn before initiation of antibiotic therapy and a Quantiferon test remained negative. Given the echocardiographic findings and the lack of improvement of his clinical condition, the patient underwent urgent surgery including mechanical mitral valve replacement, replacement of the mechanical aortic valve with graft-replacement of the ascending aorta and reconstruction of the aorto-mitral transition zone with closure of the left atrial roof by a pericardial patch. Because all tissue samples and cultures taken during surgery remained negative for bacterial infection, antibiotics were stopped after a total of 4 weeks. Instead, assuming ankylosing spondylitis-associated aortitis, a systemic corticosteroid therapy with 50 mg prednisolone daily was initiated, which led to rapid clinical improvement. 2 months postoperatively, a therapy with Infliximab (RemicadeВ®) was initiated. Discussion: Clinically evident aortic root or valvular disease is observed in less than 20% of patients with ankylosing spondylitis. To our knowledge, this is the first report an aorto-atrial fistula as a complication of aortitis associated with ankylosing spondylitis. P379 Improvements in quality of care for patients discharged after acute coronary syndrome over the last ten years Reto Auer, Baris Gencer*, Lorenz RГ¤ber, Roland Klingenberg, David Carballo, Sebastian Carballo, David Nanchen, Jacques Cornuz, John-Paul Vader, Pierre Vogt, Peter JГјni, Christian Matter, Stephan Windecker, Thomas LГјscher, FranГ§ois Mach, Nicolas Rodondi University of California (San Francisco, US); Geneva University Hospital (GenГЁve, CH); Bern University Hospital (Bern, CH); ZГјrich University Hospital (ZГјrich, CH); Lausanne University Hospital (Lausanne, CH) Background: Adherence to guidelines is associated with improved outcomes of patients with acute coronary syndrome (ACS). We aimed at determining the improvement in the rate of prescription of recommended treatment at discharge over the last ten years, taking into account reasons for nonprescription, and the rate of attendance to cardiovascular rehabilitation(CR). Methods: We measured the rate of recommended treatment at discharge, and attendance to CR among 1260 patients hospitalized for ACS in 4 academic centers in Switzerland in 2009-2010. Reasons for non-prescription were systematically collected according to guidelines. Data were compared to 577 patients hospitalized in 1999 who had their medical charts reviewed for reasons for non-prescription. We identified factors associated with attendance to CR using multivariable logistic regression adjusted for clustering by center. Results: Hundred percent of patients discharged in 2009-2010 were prescribed aspirin compared to 91% of those discharged in 1999(p<0.001). Prescription rates for beta-blockers increased from 81% to 96% (p<0.001) and angiotensin converting enzyme inhibitors/angiotensin II receptor blockers for patients with left ventricular ejection fractions <=40% rose from 80% to 100% (p<0.001). 61.5% of patients attended CR. Older age, not having a ST-segment elevation myocardial infarction and previous coronary heart disease were associated with decreased odds of CR(all p<0.05). Conclusions: We found a marked increase in adherence to ACS guidelines for drug prescriptions over the last 10 years among academic centers in Switzerland. Pre-specification of reasons for non131 prescription within clinical registries permits to identify remaining gaps in quality of care. However, barriers to attendance to CR need to be further explored. P380 Pulmonary embolism D-dimer testing and clinical judgment: a cautionary tale Joana Barbosa*, Panagiotis Antiochos, Amir Jaff, Raffaella Craighero, JГ©rГґme Burnand, Uwe Schiemann HГґpital Cantonal de Fribourg - Site de Riaz (Riaz, CH) Introduction: Although a frequent and potentially severe pulmonary embolism (PE) remains difficult to a rapidly and accurately diagnose. Plasmatic D-Dimer testing is commonly used in the evaluation of possible PE in the emergency department sparing patients unnecessary radiation. As everything in medicine, D-Dimer testing has limitations, which are essential to understand in our practice. Case Report: A 72 years-old woman presented to our emergency department with complaints of dyspnea class III/IV and a sharp chest pain radiating to both arms, neck and back for the preceding 24h. Personal history was notable for pulmonary embolism, a bladder carcinoma diagnosed three years ago and active smoking with 30 pack years. An electrocardiogram showed sinus rhythm with a Q wave in DIII. D-Dimers were within normal limits (363ng/ml) with a calculated modified Geneva score revealing ``moderate PE risk``. The patient was hospitalized in our critical care unit for rhythmic and clinical surveillance. A ``triple rule-out`` chest CT scan was undertaken and demonstrated multibilateral segmental pulmonary embolism, and coronary artery disease with significant left anterior descending (LAD) stenosis. Treatment with low molecular weight heparin was started and the patient underwent coronary angioplasty of her LAD and first marginal arteries. Conclusion: Several major clinical models have been published and tested to determine patientsвЂ™ pretest probability of PE. D-Dimer testing is considered an appropriate method for the exclusion of PE in low to moderate risk patients where it shows a negative predictive value of 95.7%. Nevertheless, definition of low-risk is not consensual. As in our case, clinical presentation of PE can be variable and misleading. A negative D-dimer testing even in the context of a вЂњmoderate risk`` patient group can lead to missing underlying PE which should be considered especially in cases where alternative diagnoses are unlikely. As our case proves once again, laboratory values have to be interpreted in the light of clinical data et clinical exam. More specifically in the case of PE, an approach of keeping a high index of suspicion for this eventually lethal disease plays a paramount role in patient care. 132 P381 A case series of omalizumab in non-allergic (intrinsic), eosinophilic asthma Lukas JГ¶rg-Walther*, Carolina Diaz, Max Pfenninger, Werner Pichler, Arthur Helbling Inselspital, University Hospital Bern (Bern, CH); Praxis M. Pfenninger (Olten, CH) Background: Omalizumab is a humanized monoclonal antibody, that binds selectively to free IgE in plasma and inhibits its binding to Fc-IgE receptors on the surface of mast cells and basophils. This results in a reduced Fc-IgE receptor level, which may be related to lower mast cell stimulation. Today it is approved for the treatment of moderate to severe persistent allergic asthma. In contrast, there are only few reports concerning the effect of this recombinant antibody in non-allergic (intrinsic) asthma. Objectives: To evaluate the effect of omalizumab in patients with non-allergic asthma. Methods: We report a case series of 4 patients with the diagnosis of severe uncontrolled intrinsic asthma, median age of 60.5 years (2 females), 3 in the context of a aspirin exacerbated respiratory disease (AERD). All patients were treated with omalizumab, during the past 3 years with dosing and treatment intervals according to the manufacturersвЂ™ recommendations. Results: After the first 4 months with omalizumab, there was a significant improvement in median forced expiratory volume in one second (FEV1, expressed in % of predicted value) [+ 40.8 %], disease control, number of exacerbations and use of basal and rescue medication. One of our patients with a positive inhalative provocation test with L-Acetylic acid (cumulative dose: 25 mg) showed a negative provocation (cumulative dose: 100mg) 4 months after initiation of omalizumab treatment. No adverse events occurred. Conclusion: Some patients with severe asthma associated with AERD and polyposis nasi without sensitization to any inhaled allergens cannot be controlled with standard asthma treatment. Therefore recurrent or prolonged use of systemic and inhaled corticosteroids including leukotriene antagonists is required. These patients representing a subgroup with AERD and an eosinophile-dominated airway inflammation may benefit from treatment with anti-IgE. Further studies are needed to confirm these findings. P382 LвЂ™ilГ©us biliaire, cause rare de lвЂ™ileus mГ©canique. Mireille Nsangu Mampasi* HГґpital Fribourgeois . (Riaz, CH) LвЂ™ilГ©us biliaire, cause rare de lвЂ™ileus mГ©canique. Nsangu Mampasi M., Leukefack JB., ThГ©odoloz C., Schiemann U., Mihai-Christian I. Service de mГ©decine, service de chirurgie, service de radiologie, HГґpital fribourgeois Riaz PrГ©sentation du cas clinique : Il sвЂ™agit dвЂ™une patiente de 90 ans, sans antГ©cГ©dent chirurgical, qui consulte les urgences pour des vomissements verdГўtres, depuis la veille, accompagnГ©e des 2 Г©pisodes de malaise sans perte de connaissance. Elle signale des constipations alternant avec des diarrhГ©es post lavement depuis environ 2 semaines. A lвЂ™examen clinique, lвЂ™abdomen est lГ©gГЁrement ballonnГ©, indolore avec des bruits abdominaux. Le bilan biologique rГ©vГЁle un discret syndrome inflammatoire avec la C- protГ©ine rГ©active Г 39 mg/L, une leucocytose Г 12,7 G/L, les enzymes hГ©patiques normales. La radiographie de lвЂ™abdomen Г vide montre quelques anses grГЄles moyennement dilatГ©es, sans niveau hydro-aГ©rique, avec un gros calcul dans la vГ©sicule biliaire. LвЂ™Oeso-gastro-duodГ©noscopie rГ©alisГ©e est peu contributive, car elle est interrompue Г cause dвЂ™une rГ©tention alimentaire qui provoque un vomissement avec broncho- aspiration modГ©rГ©e. La tomodensitomГ©trie abdominale montre un ilГ©us grГЄle biliaire avec une vГ©sicule biliaire en porcelaine fistulisant dans le duodГ©num avec la prГ©sence dвЂ™un gros calcul calcifiГ© au niveau de lвЂ™ilГ©on proximal. Une entГ©rotomie est pratiquГ©e par laparotomie avec extraction des 3 calculs au niveau de lвЂ™ilГ©on proximal respectivement de 3,5 cm, 1,5 cm et 1 cm de diamГЁtre, Г©talГ©s sur une longueur 15 cm. LвЂ™Г©volution clinque est favorable avec la reprise du transit intestinal au sixiГЁme jour post -opГ©ratoire. Conclusion : LвЂ™ilГ©us biliaire est une occlusion intestinale rare, liГ© au passage dвЂ™un calcul biliaire dans lвЂ™intestin, le plus souvent Г travers une fistule cholГ©cysto-duodenale( rarement une fistule cholГ©cystocolique ou gastrique) , soit par migration endo-luminale dвЂ™un calcul biliaire , soit aprГЁs une cholГ©cystectomie , ou lors dвЂ™une sphincterotomie endoscopique. Le diagnostic doit ГЄtre Г©voquГ© devant toute occlusion intestinale mГ©canique chez la personne ГўgГ©e (25 % Г partir de 70 ans). Le diagnostic souvent tardif se fait radiologiquement par la triade de RIGLER caractГ©risГ© par lвЂ™aГ©robilie, lвЂ™obstruction de lвЂ™intestin grГЄle et la localisation ectopique des calculs biliaires (le plus souvent dans la fosse iliaque droite). Le traitement est essentiellement chirurgical (entГ©rotomie avec / ou sans cholecystectomie). 133 P383 Long diagnostic delay in CrohnвЂ™s disease is associated with a complicated disease course and increased operation rate Stephan Vavricka*, Gerhard Rogler, Ekaterina Safroneeva, Alain Schoepfer Stadtspital Triemli (ZГјrich, CH); UniversitГ¤tsspital (ZГјrich, CH); CHUV (Lausanne, CH) Background and Aims: The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcome. Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery at distinct intervals after CD diagnosis (0 - < 2, 2 - < 6, >= 6 years) were compared for groups of patients with different length of diagnostic delay. Results: The data from a group of 200 CD patients with long diagnostic delay (> 24 months, 76th 100th percentile) were compared to those from a group of 461 patients with a short diagnostic delay (within 9 months, 1st - 50th percentile). Treatment regimens did not differ between the two groups. Two years following diagnosis, patients with long diagnostic delay presented more frequently with bowel stenoses (25% vs. 13.1%, p = 0.044), internal fistulas (10% vs. 2%, p = 0.018), perianal fistulas (20% vs. 8.1%, p = 0.023) and more frequently underwent intestinal surgery (15% vs. 5.1%, p = 0.024) than patients with short diagnostic delay. Intestinal surgery was also more frequently performed >= 6 years after diagnosis in a group with long diagnostic delay (56.2% vs. 42.3%, p = 0.005) when compared to a group with short diagnostic delay. Conclusions: Long diagnostic delay is associated with the development of increased bowel damage, necessitating increased number of operations in the years following CD diagnosis. Efforts should be undertaken to shorten the diagnostic delay. P384 Secondary prevention after acute coronary syndromes in hospitals with and without coronary intervention facilities in the French-speaking part of Switzerland Joris Welker*, Reto Auer, Baris Gencer, Jacquez Cornuz, Pierre F. Keller, Pierre Vogt, Christian M. Matter, Stefan Windecker, Thomas F. LГјscher, FranГ§ois Mach, Nicolas Rodondi, David Nanchen University of Lausanne (Lausanne, CH); UCSF, San Francisco (Californien, US); University Hospital Geneva (GenГЁve, CH); University Hospital, Lausanne (Lausanne, CH); University Hospital Zurich (ZГјrich, CH); University Hospital Bern (Bern, CH); University of Bern (Bern, CH) Introduction: The quality of care for patients with acute coronary syndromes (ACS) might differ according to the type of hospital. Particularly few data exist about secondary prevention for patients with ACS discharged from hospitals without percutaneous coronary intervention (PCI) facilities. We aimed to assess and compare secondary prevention in patients with ACS at hospital discharge according to the type of hospital defined by the availability of PCI facilities. Methods: We studied 353 men and women with ACS underwent coronary angiography with or without PCI between July 10th 2009 and November 3rd 2010 in five peripheral hospitals without PCI facilities and one referring hospital with PCI in the French-speaking part of Switzerland. All participants were either discharged from the referring hospital or transferred within one day after coronary angiography to one of the five peripheral hospitals without PCI facilities and discharged from there. All clinical information was abstracted at baseline and at discharge from medical records in each hospital. We recorded the prescription of recommended secondary prevention medication or mentioned contraindications, including aspirin, statin, beta-blocker and angiotensin-converting enzyme inhibitor (ACE) or angiotensin-II receptors blocker (ARB), inclusion in cardiac rehabilitation program and in-hospital smoking cessation intervention or mentioned contraindications. Results: Among 353 ACS patients, 262 (74.2%) were discharged from the hospital with PCI facilities, and 91 (25.8%) from hospitals without PCI facilities. The mean age (SD) was 64.1 (12.2) years and 75.6% were men. The prescription of drugs for secondary prevention was high at hospitals with and without PCI facilities, summing up to 86.3% and 84.6%, respectively (p=0.698). By contrast, only 51.6% of ACS patients in the hospital with PCI facilities and 59.3% in hospitals without PCI were enrolled in a cardiac rehabilitation program (see Figure). Higher age, low education level, and a history 134 of preexisting cardiac disease were negatively associated with cardiac rehabilitation enrollment in both types of hospital. In-hospital smoking cessation interventions were performed in 31.1% of smokers and exclusively at the referring hospital with PCI facilities. Conclusions: We found no difference in a high prescription of drugs for secondary prevention after ACS in patients discharged from hospitals with or without PCI facilities. However, there is room for improvement given the low rates of participation in cardiac rehabilitation programs or in-hospital smoking cessation counseling in the French-speaking part of Switzerland. 135 Postesession 2 - Session des posters 2 Kardiologie - Pneumologie - Gastroenterologie 2 / Cardiologie / Pneumologie / GastroentГ©rologie 2 P385 Effekte der pneumologischen Rehabilitation im Hochgebirge: Ergebnisse der Einjahreskatamnese der Davoser-Outcome-Studie (DOS) Udo Kaiser*, RГјdiger NГјbling, JГјrgen Schmidt, David Kriz Hochgebirgsklinik Davos (Davos Wolfgang, CH); GFQG (Karlsruhe, DE) Einleitung: Pneumologische / dermatologische Erkrankungen haben eine hohe PrГ¤valenz und fГјhren bei den Betroffenen und auch der Volkswirtschaft zu hohen Belastungen. Zur umfassenden Behandlung gehГ¶ren neben der kurativen Versorgung rehabilitative Angebote, die vorwiegend wohnortfern durchgefГјhrt werden. Obwohl der Nutzen dieser Behandlungen heute als nachgewiesen gilt (Kaiser 1994, 2003), werden die Angebote nicht in notwendigem Umfang genutzt. Methode: Im Rahmen der Davoser-Outcome-Studie (DOS; vgl. Kaiser et al., 2011), einer mehrere Messzeit-punkte (Aufnahme, Entlassung, 6-, 12-, 24-Monatskatamnese) und Datenquellen (Patienten, KlinikГ¤rzte, ambulante Г„rzte) umfassenden Programmevaluationsstudie, wurden somatische, funktionale, psychosoziale, behandlungsbezogene, soziodemographische und gesundheitsГ¶konomische Parameter erhoben. Hierbei kamen patientenseitig u.a. HADS, FKV-LIS, SF-12, IRES-24, SIBAR, PAREMO, SGQR, FLQZ, ZUF8, arztseitig u.a. GAF, BSS, SCORAD, PASI, FEV-1, M-Score zum Einsatz. Dane-ben wurden in Adaption Teilaspekte aus FragbГ¶gen der Arbeitsgruppe aus frГјheren Studien (z.B. EQUA, Schmidt et al. 2003, Davoser Reha-Studie I und II, Kaiser, 1994, 2003) integriert. Ziel der Studie ist u.a. die Abbildung kurz-, mittel- und langfristiger Behandlungseffekte. Die 12-Monatskatamnese wurde im August 2012 abgeschlossen. Ergebnis: Es liegen n=892 (Aufnahmemessung-A) PatientenfragebГ¶gen vor. Die RГјcklaufquote fГјr K12 betrГ¤gt 70%. Es handelt sich um 45% MГ¤nner und 55% Frauen mit einem Durchschnittsalter von 49.3 Jahren (SD 13.1 Jahre) mit vorwiegend pneumologischen Erkrankungen (71%) bei chronischem Krankheits-verlauf (80% Krankheitsdauer > 10 Jahre) und ausgeprГ¤gter MultimorbiditГ¤t (MW 2.54 Diagnosen). Tab. 1 zeigt im Vergleich Aufnahme bis K12 das AusmaГџ der VerГ¤nderungen bei ausgewГ¤hlten Outcomeparametern mit mittleren bis hohen EffektstГ¤rken: Schlussfolgerung: Die Teilergebnisse der Einjahreskatamnese belegen die Effekte stationГ¤rer Behandlungen in der Hochgebirgsklinik Davos in relevanten Outcomeparametern. In den nГ¤chsten Auswertungsschritten wird versucht, durch differenzielle Auswertungsstrategien den Nutzen fГјr unterschiedliche Subgruppen bzw. Problemkonstellationen nГ¤her zu analysieren. Schon heute kann aus den Ergebnissen abgeleitet werden, dass Massnahmen dieser Art gezielter, frГјher und hГ¤ufiger zum Einsatz kommen sollten. NГјbling, 2010). 136 P386 Asthma Monitor: a free application for the diagnosis and management of asthma Nebal Abu Hussein*, Katharina Gessler, Esther Helen Steveling, Sabrina Maier, Claudia Gregoriano, Stefania Zogg, Selina DГјrr, Emanuel Hediger, David Miedinger, JГ¶rg Daniel Leuppi UniversitГ¤tsspital Basel (Basel, CH); Fachhochschule Nordwestschweiz (Windisch, CH) Recording peak flow (PEF) is an easy and objective method to detect changes of lung function in asthmatic individuals. PEF, respiratory symptoms and the asthma control test (ACT) results can be used to determine asthma control status and their longitudinal changes. This can support the assessment of treatment response. Monitoring of these parameters might provide a better control and management of asthma. However, to achieve this graphical interpretation and calculations of indices, a daytime variability calculation is needed, which is not possible with handwritten asthma diaries. The Asthma Monitor application is a free and easy in use program, designed for Android smartphones and tablet computers. It allows patients to monitor their asthma easily by recording their PEF, symptoms, emergency medication and activities on a daily basis, in addition to the asthma control status using the ACT-test. PEF limit values can be entered to help the instructed patient to selfmanage her/his asthma. The recorded data can be displayed as graphs on screen, converted into a .pdf-document or stored as raw database file and sent to the treating physician. This application is an easy in use tool that might help asthmatic patients to better self-manage their asthma. It can be used to diagnose lung function variability in previously undiagnosed asthma or in situations, where the effect of treatment changes needs to be evaluated. P387 Single-balloon assisted colonoscopy: success rates in patients with previous incomplete colonoscopy Gian-Marco Semadeni*, Christa Meyenberger, Remus Frei Kantonsspital St. Gallen (St. Gallen, CH) Background: Cecal or ileal intubation is a well recognized measure of colonoscopy quality. Infrequently, a complete examination is unsuccessful with the standard technique. Extensive diverticulosis, history of abdominal surgery, female gender und low body mass index are factors associated with incomplete colonoscopy. The use of single-balloon overtube assisted technique in these situations has only been studied sparsely. Methods: In a prospective single-center study, single-balloon overtube assisted colonoscopy was performed in patients with previous incomplete colonoscopy in standard technique. The single-balloon enteroscope SIF-Q180 of OlympusВ® and fluoroscopy were used. Results: Between February 2008 and January 2013, 53 consecutive patients (mean age 67y, range 38-87, 32 females, 21 males,) were examined in single-balloon overtube assisted technique. The cecum was reached in 96% (51 of 53). The passage of the sigmoid colon with the SIF-Q180 endoscope was not possible in two cases: in one female patient with peritoneal carcinosis and in one male patient with extensive diverticulosis, both with a fixed, looped sigmoid colon. There were no pathologic findings in four patients (8%), twenty-nine patients (55%) showed a marked diverticulosis. In twenty-one patients (40%), there were one or several polyps found, all of which could be removed. Other findings were CrohnвЂ™s colitis, diversion colitis, angiodysplasia in the ascending colon and adenocarcinoma in the sigmoid colon. Two complications (4%) occurred. There was one single mucosal defect as a consequence of a polypectomy, which was treated successfully by clipping and prophylactic antibiotic therapy. A second patient suffered from abdominal pain and hematochezia after a diagnostic single-balloon colonoscopy without intervention. A perforation was excluded by CT scan. She had to be admitted in the hospital for surveillance for four days. Conclusions: Colonoscopy in single-balloon overtube assisted technique is a safe and effective procedure in patients with a previous incomplete or failed standard colonoscopy. 137 P388 Daily physical activity across the new combined COPD risk groups Stefanie Zogg*, Selina DГјrr, Sabrina Maier, Esther Helen Steveling, David Miedinger, JГ¶rg Daniel Leuppi UniversitГ¤tsspital Basel (Basel, CH) Background: To more precisely evaluate the impact of COPD, a combination of symptom estimation and spirometer-based classification and/or risk of exacerbation is recommended. Symptoms are assessed by COPD assessment test (CAT) or Modified Medical Research Council (mMRC) dyspnea scale. Since patients with COPD are known to practice a sedentary lifestyle, the aim of the present study was to examine physical activity (PA) across COPD risk groups based on CAT and mMRC. Methods: In 2011, patients with stable COPD were recruited at the University Hospital Basel. Participants were divided into the 4 risk groups A to D according to the revised GOLD guidelines of December 2011 (Figure 1). Based on CAT, the distribution of patients was A (n=27), B (n=36), C (n=1) and D (n=14). Using mMRC, patients were classified as A (n=10), B (n=47), C (n=0) and D (n=14). Risk groups C and D were combined for statistical analysis. PA was measured by the SenseWear Mini Armband on 7 consecutive days. Daily number of steps, time spent in PA above 3.0 METs (PA3), activity-based energy expenditure (AEE) and PA level (PAL) were analysed. Results: Complete data were available from 78 patients aged 44 to 90 (57.7% male, age 66.6+/9.7yrs, BMI 25.8+/-5.5kg/m^2, steps 4783.6+/-3337.6, PA3 94.6+/-84.9min, AEE 443.6+/-383.1cal, PAL 1.3+/-0.3METs). The interrater agreement between CAT- and mMRC-based classification was found to be k=0.73, indicating a good agreement. Based on CAT, steps (p=0.003) and AEE (p=0.007) were shown to be significantly higher in COPD risk group A compared to B. In contrast, all PA parameters, steps (p=0.015), PA3 (p=0.001), AEE (p<0.001) and PAL (p=0.006), were found to be reduced in risk group B compared to A, using mMRC. Conclusion: This study provides evidence that daily PA is significantly impaired in more severe COPD risk groups compared to mild one. Moreover, mMRC dyspnea scale focusing on the impact of dyspnea might be a good and shorter alternative to commonly used CAT. 138 P389 Procalcitonin-guided antibiotic therapy in patients with congestive heart failure and suspicion of lower respiratory tract infection: results from a randomized trial Alexander Kutz*, Eva Marianne Grolimund, Sebastian Haubitz, DГ©sirГ©e Demann, Alaadin VГ¶geli, Mirjam Christ-Crain, Robert Thomann, Werner Zimmerli, Claus Hoess, Christoph Henzen, Beat MГјller, Philipp Schuetz Kantonsspital Aarau (Aarau, CH); UniversitГ¤tsspital Basel (Basel, CH); BГјrgerspital Solothurn (Solothurn, CH); Kantonsspital Liestal (Liestal, CH); Kantonsspital MГјnsterlingen (MГјnsterlingen, CH); Kantonsspital Luzern (Luzern, CH) Introduction: Differentiation of acute heart failure from infection in patients with respiratory symptoms and a history of congestive heart failure (CHF) is challenging due to overlap of clinical symptoms and X-ray findings. The BACH Study found higher mortality rates if patients presenting with dyspnea were treated with antibiotics and their procalcitonin (PCT) levels was low indicating absence of bacterial infection. Yet, the BACH study was observational and causal inference cannot be drawn. Herein, we analyzed the effects of PCT guided antibiotic stewardship in CHF patients from a previous trial (ProHOSP). Methods: This is a secondary analysis of a previous randomized trial of adult emergency department (ED) patients with respiratory symptoms and a history of CHF. Patients were randomized to administration of antibiotics based on a PCT algorithm (PCT group) or standard guidelines without knowledge of PCT levels (control group). The primary endpoint of this analysis is the risk of adverse outcome defined as death or intensive care unit (ICU) admission within 30 days after ED admission. Results: A total of 233 patients met the inclusion criteria with 116 in the PCT guided group and 117 in the control group (Table 1). In the subgroup of patients with low initial PCT levels <0.25 Вµg/L (n=110), PCT guided patients had a significant reduction in antibiotic exposure (mean of 3.7 vs 6.5 days, difference -2.8 [95%CI -4.4, -1.2], p<0.001). Furthermore PCT guided patients had a significant lower risk for death and ICU admission (4% vs 20%, odds ratio 6.0 [1.3, 28.2], p=0.02) (Figure 1). Discussion: In CHF patients with suspicion of respiratory infection, use of a PCT protocol resulted in a significant decrease of antibiotic exposure and significantly improved outcomes in patients with low PCT levels indicating absence of bacterial infection. Whether inadequate antibiotic therapy in these CHF patients requiring diuretic treatment explains this difference in clinical outcomes needs verification. 139 P390 Impact of pre-hospital electrocardiography on ECG-to-balloon time in patients with ST elevation myocardial infarction in a rural area Georgia Mitropoulou*, Cristoph Kaiser, Serge Diotte, Jean-Luc Crevoisier HГґpital de DelГ©mont (DelГ©mont, CH); UniversitГ¤tsspital Basel (Basel, CH) Introduction: Primary percutaneous coronary intervention is the preferred reperfusion strategy in patients presenting a ST elevation myocardial infarction and should be performed within 90 minutes from first medical contact, in order to improve patient outcome. This study aims to assess the impact on ECG-to-balloon time, of pre-hospital diagnosis and direct referral to a PCI capable centre, when compared to conventional triage through a regional hospital. Method: Retrospective comparison of ECG-to-balloon times in patients with acute STEMI diagnosed with pre-hospital electrocardiography and transferred to a PCI centre, with patients referred initially to the Hospital of DelГ©mont. Results: From April 2010 through March 2012, a total of 219 patients received a pre-hospital 12 lead ECG, transmitted by the EMS personnel in the field to a cardiologist, with a final diagnosis of STEMI in 24 patients. Of the latter, 16 patients were directly referred to a PCI centre, bypassing the emergency department. During the same period, 77 patients were admitted to our emergency department with final diagnosis of STEMI and 44 of them were urgently transferred to a PCI centre. The two groups presented no significant difference in baseline characteristics (average age 66.56 years versus 63.6 years, p=0.41, percentage of female patients 37.5% versus 27.2%, p=0.44). The mean ECG-toballoon time decreased significantly in patients with pre-hospital ECG compared to patients diagnosed with initial in-hospital ECG (112 min versus 145 min, p=0.021). Hazard ratio for in-hospital diagnosis was 1.29, with confidence intervals 95% (1.04 to 1.60). Conclusion: In patients presenting an acute ST elevation myocardial infarction, residing in rural areas away from PCI capable centres, pre-hospital ECG and triage to appropriate centres helps reduce system delay. More efforts need to be undertaken in order to meet the target of time to reperfusion of less than 90 minutes. 140 P391 Congestive heart failure related to antifungal therapy with itraconazole: illustrative case report RenГ© Vollenbroich*, Daniel Weilenmann Kantonsspital St. Gallen (St. Gallen, CH) Introduction: Only a few cases of congestive heart failure (CHF) suggesting the association with the use of itraconazole, a synthetic antifungal agent, have been reported to the United States FDA Adverse Event Reporting System. To the best of our knowledge, this is the first case report describing this adverse effect in Europe. Case Report: In June 2006, a 60 year-old man was admitted to the Kantonsspital St. Gallen for the treatment of an acute myocardial infarction. Early percutaneous coronary intervention revealed a severe three vessel coronary artery disease with a significantly decreased left ventricular ejection fraction of 30%, and resulted in a good angiographic result. The patient underwent primary prophylactic ICD implantation thereafter. During regular six-month checkups, his condition proved to be stable under antiplatelet, beta blocker, ACE inhibitor, and diuretic therapy. Statin therapy was refused by the patient. In September 2012, he was diagnosed with dermatomycosis of his right lower leg and was administered oral itraconazole (200mg daily) for 1.5 months. During this period, the patientвЂ™s dyspnea worsened, his diuretic intake increased, and he stopped itraconazole therapy on his own. In early December 2012, transthoracic echocardiography revealed an increase in systolic pulmonary artery pressure from 35 to 65 mmHg. In addition, brain natriuretic peptide and serum creatinine increased (BNP: 304 to 579 ng/l, SCR: 99 to 128 Вµmol/l), as did OptiVolВ® measurements. In January 2013, 1.5 months after stopping the antifungal treatment, all these parameters significantly improved again. Discussion: Although labeling of itraconazole has been changed to alert health care professionals to adverse cardiovascular events, the possible coherence is still controversially discussed. However, in our case the patientвЂ™s stable cardiac situation for many years as well as the unchanged medical therapy prior to the intake of itraconazole, closely suggest an underlying relationship. This suspicion is supported by the fact that there has been a close temporal relation of antifungal treatment and essential parameters of CHF. Conclusion: Despite its undeniable efficiency in antifungal treatment, adverse effects of itraconazole to the cardiovascular system might be more common than currently suspected. More research is needed to fully understand the effects of triazoles in particular to patients who are at risk of cardiac decompensation. 141 P392 Cough and abdominal pain: pancreatitis due to codeine Lukas Brylski*, Martin Schelling Spital Lachen (Lachen, CH) Introduction: Drug-induced acute pancreatitis can be caused by a plurality of drugs. Codeine is an opiate which is commonly used for its analgesic and antitussive effects. Although it is a rare side effect and only a few cases have been reported, codeine ingestion provoked a pancreatitis in some persons. We report on a patient with pancreatitis after codeine ingestion and positive reexposition. Case report: A 33-year old women at our emergency department, complained of crampy abdominal pain. The patient suffered from upper respiratory tract infection and concomitant dry cough. She had taken a codeine-containing antitussive (Resyl Plus) for symptomatic treatment. Onset of abdominal pain was 90 min after ingestion. There was no history of alcohol use or abdominal trauma. She had undergone cholecystectomy six years previously. Physical examination was normal. Serum lipase was elevated at 85 U/l. Liver function tests were moderately abnormal: AST 86 U/l, ALT 53 U/l. Her symptoms resolved and she was discharged. A mild pancreatitis was diagnosed. Seven months later, the patient again took a codeine-containing compound (Codein 50mg) for similar respiratory symptoms and developed a belt like epigastric pain. Laboratory tests were comparable to the first presentation. Physical examination again was normal. A diagnosis of beginning pancreatitis due to codeine ingestion was made and the patient was advised to abstain from codeine. After overnight observation and conservative treatment, the patient recovered fully. Therefore no further radiologic evaluation has been made to confirm the diagnosis. Discussion: The presented patient had two events of acute pancreatitis. In both cases she had taken codeine before abdominal pain started. After exclusion of other possible causes and because of a close temporal relationship between drug ingestion and onset of symptoms, we believe that codeine was the trigger for the pancreatitis. As pathophysiological mechanism it has been suggested that codeine causes rapid but transient spasm of the sphincter Oddi. Laboratory studies have shown that codeine may cause a mild, transient hyperamylasemia. Furthermore our patient had a previous cholecystectomy, which is a risk factor for secondary sphincter dysfunction. Conclusion: This case demonstrates that ingestion of even low doses of codeine may cause acute pancreatitis. Codeine should be considered as a possible cause of acute pancreatitis, especially in cholecystectomized patients. 142 Postersession SFGG - Session des posters SPSG P393 Length of stay of elderly patients in a palliative care unit: influence of the day of admission Martin Schneider* HUG (Collonge-Bellerive, CH) Background: A stay in a palliative care unit should be well timed to allow rational use of resources. Many factors influence the length of stay, but little is known about the role of the day of admission, working day or weekend. Methods: The length of stay of all patients admitted to the palliative care unit of the University hospitals of Geneva between 1 December 2011 and 31 May 2012 was prospectively recorded. The data were completed by demographic and medical information. A Cox regression model was developed for the length of stay of patients over 65 years, taking into account sex, diagnosis of cancer and the admission on a working or weekend day. Admissions on holidays were coded as weekend. Results: During the observation period, 116 (87%) patients over 65 years were admitted on working days and 18 (13%) on the weekend. There were 74 (55%) women and 60 (45%) men; mean age was 81 (standard deviation [SD] 8) years. Patients admitted on working days stayed on average for 20 (SD 20) days, those admitted on the weekend 13 (SD 18) days. Patients admitted on a weekend had shorter stays with a hazard rate of 1.76 (95% confidence interval 1.03 вЂ“ 3.00) in the Cox regression controlling for sex and presence of cancer. Conclusion: In this study, patients over 65 years admitted on a weekend had shorter stays than those admitted on working days. This difference could be due to unplanned emergency hospitalisations. A better anticipation of the course of the disease and outpatient palliative care offers might reduce the need for unplanned hospitalisations. P394 Geriatric inpatient rehabilitation in periprosthetic femoral fractures: outcome compared to proximal femoral fractures Matthias Frank*, Annika Lanz, Norbert Suhm, Christian Ritter, Yvonne Zysset, Eveline Nonnenmacher, Martin Conzelmann Felix Platter Spital (Basel, CH); UniversitГ¤tsspital (Basel, CH) 143 Background: Periprosthetic femoral fractures are increasingly observed in recent years. Prolonged periods of reduced weight-bearing are typically needed postoperatively. We wanted to know if long immobilization and hospital stay affected the outcome in these patients. Methods: We retrospectively studied all patients entering geriatric inpatient rehabilitation with a diagnosis of periprosthetic femoral fracture between January 2011 and May 2012. The control group consisted of all patients admitted after surgery for a proximal femoral fracture (pertrochanteric or femoral neck). Baseline data included sociodemographic variables and the results of the geratric assessment on admission. Data on medical and surgical complications were extracted from the medical records. Results: 16 patients were identified. There were 109 patients in the control group. 10 patients were classified as B, 2 as A and 1 as C according to the Vancouver classification. 3 patients had distal femoral fractures next to a knee prosthesis. Two patients were treated conservatively, 7 patients were stabilized with an osteosynthesis (less invasive stabilizing system LISS), 7 were treated with a revision of the femoral shaft. There were no significant differences in the baseline variables and assessment between the groups (68.8 vs. 69.7% female patients, age 84.0В±8.6 vs. 81.9В±9.5 years, Barthel index 46.8В±24.3 vs. 46.1В±17.1, MMSE 23.9В±7.9 vs. 23.1В±5.9). Complications during inpatient rehabilitation were similar between the groups. 68.8% of patients in both groups could be discharged home. No differences in outcome could be detcted (similar gain in Barthel index, gait velocity, Tinetti test). Patients with periprosthetic fractures stayed significantly longer in rehabilitation (50.8В±19.2 vs. 32.4В±17.2 days, p<0.001). Conclusion: Periprosthetic femoral fractures are a specific subgroup of geriatric fracture patients. In our small sample, they were comparable to proximal femoral fractures in terms of demographic characteristics, baseline assessment and rehabilitation outcome. However, rehabilitation stays were significantly longer due to delayed weight-bearing. 144 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 6 - MГ©decine interne gГ©nГ©rale 6 P395 Are we adhering to current guidelines for blood transfusion in a Swiss hospital? Bernard Surial*, Esther BГ¤chli, Andreas Burkhart Spital Uster (Uster, CH) Introduction: Transfusion practices vary widely. One of the problems is the lack of guidelines implemented in hospitals. The optimal use should involve administering enough RBCs to maximize clinical outcomes while avoiding unnecessary transfusions that increase costs and potential harm. The latest guidelines 1 recommends adhering to a restrictive (Hb 7-8g/dl) transfusion strategy in hospitalized, stable patients compared with a more liberal strategy. Method: We registered RBC transfusions during eleven month and the hemoglobin level before transfusion in our hospital. We compared the hemoglobin levels before RBC transfusion between different wards (for instance Internal Medicine, Surgery, Intensive care unit (ICU), Emergency room (ER) and Gynecology) using ANOVA analysis. The transfusion rates of the Clinic of Internal Medicine were subdivided into the following groups: Oncology, Internal Ward and Ambulatory. Result: In total 1514 RBC transfusions were performed. In 739 cases the hemoglobin level was known. The mean level of hemoglobin (MLH) was 7,69g/dl. It showed a significant difference (p: <0,0001) between the MLH before RBC transfusion between the departments and their subgroups. The Gynecology (MLH: 7,44g/dl), the Internal Ward (MLH: 7,42g/dl) and the Oncology (MLH: 7,46g/dl) had the lowest MLH compared to the Surgery (MLH: 7,85g/dl), ICU (MLH: 7,83g/dl) and ER (MLH: 7,80g/dl). The highest MLH was measured at the Ambulatory (MLH: 7,91g/dl). Conclusion: All the wards in our analysis are following the current guidelines with their transfusion strategies. At the same time, we were able to detect significant differences between wards. A likely explanation for this finding is because of the characteristics of patient groups. Lack of data about indications for transfusion of RBC limits the reach of our results at the moment. 1 Guidelines of the American Association of Blood Bank in 2012 P396 Hemiparesis and epileptic seizure after percutaneous coronary intervention misdiagnosed as a subarachnoidal haemorrhage Dragan Despotovic*, Raphael Jeker, Ladina Signorell, Thomas BГ¶hm, Alexander Rieke Kantonsspital GraubГјnden (Chur, CH) Case report: A 73-year-old man with known coronary heart disease with status after 3-fold coronary artery bypass-operation and multiple cardiovascular risk factors such as arterial hypertension, hypercholesterolemia, diabetes mellitus and nicotine abuse presented with acute chest pain irradiated to the left arm. We diagnosed an acute NSTEMI with indication of a percoutaneous cornonary intervention (PCI) with stenting. Three hours after the intervention the patient developped a hemiparesis of the left-sided extremities. The computer tomography scan of the brain without contrast media showed a brain edema on the right side and a hyperdense zone in the subarachnoid space which was consistent with an acute subarachnoid hemorrhage (Fig. 1) and no thrombolytic therapy was performed. Some hours later the patient had a focal epileptic seizure and he was treated with antiepileptic drugs. At the ward the clinical signs didnвЂ™t match with the radiologic findings and we performed a magnetic resonance tomography. A subarachnoidal hemorrhage was excluded, but a small ischemic area in the zone of the right-sided corona radiata was discovered (Fig. 2). Conclusions: We concluded the left sided hemiparesis was related to an acute ischemic stroke at the time of the PCI, which caused a dysfunction of the blood-brain barrier. This enabled the outflow of contrast media which was injected during the PCI. The hyperdense zone in the subarachnoidal space, detected in the CT, was contrast media and not blood. Also the epileptic seizure must be considered as symptomatic seizure of the stroke and the perifocal edema. In the further evaluation the patient showed a complete recovery of the neurological symptoms. Finally this case report allows the conclusion that clinical and radiological findings must not necessarily suit each other. In doubt the clinical findings have a higher relevance and must therefore be judged as decisive factor in terms of further diagnostic measures and final diagnosis. 145 146 P397 Was there something in the soup? Differential diagnosis of increased methoxytyramine Claudine Meindl-Fridez*, Till Hauffe, Urs Schwarz, Markus Schneemann, Eric Grouzmann, Paolo Suter UniversitГ¤tsSpital ZГјrich (ZГјrich, CH); Centre hospitalier universitaire vaudois (Lausanne, CH) Introduction: A 48 year old man was admitted to our emergency department with a hypertensive emergency showing blood pressure up to 230/130mmHg. He was diagnosed with a posterior reversible encephalopathy syndrome (PRES, see poster by T. Hauffe et al.). Secondary hypertension (i.e., renal artery stenosis or primary hyperaldosteronism) was ruled out by corresponding investigations. However, we found increased levels of (free and total) plasma normetanephrine and methoxytyramine (MT) and its precursor dopamine (see Table 1). The MT remained elevated in followup visits of the patient despite an adequate hypertension therapy and well-controlled blood pressure. According to the patient, the hypertensive emergency occurred immediately after a Zen-meditation and subsequent consumption of a traditional genmai soup. An increased concentration of MT was identified in the soup by chromatography. Background: MT is the methoxylated product of dopamine by catechol-O-methyltransferase. MT is found in dopamine-producing paragangliomas and is an independent marker of metastatic pheochromocytomas. Other important differential diagnoses of increased MT are: Parkinson therapeutic agents (L-DOPA), biogenic amines in food (e.g., nuts, cheese, tomatoes, chocolate), and ingestion of certain cactuses (e.g., trichocereus pachanoi (San Pedro cactus), lophophora williamsii (Peyote)). Slices of dried trichocereus are advertised in the internet. They may be consumed in different ways (e.g., as ingredient in mind-expanding hallucinogenic soups). Table 1 summarizes the patientвЂ™s catecholamine and MT test results. Discussion: The disproportional increased MT, which remained elevated during the follow-up, was suspicious. Although the patient assured that he only consumed the genmai soup, he was well versed - much better than the medical staff- in the constituents and application of hallucinogenic cactuses. We will discuss the differential diagnoses of increased MT as well as analytic and toxicological aspects. P398 Focal colitis and widespread intestinal venal thrombosis: a case report StГ©phanie Wagner*, Claudia Brun del Re, Madeleine Rothen, Jonas Rutishauser, Annette Winkler, Rahel Wirth, Shpendin Nuredini Spitalzentrum Biel (Biel, CH) Clinical presentation: A 59-year old male presented with diarrhea, fever and abdominal pain. He was diagnosed with E. coli sepsis, possibly associated with sigma diverticulitis, and received antibiotic treatment for 18 days. On a CT scan obtained upon admission, thrombosis of the portal, superior and inferior mesenteric veins was detected, prompting anticoagulation. Thrombocytosis of up to 1300 G/L was noted. While maintaining the hypothesis of septic thrombosis, we evaluated underlying hypercoagulable states. A mutation in the JAK-2 gene was detected. A bone marrow biopsy and 147 aspiration revealed myeloproliferative disease, with a differential diagnosis of primary osteomyelofibrosis or essential thrombocytosis with progression to osteomyelofibrosis. 7 days after termination of the antibiotic therapy the patient presented with relapsing abdominal pain predominantly in the lower left quadrant. A repeat CT scan showed increased colon wall thickening without progressive intestinal thrombosis. Colonoscopy revealed focal inflammation of the cecum and sigma. In the biopsies inflammatory changes were found. The patientвЂ™s symptoms decreased spontaneously. Discussion: Few cases of septic thrombosis in relation to diverticulitis have been published. In our patient, a hypercoagulable state resulted from myeloproliferative disease, associated with a JAK-2 V617F mutation and thrombocytosis. We surmise that bacterial sepsis and hypercoagulability favored widespread intestinal thrombosis. Conclusion: This case illustrates the importance of testing for hypercoagulability in patients presenting with thrombosis at unusual sites. Even though associated acute disease may be present, the diagnosis of an underlying myeloproliferative disorder should not be missed. P399 Die HypokalzГ¤mie, welche durch Magnesiumzufuhr korrigiert wurde Maria Trachsel*, Cornelia Keller, Peter E. Ballmer Kantonsspital Winterthur (Winterthur, CH) Fall: Eine 66 jГ¤hrige Patientin stellte sich vor wegen SchwГ¤che, Schwindel und Hypotonie sowie Diarrhoe unter Langzeittherapie mit Tavanic wegen einer HГјftotalprothesen-SpГ¤tinfektion. Im Labor prГ¤sentierte sich eine ausgeprГ¤gte HypokalzГ¤mie (albuminkorrigiertes Kalzium 1.33 mmol/l) sowie eine schwere HypomagnesiГ¤mie (0.22 mmol/l). Das 25-OH-VitaminD lag bei 15 Вµ g/l, das Parathormon bei 44 ng/l (Referenzbereich 12-72ng/l). Die HypokalzГ¤mie war oligosymptomatisch: Es bestand ein intermittierendes Kribbeln perioral und in den Fingerspitzen. Chvostek- und TrousseauZeichen waren positiv. Im EKG war keine QT-Zeit-VerlГ¤ngerung zu sehen. Als Ursache der HypokalzГ¤mie gingen wir von einem funktionellen Hypoparathyroidismus (im Vergleich zur Schwere der HypokalzГ¤mie inadГ¤quat tiefes Parathormon) infolge einer durch protrahierten Durchfall verursachten, schweren HypomagnesiГ¤mie aus. Unter Magnesiumsubstitution, initial intravenГ¶s, dann peroral, und symptomatischer Therapie des Durchfalls normalisierten sich sowohl Magnesium- als auch Kalzium-Werte rasch, die diskreten HypokalzГ¤mie-Symptome verschwanden. Diskussion: Die klinischen Symptome einer HypokalzГ¤mie hГ¤ngen vom Schweregrad und der Entstehungsgeschwindigkeit der HypokalzГ¤mie ab und reichen von diskreten Zeichen einer erhГ¶hten neuromuskulГ¤ren Erregbarkeit (ParГ¤sthesien) Гјber MuskelkrГ¤mpfe und Hypotonie bis zu tonischen KrampfanfГ¤llen und Laryngospasmen in schweren FГ¤llen. Zu typischen klinischen Zeichen gehГ¶ren das Chvostek-Zeichen (Kontraktion der Gesichtsmuskulatur beim Beklopfen des N. facialis) und das Trousseau-Zeichen (PfГ¶tchenstellung der Hand nach Aufpumpfen der Blutdruckmanschette Гјber den systolischen Blutdruck). Charakteristische Zeichen im EKG sind QT-Zeit-VerlГ¤ngerungen und STStreckenverГ¤nderungen. Die hГ¤ufigsten GrГјnde einer HypokalzГ¤mie sind ein PTH-Mangel, insbesondere nach Operationen im Bereich der SchilddrГјse, oder aber ein Vitamin D-Mangel. Eine schwere HypomagnesiГ¤mie kann, wie in unserem Fall, zu einer verminderten PTH-Sekretion und PTH-Resistenz mit konsekutiver HypokalzГ¤mie fГјhren. In solchen FГ¤llen sollte primГ¤r Magnesium und nicht Kalzium substituiert werden. Parallel muss die Ursache des chronischen Magnesiummangels behandelt werden. 148 149 P400 A 36 year-old man with an unusual kind of proctitis Thomas StГ¶ckli*, Christophe Petrig Medizinische Klinik (Solothurn, CH); Gastroenterologiezentrum (Solothurn, CH) Case report: A 36 year-old man was admitted in May 2012 with abdominal pain in the left lower quadrant, loss of mucus and blood as well as pain upon defecation. He reported receptive anal intercourse with a single male partner one month before admission. He had a past medical history of syphilis in 2009, treated appropriately with penicillin. His last HIVserology was negative in 2010. On physical examination he had abdominal pain in the left lower quadrant, no fever. Examination of anus and genitals was unremarkable. HIV-serology was negative, serology for syphilis showed evidence of past infection. Since the patient had received one dose of ceftriaxone (2g) intravenously, no diagnostic test for rectal gonorrhea was requested. A colonoscopy with biopsies was performed. Macroscopically, inflammatory changes in the anal and rectal mucosa with swelling and fibrinous erosions were observed (A). Colon and distal ileum appeared normal. Rectal histology showed hyperplastic crypts and infiltration of leucocytes within the lamina propria (B). Real-time PCR on a rectal biopsy sample for Chlamydia trachomatis was positive for Lymphogranuloma venereum (LGV) serovar L2b. 150 The patient was discharged with doxycycline 100mg po twice daily for three weeks and subsequently made a full recovery. Comment: Lymphogranuloma venereum (LGV) is a sexually transmitted disease caused by Chlamydia trachomatis serovar L1, L2 and L3. The classical presentation in both sexes includes genital ulcers or papules and inguinal lymphadenopathy. In its classical presentation, LGV is endemic in Africa, India, South East Asia, Central and South America and the Caribbean. In Europe, including in Switzerland, an increasing number of atypical cases of LGV presenting with proctitis in men who have sex with men (MSM) have been described in recent years. A large proportion of these patients have concomitant HIV-infection. Since rectal LGV can cause chronic inflammation with formation of fistula and fibrosis, timely diagnosis and appropriate antibiotic treatment is crucial. Most experts recommend treatment with doxycycline 100mg po twice daily for three weeks. Real-time PCR is an elegant new tool for detecting Chlamydia trachomatis L1, L2 and L3. A specific protocol was developed at the Institute of Clinical Microbiology, University Hospital of Basel. Clinical samples can be submitted for research purposes and will be analysed free of charge (contact information: Tel. 061 265 5805). 151 P401 Therapeutic drug monitoring of daptomycin: a retrospective monocentric analysis Claudine Reiber*, Oliver Senn, Daniel MГјller, Gerd A. Kullak-Ublick, Natascia Corti University Hospital Zurich (ZГјrich, CH) Objectives: Daptomycin is a lipopeptide antibiotic with rapid concentration-dependent bactericidal action against Gram-positive organisms. Target daptomycin plasma concentrations have been determined in animal models for some pathogens but data on optimal exposure in humans are still lacking. Measurement of daptomycin plasma concentration is available at our institution since 2009 and is performed regularly. The aim was to assess variability of daptomycin plasma concentrations and the main determinants influencing daptomycin exposure. Methods: We retrospectively collected data in patients with at least one determination of daptomycin plasma concentrations during the period of January 2009 to February 2012 at the University Hospital of Zurich. Samples were analyzed by LC-MS/MS. As daptomycin is mainly eliminated by the kidneys, exposure in patients with no renal replacement therapy (nRT), intermittent RT (iRT) and continuous RT (cRT) was compared. A trough level (Cmin) of at least 10mg/l and a minimal peak level (Cmax) of 50mg/l were defined as optimal based on animal data. Results: 90 patients were identified with a mean (SD) age of 59 В±16years and a mean body weight of 74 В±21kg with 15 (16%) patients having a BMI >30. The mean total daptomycin dose was 448mg В± 133mg (range 175 -1000mg). In 22% daptomycin was administered every 48 hours and in 1% every 36 hours. Mean Cmax was 66.2mg/l (n=247, range 20-236mg/l) and mean Cmin was 16.7mg/l (n=116, range 2-68mg/l). Cmax and Cmin levels were significantly lower in cRT (52В±20mg/l and 9.5В±7mg/l, respectively) compared with nRT (75.6В±42mg/l and 21.4 В±16mg/l, p<0.0001). Cmin below 10mg/l was found in 69% of cRT, in 35% of iRT and 26% of nRT and Cmax was below 50mg/l in 52% of cRT, 8% of iRT and 27% of nRT. When controlling for plasma creatinine and albumin concentration, dose interval, administered dose/kg and BMI, cRT remained significantly associated with an increased risk of a Cmin level below 10mg/l (OR= 3.1, p= 0.001) compared to nRT. There was an inverse and independent association between administered dose/kg and Cmax below 50mg/l (OR=2.0, p=0.003). Trough levels >20mg/l were mainly seen in nRT patients with renal impairment with only two cases of mild CK elevation. 152 Conclusion: Daptomycin exposure is highly variable depending on renal function and renal replacement therapy used. Patients undergoing cRT had the highest proportion of low daptomycin exposure with the highest risk for possible under dosing. P402 Influence of parenteral nutrition on blood rheology and platelet aggregation in vitro Sergio Compagnoni*, Thomas Schulzki, Walter H. Reinhart Kantonsspital GraubГјnden (Chur, CH) Background: Parenteral nutrition is an all-in-one emulsion composed of 3 components: Glucose, amino acids, and lipids. Because of its high osmolality, it must be delivered via a central venous catheter. We have studied the influence of parenteral nutrition in vitro on red blood cell (RBC) morphology, blood rheology, and platelet aggregation. Methods: Blood was drawn from healthy volunteers. A plasma volume of 0, 4, 10, and 25% was replaced by a same volume of NuTRIflexВ® Omega special (B. Braun Medical AG, Sempach, Switzerland). In a second set of experiments, the isolated components of NuTRIflexВ® were tested, namely glucose, amino acids, and lipids at plasma concentrations of 10, 10 and 5%, respectively (corresponding to their concentration with 25% NuTRIflexВ®). Besides hematological analysis, viscosity was measured (Contraves LS-30) and platelet aggregation was assessed with a platelet function analyser PFA-100. Results: Changes were concentration-dependent. The mean RBC volume (MCV) measured by an electronic particle counter increased (89.1В±3.3 fl and 96.9В±6.4 fl for control and 25% NuTRIflexВ®, respectively, p<0.05) due to a glucose uptake and consecutive RBC swelling. In contrast, the MCV calculated from the centrifuged hematocrit decreased from 90.6В±3.8 to 80.8В±4.3 fl (p<0.05), indicating that in reality the hyperosmolar amino acid solution caused RBC shrinkage. Whole blood viscosity at a high shear rate of 69.5s-1 was 4.53В±0.56 and 4.83В±0.37 mPa.s for control and 25% NuTRIflexВ®, respectively. At a low shear rate of 0.1s-1, viscosities were 43.2В±9.5 and 15.8В±5.2 mPa.s (p<0.05) suggesting a decreased RBC aggregation, which was confirmed by the RBC sedimentation rate (20.8В±10.2 and 2.7В±1.3 mm/2h, p<0.05). Plasma viscosity was 1.31В±0.07 and 1.27В±0.04 mPa.s. RBC morphology revealed some degree of echinocytic shape transformation (20.7В±19.1% versus 9.0В±5.3% echinocytes) with concomitant hemolysis (LDH 335В±47 and 1036В±208 U/l, respectively, p< 0.05). Platelet aggregation was decreased: The pore closure time in the PFA-100 instrument was prolonged already with 4% NuTRIflexВ® (from 190В±33 to 256В±38s, p<0.05) and was >300s for 10 and 25%. The strongest platelet inhibition was seen with the lipid component. Conclusions: The parenteral nutrition NuTRIflexВ® induced in vitro a concentration-dependent decrease in RBC volume, an echinocytic shape transformation, and a decrease in RBC and platelet aggregation. These changes may have clinical implications. 153 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 7 - MГ©decine interne gГ©nГ©rale 7 P403 A 65 year-old man with a skin lesion on his neck and cervical lymphadenopathy after collecting raspberries in a forest Andreas Plate*, Thomas StГ¶ckli BГјrgerspital Solothurn, Medizinische Klinik (Solothurn, CH); BГјrgerspital, Medizinische Klinik (Solothurn, CH) Case report: A 65 year-old male patient was admitted in July 2012 with night sweats, fever up to 39В°C, loss of appetite and malaise since 3 days. One week earlier, he had been in a forest near BГ¤tterkinden (BE), collecting raspberries. He had noticed an insect bite on the back of his neck. Physical examination showed a wound on the back of his neck with a small central ulcer, at the site of the previous insect bite (A). In addition, cervical and nuchal lymphadenopathies on the left side were found. At the time of admission, the patient was afebrile and in good condition. Laboratory tests showed elevated markers of infection, such as Procalcitonin and C-reactive protein. The patient was hospitalized and treated with intravenous Piperacillin/Tazobactam. During the next three days, he had episodes of fever up to 39ВєC. On day four, his condition seemed to improve. He therefore was discharged with amoxicillin/clavulanic acid 1g po twice daily. However, the patient continued to have fever and night sweats at home and was therefore referred to our infectious diseases outpatient clinic for reevaluation one week later. The antibiotic treatment was changed to doxycycline 100mg po twice daily. Further serological tests were requested. The Microagglutination Assay for Franciscella tularensis came back highly positive for IgM (475 U/ml) as well as IgG (139 U/ml). After treatment with doxycycline for a total of three weeks, the patient recovered completely. Serological follow up three weeks later showed an increase of the IgG titer to >300 U/ml, consistent with recent infection. Comment: Tularemia is caused Franciscella tularensis, a gramnegative bacteria. It is primarily a zoonotic disease affecting rabbits, rodents and occasionally other animals. Transmission to humans occurs through insects, such as bites by ticks or flies, or contact with infected animals. Clinical symptoms are highly variable, depending on the site of entry of the organism. The patient presented here had an ulceroglandular form of tularemia. Presumably, the organism was introduced by an infected insect. At the entry site on the neck, a typical skin lesion with a central ulcer was formed, followed by cervical and nuchal lymphadenitis, fever and malaise. Betalactam antibiotics are not effective against Franciscella tularensis, in contrast to doxycycline. This might explain the patients initial treatment failure. In Switzerland, about 5 -10 cases of tularemia are reported every year. 154 P404 This giggling does not freeze NoГ©mie StГ¤hli*, Lea Aerne, Thomas Bregenzer Spital Lachen (Lachen, CH) Introduction: Ethylene glycol (EG) as a frequent ingredient of antifreeze and other industrial products is relatively nontoxic. But diagnostic and therapeutic delay in EG intoxication can result in severe organ dysfunctions or death (lethal dosis: >= 1g/kg). After ingestion, EG levels peak at 2 - 3 hours. By oxidizing EG (mainly hepatic Alcohol dehydrogenase (ADH)), glycolate, glyxylate and oxalate may accumulate and cause severe end-organ damages (seizures, pulmonary edema, hypotension, renal failure). The anion gap in metabolic acidosis proportionally correlates with the accumulation of toxic metabolites. Immediate ADH inhibition with fomepizol is the treatment of choice. Ethanol may also be used. Case report: A 51 year old woman came to our emergency department (ED). Eight hours (h) earlier she drunk some swallows from a soda drink bottle which she found in her car and thought it was a multi-vitamin drink bought by her sister who used her car before. But it was an originally labeled lemonade bottle filled with orange-colored antifreeze from her car mechanic. Dizziness, headache, nausea and intermittent palpitation developed 3.5 h later. After inducing vomiting she went to bed. When she called us, we recommended her to start treatment immediately by drinking ethanol (wine or hard liquor) and come to the ED. When she arrived she was boozed and giggling with a blood alcohol level of 0.9 0/00. BGA revealed mild respiratory alkalosis and pathological osmolal gap. Oral treatment with ethanol was continued until the antidote fomepizol was available and administered according to guidelines. The EG-level after 14 h of therapy was 29mg/l (nontoxic <200mg/l), and fomepizol was stopped. All clinical and laboratory controls were normal except a mild transient hypocalcaemia. No oxalate crystals were seen in urine analyses. The patient left the hospital without sequelae after 45 h of treatment. Discussion: A forensic testing of the orange liquid confirmed the presence of 50 % of EG in water. Since there was no anion gap acidosis without treatment 8 h after ingestion, the initial EG blood level (not available) must have been low. Osmolal gap may have been elevated due to EG and/or ethanol in the serum. ADH inhibition therapy may have contributed to the favorable outcome. Conclusion: Anion and osmolal gap may help to recognize EG intoxication in unclear metabolic acidosis. Immediate ADH inhibition is crucial. Ethanol serves as empiric treatment until fomepizol is available. P405 Discontinuation of recommended therapies one year after an acute coronary syndrome: results from a prospective cohort Baris Gencer*, Nicolas Rodondi, Reto Auer, David Carballo, Lorenz RГ¤ber, David Nanchen, Pierre Vogt, Sebastian Carballo, Philippe Meyer, Pierre-FrГ©dГ©ric Keller, Christian Matter, Stefan Windecker, Thomas LГјscher, FranГ§ois Mach Geneva University Hospital (GenГЁve, CH); Bern University Hospital (Bern, CH); University of California (San Francisco, CH); Lausanne University Hospital (Lausanne, CH); Groupe mГ©dical Ziggurat (Porrentruy, CH); ZГјrich University Hospital (ZГјrich, CH) Background: Adherence to recommended medication is a key factor to decrease the recurrence of acute coronary syndrome (ACS), but very limited data exist about reasons of discontinuation. We aimed at determining the prevalence and reasons of therapy discontinuation one year after ACS. Method : We studied 1385 men and women from a prospective cohort study of consecutive patients hospitalized for an ACS from July 2009 to December 2010 (18 months) in four Swiss academic hospitals. We measured the rate and the pre-specified reasons of medication discontinuation for aspirin, statins, beta -Blockers and Angiotensin Converting Enzyme Inhibitors/AngioTensin II receptor blockers (ACEI/ATII)one year after ACS. We assessed medical adherence with Medical Adherence Scale (MAS) questionnaires. With the use of logistic regression we identified factors associated with medication discontinuation. Results: Among 1385 patients with ACS followed-up during one year, the discontinuation rate of prescribed treatment one year after hospital discharge was 2.9% for aspirin, 6.5% for statins, 16.5 % for beta -blockers and 15.6% for ACEI/ ATII(7.9% if heart failure was documented). More than 70% of patients reported that treatment was stopped by their physician, while potential side effects were an uncommon reason, except for statins (45.4%) and ACEI/ATII (32.5%). The preexisting use of any medication, the diagnosis of ST-segment elevation ACS, an attendance to rehabilitation program and 155 a reported complete medication adherence (Medication Adherence Scale <1) were all negatively associated with the one year cardiovascular medication discontinuation. Conclusion: Adherence to medication after an ACS differs according to therapeutic drug classes with the highest rate of discontinuation for beta -blockers. An attendance to rehabilitation program decreased cardiovascular discontinuation at one year. Interestingly, patients attributed the reasons of therapy discontinuation to the treating physicians' decision. These results indicate that there is a need to better inform and educate both patients and physicians. P406 Impact of extensive reform of discharge letter on general practitioners, resident work and management Antoine Garnier*, David Gachoud, Mariangela Gagliano, GГ©raldine Gilliot, Milva Cappai, Claudio Sartori, GГ©rard Waeber, Marco Martinuz Centre Hospitalier Universitaire Vaudois (Lausanne, CH) Background: Communicating medical information is a major challenge because of the number of health providers and increasing cutting edge medical care. Discharge letter(DL) is important but often considered as a burden. In 2011, the Service of Internal Medicine, counting 173 beds, sent 4090 DL. They were issued in an average of 41.2 days. Furthermore, electronic medical record (EMR) were introduced in CHUV. Dictation has lost usefulness. Short medical report(faxmed), produced electronically at the day of discharge, are duplicating DL but without validation of a supervisor. For the chiefs residents and the head of service, it is time to initiate a reform. We must adapt to computerization, maintain quality and reduce delays. Method: A first task force met late 2011 and developed the concept: no more dictation; writing style has to be telegraphic and synthetic.The DL is extracted from the list of problems build during the stay. Comments are split in 3: background - discussion - proposal.The faxmed is abandoned. But difficulties threaten the reform: resistance to the loss of prose, disagreement on structure and practical problems. After problem identification, in July 2012, a new task force is created, more strictly coordinated and interdisciplinary (physicians, administrator, secretary and IT support). Responsibilities are divided into 4 areas: EMR, content structure, layout, and standardization of procedures. General practitioners(GP) are surveyed. Tests are conducted in a 25-beds unit. Results: After 2 months, it appears that the reform induced cascades of changes in way of thinking, working and documenting EMR throughout the stay.The secretariat's work is also redefine.EMR and delays monitoring are improved. Within the next 3 months, the process is extended to the six other units.Doctors have been specifically trained and coached. Interaction between end-users and task force allowed further improvement.In December 2012, the head of service endorses the reference document. Residents and GP are 156 satisfied.The reflections of the DL shifted upstream of the stay. Although exciting, good synthesis isn't so easy to do. Errors appear more evidently and supervisors still has an important work load. December 31, the mean delay was 11 days. Conclusion: Despite a large university service, a deep change has been achieved in less than 6 months. This success lies in a coordinated and interdisciplinary task force. The main medical benefit is an upstream shift of the medical reflections. P407 Lipid-lowering therapy modification and LDL-C goal achievement after an acute coronary syndrome: a prospective Swiss cohort Baris Gencer*, FranГ§ois Mach, Reto Auer, David Carballo, Lorenz RГ¤ber, David Nanchen, Pierre Vogt, Sebastian Carballo, Philippe Meyer, Pierre-FrГ©dГ©ric Keller, Christian Schmied, Christian Matter, Stefan Windecker, Thomas LГјscher, Nicolas Rodondi Geneva University Hospital (GenГЁve, CH); University of California (San Francisco, CH); Bern University Hospital (Bern, CH); Lausanne University Hospital (Lausanne, CH); Groupe MГ©dical Ziggurat (Porrentruy, CH); ZГјrich University Hospital (ZГјrich, CH) Background: Poorly controlled low-density lipoprotein cholesterol (LDL-C)levels after an acute coronary syndrome ACS)are common. Although guidelines recommend an aggressive approach, no study evaluated the lipid-lowering therapy modification performed by physicians to reach LDL levels goals one year after an ACS. Methods: We studied 924 men and women from a prospective cohort study of consecutive patients hospitalized for ACS from July 2009 to December 2010 (18 months) in four Swiss academic hospitals. We systematically collected data on lipid-lowering treatment and measured LDL-C levels at baseline and after one year. We defined "appropriate care" as the continuation of the established therapy or the switch to a high potency statins in those who did not reach the LDL-C goals. We measured adherence with Medial Adherence Scale (MAS) questionnaires. Results: Among 924 patients followed-up one year after an ACS, only 31.3% achieved the current LDL-C goal of < 1.8 mmol/l. In patients taking high potency statins with complete medical adherence, only 40.2% reached an LDL-C goal < 1.8 mmol/l. At one year, 94.4% of participants continued their statins therapy, but only 57.1% had high potency statins and 38.5% of patients reported to have some degree of non-adherence (MAS >= 1). Appropriate care of lipid-lowering therapy was delivered to 55.3% of patients with poorly controlled LDL-C. Conclusion : Less than one third of patients achieved recommended LDL-C goal one year after ACS, and appropriate care was delivered to 55% of patients with poorly controlled LDL-C. Although patients' adherence and physicians' therapy modification should be improved, new therapeutic approaches are needed to be able to reach the current LDL-C goals. 157 P408 What are your patients searching on the internet while hospitalised? Ameena Jesaimani*, Christophe Luthy, Natalia Pletneva, Michel Kossovsky, Anne-FranГ§oise Allaz, Christine Cedraschi, ValГ©rie Piguet HUG (GenГЁve, CH); Health on the Net (GenГЁve, CH) Objective: Cross-sectional study assessing Internet use in hospitalized patients in a division of general medical rehabilitation (GMR) at the Geneva University Hospitals. Methods: The survey was carried out one day/week from July-December 2012. A questionnaire investigating various aspects of Internet use was given to patients hospitalized at the GMR during this time period. Results: 245 patients were contacted; from the 159 (65%) included, 101 (64%) never used Internet (group A); 36 (23%) used it at home only (group B) and 22 (14%) at home and at the hospital (group C). Patients in group A were significantly older, less educated and had a higher chronic medication intake (Table 1). Groups B and C displayed no significantly different sociodemographic characteristics, but more patients in group C were on chronic medications (82% vs group B 67%; p=.03). Group C reported a higher everyday access to Internet (81% vs group B 50%; p=.001) through mobile devices, and 86% came to the GMR with at least one device (Table 2). Online activities were similar in both groups, but more patients in group C searched for health information which concerned their own health (73% vs group B 24%; p=.000); these patients were also eager to share health information with relatives or health professionals and to get better, individualized and interactive health information. Conclusions: Only few patients stayed connected to Internet when hospitalized, but they may well be representative of future patients, with increased requests for interactive health information. 158 P409 Rectus sheath haematoma: a rare but dangerous cause of acute abdominal pain Lea Landolt*, Tobias Hoefflinghaus, Esther BГ¤chli Spital Uster (Uster, CH) Introduction: Rectus sheath hematoma (RSH) is a rare complication of anticoagulant therapy and can be life-threatening. Our aim was to analyze clinical features, diagnosis, treatment and outcome of these cases in a general hospital. Case Report: During a period of 24 months, 8 cases of RSH were diagnosed (0.1% of all inpatients). Mean age was 79,4 years (y, SD+/-14.1). 75% were female. 7 patients (pts) were on therapy with vitamine K antagonists (VKA), 2 in combination with Aspirin (ASA), 4 had low molecular weight heparin (LMWH) for bridging of VKA therapy. 4 pts had INR levels between 3.1вЂ“4.4. One pt with liver cirrhosis and low platelet count had ASA and LMWH prophylactically. Five pts (63%) were coughing. Main symptom was localized pain in 7 pts. One pt was incidentally diagnosed on a CT scan performed for different reason. 7 pts had a palpable mass of the abdominal wall. 5 RSH were diagnosed with CT, 2 with ultrasound, 1 clinically. All pts were treated conservatively. In 7 pts vitamine K and BeriplexВ® was substituted. 4 pts received blood transfusions (1-4 units). The mean drop of hemoglobine (Hb) was 37g/l (SD+/- 22g/l). The renal function was chronically impaired in 7 pts (mean creatinine clearance 51ml/min +/-12.4) and declined further. 3 out of 8 pts died (38%, age 90-92y, female). In these patients the observed change in Hb was 42-58g/l, 2 pts had combination of VKA, LMWH and ASA, 1 pt had VKA only. Discussion: Our series shows a substantial mortality (38%) and morbidity of RHS - especially in elderly female pts with VKA in combination with antiaggregation therapy. Coughing was present in 63% and is an accepted risk factor. Our findings were comparable to a review with 126 cases of RSH published in 2006 , where 64% were women, 69% were on VKA, 29% had a cough, 84% abdominal pain and 63% a palpable abdominal mass. Mostly, diagnosis was made by CT. 86% were treated conservatively, 7.9% had surgery or embolization of the bleeding vessel. Mortality was 1.6% but mean age was lower (67.9y). Conclusion: Acute abdominal pain in pts under anticoagulant and/or antiaggregation therapy combined with renal impairment should always raise suspicion about RSH. Extensive blood loss, shock and aggravation of renal failure can be fatal. In majority of cases the hematoma is palpable and should prompt a CT scan of the abdomen. It is crucial to normalize coagulation parameters and to correct intravascular volume depletion to avoid shock and further decline of renal failure. 159 P410 What do we know about online searches about medication? A review of the literature Ameena Jesaimani*, Victoria Rollason, Christine Cedraschi, Christophe Luthy, Marie Besson, Celia Boyer, Jules Alexandre Desmeules, ValГ©rie Piguet University Hospital of Geneva (GenГЁve, CH) Background: Internet has become a global network easy to access from anywhere. One of the most common reasons for accessing Internet is searching for health information (HI). Objective: To examine the use of Internet for seeking HI among patients and the general population in order to investigate who searches for HI on Internet and for what purposes, with a specific focus on medication. Method: We conducted an electronic search using: PubMed, Cochrane library, Banque de DonnГ©es en SantГ© Publique and Google scholar for studies published up to March 2012. Inclusion criteria were : the general population or patients looking for HI and for medication information (MI) on the Internet, aged between 15 to 80 years, not suffering from cancer or AIDS. Results: Of the 102 retrieved studies, 67 met the inclusion criteria (with a focus on MI, n=23). The majority of studies were conducted in North America (45%), followed by Europe (33%), Middle East and Asia (13%) and Australia and New Zealand (9%). More than half of the studies included the general population, and 42% evaluated outpatients. Most surveys were conducted by phone (n=26) or internet (n=11) interviews/questionnaires (n=23) and by face-to-face interviews (n=9). About half of the general population and 50-99% of adults suffering >=1 chronic disease used Internet to search for HI, mainly about a specific disease, its treatment, exercise and diet. Regarding medications, about half of the online HI seekers, whether patients or not, looked for MI concerning side effects, drug safety, interactions, update on drugs currently consumed, new drugs, over-thecounter or alternate medications. Women, adults < 50 years, well educated, searched significantly more frequently for MI as well as for HI. The reasons to search online for MI were convenience, broad range of information and peers' opinions. The online searches for MI did not replace health professionals' information, but offered additional information and also a crosscheck. Online MI could reassure or be an incentive to ask questions to the treating physicians but also confuse. Conclusion: Further studies should provide health professionals with more details on patients' expectations about online MI. This knowledge should enable them to develop online quality MI, including Internet interactive possibilities to improve MI, in particular for self-management of chronic diseases. 160 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 8 - MГ©decine interne gГ©nГ©rale 8 P411 Socioeconomic status and quality of care in a population-based sample of diabetic patients in the canton of Vaud Aline Flatz*, Bernard Burnand, Isabelle Peytremann Bridevaux Institut universitaire de mГ©decine sociale et prГ©ventive (Lausanne, CH) Introduction: Low socioeconomic status (SES) is associated with an increase in the prevalence of many diseases such as diabetes mellitus as well as with worse outcomes. Further, associations have been found between low SES and worse quality of care. In this study we aimed to explore this relationship in the Swiss context. Methods: We used data from a population-based random survey performed among 406 adult diabetic patients living in the canton of Vaud. Data on patients' and diabetes characteristics, processes of care, diabetes outcomes, use of health services and quality of life were collected with a self-administered questionnaire. Dependent variables included 6 processes of care received during the previous 12 months: HbA1C, lipid, microalbuminuria, fundoscopy, feet examination and influenza vaccination. We assessed the relationship between education level (primary, secondary and tertiary) and quality of care as measured by processes of care as well as between income and quality of care using regression analysis. Adjustment was made for age, gender and presence of co-morbidities. Results: Mean age was 64.4 years, 40.6% were women; 68.5% reported type 2 DM, 12.8% type 1 DM and in 18.7% the type was undetermined. Most patients had secondary education (55.6%), 19.1% had primary and 25.3% tertiary education. Statistically significant results of adjusted regressions showed that compared to patients with primary education, patients with a secondary or tertiary education were more likely to get a fundoscopy (OR 2.1 95% CI 1.2-3.7, OR 2.6 95% CI 1.3-5.0, respectively) and also more likely to get a feet examination by a physician (OR 1.8 95% CI 1.0-3.1; OR 2.5 95% CI 1.35.1, respectively). When using composite indicators of processes of care we observed that patients with secondary or tertiary education were more likely to receive ?5/6 PoC (OR 2.23; 95%CI 1.23-4.04, OR 2.83; 95%CI 1.42-5.61, respectively) compared to patients with primary education. No associations were found between income and quality of care. Conclusion: Diabetic patients with low education were less likely to have received the recommended annual fundoscopy and feet examination than better educated patients. These data are in line with the results of other studies performed in various countries and provide some more evidence for the presence of health disparities in Switzerland. P412 Treatment with intravenous immunoglobulin G (IVIgG) of unspecific myositis with features of inclusion body myositis (IBM) Florence Vallelian*, Ulf Petrausch, Dominik Schaer UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Introduction: IBM is characterized by parallel autoimmune inflammation and muscle degeneration and results in proximal and distal weakness of the legs and arms. One of the serious complications is dysphagia. Histological features include typical intramuscular vacuoles, amyloid accumulation and infiltration of CD8 positive T cells. However, vacuoles can be absent in the early phase of this disease. In general, response to any treatment is poor. A possible treatment is the combination of methotrexate or azathioprine with steroids. IVIgG was used in some patients resulting in clinical response. However, placebo-controlled studies have failed show significant benefit. Patient: We saw in 2010 a 73 years old male patient with progressive proximal weakness and pain of both legs and difficulties to swallow. To further evaluate the weakness muscle biopsy of M. vastus lateralis was performed showing T cell infiltration. Due to missing vacuoles the diagnosis of IBM could not established formally. As sign of inflammation the MRI showed enhancements in M. sartorius, M. vastus intermedius on both sides and in the corpus breve of M. biceps femoris on the left side. At that time the creatine kinases (CK) was 2033 U/l. Therapy: Therapy was started with working diagnosis of unspecific myositis with features of IBM. The patient received azathioprine (1.5mg/Kg BW) and prednisone (1mg/kg BW). After 3 month the immunomodulation resulted in improved muscle strength and reduced dysphagia. The CK dropped to 214 U/l. Prednisone was tapered to a dose of 10 mg daily. At that time the patient started to complain 161 about pain and weakness in the proximal muscles of the arms and legs which could not be controlled by increased prednisone and azathioprine (2mg/Kg BW). As second line therapy IVIgG with 5 mg prednisone daily was initiated after measuring base line muscle strength. For 3 times every 4 weeks on 4 consecutive days 40g VIgG were infused (3x1.5g/Kg BW) with no side effects. After this therapy the muscle strength again was measured showing a significant improvement. The nadir of the CK was reached 8 weeks after stopping IVIgG with continued low dose prednisone. The most recent CK values are indicating a relapse suggesting temporal efficacy of IVIgG to control myositis. Conclusion: The case indicates that IVIgG with low dose steroids can induce an objective response as second line treatment option in a patient with unspecific myositis. P413 Lime Tree Project: health promotion by intersectorial action within a community-campus-local authority partnership Sandrine Motamed* UniversitГ© de GenГЁve et HUG (GenГЁve, CH) The Lime Tree Project is a 10 year old partnership of a Swiss community, its local authority and the university. Its aim was to help the residents to identify and express their own health needs and to meet the challenges that were mainly socio-economic and psycho-social in nature. The inhabitants drew together to develop, across many sectors, a more just society which over the years has resulted in a novel concept of healthy living. Meinier is a county near the city of Geneva. Following an initial study undertaken by students of the University of Geneva (Institute of Social and Preventive Medicine, ISPM) aiming to identify its residents' health needs, the local authority formally engaged the ISPM to try to resolve the problems disclosed, which were of socio-economic and psycho-social nature. Numerous meetings of the inhabitants gradually allowed dialogue within the community to develop, leading them to precisely define their requirements. Old people felt isolated and wished to remain in the village, even when they lost their autonomy, rather than enter a nursing home elsewhere. Young families could not get established because of a lack of available housing, the financial burden and nonexistent day care facilities for children. Social links between people had diminished, especially between the generations. Further difficulties arose from poor mobility, both for work and leisure. Given these findings the inhabitants drew together to develop a more equitable society, in a partnership between the authorities and our Institute. A participative intersectorial approach allowed a global program to be put together, which particularly united housing, urbanism, ecology and mobility. An architectural competition brought this first, 5 year long, phase to a close. The project, driven completely by community participation, is in its tenth year, its 40 million dollar budget adopted by community vote. One prominent aspect is the new village center, with its sheltered housing for the elderly, affordable accommodation for young families, child day care, a games library, shops and a restaurant as well as an intergenerational park and living space. The learning and experience gained in terms of community participation and of behavioral and social health determinants has been very important for all concerned. The Lime Tree Project demonstrates that a collaborative approach to implementing effective intersectorial health promotion works at county level in Switzerland. P414 Cooperation between Hospice Ticino and Cardiocentro Ticino for terminal patients with cardiovascular pathologies Augusto Bernasconi*, Stefanos Demertzis, Nicola Ferrari, Marianne Lang, Bea Marx, Monica Ranzi, FranГ§ois Regoli, Claudio Benvenuti, Tiziano Moccetti Hospice Ticino (Lugano, CH); Cardiocentro Ticino (Lugano, CH); SUPSI (Lugano, CH) Introduction: On the hypothesis that some patients with heart complaints can benefit from palliative care, a cooperation project between Hospice Ticino (HT), home medical and nursing organization, and Cardiocentro Ticino (CCT) was initiated. Cardiology has developed instruments for patients whose condition in the end is symptomatic of their illness. Palliative care is readily available for patients who are suffering from oncological disease and only 4% of patients followed by HT have strictly cardiovascular diagnoses. The aim was to offer a taking in charge for terminally-ill patients with heart complaints and the objectives were to define the mutual responsibilities of the CCT and HT medicalnursing teams, to identify needs and offers of care and criteria of inclusion, and to propose operational procedure. 162 Methods: A working group consisting of five doctors and two nurses met once a month. Professional expertise was shared along with literature and brief experiences of their mutual activity. The principal problems were acknowledged and enabled the identification of the criteria for inclusion. Regarding the procedure for taking patients in charge, it meant discussing the operational instructions of announcement to HT and the procedure of communication to be adopted to update all the professional figures involved during the course of the patientsвЂ™ illness. Results: Five papers were drafted: shared papers; medical criteria for taking in charge into palliative therapy; the needs of the terminally-ill patient with heart complaint from the nursing point of view; criteria for inclusion (specifically of patients suffering from cardiovascular pathologies); communication between care providers, patients and family. Since 26th July 2012, five patients have been discussed and followed. Conclusion: The first piece in the creation of an integrated system, between hospitals and local area, of all the doctors and care providers involved in the consultation and in the palliative care of patients suffering from chronic heart diseases. P415 Effect of the GABAA ligands clobazam and clonazepam on the modulation of pain transmission in humans Marie Besson*, Alain Matthey, Youssef Daali, Pascal Vuillemier, Michele Curatolo, Pierre Dayer, Zeilhofer Hanns Ulrich, Jules Desmeules Hopitaux Universitaire de GenГЁve (GenГЁve, CH); Insel Spital (Bern, CH); Insel spital (Bern, CH); University of Zurich (ZГјrich, CH) Background: Facilitation of spinal GABAergic inhibition with benzodiazepines (BZD) reverses pain sensitization in rodents. In human, the use of BZD in pain is limited by their sedative effect. We previously demonstrated the antihyperalgesic effect of clobazam, a 1,5-BZD, in mice and its lack of sedation at effective doses. Hence we designed a pharmacokinetic-pharmacodynamic study to explore the effect of antihyperalgesic effect of BZD in healthy volunteers. Methods: Randomised double blind cross over controlled study in 25 healthy volunteers comparing clobazam 20mg to clonazepam 1 mg (positive control) and tolterodine 1,37mg (active placebo) two weeks apart. The primary outcome was the effect on the size of secondary hyperalgesia elicited by the UVB irradiation of the skin of the forearm (sun burn model). Quantitative sensory testing, nociceptive flexion reflex and the cold pressor test were also performed. Sedation was measured by a visual analog scale (VAS), the digit substitution symbol test (DSST) and saccadic eye movements (SEM) recording. Blood samples were taken to determine the pharmacokinetic of clobazam. Results : we observed a reduction of the area of the secondary hyperalgesia with clobazam and clonazepam. The maximum of the effect was seen at t= 2h [median of the difference between t=2 and baseline (MOD2-0) (+/-CI) vs placebo: 19.2 cm2 (-2.7-37.9) p=0.07 for clobazam and 29.6 cm2 (2.055.1), p=0.03, for clonazepam], in line with the expected Tmax of the compounds. Regarding sedation, at t=2h, we saw an effect of the two active compounds on the VAS [MOD2-0 (+/CI) vs placebo: 14 mm (1.0-21.5), p=0.03 for clobazam and 26 mm (14.0-37.5), p<0.001 for clonazepam] and on the peak velocity of the SEM [MOD2-0 (+/-CI) vs placebo: 30.8 deg./s. (6.6-60.6), p<0.01 for clobazam and 55.2 deg./s.(24.5-85.0), p<0.01 for clonazepam]. The DSST was only impaired by clonazepam [MOD2-0 (+/-CI) vs placebo: 11.0(5.0-18.0), p=0.03]. These effects disappeared at t=8h except that clonazepam still impaired SEM [median of the difference between t=8 and baseline (+/-CI) vs placebo: 28.3 deg./s. (5.3-52.7), p=0.01]. Conclusion: clobazam and clonazepam decreased the area of secondary hyperalgesia in the sunburn model, which suggests that GABAA receptor ligands are involved in the modulation of pain sensitisation in human. Clobazam was less sedative than clonazepam and therefore a suitable вЂњtool compoundвЂќ to assess the role of GABAergic pathways in human. P416 Human immunodeficiency virus (HIV) screening in the emergency department: patientsвЂ™ perspectives Olivier Hugli*, TimothГ©e Favre-Bulle, Dimitri Baudat, Katharine Darling, Matthias Cavassini CHUV (Lausanne, CH) Introduction: Blood tests are frequently performed when a patient is admitted in the emergency department (ED) or before surgery. A study at our institution demonstrated the following: 38% of 163 patients who had had an operation believed that a screening HIV test was systematically part of the preoperative blood work-up; of those, 96% interpreted the lack of information regarding the test result as a proof of a negative HIV test; 80% of patients were in favor of a systematic HIV test (1). The goal of our study is to assess among ED patients, a) the proportion of patients with the same erroneous belief and, b) the proportion of patients in favor of a systematic HIV screening test. Methods: Patients who were admitted to the ED of our hospital (50,000 patients / year) and had blood drawn were asked 2 questions: 1) Did they believe that an HIV screening test was part of their blood work-up? 2) Would they agree with a systematic HIV screening test. Exclusion criteria were: refusal to participate; age =< 16 years or > 70 years; patients admitted > 12 hours or who left before being interviewed; clinical instability; transfer from another hospital; dementia, psychosis or any other cause that precluded informed consent; intoxication; known HIV+ status, and prisoner. Results: 472 patients were screened, and 84% excluded based mainly on age > 70 years (48%), no blood drawn (19%), or who had left before being interviewed (10%). Of the 121 eligible patients, 104 (86%) were included in the analysis. Their mean age was 44В±16 (SD) years; 52% were women; 90% Europeans; 26% believed to have been screened for HIV, without significant differences across age or by gender or origin; 79% were in favor of a systematic HIV test in the ED. Conclusion: In our sample of middle-age European patients, a quarter believed erroneously that HIV screening is part of a standard blood work-up in the ED. Age or gender are not associated with this belief. Our study confirms the results previously obtained in a group of patients who were operated on. Our results suggest that there is a need for better information regarding the policy governing HIV screening in our hospital. As the vast majority of patients support systematic HIV screening in the ED, the question of a generalized opt-out strategy appears justified in this setting. (1) Albrecht E et all. An analysis of patients' understanding of 'routine' preoperative blood tests and HIV screening. Is no news really good news? HIV Med.2012;13:439-43 P417 Successful treatment of extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli-prostatitis with ceftriaxone Flann Benjamin Postert*, Thomas Bregenzer Spital Lachen (Lachen, CH) Introduction: Prostatitis with quinolone and co-trimoxazole resistant enteobacteriaceae is difficult to treat. If there is an additional extended spectrum betalactamase (ESBL), usually reported as resistant to all cephalosporins, there are no established treatment options since tissue penetration of antibiotics with activity against ESBL-producing gram-negatives is low. Case report: A 87-year-old patient in remission after transurethral resection of urothelial cancer suffered from recurrent septic urinary tract infections (UTI). He was referred to our emergency department with a third episode of bacteremic UTI with E. coli resistant to amoxicillin, co-trimoxazole and quinolone, susceptible to cephalosporins and aminoglycosides. E. coli-prostatitis was diagnosed clinically with the same resistance pattern. The patient recovered completely after a ten days course of ceftriaxone. New symptoms of UTI and prostatitis occurred one week later. We initiated an intravenous six weeks course with ceftriaxone once daily at our outpatient clinic while waiting for results of a new urine culture. Resistance test results were available four days later. The patient was already asymptomatic. However the E. coli now was identified as an ESBL-producing strain. Ceftriaxone treatment was continued as scheduled. Repeated urine cultures during 3 months after treatment remained sterile. When the patient had transurethral prostatectomy for obstructive prostate hyperplasia no infectious complications occurred. During a follow-up of 12 months no UTI occurred and repeatedly performed urine cultures remained sterile. Discussion: Despite ESBL production the treatment with ceftriaxone was clinically successful and there was no relapse during 12 months of follow-up. ESBL-producing enterobacteriaceae in urin cultures do not mean that cephalosporins are clinically inactive. In children with acute pyelonephritis it has been shown that empiric therapy with ceftriaxone is equally effective in those with and without ESBL-producing E. coli. Conclusion: UTI with ESBL-producing E.coli may respond to treatment with ceftriaxone. According to the 2010 EUCAST recommendations it may be valuable to report resistance results in ESBLproducing enterobacteriaceae вЂњas foundвЂќ. 164 P418 Alcohol intoxication in the Oberaargau district: a ten year trend Alexander Imhof*, Peter Schott medizinische Klinik, SRO AG (Langenthal, CH) Background: Many authors reported an increase in alcohol intoxication, particularly in large cities. However, there are only few clinical data about alcohol intoxication in hospitals in a rural part of an industrial country. The aims of this study were trends over time in the numbers of alcohol intoxications and trends with respect to gender and age distributions of intoxicated patients. Methods: We conducted a retrospective study over a 10-year period in patients admitted to our emergency department. Patient details and blood alcohol levels were obtained from the laboratory information system for all samples sent from the emergency department. Results: During the study period, 3527 alcohol tests were sent to the laboratory. The median age of all patients with alcohol tests was 43.7 years (range: 13.2-93.9). 66.7% of the patients were male. The median alcohol level was 11 mg/100ml (0-7.3). In 1946 (55.2%) patients the alcohol level was >80mg/100ml and the median age in these patents was 40.9 years (13.2-92.9). The median of annual increase of patients with a level >80mg/100ml was 9.1% (-7.0% (2008/2009) to 29.3% (2002/2003). A significant increase of alcohol intoxication was found in all age groups. However, the age distribution of our intoxicated patients showed a peak in the age group 40-55, followed by patients under 25 years of age. Conclusion: In our population, episodic drinking is not only a problem of young persons; it also concerns the age group between 40-55 years. Preventive measures should not only be limited to younger adults. P419 Access to healthcare for undocumented people in Switzerland: differences between cantons and clinical issues Marius Besson*, Monica Varcher, Patricia Hudelson Consultation ambulatoire mobile de soins communautaires (CAMSCO) Background: Between 100вЂ™000-250вЂ™000 undocumented people (referred to as вЂњsans-papiersвЂќ in Switzerland) are estimated to live in Switzerland, mainly in urban areas. This population generally lives in precarious conditions with poor access to health care and health insurance, but barriers to care vary greatly between Swiss cantons. We describe and discuss intercantonal differences in access to care for this vulnerable population in Switzerland. Methods: The national platform, вЂњHealth care for undocumented migrantsвЂќ was created in 2006. Its members include Swiss health structures involved in providing health care to undocumented migrants, and its main objective is to promote exchange about about health practices across the different cantons. We obtained informations from the platform on socio-medical structures existing in 12 Swiss cantons, with the aim of describing the challenges faced in providing convenient access to health care for undocumented migrants. Results: Two main approaches to providing health care to undocumented migrants were identified. In the cantons of Geneva and Vaud, we have specifics programs dedicated to this population, organized around primary care consultations and interdisciplinary teams (nurses, social workers, doctors). These structures belong to the public health system and work closely with the public hospital and emergency services. Collaboration and partnership with private networks of institutions working with vulnerable populations are also well developed. In the other cantons we find mainly private initiatives dedicated to help undocumented people in needed of medical care. These structures vary in size and, and may include social workers, nurses and private doctors. Collaboration with the public health system is more complex and at times difficult. Conclusion: the Swiss health care system provides varied responses to the need for access to health care for undocumented migrants. The quality, size and clinical efficiency of care differ greatly between cantons. From a clinical, public health and ethical perspective, we believe that an approach based on active involvement of public authorities and public health structures along with close collaboration with private socio-medical sector is the best option for respecting the right to health care for undocumented migrants. 165 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 9 - MГ©decine interne gГ©nГ©rale 9 P420 A brief assessment tool for the early diagnosis of geriatric syndromes in primary care: the AGE programme Nicolas Senn*, Jacques Cornuz, Pakize Palan, Christophe BГјla, StГ©fanie Monod Policlinique MГ©dicale Universitaire (Lausanne, CH); centre hospitalier universitaire vaudois (Lausanne, CH) Introduction: The ageing of the population associated to the increase of prevalence of chronic diseases and functional dependency are major public health challenges. Early diagnosis and management of geriatric syndromes has been shown to delay functional decline, decrease the risk of institutionalization, and improve quality of life in older persons. However, geriatric syndromes are often underdiagnosed by primary care physicians what delays their adequate management. This is partly due to the lack of adapted efficient tools to comprehensively assess old patients for major geriatric syndromes in primary care. The AGE (Active Geriatric Evaluation) program is a collaborative project between a primary care institution and a specialised geriatric unit that aims at developing a brief assessment tool adapted to the primary care setting. We describe here the development of this program. Method: The brief geriatric exam assesses nine geriatric syndromes: 1) cognitive impairment; 2) mood disorder; 3) functional impairment; 4) urinary incontinence; 5) malnutrition; 6) gait and balance impairment; 7) osteoporosis; 8) hearing impairment; 9) visual impairment. The AGE program is developed along 3 phases: 1) Validation of the geriatric consultation as gold standard; 2) investigation of the performances of the brief geriatric exam; 3) assessment of the effectiveness of the brief geriatric exam in routine primary care practices. Results: Phase 1 (validation of the geriatric consultation) will be completed in February 2013. A convenience sample (N=19) of patients from geriatric ambulatory consultations and home visits have been evaluated by two independent geriatricians. Phase 2 will start in February 2013 with a small pilot study that will establish the feasibility of the brief geriatric exam in primary care practice. Further results will be presented during the meeting. Conclusion: This program is designed to develop a brief geriatric exam to be used by primary care physicians aiming at improving early diagnosis of geriatric syndromes. This original 3-phase project guarantees the continuity and homogeneity in the development of the intervention and could serve as an example of research collaboration between specialists and primary care physicians. Furthermore, this program has the potential for developing new model of care for elderly people in primary care. P421 Prediction of potentially avoidable readmission risk in a division of general internal medicine: developing a locally predictive model from retrospective data. Marc Uhlmann*, Anne-Claude Griesser, Olivier Lamy, Hong Dung Duong, Estelle LГ©cureux CHUV (Lausanne, CH) Introduction: The rate of readmissions (RA) potentially avoidable within 30 days after discharge (RAPA) is an inpatient quality of care indicator. Considering the burden and cost of RA, many models have been developed to screen high risk patients in order to implement preventive measures. Unfortunately the predictive value of these models is often disappointing, especially when applied in another setting. The LACE index (Length of stay (LS), Acuity of admission, Charlson comorbidity score (CCS) and number of Emergency department (ED) visits in the previous 6 months) is the best validated. We tested the LACE index in our population and derived retrospectively our own model. Method: All hospitalizations between 1.1.2009 and 31.12.2011 in our 200 acute care beds division of general internal medicine were analyzed. Our model was derived from several data including: demographic data, entry mode, LS, CIM10 diagnosis, CCS, any surgical intervention during stay (CHOP), DRG severity, number of admissions during previous 6 and 12 months, laboratory values, number and types of medications. Results: 11вЂ™073 admissions were analyzed. 93% came from home or long-term care facility. Mean age was 72.0 +/- 16.8y, 50.3% were females. 14.2% were readmitted of which half were classified RAPA. 166 Patients with early RA were more often <=73y, men, with oncological diagnosis, received more medications (diuretics, steroids, opiates) and had more often laboratory abnormalities (p<0.0001 for each item). The LACE index had an AUC of 0.611 to predict RAPA. 6729 stays fulfilled all criteria to derive our model to predict RAPA (versus not readmitted). This multivariate logistic regression model includes 5 variables: number of admissions during previous 12 months >= 1 (OR:1.96, z=8.1), oncological diagnosis with metastases (OR:2.81, z= 7.3), sodium <135 mmol/l (OR:2.15, z=5.6), CCS>1 (OR:1.46, z=3.9), and LS > median value (11 days, OR:1.36, z=3.7). Our model has an AUC of 0.696. Conclusion: The low predictive value of the LACE index in our population to predict early RA is not surprising. There are major differences between the Canadian and Swiss setting. For example, admission rate through the ED (58% vs 93%) as well as median LS. Building a predictive model derived from local data is necessary. In order to implement targeted preventive measures, it should aim high risk patients for RAPA and be easily applicable. Nevertheless, our model needs further development and validation with the 2012 data. P422 Pregnancy-associated cardiomyopathy: a very rare case of severe cardiomyopathy in a patient with a twin pregnancy Maude Grueber*, Marco Macinetti, Daniel Hayoz HГґpital cantonal Fribourgeois (Fribourg, CH) Introduction:In the western population peripartum cardiomyopathy is an infrequent and serious condition. Non-compaction cardiomyopathy is a rare genetic disease, sharing the morphologic features of hypertrophic and dilated cardiomyopathies. It occurs from the embryonic arrest of myocardial maturation altering the compaction of myocardial fibres. Clinical manifestations are early heart failure (HF), systemic embolization, atrial and ventricular arrhythmias which can lead to sudden cardiac death. Familial forms represent up to 18% of cases, usually with a dominant autonomic transmission. Case report:We report the case of a 28 years old woman in previously good condition, presenting in the emergency department on Christmas-eve in acute respiratory distress. The patient is close to the term of a twin pregnancy, reported as normal during the routine follow-up consultations. The history of the patient is characterized by an increasing dyspnoea associated to a foamy cough. Following evaluation, we diagnosed an acute pulmonary oedema. The ECG showed signs of left ventricular hypertrophy. Due to pre-eclampsia caesarean delivery was rapidly performed. After delivery, the clinical status improved under medical therapy for heart failure. The first echocardiography showed a severe reduction of the left ventricular (LV) function (15%) with a dilated LV, with an image of hypertrabeculation. A cardiac-MRI confirmed the elevated trabeculated mass of the LV with a ratio of noncompacted/compacted myocardium of 3.2. After 2 weeks of medical treatment, we observed a significant clinical improvement as well as a LV ejection fraction of 36%. The twins are presently in a good general status and they have been referred to paediatric cardiologist for further evaluation. Discussion:Echocardiography is the most frequently used imaging modality to establish the diagnosis of non-compaction cardiomyopathy, followed more recently by cardiac MRI. Different diagnostic criteria exist based on the myocardial anatomy observed on the images. Treatment focuses on the correction of heart failure and the prevention of arrhythmic events. Systemic cardioembolic events are associated with the disease and anticoagulation must be individualized based on a risk/benefit analysis. Medical devices are considered for heart support according to the guidelines for HF treatment and heart transplantation should be considered when HF is refractory to optimal medical and device therapies. P423 Vertebral fracture discrimination by bone mineral density (BMD), microarchitecture estimation (TBS), and FRAX in stand-alone, combined or adjusted approaches: the OsteoLaus study Olivier Lamy*, Marc-Antoine Krieg, Delphine Stoll, BГ©rengГЁre Aubry-Rozier, Marie Metzger, Peter Vollenweider, Gerard Waeber, Martin Preisig, Didier Hans University Hospital of Lausanne (Lausanne, CH) Introduction: Trabecular Bone Score (TBS), a novel grey-level measurement derived from lumbar spine DXA image texture, is related to microarchitecture (MA) and fracture risk independently of Bone 167 Mineral Density (BMD). FRAX estimates the 10-year probability of hip and major osteoporotic fracture (MOF) using clinical risk factors (CRF) and femoral neck BMD. An adjustment of FRAX probability according to lumbar spine TBS was recently proposed. The aim of the study is to compare the performance of FRAX versus TBS adjusted FRAX to better identify women at high fracture risk. Material and Method: The OsteoLaus cohort (a sub- study of Colaus; women 50 to 80 years living in Lausanne) started in 2010. CRF for OP, FRAX, lumbar spine and hip BMD, vertebral fracture (VF) assessment by DXA and MA evaluation by TBS were recorded. Sensitivity and specificity in regard to VF grade 2&3 has been calculated for all bone modalities as stand-alone or combined approaches. The adjustment of FRAX by TBS has been applied as proposed by Leslie WD et al. Integrated discrimination index and net reclassification improvement have also been investigated. Results: We included 911 women: mean age 65.2В±7.9 y, BMI 25.7В±4.4, mean lumbar spine BMD 0.931В±0.163 (T-score -1.04 SD), TBS 1.289В±0.100. As expected, correlation between BMD and site matched TBS is low (r2=0.16). Prevalence of VFx grade 2/3 and MOF are 7.5% and 15.0% respectively. Spine BMD (-2.5 T-score threshold)Se 29.4%, Sp 82.7%; Lowest BMD (-2.5 T-score threshold)Se 35.3%, Sp 80.9%; Spine TBS (-1.200 threshold) Se 51.5%, Sp 77.1%; FRAX MOF (20% threshold) Se 38.2%, Sp 94.8%; Lowest BMD or TBS thresholds Se 64.7%, Sp 65.4%; Spine TBS or FRAX MOF (20%thresholds) Se 63.2%, Sp 74.4%; TBS adjusted FRAX All fracture (20% threshold)Se 50.0%,Sp 89.9%. When used to reclassify fracture risk, this gave a significant increase in integrated discrimination index for VFx (+2.5%, P<0.001), with net reclassification improvement +7.6% for VFx (P<0.001). Conclusion: While the optimal threshold for TBS should be investigated, an incremental improvement in fracture identification was seen by using lumbar spine TBS in combination with FRAX. If validated in prospective cohorts, lumbar spine TBS may become clinically useful for enhancing fracture prediction from FRAX. Such simple way to take TBS into account would allow the use of current medical society recommendations regarding osteoporosis management with only minor adaptation. P424 Severe agranulocytosis induced by metamizol, a case report Marisa KГ¤lin*, Bernard Surial, Natascia Corti, Georg Tscherry, Esther BГ¤chli Spital Uster (Uster, CH); UniversitГ¤tsspital ZГјrich (ZГјrich, CH) Introduction: Metamizol is a highly potent second-line medication for the treatment of pain and fever, which are unresponsive to Paracetamol or non-steroidal anti-inflammatory drugs. Due to several large studies showing a possible association with agranulocytosis after long-term intake, its usage has been discussed controversially, and is therefore restricted in many countries. We report a case of severe neutropenia induced by Metamizol. Case presentation: An 81-year-old female patient presented to our emergency department with a history of fever, malaise and sore throat and perianal pain for 3 days. The clinical examination was normal except for oral ulcers. Due to a chronic pain syndrome she was taking Paracetamol, Metamizol and transdermal Fentanyl within the last months. Laboratory analysis showed inflammation (C reactive protein level 332 mg/l) and severe agranulocytosis (neutrophil count 100/ul) with otherwise normal blood values. A chest radiograph showed no infiltrate, urine and blood culture were negative. A peripheral blood smear showed no evidence for hematologic malignancy. A presumptive diagnosis of drug-induced agranulocytosis due to Metamizol was made and its administration was discontinued. After treatment with piperacilline/tazobactam and granulocyte colony-stimulating factor, agranulocytosis, fever and mucous eruptions resolved on day 6 after admission. Discussion: Neutropenic fever syndrome represents a rare, but potentially lethal complication of longterm treatment with Metamizol. Despite of this fatal side effect, Metamizol is increasingly being used in Switzerland. In our hospital with 10вЂ™000 inpatients being treated yearly, we have been using 52вЂ™045 grams of Metamizol in 2012 compared to 97вЂ™566 grams of Paracetamol and 18вЂ™300 grams of Ibuprofen. With only 5 cases being reported to Swissmedic between 1997 and 2005, underreporting and/or under-recognition of this condition seem likely. To date, no conclusive incidence rates are available, and its prevalence can only be estimated with the use of case reports. Therefore, complete blood count must be performed in every patient who presents with fever under chronic treatment with Metamizol, and its administration must be stopped. In studies, patients treated with hematopoietic growth factor had shorter duration of neutropenia and a lower rate of infectious or fatal complications, so its use should be considered in patients with agranulocytosis and/or life-threatening infectious conditions. 168 P425 Should a вЂ�prosthetic deviceвЂ™ be a major Duke criterion? Seraina von Moos*, Christina Gold, Isabelle Kunz, Joachim ThГ¶ne UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) Introduction: The Duke criteria for endocarditis are well known, including major criteria (2 positive blood cultures, positive echocardiography with vegetations) and minor criteria (predisposition, fever, septic emboli, immunological reactions). Nevertheless, there is often a diagnostic delay. Case presentation: In september 2012, a 54 year old man, was referred to the university hospital Zurich with repeated episodes of fever and chills since easter 2012; after a surgical intervention for a trivial thumb injury. In June he was diagnosed with right sided lung emboli in a peripheral hospital and anticoagulation was started. At that time a diagnostic work-up for fever of unknown origin including several blood cultures remained negative. Similarly, a transoesophageal echocardiography performed end of august did not show any vegetation. In the personal history a sick sinus syndrome was known, treated in 1987 with a pacemaker, changed in 1998. At the emergency visit in September the patient reported progressive dyspnea. Clinical exam revealed right basal crackles and conventional radiography showed suspicion of a right sided infiltrate. Subsequent antibiotic treatment led to transient symptom amelioration. A new deterioration motivated accomplishment of a 18-FDG PET-CT showing novel left sided lung infiltrates, in the differential diagnosis described as new emboli. Repeated blood cultures (in totally 12) always remained without growths even for the HACEK group. A PCR and Serology was negative, too. As fever episodes were accelerating, a novel transoesophageal echocardiography was performed begin of January, showing a 3 cm thrombus adherent to the pacemaker electrode together with several tricuspidal vegetations. Pacemaker cultures were positive for coagulase negative staphylococcus. Under a medical tri-therapy and surgical removal of the pacemaker the patient recovered. Discussion: Here we report a classical right heart endocarditis associated with repetitive fever and septic lung emboli in a patient with a pacemaker. There was a considerable diagnostic delay, as major Duke criteria remained negative. Nevertheless suspicion of endocarditis needs to be kept high in patients with predisposition. Could inclusion of вЂ�prosthetic deviceвЂ™ in the major Duke criteria accelerate the diagnosis of endocarditis? P426 Communication strategy by adversaries to health protection during debate of the federal smoking ban, 2008-2012 Rainer Kaelin* on behalf of Initiativkomitee Schutz vor Passivrauchen Background: The swiss legislative process towards a national smoking ban in public places started in 2004 by the signature of the WHO framework convention of tobacco control and the initiative of MP F. Gutzwiller MD. By 10/2008 it had resulted in a federal Alibi"Gastro-boro"Law, elaborated under heavy pressure of lobbying, failing to meet WHO standards and passed by the national council (NC)with just 89 yes/88no. Therefore the Swiss lung league (SLL, federation of cantonal lung leagues)launched a popular initiative aiming the law proposal of the NC's health commission that originally was backed by the federal council. Despite 120 000 signatures collected by 2010 and the support of a large alliance of health organizations, the initiative was refused by 66% in a popular vote 9/2012 after heavy campaigning. Since 2008 the "economy's alliance for moderate prevention policy" was founded by USAM (defending economy's interest), with the Tobacco industry and political parties as members/supporters, the links between politicians and industry might have favored efficient desinformation of the public. Aim/Method: Analysis of official statements, their timing with media reports. Results:A.The highly respected director of the federal office of health Prof.Zeltner was denigrated in the USAM's journal as "health Taliban"; this was regularly repeated in media articles reporting on preventive issues. In the right wing journal Weltwoche, Prof. Stadler, Universitiy professor of immunology, wrote about the decline of coronary syndromes as false and disqualified the passive smoke issue as an invention. B. The initiative was refused in the NC by 130 yes/60no,indicating far more support of the federal law than by its adoption. Despite of its original position, the federal council described the initative as extreme, suggesting that a general smoking ban was its aim.C. During the campaign before the vote, publicity and media reports repeated these statements Conclusion: During the elaboration of the federal smoking ban and the subsequent public debate of the law proposal of the initiative, politicians, economy and media diffused coherently the same message: prevention is generally controversial, prevention specialists are zealotes,the actual law 169 works at satisfaction, the proposed improvement is an absolute smoking ban. The efficient communication strategy suggests efficienbt links in the USAM's network, in the interest of the Tobacco industry. P427 Polyneuropathie als FrГјhkomplikation eines Diabetes mellitus Typ 1 Paula Rosegger*, Philippe Rochat, Beat Frauchiger Kantonsspital Frauenfeld (Frauenfeld, CH) Einleitung: Bei einem 32-jГ¤hrigen Patient mit Diabetes mellitus Typ 1 (DM1) wurde bereits 2 Monate nach der Diagnose eine kardiovaskulГ¤re und gastrointestinale autonome und periphere Polyneuropathie (PNP) festgestellt. Das frГјhe Auftreten dieser Komplikation im Krankheitsverlauf ist ungewГ¶hnlich. In der Literatur sind nur EinzelfГ¤lle beschrieben und sie ist mit einer schlechten Гњberlebensprognose verbunden. Fall: Die Zuweisung erfolgte wegen rezidivierenden Synkopen, postprandialen Bauchschmerzen und Fussbrennen. Bei Eintritt war der Patient kachektisch, die Achillessehnenreflexe fehlten bds, Vibrationssinn malleolГ¤r je 6/8. Der Blutzucker war 20 mmol/l, das HbA1c 9,1%. Positive Anti-GADund -IA2-AK bestГ¤tigten den vor 2 Monaten diagnostizierten DM1. Neurographisch (EMG) bestand eine sensomotorische, beinbetonte, demyelinisierende, axonale PNP. Ewing- und Schellong-Test [Tab] zeigten Zeichen der autonomen PNP (Herzfrequenz- und BlutdruckvariabilitГ¤t bei ProvokationsmanГ¶vern pathologisch, persistierende Ruhetachykardie). Die Magendarmpassage zeigte eine Gastroparese mit klinischer Besserung unter Motilium, nicht aber unter Erythromycin. Die Suche nach weiteren PNP-Ursachen blieb negativ (Porphyrie, Bleispiegel, Hypothyreose, Alkohol unregelmГ¤ssig, normales CDT, Vitamin B12, Folat, BSR, CRP, ANA, ANCA, RF, Proteinelektrophorese, Neoplasie [Abdomen-CT, obere und untere Endoskopie], Borrelien, EBV, TPHA, HIV, HBV, HCV). Es bestanden keine Hinweise auf eine chronische inflammatorische demyelinisierende PNP (Lumbalpunktion, EMG). Ein Synacthentest war normal. Wir hatten keine sicheren Hinweise auf weitere diabetische SpГ¤tfolgen (Niere, Augen, Pulse). Wegen arterieller Hypertonie Verzicht auf Fludrocortison und Midodrine. Betablocker besserten die invalidisierende Orthostase nur gering. Die anschliessende stationГ¤re Neurorehabilitation blieb ohne wesentlichen Erfolg. Die Blutzuckerwerte sanken unter Insulin auf 59mmol/l. Die ParГ¤sthesien besserten sich schliesslich unter Gabapentin. Schlussfolgerung: Die PNP tritt beim DM1 in AbhГ¤ngigkeit der Blutzuckereinstellung und der Krankheitsdauer typischerweise erst nach Jahren bis Jahrzehnten auf. Dieser Fall zeigt die mГ¶gliche, seltene FrГјhmanifestation der PNP inklusive Befall des autonomen Nervensystems bereits 2 Monate nach Erstdiagnose eines schlecht eingestellten DM1 nach sorgfГ¤ltigem Ausschluss der Differentialdiagnosen. PrimГ¤res Therapieziel ist die EuglykГ¤mie. Die medikamentГ¶se Symptomlinderung ist schwierig. 170 P428 Evaluation of ankle-brachial index measurements performed by medical students Matteo Monti*, Luca Calanca, Adriano Alatri, Lucia Mazzolai Centre Hospitalier Universitaire Vaudoise (Lausanne, CH) Introduction: Ankle-brachial index (ABI) is a relatively simple, inexpensive, and non-invasive test used by angiologists for diagnosis of peripheral artery disease (PAD). ABI is also a predictor of cardiovascular (CV) events and mortality in PAD patients. ABI measurements performed by angiologists show good accuracy and reproducibility with a sensitivity and specificity of 89-95% and 95-100%, respectively. ABI measurement could be a valuable tool for general and internal medicine physicians for patients screening and CV morbidity evaluation. In the present study we evaluated accuracy of ABI measurements, performed in hospitalized patients, by 6th year medical students after a short training period. Methods: Consecutive hospitalized patients (> 60 years) with at least one CV risk factor (diabetes, hypertension, dyslipidemia, previous cardiac- or cerebro-vascular disease myocardial, active or past smoking) were recruited. ABI's were measured according to standard method (highest ankle systolic pressure over highest humeral systolic pressure) using a hand held Doppler probe. ABI values were calculated separately for each limb. All participating students received a short training period (3 hours) by an experimented angiologist before study start. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (VPP), and Kappa test weighted were calculated according to results obtained in patients with or without PAD (as assessed by the angiologist). 171 Results: Fifty-nine consecutive patients (27 women) were recruited. In 2 patients, for technical reasons (leg ulcers), ABI was calculated in one leg only therefore, a total of 116 ABI's were available for analysis. According to the reference group ABI resulted: normal (>0.9-1.4) in 62.1% of cases, abnormal (>1.4) in 18.1%, mild PAD (0.9-0.7) in 7.8%, moderate PAD (0.69-0.5) in 10.3%, and severe PAD (<0.5) in 1.7% of cases. Overall, sensitivity, specificity, VPN, and VPP were 75.0%, 87.5%, 85.1% and 78.6%, respectively. Resulting kappa test weighted was of 0.5854 (moderate agreement). In 5 cases, students were not able to determine ABI. Among CV risk factor, only blood pressure was significantly higher in PAD (p<0.001) compared to non PAD patients. Conclusions: ABI measurements require well trained personnel and a short training period is not sufficient to guarantee adequate accuracy and reproducibility. 172 Postesession 3 - Session des posters 3 Allgemeine Innere Medizin 10 - MГ©decine interne gГ©nГ©rale 10 P429 Not in the right space: left lateral cardiac displacement due to an unusual cause Niels Holm*, Esther BГ¤chli, Tobias Hoefflinghaus Spital Uster (Uster, CH) Case report: A 69 year old male patient was admitted to the intensive care unit because of septic shock of unknown cause. The patientвЂ™s history was remarkable for alcoholic liver disease with cirrhosis and lung emphysema. The chest X-ray (CXR) revealed an enlarged and displaced cardiac silhouette of atypical shape without signs of congestive heart failure. Electrocardiogram (ECG) showed right axis deviation, leftward displaced transition zone in the precordial leads and significant changes of QRS axis and R wave amplitude between admission and follow-up. Echocardiographic images were hard to obtain, atypical lateral views were required. Computed tomography of the chest revealed cardiac displacement into the left thoracic cavity. Congenital absent pericardium (CAP) was assumed. Shortly after, the patient died of lung failure. Autopsy confirmed pneumonia as cause of death and incidentally revealed a complete isolated absence of the pericardium and a displaced heart to the left. Discussion: CAP was first described by Colombo (1559). The etiology of this anomaly is an incomplete development of the transversal septum and the pleuropericardial folding in the early embryonic stage. The prevalence is unknown; various authors have described isolated forms in surgical or pathological series of 0.0001% to 0.044%. One third of all cases were associated with other cardiac lesions, like atrial septal defect, bicuspid aortic valve and tetralogy of Fallot. Patients can present asymptomatic or with atypical chest pain, largely nonexertional and with postural dependency. Partial defects can lead to cardiac herniation with shock or sudden death. Clinical examination may show lateral displacement of the heart. ECG often displays a partial right bundle block pattern and a deviated transition zone to the left. CXR can show a levoshift with loss of the right heart border. Often lung tissue is interposed between main pulmonary artery and aorta. Echocardiographic examination requires unusual views and is difficult to interpret because of cardiac hypermobility leading to abnormal swinging and ventricular septal motion. CXR combined with magnetic resonance imaging are key to establish the diagnosis. In patients with debilitating symptoms pericardial reconstruction is a curative option. Conclusion: Isolated CAP is a rare congenital anomaly and may cause acute chest pain, shock and sudden death. However, in our case it was an incidental finding and not related to the outcome of this patient. P430 Striving for perfect laboratory values might cause harm Teresa Stelzer*, Ludwig Theodor Heuss, Konstantin Burgmann Spital Zollikerberg (Zollikerberg, CH) Introduction: Statins are lipid-lowering drugs, well established in secondary and primary prevention of cardiovascular events. The major side effect is myotoxicity, which can lead to life threatening renal failure. Case report: A 55 year-old woman, suffering from type-1 diabetes and hypertension, was admitted to our emergency unit for generalised myalgia. Her daily medication consisted of amlodipin, telmisartan, hydrochlorothiazide, atorvastatin and insulin. Laboratory findings were: ASAT 1674U/l, ALAT 1371U/l, CK 40096U/l, Na+ 125mmol/l. Other values, including differential blood count, creatinine, CRP and TSH were normal. A1c-level was 5.6%. The patient was transferred to the ICU for acute rhabdomyolysis, and intravenous hydration according to guidelines was performed. Within few days, CK normalised and symptoms disappeared. Renal function was not impaired. Two weeks before, the patient received telephone advice from her general practitioner after obtaining laboratory results showing a LDL-level of 2mmol/l despite statin therapy: She was told to double the dose, meaning 160mg of atorvastatin per day (max. daily dose 80mg). Discussion: Statin-induced myopathy is rare and its pathophysiological mechanism is poorly understood. Nevertheless, myotoxicity is clearly dose-dependent and, since most statins are metabolised via CYP450-enzymes, various drug interferences can occur. Other comorbidities such as diabetes, hypothyreosis and impaired renal or hepatic function further increase the risk of myotoxicity. Statin-induced hepatopathy is also well known. In primary and secondary prophylaxis of cardiovascular events, target LDL-level <2.6mmol/l is widely recognised. For individuals at high risk, as in macrovascular disease, LDL-level should be even 173 lower, <1.8mmol/l. Whether this strict goal also applies to diabetic patients (so-called вЂњhigh-risk equivalentвЂќ), is not clear. Obviously, the general practitioner was not aware that the patient was already taking the maximum daily dosage of atorvastatin. Conclusion: In our case, rhabdomyolysis seems to be clearly due to a statin overdosage. Furthermore, elevated ASAT/ALAT-levels and hyponatremia are likely correlated to drug-related side effects (statin, thiazide). We conclude that the prescription of drugs should always be considered weighing the risks posed to the individual. Aiming for too ambitious metabolic control should be avoided, especially as LDL-targets in primary prevention are not clearly established. P431 More than honey: honey consumption followed by bradycardia and syncope in the emergency department Gonca Suna*, Sarah Schatzmann, Hans JГјrg Beer Kantonsspital Baden (Baden, CH) Background: Consumption of honey is generally thought to have multiple health benefits. However, honey contaminated with grayanotoxins can lead to severe hypotension and bradycardia. Case description: In this case report, we present a 46-year old patient with severe hypotension and bradycardia after the intake of turkish honey. Following a period of malaise the patient developed nausea, vomiting and collapsed from hypotension. In the E.R., bradycardia of <40/min and a blood pressure of 70/40mmHg were found. The patient was subsequently treated with intravenous saline and metoclopramide and after an uneventful overnight stay he was discharged the following morning. The patient had known arterial hypertension and a positive family history for coronary heart disease, but there was no history of bradycardia or sick sinus syndrome. The relevant detail of his history was the consumption of turkish honey half an hour prior to the onset of his symptoms. Discussion: Hypotension and bradycardia are common findings in an emergency department. However, a very uncommon reason for these symptoms is intoxication from grayanotoxincontaminated honey, also called вЂњmad honeyвЂќ. This toxin is found in honey produced from the nectar of some species of rhododendron and other plants of the Ericaceae family, growing in the black sea region of Turkey, as well as in Brazil, Japan, Nepal and Northern America. The target of grayanotoxins are neuronal voltage-gated sodium-channels, increasing their sodium permeability. The cells remain in a state of depolarisation and therefore in an activated state. The resulting peripheral vagal stimulation is suggested to be the mechanism of bradycardia. Intoxication is characterized by nausea, vomiting, hypotension and bradycardia, but severe complications such as complete atrioventricular block III and consecutive syncope have also been described. History of honey intake is the key to diagnosis and treatment is managed with saline infusions and atropine. In rare cases it is necessary to implant a temporary pacemaker. Conclusion: Grayanotoxin-induced bradycardia, hypotension and syncope after ingestion of honey derived from pollen of certain rhododendron species can be added to the rare differential diagnoses of syncope in the emergency room. P432 Detoxification of gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL)dependence with pharmaceutical GHB: a case study Barbara Broers*, Juan Garcia Martinez, Karim Bendjelid, Cor de Jong HГґpitaux Universitaires GenГЁve (GenГЁve, CH); NISPA (Nijmegen, NL) Introduction: Gamma-hydroxybutyrate (GHB) and its analog gamma-butyrolactone (GBL) are used recreationally for their (dose-dependent) euphoric, relaxing, aphrodisiac and anti-anxiety effects. The prevalence of these easily available drugs may be increasing, and with it problems related to intoxication, tolerance and dependence. In case of dependence, withdrawal is often characterized by severe autonomic instability, and by agitation, confusion, life-threatening delirium and seizures. Symptoms can be uncontrollable, even with to high dosages of benzodiazepines (GABA-A ergic), while GHB activates GABA-B and GHB-specific receptors. Symptoms can last up to 2 weeks and patients often need intensive care. A Dutch group developed a tapering scheme using pharmaceutical GHB (in CH available as XyremВ®, UCB-Pharma SA, Bulle) and published a case-series on controlled withdrawal within one week, without complications and low level of medical care 1. Method: case study Result: a 32 years old male patient presented with a GBL dependence (consuming at least every 2 hr for up to 16-20 gr daily), and benzodiazepine dependence (100 mg chlorazepate/day). He gave 174 informed consent for off-label use of XyremВ® if benzodiazepines would not allow control of withdrawal symptoms. Withdrawal symptoms started within 2 hours after last intake of GLB. Despite 100 mg chlorazepate and 20 mg of lorazepam over 7 hr, he developed severe hypertension, agitation and confusion, also not calmed by intravenous perfusion of 10 mg/hr of lorazepam. He was transferred to the IC and sedated with propofol (50mg/hr intravenous perfusion). The next morning, still agitated, the patient received 1.5 gr oral XyremВ©. Within 15' the patient calmed down, agitation and confusion disappeared, and iv benzodiazepines could be stopped. The patient received XyremВ® every 3 hours in digressive doses (0.25 g/dose/day) and was fully detoxified in 6 days without any complication. Conclusion: GHB and GBL withdrawal symptoms are potentially life threatening despite high dosage benzodiazepines. Applying of a general principle in addiction medicine, using a simile, controlled tapering under clinical control with a pharmaceutical brand GHB (XyremВ®) appears safe, efficacious and feasible in a case series, warranting further clinical research. 1 Eur Addict Res 2012;18:40-45 P433 Is the restriction of tobacco products sales to minors associated with different modes of tobacco consumption among young Swiss men? Carole Clair*, Roland Fischer, Gerhard Gmel, Jacques Cornuz Policlinique MГ©dicale Universitaire (Lausanne, CH); Centre de traitement en alcoologie (Lausanne, CH) Introduction: Tobacco control measures are effective to prevent the harms caused by tobacco consumption. Some measures such as restriction of tobacco products sales to minors have the potential to decrease the prevalence of cigarette smoking, among young people whose smoking habits are not strongly implemented. However, young people might adopt other modes of tobacco consumption, not legally obtained, to replace cigarette smoking. We aimed to describe the association between legislation on tobacco products sales to minors and cigarette smoking as well as other form of tobacco consumption such as smokeless tobacco and waterpipe, which are usually not legally obtained. Methods: We did a cross sectional analysis of the baseline data of a Cohort Study on Substance Use Risk Factors (C-SURF). All young men at the national Swiss army recruitment centers were invited to participate in this study. Participants filled out a computer based questionnaire on socio-professional background and substance use. Descriptive statistics and multivariable-adjusted logistic regression were performed. Results: We included 5,990 participants, mean age was 19.5 years and 55% were French speaking. Self-reported smoking prevalence was 47% (26.1% daily smokers, 21.3% occasional smokers), consumption of smokeless tobacco during the last 12 months was 26.8% and of waterpipe 36.2%. Regarding tobacco products sales to minors, 24% lived in cantons where there was no legislation, 43% in cantons where sales were forbidden to people < 16 years old and 33% in cantons where sales were forbidden to people < 18 years old. Restriction of sales to minor did not influence significantly cigarette smoking but it was significantly associated with smokeless tobacco and waterpipe consumption. Living in cantons where sales were forbidden < 16 was significantly associated with consumption of smokeless tobacco (multi-adjusted OR 1.49, 95% CI 1.23-1.80) compared with living in cantons without legislation and living in cantons were sales were forbidden < 18 was associated with consumption of smokeless tobacco (multi-adjusted OR 1.26, 95% CI 1.05-1.52). Similarly, living in cantons where sales were forbidden (< 16 or < 18) was associated with waterpipe consumption compared with living in cantons without legislation (multi-adjusted OR 1.25, 95% CI 1.05-1.48 or 1.28, 95% CI 1.08-1.51, respectively). Conclusion: Restriction of sales to minor is associated with consumption of smokeless tobacco and waterpipe. P434 Patient characteristics of adult primary immunodeficiencies in Bern Michaela Bitzenhofer-GrГјber*, Peter Jandus, Urs Steiner, Werner Pichler, Arthur Helbling Inselspital, 3010 Bern (Bern, CH); HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); Spital Tiefenau (Bern, CH) Background: Primary immunodeficiencies (PID) constitute a large group disease, including at least 176 conservatively defined hereditary disorders affecting the development and function of the immune system. The number of known PIDs has increased considerably over the last 20 years. The European 175 Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. Methods: Clinical and biological features of 64 adults (> 18 years) with PID were registered in ESID online patient registry by the allergy-immunology outpatient clinic at the University Hospital of Bern to illustrate the clinical characteristics and distinctions of our patients. Results: We present preliminary data of 64 adult patients, all with defined antibody immunodeficiency. Subclass deficiencies (n= 25, 39%) were the most common category followed by the common variable immunodeficiency (n= 23, 36%), unclassifiable hypogammaglobulinemia (n= 14, 24%), and selective antibody deficiencies (n= 2, 3%). CVID patients showed frequently a non allergic bronchial hyperresponsiveness (n= 7, 30%) and bronchiectasis (n= 9, 39%). 15 of 23 CVID patients were substituted with immunoglobulins, 12 of 23 CVID patients showed complications not directly related to infections: sarcoid like lesions (n= 3), autoimmune disease (n= 6) and lymphoma (n= 3). Patients with subclass deficiencies had more atopic diseases and skin infections. Flow cytometric evaluations of CD4, CD8, and B-cells revealed lower levels in CVID group than in other groups. No significant difference was found for B-cell subpopulations. Conclusion: All over Europe, the number of patients with PID is still unknown. In our center devoted to adult medicine, the vast majority of patients have predominant antibody deficiencies, although some patients with CVID have low T-cell numbers and functions. CVID patients have more noninfectious complications, which need to be followed to prevent morbidity and mortality. The collection of data allows to find warning signs because of the growing knowledge of clinical manifestation of PID in adults for a better diagnosis and lower diagnostic delay. P435 Should doctors tell their patients of the cardioprotective treatment effects of antihypertensive medications and lipid-lowering drugs? The implementation of the concept of shared decision making Vladimir Sibalic*, Silke Henzen, Daniel Reuss, Guy Bourgeois, Marcel Schai, Sandra Simic, Aida Karajkovic, Georg Stoffel Private University in the Principality of Liechtenstein (Triesen) (St. Gallen, CH); Collegium for Research in Primary Care (Sevelen, CH); Collegium for Research in Primary Care (Arbon, CH); Praxis (St. Gallen, CH); Collegium for Research in Primary Care (Winterthur, CH) Introduction: Physicians hesitate to discuss with patients the expected treatment effect of cardiovascular agents. They are afraid of disappointing the patients and to reduce the therapeutic adherence. Shared decision making is characterized by the interaction of patientвЂ™s individual preferences and the professional medical contribution of the physicians. For clinical decision making, it is meaningful to use the measure "number needed to treat", to explain the patients the potential treatment effect. Methods: This ongoing interrogation takes place in six primary-care offices in the Swiss Cantons St.Gallen, Thurgau and Zurich. The study question addresses the patientвЂ™s wishes to learn more about the treatment effect of drugs. It tests the readiness to take medications despite the lack of certainty for the intended positive result. The key-study question is as follows: вЂњWould you take a newly developed drug that has shown to prevent a myocardial infarction in 1 out of 50 patients (or 100-thousand out of 5-million patients) within 5 years? The remaining 49 patients would have taken the drug for 5 years without any benefit, because they wouldnвЂ™t have had a myocardial infarction anyway. In other words, 49 patients would have had taken the drug quasi without senseвЂњ. All patients over the age of 18 were asked to participate. The patient-comorbidities were noted. The preliminary results of the first week studyperiod are shown. Results: 102 patients were asked to participate. 92 filled out the questionnaire. 50% were male. Mean age was 52 years (SD 18.9) (SEM 1.99). 21.7% had cardiovascular comorbidity. 41% were not chronically ill. 53.3% of all would agree to take the pill. 31.5% would refuse. 15.2% were irresolute. 75% of cardiovascular patients would agree to swallow the drugs. 0% did not understand the question. 55.5% were disappointed by the treatment effect. 77.2% wanted to learn more about drug-effects. 37% felt well after the interrogation. 31.5% felt indisposed or surprised. None were frightened. 30.4% showed no emotions. 89.1% found this interrogation reasonable. Conclusion: The patients seem to know better how to deal with uncertainty than physicians might expect. The physicians should consider telling the patients the whole story about the expected treatment effect of prophylactic cardiovascular medications, because patients on higher cardiovascular risk are known to profit most from treatment and they are very likely to agree the therapy. 176 P436 Drug-related problems in a general internal medicine service Bertrand Guignard*, Caroline Samer, Arnaud Perrier, Pascal Bonnabry, Pierre Dayer, Jules Desmeules HГґpitaux Universitaires de GenГЁve (GenГЁve, CH) Introduction: Some patients admitted to internal medicine wards receive a large number of drugs and are at risk of drug-related problems (DRPs) that may be associated with morbidity and mortality. The aim of the present study was to detect suboptimal drug use in 2 pilot wards of a general internal medicine service and to offer a pharmacological and pharmaceutical evaluation to improve drug prescription. Method: This was a prospective study conducted during 6 months in 2 internal medicine wards in a 2вЂ™000-bed university hospital. Physician rounds were attended once every other week in each ward by a clinical pharmacist and a clinical pharmacologist. All patients met during the physician rounds were included. Prescriptions were analyzed through an assessment grid to detect DRPs. Treatment optimizations were suggested to prescribers during the round. The main outcome measures were: (1) most frequent DRPs and involved drugs or drug classes; (2) types of intervention required: no intervention, verbal suggestion of treatment optimization, or specialized written consultation; (3) acceptance rate by prescribers. Results: 145 patients (mean age 68 (21-99); 48% female) were included with 1523 prescriptions (mean of 10.6 (0-21) prescriptions per patient). 383 DRPs were identified (mean of 2.6 (0-12) DRPs per patient). The most frequently identified DRPs were: (a) drug interactions (21%), (b) untreated indications (18%), (c) overdosage (16%) and (d) drug used without a valid indication (10%). The most frequently involved drugs or drug classes were (a) for drug interactions: tramadol, antidepressants and acenocoumarol; (b) for untreated indications: calcium-vitamin D, statins and aspirin; (c) for overdosage: proton pump inhibitors and paracetamol; (d) for drug used without a valid indication: proton pump inhibitors and aspirin. 51% of the identified DRPs were considered as clinically not relevant and were not reported to the prescribers, 42% were reported with a verbal suggestion of treatment optimization, and 7% were considered as complex and triggered a specialized written consultation by a clinical pharmacologist. Suggestions of treatment optimization were accepted by prescribers in 84% of cases. Accepted suggestions were applied by physicians in 64% of cases. Conclusion: The most frequently identified DRPs were drug interactions. Half of the identified DRPs required a suggestion of treatment optimization, which was accepted and applied by prescribers in most cases. P437 Depister le VIH ? Oui mais pas sans pouvoir offrir un traitement Sophie Durieux-Paillard*, Alexandra Calmy, Marius Besson Programme santГ© migrants, HUG (GenГЁve, CH); consultation maladies infectieuses, HUG (GenГЁve, CH); consultation ambulatoire mobile de soins communautaires HUG (Besson, CH) Introduction: Depuis 7 ans, en Suisse, dans le cadre de la lutte contre le VIH/sida, l'Office fГ©dГ©ral de la santГ© publique promeut une stratГ©gie de "VCT" (voluntary counselling and testing) auprГЁs des populations les plus Г risque. Les migrants sont l'une de ces cibles. ParallГЁlement au developement d'un concept de VCT adaptГ© aux caractГ©ristiques des migrants(recours aux interprГЁtes, discours adaptГ© au niveau d'Г©ducation, formulation culturelle adГ©quate), s'est posГ©e la problГ©matique Г©thique de dГ©pister des migrants sans statut lГ©gal alors que ces personnes ne peuvent pas accГ©der Г une thГ©rapie antirГ©trovirale (TARV), faute de moyens pour le financer. Le cout des TARV et le caractГЁre chronique de ces traitements, rendaient inenvisageables leur prise en charge par un financement institutionnel. Enfin, ne pas traiter des patients VIH prГ©cocement les exposent Г des complications sГ©vГЁres, dangereuses et Г©galement coГ»teuses. Methode: recherche de fonds afin de financer les cotisations de caisse-maladie, pour une durГ©e maximale d'un an, aux patients dГ©pistГ©s positifs pour le VIH et nГ©cessitant un traitement, si aucune alternative n'est possible. Durant cette annГ©e d'assistance financiГЁre, une Г©quipe psycho-sociale assure un travail de soutien afin de permettre au patient, soit de retrouver une capacitГ© de travail lui permettant d'ГЄtre autonome, soit d'obtenir un statut administratif lui donnant accГЁs Г l'aide sociale, soit de bГ©nГ©ficier d'une aide au retour si la TARV est accessible dans son pays. 177 Resultats: un financement de 60'000 FS a Г©tГ© trouvГ©, dans le cadre d'un partenariat public/privГ©. Pendant une durГ©e de 18 mois, 30 situations de patients migrants prГ©caires ont Г©tГ© examinГ©es et 10 personnes ont Г©tГ© elligibles pour un appui par le fonds. La durГ©e moyenne du soutien financier a Г©tГ© de 7.8 mois. 6 patients ont rГ©cupГ©rГ© une capacitГ© de travail leur permettant d'ГЄtre autonome bien que sans statut lГ©gal, 1 a obtenu un permis de sejour stable, 2 sont retournГ©s dans leur pays d'origine et un dans un pays tiers. Aucun n'a nГ©cessitГ© d'hospitalsiation durant la pГ©riode de suivi. Conclusion: il est Г©thiquement inacceptable de promouvoir le dГ©pistage du VIH/sida si les patients dГ©pistГ©s positifs n'ont pas accГЁs Г une TARV. Dans le systГЁme de santГ© suisse actuel, une projet comme le notre constitue une solution pragmatique permettant de promouvoir le dГ©pistage auprГЁs des populations les plus Г risque, tout en assurant aux patients une qualitГ© des soins adГ©quate. 178 Postersession SGH - Session des posters SSH Hemostasis, Vascular Biology and Transfusion P438 Alpha-linolenic acid decreases platelet storage lesions (PSL) in platelet concentrates: pilot study Simona Stivala, Sara Meyer, Martin Reiner*, Thomas LГјscher, Andreas Buser, Hans JГјrg Beer Cantonal Hospital of Baden (Baden, CH); Blood transfusion Center, Division of Hematology, University Hospital Basel (Basel, CH); Cantonal Hospital Baden (Baden, CH); Department of Cardiology, University Hospital (ZГјrich, CH); Department of Internal Medicine, Cantonal Hospital Baden (Baden, CH) Background: PSL comprises deleterious effects on platelets during storage in platelet concentrates (PCs) and pathogenic contaminations. The latter is prevented by the application of вЂњIntercept Blood System (IBS)вЂќ. We previously demonstrated that the plant-derived omega-3 fatty acid alpha-linolenic acid (ALA) reduces platelet activation and aggregation, furthermore arterial thrombosis and increases platelet survival by reducing its clearance in mouse models. Aim: Addition of ALA to PCs a) reduces platelet baseline activation and b) preserves function/activatability during storage in IBS-treated and untreated PCs. Methods: 8 PCs were obtained from 4 healthy volunteers and divided in an IBS-treated (n=4) and untreated (n=4) group. Each group was subdivided and incubated with ALA (30 uM, n=2) or vehicle (ethanol, n=2). Bags were stored for 10 days and samples were analyzed daily by aggregometry, platelet aggregation on collagen and adhesion to VWF under shear stress. Receptor expression/activation/cleavage was determined by flow cytometry. Results: At day 10, platelet aggregation on collagen was increased in both IBS-treated (covered area: 68.848 um2 vs 39.243 um2) and untreated PCs (102.779 um2 vs 68.729 um2) in addition adhesion to vWF was higher. ALA augmented Thrombin-induced (0.5 U/ml) aggregation in bags exposed to IBS (AUC: 59В±51 vs 15В±11) as well as in untreated PCs (AUC: 27В±14 vs 14В±7) at d10. GPIb cleavage from the platelet surface was diminished by ALA in untreated bags (d1=100%, d10= 69В±10% vs 63В±7%) but was comparable when exposed to IBS treatment at d10. ALA further decreased spontaneous P-selectin expression in PCs with and without IBS treatment. At day 1, ALA inhibited platelet aggregation in response to thrombin (0.5 U/ml) and additionally platelet aggregation on collagen. Conclusions: ALA inhibits spontaneous platelet activation and preserves platelet function during storage in IBS-treated and untreated PCs. However, effects of IBS treatment on platelets need further investigation. P439 Congenital fibrinogen disorders: unexpected clinical phenotypes associated with two novel missense mutations Alessandro Casini*, FranГ§oise Boehlen, Marguerite Neerman-Arbez, Philippe de Moerloose HUG (GenГЁve, CH); CMU (GenГЁve, CH) Introduction: Despite the important increase of knowledge in molecular assessment of fibrinogen disorders, relationship between genotype and phenotype are not completely established. We report here a new mutation of FGA in an asymptomatic dysfibrinogenemic patient and a new mutation of FGB in an afibrinogenemic patient that experienced severe bleeding and thrombosis. Method: After isolation of genomic DNA, exons and intron-exon junctions of the fibrinogen genes were amplified by polymerase chain reaction (PCR) and sequenced. Results: Patient 1. A 52 years old Caucasian female was referred for low fibrinogen activity (0.8 g/L) detected on preoperative screening (antigen 3.5 g/L). She reported no notable bleeding, even after various tooth extractions and a surgery for varicose veins. Proband's father, sister and two children also had low levels of fibrinogen activity and are asymptomatic. DNA analysis showed heterozygous missense mutation at residue 17 of the exon 2 of FGA encoding the fibrinogen alpha-chain: FGA: c. 107 G>A (GGC>GAC, p.Gly36Asp, numbering from the initiator Met or Gly17Asp in the mature alphachain minus the signal peptide). This dysfibrinogenemia is associated with a delayed polymerization as result of the abnormal structure of the knob A site. Mutations in this region are usually associated with a bleeding phenotype. 179 Patient 2. A 30 years old Algerian male, diagnosed with afibrinogenemia (no fibrinogen and indefinitely prolonged coagulation times) in early childhood, was hospitalized for a pulmonary embolism. He reported a severe bleeding phenotype with prolonged bleeding after circumcision and massive hemoptysis. Proband's parents were consanguineous. DNA analysis showed homozygous missense mutation in exon 6 of FGB encoding the fibrinogen beta-chain: FGB: c. 895 T>C (TAT>CAT, p.Tyr299His, numbering from the initiator Met or Tyr269His in the mature beta-chain minus the signal peptide). This mutation is located in the sequence of globular C terminal domain which is crucial for the expression of viable protein since evidence suggests that the supply of the B beta -chain is a ratelimiting factor in either assembly or secretion of the fibrinogen hexamer. Missense mutations reported in this region are associated with bleeding phenotype. No thrombotic events in patients with mutation in this region have been reported so far. Conclusion: We report two new mutations causing fibrinogen disorders with unusual clinical phenotypes. P440 Impact of haemophilia on cancer detection and management: a retrospective study Philippe de Moerloose*, Christine Biron, Roseline D'Oiron, HervГ© Chambost, Jean-FranГ§ois Schved, Cedric Hermans HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); HГґpital St Eloi (Montpellier, FR); Kremlin BicГЄtre (Paris, FR); La Timone (Marseille, FR); HГґpital St Luc (Bruxelles, BE) Introduction. Lymphoma and hepatocarcinoma secondary to blood-borne transmitted diseases are well known malignancies in persons with hemophilia (PWH). However with increasing life expectancy more PWH are confronted with other malignancies such as prostate or colorectal cancers, requiring a close collaboration between oncologist and the haemophilia specialist. Aim and Methods. The aim of present study was to collect retrospectively in the last 10 year-period cases of cancer that occurred in PWH in five European hemophilia treatment centers (Brussels, Geneva, Marseille, Montpellier and Paris) from three countries and to analyze the impact of haemophilia on cancer detection and its management. Results. A total of 46 malignancies occurred in 1267 PWH during the observation period. Eighteen tumors were fatal (39%). The most common types of malignancy were hepatocellular carcinoma (12/46) and urogenital tract tumors (9/46). Bleeding revealed a neoplasia in 4 patients and a change in bleeding pattern in relation with cancer was observed in 2 patients. No bleeding was associated with chemotherapy or radiotherapy but some bleeding complications occurred with surgical procedures in spite of adequate clotting factor substitution. After cancer diagnosis, five patients switched from on demand to prophylaxis substitution (either for a short or for a long term period). In the majority of cases the treatment protocol was not modified because of hemophilia. Conclusion. Our study emphasizes that in adults PWH a change in bleeding should raise the suspicion of malignancy and also that a PWH should benefit from the same oncologic treatment as other persons with cancer but no hemophilia. P441 Albumin reverses echinocytosis induced by metabolic depletion and storage of erythrocytes Sophie A. Reinhart*, Thomas Schulzki, Walter H. Reinhart Kantonsspital GraubГјnden (Chur, CH) Background: In vitro incubation of red blood cells (RBCs) and RBC storage for transfusion purposes leads to a time-dependent echinocytic shape transformation of RBCs. We have recently observed that albumin can restore to a great extent a normal discocytic shape of these RBCs. In the present study we have investigated this phenomenon in more detail. Methods and Results: Blood from healthy volunteers, anticoagulated with either heparin, citrate or EDTA, was incubated at temperatures of 5В°, 22В° or 37В°C for 0, 24, and 48h, respectively. A temperature- and time-dependent decrease of glucose and ATP, increase of lactate and LDH, erythrocytes swelling and echinocytic shape transformation were observed, irrespective of the anticoagulant, indicating a calcium-independent mechanism. The morphology was analysed on wet preparations of glutaraldehyde-fixed RBCs. The degree of echinocytic shape transformation correlated with the increase in high shear blood viscosity. Echinocytosis was partially reversible when RBCs were resuspended in a large volume of buffer containing 0.2% human serum albumin, which was 180 specific for albumin, since molecules with a similar molecular weight (dextran 70, heat shock protein, protein C) had no effect. This effect of albumin was further studied by a systematic variation of the concentration (0.05-3.2%), hematocrit (0.05-64%) and incubation time (1s-3h36min). The shape restoring effect of albumin was concentration-dependent with a threshold level around 0.1%, it correlated inversely with the hematocrit and showed the time-dependence with a marked shape recovery already after 1s and a further gradual recovery over 1min. RBCs stored under blood banking conditions for 7 weeks underwent a more marked echinocytosis. Nevertheless, RBC resuspension in 0.2% albumin led to a rapid shift towards a discocytic shape, which was seen even for the most severe forms of echinocytosis. The lower the hematocrit of the suspension, the better the shape recovery. Adding albumin to stored RBC units to reach a hematocrit of 40% induced a concentrationdependent shape recovery. When stored RBCs were resuspended in fresh-frozen plasma and mixed with fresh blood, a partial shape recovery was found. Conclusions: Human serum albumin has a capacity to reverse echinocytosis that occurs during metabolic depletion and storage of RBCs. These observations may have an impact on transfusion medicine and have the potential to improve the outcome of blood transfusions. P442 Underestimation of positive Anti-PF4-Antibodies (HIT IgG) in patients with myeloproliferative neoplasia and thrombocytosis: effect on vascular complications Eva Steinmann*, Thomas Lehmann, Patricia Muesser, Lukas Graf, Dimitrios Tsakiris University Hospital Basel (Basel, CH) Introduction: Heparin induced thrombocytopenia (HIT) is a thrombotic syndrome triggered by autoantibodies against platelet factor 4 (PF4), a protein released from the alpha-granules of platelets. There is suggestive evidence that a higher turn-over in platelets is associated with higher incidence of HIT antibodies. Thus patients with myeloproliferative neoplasias (MPN) might be at risk for developing HIT which can be masked by high platelet counts. Patients and methods: We retrospectively reviewed clinical records of 130 patients with MPN (51 with essential thrombocythemia, 76 polycythemia vera (PV) and 3 unclassifiable). Number and localization of thrombosis were recorded from diagnosis of disease by duplex ultrasonography or spiral CT. Laboratory parameters (blood cell counts and JAK2-allele burden were registered at the time of diagnosis. Specific Anti-PF4-IgG antibodies were tested by ELISA (ZYMUTEST) in deep frozen serum samples taken at time of diagnosis or later. Results: Patients with MPN showed higher platelet and leucocyte counts (average 759 and 11.0 G/L). Further 67/130 (52%) had splenomegaly, 91/130 (70%) had positive JAK2V617F, and 55/130 (42%) had developed thrombotic complications during the course of disease. The most common thrombotic events were stroke or venous thrombosis. Most patients (65%) with thrombotic complications had higher leucocytes than 10.0 G/L. HIT antibodies were detected in 22 patients (17%) by the qualitative screening assay for IgG, IgM and IgA isotypes. Specific HIT IgG antibodies, were detected in 7 (5.4%) patients. Only 4 of these 7 patients developed thrombotic complications, a non-significant result. Unfortunately state of positivity was not known at time of the thrombotic events. All patients with HIT IgG had PV. All had splenomegaly and were JAK2 V617F or JAK2 Exon 12 positive, 6/7 (86%) had leukocytes higher than 10.0 G/L. Two patients had thrombocytopenia (140 and 73 G/L) at time of HIT IgG detection, but both patients had never developed thrombotic complications. Conclusions: Vascular events are one of the most common complications of MPN. Specific HIT IgG antibodies seem to have a higher prevalence in patients with MPN compared to historical controls without MPN, but positive HIT IgG antibodies are probably not associated with more frequent thrombosis in this group. Thrombosis in MPN is probably a multifactorial event. 181 P443 Impact of changes in haematocrit level and platelet count on thromboelastometry parameters Michael Nagler*, Silvio Kathriner, Lucas Bachmann, Walter Wuillemin Inselspital University Hospital (Berne, CH); Luzerner Kantonsspital (Luzern, CH); medignition Inc. (Zug, CH) Introduction: To what extent haematocrit levels (Hct) and platelet counts (PLT) influence the measurement of parameters of thromboelastometry when assessed with the ROTEMВ® device is unclear. We investigated to what extent thromboelastometry measurements depend on Hct and PLT. Methods: Whole blood samples were taken for in-vitro preparations of mixtures with three different levels of PLT and a varying Hct. Maximum clot firmness (MCF), clotting time (CT), clot formation time (CFT) and alpha angle for INTEM, EXTEM, FIBTEM and APTEM was recorded. Results: Measurements depended substantially on Hct and PLT. MCF readings were systematically lower with increasing Hct (0.2 vs. 0.4: -7.8 (-8.3 to -7.2); p<0.001, 0.2 vs. 0.55: -14.5 (-17.3 to -14.3); p<0.001) but higher with increasing PLT (50 vs. 125x109/l: 8.2 (4.2 to 12.3); p=0.005, 50 vs. 250x109/l: 12.0 (7.2 to 16.8); p=0.002). CT readings were systematically higher with increasing Hct (0.2 vs. 0.4: 9.2 (6.2 to 12.1); p=0.001, 0.2 vs. 0.55: 38.2 (21.5 to 54.9); p=0.003) while increasing PLT had no influence. CFT readings were also systematically higher with increasing Hct (0.2 vs. 0.4: 83.8 (40.2 to 127.6); p=0.006, 0.2 vs. 0.55: 226.2 (110.7 to 341.7); p=0.006) but systematically lower with increasing PLT (50 vs. 125x109/l: -144.0 (-272.3 to -15.6); p=0.036, 50 vs. 250x109/l: -189.2 (-330.4 to -48.0); p=0.02); readings of the alpha angle showed a similar pattern. Conclusions: Our results suggest that readings of thromboelastometry parameters need to be adjusted by Hct and PLT to avoid potential confounding and miss-interpretations in clinical practice. 182 Postersession SGH - Session des posters SSH Clinical Hematology P444 Efficacy of azacitidine in acute myeloid leukaemia: a retrospective study Cornelia GemГјnden*, Rudolf Benz, Oliver Senn, Jeroen S. Goede, Markus G. Manz, Bernhard Gerber UniversitГ¤tsSpital ZГјrich (ZГјrich, CH); Kantonsspital MГјnsterlingen (MГјnsterlingen, CH); UniversitГ¤t ZГјrich (ZГјrich, CH) Background: Treatment for acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy is challenging. Given its activity in myelodysplastic syndrome, Azacitidine is thought to be a potential therapeutical alternative to low-dose Cytarabin in this patient population. Methods: We retrospectively analyzed all patients with AML treated with Azacitidine at the University Hospital Zurich or the Kantonsspital MГјnsterlingen. Treatment schedule: Azacitidine 100mg/m2 subcutaneously on days one to five or Azacitidine 75mg/m2 subcutaneously on days one to seven of a 28 day cycle. Observation period: September 2004 to February 2012. End of follow-up: 31st of May 2012. Primary end-point: Overall-survival. Secondary end points: Hospitalization days and transfusion independency. Results: Forty patients were included in the analysis of whom 22 (55%) had de novo AML, 15 (38%) AML relapse, and 3 (7%) underwent a bridging therapy prior to allogeneic stem cell transplantation. The median age was 67 years, 21 (52%) patients were female, 19 (48%) patients were transfusion dependent and the median bone marrow blast count was 43% (interquartile range 26-80). According to the HOVON/SAKK 102 risk stratification patients were classified in a good-risk, intermediate-risk, poor-risk or very-poor risk group in 6 (15%), 8 (20%), 18 (45%) and 6 (15%), respectively. For two (5%) patients these data are lacking. Median overall-survival was 591 (337-824) days in the whole treatment group and 403 (232-683) days in patients with de-novo AML. After censoring for the hospitalization days during the first treatment cycle, patients had to be hospitalized for a median of 6 (0-21) days (whole treatment group) and 5 (0-15) days (de novo AML), respectively. Transfusion independency occurred in 3 (16%) patients. No serious adverse events related to Azacitidine were noted. Conclusion: Treatment with Azacitidine is safe for AML patients unfit for intensive chemotherapy. Once the outpatient treatment was established, only few hospitalization days were needed. However, only a minor effect on transfusion dependency was seen. Large randomized trials (e.g. NCT01074047) will have to address the question whether Azacitidine is superior to the standard of care in this patient population. P445 Favourable long-term outcome in patients with 13q deletion and severe aplastic anaemia Andreas Holbro*, Martine Jotterand, Jakob Passweg, Andreas Buser, AndrГ© Tichelli, JГ¶rg Halter, Dominik Heim, Martin Stern, Alicia RovГі University Hospital Basel (Basel, CH); University of Lausanne (Lausanne, CH) Introduction: The prognostic significance of cytogenetic abnormalities in aplastic anemia (AA) are controversial. Del(13q) has been reported to occur in patients with MDS and other hematologic malignancies. Additionally, cases of patients with bone marrow failure syndrome with del(13q), who showed good response to immunosuppressive therapy have been reported. Methods: We retrospectively analyzed outcome of patients diagnosed as AA with del(13q) at our institution. Results: For 86/353 (24%) patients cytogenetic analysis at any time during the disease course was available. We identified six patients (7%) with del(13q). Table 1 shows patients characteristics. Median age at diagnosis was 50.5 years (range: 22-71 years), half were male. One patient was diagnosed with very severe AA, three patients with severe AA and two with AA. Del(13q) was detected at diagnosis in four patients. One patient (UPN 936) had a normal karyotype at diagnosis and developed del(13q) after a first course of antithymocyte globuline (ATG), and cyclosporine A (CYA). Two years later this patient relapsed and received a second course of ATG and CYA with disappearance of the del(13q) clone. She reached a partial response (PR) and remains under immunosuppression with CYA, free of transfusions 86 months after last ATG. One patient diagnosed in 1987 with SAA (UPN 410) was treated with ATG in 1990, cytogenetics at diagnosis were not available. She reached a 183 complete response with persisting macrocytic anemia. Del(13q) was documented 10 years after ATG. She remained hematologically stable for 276 months until her death in a car accident. In two patients, del(13q) was no longer detectable at last follow-up. All patients except one are still alive after a median follow-up of 105 months (range: 84-276 months). None of the patients showed progression to acute myeloid leukemia or MDS. Conclusion: Patients with bone marrow failure without dysplasia and isolated del(13q) should be classified as AA and treated accordingly as they represent a subgroup of patients with favorable outcome. P446 Herpes zoster is a frequent event following autologous transplantation and associated with favourable prognosis in myeloma patients Christine Kamber*, Stefan Zimmerli, Marion Bleckmann, Thomas Pabst UniversitГ¤tsspital (Bern, CH) Background: Herpes Zoster (HZ) is reported to occur in 17-50% of patients after allogeneic stem cell transplantation. In contrast, only few data are available on the incidence of HZ following autologous transplantation (ASCT). Consequently, evidence-based guidelines for prophylaxis against HZ are widely missing for ASCT. Methods: We analyzed all consecutive patients (n=380) with multiple myeloma, lymphomas, or AML undergoing ASCT between January 2005 and March 2012 at the University Hospital of Berne, Switzerland for the occurrence of HZ. After leukocyte recovery, patients received no routine antiviral prophylactic treatment. Clinical records verifying HZ were assessed in all patients. In addition, patients alive (n=274) were also investigated using a standardized questionnaire. Results: Information on the incidence of HZ was obtained from 100% of the patients undergoing ASCT in this period, and the questionnaire was obtained from all patients alive. We found that 100 of the 380 patients (26.3%) of our cohort had a HZ. 75 patients (19.7%) developed HZ after ASCT, and 25 (6.6%) patients had HZ during induction chemotherapy before transplantation. 54 of the 75 (72%) patients with HZ after ASCT had the event within the first year after transplantation, peaking at five months after ASCT. 63% of the patients with HZ considered the burden of HZ to be high or rather high, and 70.7% reported significant post herpetic neuropathy. Finally, we found that the occurrence of HZ in myeloma patients was an independent factor predicting better overall survival (p=0.034). A similar trend for improved survival was observed in lymphoma patients with HZ (p=0.072). Conclusion: HZ is a frequent event following autologous transplantation with significant morbidity and it is associated with a more favorable course in myeloma patients. Our data provide the rationale for subsequent prospective studies evaluating prophylactic strategies against HZ for patients undergoing ASCT. 184 P447 A single centre cohort of systemic light chain AL-amyloidosis patients: highdose chemotherapy with autologous stem cell transplantation is associated with a more favourable outcome than conventional chemotherapy Joelle Raschle*, Yara Banz, Thomas Pabst UniversitГ¤tsspital (Bern, CH) Background: High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) has been reported to confer favourable outcome in systemic light chain AL-amyloidosis, a rare clonal plasma cell disorder. However, data on treatment and outcome of AL-amyloidosis patients in Switzerland are missing so far. The aim of this study was to establish a single centre cohort of light chain amyloidosis patients and to compare the outcome of amyloidosis patients treated with conventional chemotherapy versus HDCT with ASCT. Such a cohort may later be extended to establish a Swiss cohort of amyloidosis patients. Methods: Patients with biopsy confirmed immunoglobulin light chain AL-amyloidosis diagnosed between January 1995 and December 2012 were included in this single centre retrospective analysis. We comprehensively determined clinical characteristics and stratified the population into two groups: patients treated with conventional chemotherapy or with HDCT and ASCT. Results: 63 patients with systemic light chain AL-amyloidosis were identified. 50 patients were treated with conventional chemotherapy and 13 patients with HDCT and ASCT. After a median follow-up of 31 months, one death occurred in the HDCT/ASCT group and 23 deaths in the conventional chemotherapy group (P=0.0116). Patients undergoing HDCT and ASCT had a trend for better overall survival (OS) compared to patients treated with conventional chemotherapy regimens (P=0.0651). Whereas the group of patients with HDCT and ASCT did not yet reach the median OS, patients treated with conventional chemotherapy had a median OS of 53 months. The median time to progression (TTP) of the entire study population was 19 months, with a median TTP not yet reached in the HDCT/ASCT group and with 15 months in the conventional therapy group (P=n.s.). Patient characteristics between the two groups differed for the age of the patients (59 years for patients treated with HDCT/ASCT versus 69 years; P=0.0006) and the Troponin-T value (0.015 versus 0.08 Вµg/l; P=0.0279). Conclusion: To our knowledge, this is the first study in Switzerland aiming to comprehensively characterize patients with systemic amyloidosis. Our results suggest that light chain AL-amyloidosis patients which are considered fit enough to ultimately undergo HDCT and ASCT have a better outcome than patients treated with conventional chemotherapy. P448 Analysis of haemoglobin by top-down mass spectrometry Pierre Lescuyer*, Didia Coelho GraГ§a, Adelina Acosta Martin, Lorella Clerici, Yury Tsybin, Ralf Hartmer, Markus Meyer, Denis Hochstrasser, Kaveh Samii, Alexander Scherl HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); FacultГ© de MГ©decine de GenГЁve (GenГЁve, CH); Ecole Polytechnique FГ©dГ©rale de Lausanne (Lausanne, CH); Bruker Daltonics (Bremen, DE) Introduction: Mass spectrometry (MS)-based methods have the potential for changing dramatically the way proteins are analyzed in clinical laboratories. In particular, MS offers new opportunities for targeting protein modifications. In order to critically evaluate these possibilities in the context of a clinically relevant application, we developed MS-based assays for qualitative and quantitative analysis of normal hemoglobin chains and hemoglobin variants. We present a top-down MS approach with electron transfer dissociation (ETD) for the identification of sequence variants and the precise quantification of globin chains. Method: EDTA blood samples were obtained from patients suffering from various hemoglobin disorders and healthy controls. Hemoglobin was recovered in aqueous solution after washing and lysis of red blood cells. A reverse-phase nanoscale liquid chromatography hyphenated to an ion trap with ETD capabilities (Amazon Speed ETD, Bruker Daltonics) was used for top-down analysis. Selected Reaction Monitoring with ETD was used for the identification of hemoglobin variants. For quantification of globin chains, specific chains and charge states were isolated in the ion trap and ejected without activation. Relative quantification between the globin chains was performed on the direct measurement of these signals. Results: ETD provided specific fragments covering more than 70% of the beta globin sequence. Variants such as hemoglobin S, C, and E could thus be identified. Although hemoglobin D and O were not analyzed by today, specific fragments surrounding these mutations were present indicating that 185 these variants could be detected as well. Quantification of the hemoglobin A2 delta chain was achieved over a concentration range spanning from 3% to 18% of total hemoglobin with coefficients of variation below 10%. Preliminary data suggests that similar analytical performances can be obtained for the quantification of hemoglobin F and glycated hemoglobin (HbA1c). This MS method could then be applied for the quantification of HbA1c in patients carrying hemoglobin variants or in the presence of elevated concentrations of modified hemoglobin, such as carbamylated hemoglobin. Conclusion: The presented method could be an alternative for the direct, rapid and comprehensive analysis of various clinically relevant hemoglobin variants and post-translational modifications. P449 The use of multiplex ligation-dependent probe amplification (MLPA) for the diagnosis of large deletions in haemoglobinopathies (Hbpathies) and thalassaemic syndromes Tonguy Araud*, FrГ©dГ©ric Guerry, Pierre-Alain Menoud, Georgios Georgiou, Kaveh Samii, Lorella Clerici, Regis Darbellay, Diego Andrey, Photis Beris Unilabs Suisse (GenГЁve, CH); HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); HГґpitaux Universitaires de GenГЁve (GenГЁve, CH) Introduction: MLPA (Multiplex Ligation-dependent Probe Amplification) technique is a powerful method that can be used for detection of genomic deletions. Although well-characterised deletions and amplifications can be detected by PCR, the exact breakpoint site of most deletions is unknown. Southern blot analysis was used in the past to investigate such cases but will not always detect small deletions and is not ideal for routine. We applied this technology to diagnose cases with thalassemia where a deletion was highly suspected. We present here our experience with two such cases. Patients and methods: Case 1: A 35 years old male with Russian and French origins, was investigated because of microcytic anemia (Hb 136g/l; MCV 67.8fl). HbA2 2.2%; HbF 7.8% and HbA 78.4%. No abnormal Hb was found in IEF. Alpha2 (HBA2), alpha1 (HBA1) and beta (HBB) globin genes were sequenced in an automated sequencer after amplification of the DNA with appropriate primers. A deletion in the b-globin cluster (region 5Вґ-HBE1 to HBB-3вЂ™) was looked by using MLPA technology (MRC-Holland, P102-B2). Case 2: A 30 years old lady from Kenya was found to have HbS 66%, HbF 15.2%, an abnormal Hb 10.3% and HbA2 0.7%. Hb 100g/l; MCV 60.1fl. Iron status was normal. Common deletions in the a-globin cluster were analysed by PCR, and Sanger sequencing. Deletions in the b-globin cluster were looked by using MLPA technology. Results: Case 1: No mutation has been detected in alpha1 and alpha2 genes as well as in beta gene. MLPA analysis of the b-cluster, revealed the Mediterranean /SE-Asian form of (delta-beta)thalassemia, heterozygous state. The exact type of deletion is under investigation. Case 2: Alpha globin analysis revealed a-globin triplication in one chromosome 16. Analysis of the whole b-cluster showed a 22.5kb deletion starting at Agamma (HBG1) and finishing in the b-gene. This deletion creates a fusion Agamma-beta gene known as Hb Kenya. Comments and conclusions: These two cases illustrate the utility of this MLPA in the diagnosis of Hbpathies and thalassemia syndromes secondary to deletions. This technique is particularly useful when investigating cases of the deletional form of HPFH (Hereditary Persistance of Fetal Hemoglobin)and cases of microcytosis secondary to non-common a-thalassemic deletions. The existence of a commercial kit for investigation of both alpha and beta globin clusters in chromosomes 16 and 11 respectively, makes this technology affordable to all Hbpathies laboratories P450 A surprising cause of Coombs-negative haemolytic anaemia Rahel Schwotzer*, Brigit Brand, Abraham Licht, Beat MГјllhaupt, Kornelius Arn UniversitГ¤tsSpital ZГјrich (ZГјrich, CH) A 16-year old female of greek origin was referred with a three week history of diffuse abdominal pain and two days history of nausea, vomiting and intermittent fever. The patient did not take any drugs and travelled to Greece for a vacation two months ago. Physical examination revealed jaundice and an abdomen tender to palpation. Laboratory work-up was remarkable for anemia (Hb 98 g/l at presentation, 72 g/l after 12 hours), a platelet count of 153 G/l and a reticulocyte count of 128 G/l, with elevated LDH (1023 U/l) and bilirubin (256 mcmol/l), and an undetectable haptoglobin. The transaminases were only slightly elevated. Direct Coombs test was negative and the coagulation assay showed an INR of 2.3. At that time we discussed the differential diagnosis of a microangiopathic haemolytic anemia (TTP/HUS), an 186 erythrocyte enzyme defect, or a leptospirosis (travel to Greece) as possible causes of the haemolytic anemia. The peripheral blood smear did not reveal any fragmentocytes, no evidence for Malaria on a thick-smear preparation. 16 hours after presentation haemoglobin concentration dropped to 61 g/l making red blood cell transfusions necessary, and the coagulation assays deteriorated including a low factor V (minimal 35%). Serological testing for viral hepatitis and HIV were negative. Upon hepatologist consultation acute WilsonвЂ™s disease was suspected and evaluation for urgent liver transplantation was initiated. Elastographic examination of the liver (FibroScan) showed elevated liver stiffness compatible with cirrhosis and the serum coeruloplasmin was below 200 mg/L, while the 24hour urinary copper excretion was elevated (49.2 mcmol). A slit lamp examination did not show Kayser-Fleischer rings. Treatment with the copper chelator trientine dihydrochloride was initiated at a dose of 1500 mg per day. Transjugular liver biopsy confirmed the diagnosis of WilsonвЂ™s disease with 1355 mcg/g copper per dry weight. Chelation therapy ameliorated the liver function, thus liver transplantation became unnecessary. The hemolytic activity stabilized with spontaneous rise of the haemoglobin concentration. The diagnostic evaluation of acute onset coombs-negative hemolytic anemia can be a challenge. While not a common finding, it may be the initial presentation of acute WilsonвЂ™s disease, with direct copper toxicity as suggested mechanism. In our case the concomitant hepatopathy lead to the diagnosis, in addition the age of onset and the ethnicity are quite typical. P451 International registry for patients with hereditary thrombotic thrombocytopenic purpura (TTP): Upshaw-Schulman syndrome Magnus Mansouri Taleghani*, Yoshihiro Fujimura, James N. George, Ingrid Hrachovinova, Paul Knoebl, Bernhard LГ¤mmle, Petter Quist-Paulsen, Reinhard Schneppenheim, Johanna A. Kremer Hovinga Bern University Hospital and the University of Bern (Bern, CH); Nara Medical University (Nara, JP); University of Oklahoma Health Sciences Center (Oklahoma City, US); Institute of Hematology and Blood Transfusion (Prag, CZ); Medical University of Vienna (Wien, AT); St. Olavs Hospital Trondheim University Hospital (Trondheim, NO); University Medical Center Eppendorf (Hamburg, DE) Introduction: Hereditary TTP, also called Upshaw-Schulman syndrome (USS), is a rare, and recessively inherited disorder, due to homozygous or compound heterozygous mutations in the ADAMTS13 gene. Clinical presentation varies from mild thrombocytopenia to severe recurrent TTP episodes leading to end organ damage or death. The first occurrence of USS ranges from neonatal period up to older age. Due to the rareness of USS evidence based guidelines on prophylaxis with fresh frozen plasma (FFP) and knowledge of long-term outcome are lacking, which emphasizes the need of a multicenter cooperation. Method: An electronic database system for USS patients and their interested family members (www.ttpregistry.net, ClinicalTrials.gov NCT01257269) has been established to gather baseline and long-term follow-up data. They contain the clinical courses and performed laboratory investigations in order to identify yet unknown TTP episode triggers and factors influencing the clinical course, eventually leading to improved therapy and better understanding of this disease. Eligibility criteria are: - ADAMTS13 activity <=10% on two separate occasions at least 1 month apart and - Absence of a functional ADAMTS13 inhibitor and - >=2 ADAMTS13 gene mutations and/or a positive infusion trial (full recovery and plasma half life of 2-3 days of infused plasma) or - Being a family members of a confirmed patient Information is collected retrospectively up to enrollment as well as prospectively every 12 months and when TTP episodes occur. Analysis of ADAMTS13 related parameters including molecular analysis of the ADAMTS13 gene are offered free of charge for patients and family members. Results: Today, 30 participants from 7 different countries (CH, CRO, CZ, NOR, PL,TU, USA) have been entered into the database and another 8 countries (AUT, CAN, D, DAN,FIN, IND, IL, JP) have confirmed their participation with 1 to over 40 patients per study site with data acquisition in progress. A first point of interest is the investigation of episodes of thrombocytopenia during infections or pregnancies in a number of obligatory or confirmed heterozygotes, so far generally reported as being asymptomatic. Conclusion 187 Establish an international network and knowledge platform to exchange information and experience on USS will help to improve diagnosis, treatment and prevention of acute episodes for affected patients. All Physicians are invited to contact us for diagnostics and enrollment of their patients with USS. P452 Design and establishment of a biobank for a multicentre and interdisciplinary prospective cohort enrolling elderly patients with venous thromboembolism (SWITCO65+) Marie MГ©an*, Drahomir Aujesky, Bernhard LГ¤mmle, Christiane Gerschheimer, Sven Trelle, Anne Angelillo-Scherrer Inselpital (Bern, CH); CHUV (Lausanne, CH) Introduction : In the field of haemostasis, many preanalytical variables influence the results of coagulation assays and may affect the quality of the subsequent results. Methods to limit these results variations should be foreseen when building a biobank in the field of haemostasis. Our description of the biobank of the Swiss Cohort of Elderly Patients with Venous Thromboembolism (SWITCO65+) is intended to facilitate set-up of other biobanks in the field of haemostasis. Methods: SWITCO65+ is a multicentre cohort that prospectively enrolled consecutive patients (pt) aged >= 65 years with VTE at nine Swiss hospitals from 09/2009 to 03/2012. The pt will be followed up until December 2013. The cohort includes a biobank with biological material from each participant taken at baseline and after twelve months of follow-up. Whole blood from all participants was assayed with a standard haematology panel, for which fresh samples are required. Two buffy coat vials, one PAXgene Blood RNA System tube and one whole blood sample were also collected at baseline for RNA/DNA extraction. Blood samples were processed and vialed within one hour of collection and transported in batches to a central laboratory where they were stored in ultra-low temperature archives. Use of barcoding and electronic databases ensured efficient management of the biobank. All analyses of the same type were performed in the same laboratory in batches. Using multiple core laboratories increased the speed of sample analyses and reduced storage time. Results : Of the 1003 enrolled pt, 905 (90.2%) had a blood collection at baseline. Only a small minority of pt refused to provide blood samples for genetic analyses (6.5%). The SWITCO65+ RNA/DNA depository was designed to permit both genome wide association and replication studies, with the single limitation that 99.8% of the patients were Caucasians. After an average follow-up time of 512 days, 799 (80.1%) pt were still participating, 150 (15.0%) had died, 1 (0.1%) was lost to follow-up, 47 (4.7%) patients had withdrawn their consent, but only 6 (0.6%) pt did not allow us the use of their data and blood samples. By November 2012, 20,802 vials were stored in the central SWITCO65+ biobank and 7,852 vials had already been sent for subsequent analyses in one of the participating laboratories. Discussion : After recruiting, processing and analyzing the blood of 905 pt, we determined that the adopted methods and technologies were fit-for-purpose and robust. P453 Association of (delta-beta)-thalassaemia with the T>C; 12nts 5Вґ to the poly A site mutation, confirms that the later constitutes a beta-silent thalassaemia state Kaveh Samii*, Lorella Clerici, Regis Darbellay, FrГ©dГ©ric Guerry, Tonguy Araud, Georgios Georgiou, Pierre-Alain Menoud, Photis Beris HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); Unilabs Suisse (GenГЁve, CH) Introduction: Silent b-thalassemia is defined when the simple carrier has normal hemogram without the b-thalassemic markers: normal HbA2 and HbF; normal MCV and MCHC. Such cases are diagnosed because when associated with the classical b+ or b0 thalassemias, they create a phenotype close to thalassemia intermedia and always more severe of the known classical bthalassemia state. Here we provide evidence that the c.*+96T>C (rs34029390); 12nts 5Вґto the poly A site mutation, constitutes a silent b-thalassemia state. Patients and methods: The propositus, a 5 years old male child with Russian, French, German and Polish origins, was investigated because of microcytic anemia (Hb 103g/l; MCV 65 fl). HbA2 2.6%; HbF 18.6%; HbA 68.2%. Iron status was normal. His father has slight anemia with severe microcytosis (Hb 136g/l; MCV 67.8 fl) with HbA2 2.2%; HbF 7.8% and HbA 78.4%. His mother besides a slight anemia (Hb 114g/l), has normal MCV, HbA2 and HbF (87.6fl; 2.4%; 0.7% respectively). No abnormal 188 Hb was found in IEF of Hbs of all members of the family. Alpha2, alpha1 and beta globin genes were sequenced in an automated sequencer after amplification of the DNA with appropriate primers. A deletion in the b-globin cluster was looked by using MLPA technology. Results: No deletion or point mutation was found in both a-globin genes in all members of the family. In the father one chromosome 11 has the beta CD2 C>T polymorphism (c.[9C>T], p.His3His) while the other chromosome carries the Mediterranean form of (delta-beta)-thalassemia. In the mother one bgene is normal. The other is carrying the T>C; 12nts 5Вґ poly A site mutation. The propositus is found double heterozygous for the (delta-beta)-thalassemia of his father and for the T>C; 12nts 5Вґ poly A mutation of his mother. Comments and conclusions: The T>C substitution at nucleotide +1570 of the b-globin gene was first described in 1992 by Cai et al as a novel typical b-thalassemia mutation (Blood 1992). Later the same authors revised their communication by reporting data indicating that this mutation represents a polymorphism. We now show that this mutation constitutes a silent b-thalassemic trait. In fact combination with (delta-beta)-thalassemia creates a rather severe anemia not seen in the simple heterozygous state, with highly increased HbF values. Further more, in the simple heterozygous state hemogram, HbA2 and HbF values are normal. How this point mutation decreases beta mRNA expression or stability is not known. P454 Identification of the SF3B1 mutation in two cases with refractory anaemia with ring sideroblasts with high platelet count (RARS-T) and one with refractory anaemia with ring sideroblasts (RARS) Georgiou Georgios*, Michael Franceschi, Jean-Luc Mandier, Pierre-Alain Menoud, Photis Beris Unilabs Suisse (GenГЁve, CH) Introduction: Approximately 20% of Refractory Anemia with Ring Sideroblasts (RARS) present with high platelet count (RARS-T). They belong to the provisional entity of the MDS/MPNs clonal myeloid neoplasms according to WHO classification. Recently massive parallel sequencing technology identified recurrent somatically acquired mutations in SF3B1 in RARS and RARS-T patients. We present 2 cases of RARS-T and one RARS with three different mutations in SF3B1 gene. Patients and methods: Case 1: Mr C. M. born on 1945. Hb 98g/l; MCV 108fl; GB 6G/l; Plt 468G/l. Serum iron 39.6umol/l; transferine saturation 82%; ferritine 536ug/l; B12 1вЂ™164pmol/l; folates 90nmol/l; Epo 114U/l. Bone marrow: 75% ring sideroblasts; blasts ~2%. Caryotype: 46, XY. Case 2: Mr F.A. born on 1950. Hb 112g/l; MCV 104fl; GB 8.1G/l; Plt 1.125G/l. Serum iron 19.9umol/l; transferine saturation 34%; ferritine 238ug/l; Bone marrow: 55% ring sideroblasts; blasts <2%. Caryotype: 46, XY. Case 3: Mr Z.M. born on 1932. Hb 114g/l; MCV 105fl; GB 5.3G/l; Plt 291G/l. Serum iron 17umol/l; transferine saturation 29%; ferritine 623ug/l; Bone marrow: 65% ring sideroblasts; blasts ~1%. Caryotype: 46, XY, del(20)(q11;q13). We screened the three patients for the presence of JAK2 V617F mutation (peripheral blood DNA extraction and pyrosequencing) and for SF3B1 mutations (direct Sanger sequencing of exons 11-16). After peripheral blood RNA extraction and reverse transcription to cDNA, an amplicon of 1kb was generated using the primers 5`-TGACCAGCCATCTGGAAATC-3` (forward, exon 10) and 5`-CACCATCTGTCCCACAACAC-3` (reverse, exon 17). Results: Patient 1 had the SF3B1 K700E mutation and was JAK2 V617F positive; patient 2 was found to have the SF3B1 R625C mutation and patient 3 the SF3B1 K666R. The last two patients were JAK2 V617F negative. Comments and conclusions: SF3B1 is a gene encoding an RNA-splicing factor. In recent studies, 79% of RARS patients and 66.7% of RARS-T patients were found to carry different mutations in this gene. (Papaemmanuil E et al N Eng J Med 2011). All our patients were positif for a previously described mutation within SF3B1 gene. Preliminary data indicate a favourable clinical predictor of this mutation (Malcovati L et al Blood 2011). One of our three patients has a survival of >15 years. We believe that mutations at SF3B1 should be looked in every new case of RARS /RARS-T to confirm the better clinical outcome of these patients which certainly will have an impact in therapeutic decisions. 189 P455 Iron absorption test in iron deficiency Petra Fellmann*, Mario Bargetzi Kantonsspital Aarau (Aarau, CH) Introduction: In earlier days the iron absorption test (IAT) was used as a diagnostic tool for iron deficiency, but became less important since there are other parameters to define iron deficiency like ferritin and the soluble transferrin receptor. The aim of our study was to see, whether the IAT could be used for disorders, that lead to decreased iron absorption. Methods: We retrospectively analyzed medical records of 131 patients, who had been referred to our center with the diagnosis вЂћiron deficiencyвЂњ between 2005 and 2010. The IAT was performed the following way: 200mg of iron (Fe++) were administered per os, the serum iron concentration was measured before, 2 and 4 hours after the iron intake. A normal test result was defined as increase of serum iron concentration of 50-200% after 2 or 4 hours. An absolute value over 35micromol/l was defined as an increased absorption. A low iron level at the beginning with an increase <50% was defined as malabsorption (Fig. 1). Results: Mean age of all patients was 50 years (range 16-90y), 86% were female. An IAT was performed in 24% (n=32). 69% (n=22) showed an increased absorption, 25% (n=8) had normal values and 6% (n=2) had a decreased absorption. Half of the patients with IAT had an upper endoscopy. 40% (n=6) of patients with normal or increased absorption in the IAT had a normal endoscopy, in 60% (n=9) there were abnormal findings. Patients with decreased iron absorption in the test had equal distribution of normal and abnormal findings (Fig. 2). 60% (n=19) of patients with IAT were currently taking an iron pill and had a low ferritin despite anamnestically adequate oral iron substitution. Only one of these patients had a decreased absorption in the IAT, the other 18 patients had a normal or increased iron absorption test. 16% (n=5) of the patients with IAT were taking a proton pump inhibitor (PPI), 3 of them had a normal or increased iron absorption, 2 hat a decreased absorption. Conclusions: The IAT is not reliable in order to indicate an iron malabsorption (lack of sensitivity). But it is probable, that the IAT can indicate poor drug complicance regarding the fact, that patients with insufficient increase of ferritin during oral iron substitution had (except one patient) a normal/increased iron absorption test (good specificity). The intake of PPIs might have influenced the iron absorption in the IAT in this study. 190 P456 A case of chronic eosinophilic leukaemia with translocation t (8; 9) (p22; p24) and PCM1-JAK 2 fusion gene Mihaela Precup*, Paul Pugin, Valerie Parlier, Esther GaramvГ¶lgyi, Marc Kueng, Jacqueline Schoumans, Yves Chalandon, Daniel Betticher, Emmanuel Levrat HГґpital Cantonal Fribourg (Fribourg, CH); CHUV (Lausanne, CH); Promed (Marly, CH); HUG (GenГЁve, CH) Introduction: Translocations involving the gene JAK2 (janus-activated kinase) are found in a wide range of myeloproliferative disorders. One of the translocations rarely described to date and considered as bad prognostic factor is the translocation t (8; 9) (p22;p24) with fusion of genes PCM1 (pericentriolar material 1) and JAK2, morphologically resulting in a myeloproliferation with eosinophilia and myelofibrosis. We report on a case with this fusion transcript PCM1-JAK2 in the framework of a chronic eosinophilic leukemia not otherwise specified (CEL-NOS). Clinical case: A 47-year old patient with a history of a bipolar disorder has been investigated for a skin infiltration on the anterolateral side of the right leg associated with palmo-plantar pustulosis. Night sweats and fatigue lasted for several months .The CT scan showed hepatosplenomegaly without significant lymphadenopathy. Complete blood count: leukocytosis 16.0 G/l, neutrophils 1,6 G/l, eosinophils 4 G/l, lymphocytes 2,3 G/l, myelocytes 1,6 G/l , no blasts or erythroblasts; hemoglobin 112 g/l, platelets 150 G/l. The bone marrow (BM) biopsy revealed a hypercellularity , with hyperplasia and atypia of myelopoiesis together with marked eosinophilia, normal megacaryopoiesis, atypia of erythropoiesis and slight reticulinc fibrosis (MF1) without blast excess. BM cytogenetic showed translocation t(8;9)(p22;p24) in 20/22 analyzed metaphases.The interphase FISH confirmed the PCM1-JAK2 rearrangement in 129 (64.5%) nuclei studied. The skin biopsy revealed an eosinophilic dermatosis with few immature myeloid elements. Based on these results the diagnosis of CEL-NOS was made. We started a therapy of Interferon-Alpha 2a (3 million units 3 x/wk) and Prednisone (1mg/kg/day, progressively tapered to 5 mg/day over 3 months). We observed a significant regression of skin lesions and disappearance of the peripheral eosinophilia. The BM biopsies after 5 and 12 months of treatment demonstrated the persistence of the above described morphological and cytogenetic changes, but an increased reticulinic fibrosis (MF2). Conclusion: our case demonstrates a hematological favorable evolution under IFN alpha 2a /prednisone therapy for a CELвЂ“NOS with PCM1-JAK2 fusion gene, entity rarely described so far, without however cytogenetic response. We intend to introduce ruxolitinib, a JAK2 inhibitor which has been shown to induce complete cytogenetic remission in a similar situation. 191 P457 Lenalidomid-induced pneumonitis Rania Mohamed*, Monika Nagy Hulliger, Gregoire Gex, Christian Juillet, Yves Chalandon Hopital du Valais (Sion, CH); Hopital Cantonal de Geneve (GenГЁve, CH) Background : Lenalidomide is an immunomodulatory agent, more potent than thalidomide and also a less toxic analog of it, approved for use in myelodysplastic syndrome. In combination with dexamethasone itвЂ™s widely used for refractory or relapsed multiple myeloma. Myelosuppression is the most severe known side effect of lenalidomide, although pulmonary toxicity is probably underreported. The exact mechanism of lenalidomide-induced interstitial pneumonitis is unknown, but inhibition of prostaglandin E(2) secretion by lenalidomide is supposed, as well as promoting proliferation of fibroblast cells and collagen synthesis. Case: We report here a clinical case of pulmonary toxicity without pulmonary symptoms. A 59 years old patient was treated in the frontline setting with bortezomib/dexamethasone for an IgA lambda type myeloma diagnosed in March 2012. Because of life threatening side effects of bortezomib (severe paralytic ileus and serious perturbation of hepatic tests), without sign of pulmonary toxicity (normal chest X-ray), the treatment was changed and lenalidomid introduced. After his sixth cycle of lenalidomid the patient was hospitalized for a febrile agranulocytosis in September 2012. He presented neither dyspnea, nor cough nor expectoration. Classical workup didnвЂ™t identify infection and broad spectrum antibiotic was rapidly introduced. Chest examination revealed bibasal fine crackles. A thoracic CT scan showed focal ground-glass attenuation. After four weeks, the patient remained asymptomactic, without fever. A new thoracic CT showed persistence of ground glass attenuation and new parenchymal bands. The patient was not taking any drug with known pulmonary toxicity and denied any inhalation exposure to toxins or allergens. A bronchoalvolar lavage was performed. Extensive cultures and PCRs were all negative and the differential cell count showed increased number of lymphocytes (63%), without monoclonality in flow cytometry. Lenalidomid treatment was interrupted. 2 months later, a new thoracic CT revealed total resolution of aforementioned infiltrates. Conclusion: Although pulmonary infection is a frequent complication of multiple myeloma treatment, physicians should be aware of lenalidomid pulmonary toxicity, particularly among patients presenting with atypical radiologic infiltrates not responding to antibiotics. P458 Characteristics of the diagnostic approach of patients investigated for mild bleeding disorders in two university hospitals FranГ§oise Boehlen*, Anne Angelillo-Scherrer, Gabrielle Martin, FranГ§oise Bonfils, Rachel SpycherElbes, Linda Guida, ValГ©rie Leclair-Rezbach, Nicolas von der Weid, Pierre Fontana HГґpitaux Universitaires de GenГЁve (GenГЁve, CH); Centre Hospitalier Universitaire Vaudois (Lausanne, CH) 192 Introduction: The diagnosis of mild bleeding disorders (MBD) is often a challenge, partly due to the lack of standardisation in the diagnostic approach. We aimed to evaluate the characteristics of the clinical and biological diagnostic procedures performed in patients referred for a suspicion of MBD in two university hospitals (Geneva and Lausanne). Methods: We performed a retrospective analysis of consecutive patients referred to both pediatric and adult haemostasis/hematology outpatient clinics of the university hospitals of Geneva and Lausanne between January 2009 and December 2010 for investigation of a putative bleeding disorder. We collected the characteristics of the patients as well as the clinical and biological evaluation that were performed. Results: Up to now, 218 charts were included (109 in each centre, including 37 children). Mean age was 42.4 В± 17.3 years with 70% of female patients in adults and 9.7 В± 4.1 years with 46% of female patients in children. Characteristics of patients in Lausanne and Geneva did not differ in terms of age and sex ratio. Patients were referred for a biological anomaly in 16%, a relative screening for a familial history of MBD in 12% or for a personal bleeding history in 72% of cases. A standardized bleeding questionaire was used in 14% of cases in Lausanne and in 91% of cases in Geneva (p<0.001). A standardized assessment of menses was performed in 2% of adult women in Lausanne and 77% in Geneva (p<0.001). The proportion of platelet function tests, dosage of coagulation or von Willebrand factors was similar in both centres but the agonists used to evaluate platelet function were different. Conclusion: The diagnostic approach of patients referred for investigation of a putative MBD differed significantly in Geneva and Lausanne mainly regarding the initial clinical assessment and the platelet function evaluation. The ongoing standardisation of this approach in both hospitals may help in identifying patients at risk for a bleeding event. P459 Splenic infarction in a young man: blood smear as clue to the underlying cause Marcelo Caballero*, Lorenzo Alberio, Pascal KГ¤mpfen, Drahomir Aujesky, Bernhard LГ¤mmle Inselspital, UniversitГ¤tsspital Bern (Bern, CH); Inselspital, Bern University Hospital and University of Bern (Bern, CH) We report the case of a 26-year-old man admitted to our hospital for abdominal pain and fever. He had been well until 5 days before admission when he felt feverish and developed acute left-sided upper abdominal pain. Clinical examination showed reduced general health, the temperature was 39 В°C, the left upper abdomen was tender to palpation. and the spleen was palpable at the left costal boarder. There was no lymphadenopathy. Computed tomography showed a hypodense lesion of the inferior part of the spleen consistent with a splenic infarction (Fig. 1). Our initial differential diagnosis included a cardioembolic splenic arterial occlusion, a myeloproliferative or lymphoproliferative neoplastic disease, or paroxysmal nocturnal hemoglobinuria. On the first hospital day, paroxysmal nocturnal hemoglobinuria, and lymphoproliferative neoplastic disease were excluded by flow cytometric immunophenotyping, and Lupus anticoagulant and anticardiolipin antibodies were negative. Visual inspection of the blood smear showed many highly atypical lymphocytes (Fig. 2) and subsequent EBV and CMV serology testing revealed an acute CMV infection. The patient was treated with analgesic medication and recovered within a few days. Acute CMV or EBV infection may rarely be associated with arterial splenic infarction. In some cases, an accompanying thrombophilic defect, such as transient or permanent antiphospholipid antibodies, protein C deficiency or an underlying spherocytosis with mild splenomegaly, have been reported. Our patient was an immunocompetent man with no preexisting health problems. The blood smear hinted to acute viral infection, and, therefore, foreseen echocardiography, bone marrow examination and screening for JAK2 V617F or bcr-abl mutation were canceled. This case highlights the importance of examining the blood smear in order to avoid unnecessary and costly tests in a patient with splenic infarction. 193 P460 Thrombosis of palmar and interdigital arteries in hypereosinophilic syndrome Cristina Gallardo*, Marco Mancinetti, Daniel PГ©riard, Daniel Hayoz HFR Fribourg HГґpital Cantonal (Fribourg, CH) Introduction: Hypereosinophilic syndrome (HES) can be identified by three diagnostic criteria: blood eosinophilia (> 1500/mm3) for longer than 6 months (or shorter in the presence of symptoms requiring treatment), no other evident reason for the eosinophilia, signs/symptoms of organ involvement. Case report:: A 69 years old male patient presented to the emergency department with a history of painful and cyanotic fingers bilaterally, evoking ischemic injury. We performed a duplex ultrasonography which demonstrated a thrombosis of both superficial palmar arches and several interdigital arteries. Anticoagulation was introduced and the patient was admitted to our medical department for further investigations. He reported a history of multiple organ damages (skin, lung, gastrointestinal, vascular involvement) associated with hypereosinophilia evolving since three months. Allergic tests, FAN, ANCA and RAST for aspergillus fumigatus were normal. A thoracic scan 194 demonstrated emphysema. The bronchoscopy with BAL showed eosinophilia but neither vasculitis nor aspergillosis. A cutaneous biopsy demonstrated dermatitis with presence of eosinophils in the derm without vasculitis. The gastroscopy showed a chronic inactive gastritis with rare eosinophils. Echocardiography and stress test were both normal. We performed a bone marrow aspiration and biopsy showing no specific findings. We retained the diagnosis of idiopathic hypereosinophilic syndrome, without PDGFRA, PDGFRB, FGFR1 rearrangements and absence of FIP1L1-PDGFRA chromosomal fusion. We introduced a corticosteroid therapy which was followed by a fast decrease of the eosinophilic count. Discussion: Thrombotic events are known as one of the most serious complications of hypereosinophilic syndrome but digital damage is rarely described. In hypereosinophilic syndrome, occlusion of intermediate- to large-sized arteries frequently causes peripheral ischemia and even digital gangrene. Involvement of smaller vessel can also occur. Systemic corticosteroid remains the first-line treatment of HES when specific mutations arenвЂ™t identified. It seems that thromboembolic disease associated with HES is particularly difficult to control and anticoagulation is not usually initiated empirically in the absence of a previous event. P461 Primary germ cell tumor-associated acute megakaryoblastic leukaemia Karolina Polchlopek*, Monika Nagy Hulliger, Nhu Nam Tran Thang Ducommun, Pierre-Yves Dietrich, Yves Chalandon Hopital Cantonal de Geneve (GenГЁve, CH) Background: The association between primary germ cell tumors (GCT) of the mediastinum and hematologic malignancies is a known entity, but there are only few cases described in the literature. We report a case of a young male with mediastinal GCT and acute megakaryoblastic leukemia. Case: A 22-year-old man, previously in good health condition, was admitted to the emergency room for epistaxis and fatigue. Full blood count showed severe thrombopenia (16 G/l). Chest X rays revealed a mass in the anterior mediastinum. Lactate dehydrogenase were highly elevated (4668 U/l) and alpha-fetoprotein level was mildly elevated (45 ug/l). The blood film showed very rare megakaryoblasts. The imprints and the histopathology of the biopsy revealed a massive infiltration by maturing dysplastic megakaryocytes with platelet glycoproteins CD41 (glycoprotein IIb/IIa) and CD61 (glycoproteine IIIa) expression. The histology of the mediastinal mass showed a GCT combined with leukemia components. The diagnosis of acute megakaryoblastic leukemia (M7 according to the French-American-British classification) associated with mediastinal germ cell tumour was identified. The cytogenetic analysis showed a characteristic karyotype for this entity with an isochromosome 12p (i12p). After the first cycle of induction chemotherapy consisting of cisplatin, etoposide, mitoxantrone and cytarabine to have combined activity against both types of tumor, the serum levels of AFP and LDH decreased to normal range, the thrombopenia improved. The immunohistochemistry of bone marrow biopsy indicated a leukemia free state. The patient is actually being treated with a fourth cycle of chemotherapy including only cisplatin and etoposide targeting the germ cell tumor due to poor hematopoiesis recovery. An allogeneic hematopoietic stem cell transplantation with a mismatched unrelated donor is planned due to known very poor prognosis. All patients described to date with this kind of combined germ cell tumor with leukemia, except a case of a child that received cord blood transplant after 6 cycles of chemotherapy including cytarabine, mitoxantrone, idarubicin, etoposide and cisplatine, died. (H Hiramatsu et al. BMT 2008;41:907-908). Conclusion: This rare type of mediastinal germ cell tumor associated with hematologic malignancy has a dismal prognosis. Combining chemotherapy aimed at targeting both tumors followed by allogeneic hematopoietic stem cell transplantation may offer the only possibility of cure. P462 Clinical course in a young man with severe haemolytic anaemia due to severe pyruvate kinase deficiency Anelia Siderow*, Roland A. Ammann, Nasser Semmo, Franziska Demarmels, Bernhard LГ¤mmle University Hospital, Inselspital and University of Bern (Bern, CH); Inselspital and University of Bern (Bern, CH); Department of Visceral Medicine and Surgery, University Hospital, Inselspital and University of Bern (Bern, CH) Congenital non-spherocytic hemolytic anemias are rare enzymatic defects leading to a defective erythrocyte stability and constitutional hemolytic anemia of variable severity. 195 We report on a now 18-year-old man with severe, probably homozygous or double heterozygous pyruvate kinase deficiency (PKD). In the neonatal period he was anemic, showed a bilirubin up to 500 umol/l and needed exchange transfusions. Red blood cell (RBC) transfusions were then given every 4 weeks, together with iron chelation. At the age of 13 years a partial splenectomy together with cholecystotomy for bilirubin stones was performed and greatly improved hemolytic activity. Bilirubin decreased from about 220 to 20-40 umol/l, hemoglobin increased from 70-80g/l (with frequent RBC transfusion requirement) to 80-95 g/l and RBC transfusions were needed only twice yearly. Iron chelation could be withdrawn and despite a steady increase of hemolytic activity associated with progressive hypertrophy of the remnant spleen, hemoglobin remained > 80g/l. In November 2012, at an age of 17 years, severe upper gastrointestinal hemorrhage from isolated cardiac varices resulted in a hemoglobin fall to 53 g/l. No generalized portal venous hypertension was found and a suspected (partial) splenic vein thrombosis could neither be proven nor excluded. In January 2013 hemoglobin has stabilized at 88g/l, hemolytic activity is high with 30% reticulocytes (750 G/l), bilirubin of 280 umol/l and lactate dehydrogenase of 1400 U/l. Given the clear benefit of earlier partial splenectomy in this patient, total splenectomy, after completion of the necessary vaccinations, is planned. At the same time, splenectomy will reduce the risk of rebleeding from cardia varices, thus killing two birds with one stone. This case is presented to draw the attention of hematologists, pediatricians and internists to this rare constitutional hemolytic enzymopathy. P463 Intravascular large B-cell lymphoma: diagnostic pitfalls and therapeutic recommendations Martin D. Berger*, Yara Banz, Thomas Pabst UniversitГ¤tsspital (Bern, CH) Background: IVLBCL is a rare type of extra-nodal large B-cell lymphoma characterized by the growth of malignant lymphoid cells within the lumina of small blood vessels, predominantly capillaries. The clinical manifestation may vary, but is typically associated with an aggressive course. Delay during diagnostic work-up, mainly due to the unexpected histological presentation, is the prominent cause of the usually unfavourable outcome of this lymphoma type. Case presentation: A 48 year old male patient was admitted because of fatigue, poor exercise tolerance, weight loss and progressive dyspnoea. His clinical condition further deteriorated and the patient was referred to the ICU because of hemodynamic instability. Laboratory tests revealed bicytopenia (haemoglobin 11g/dl and platelets 31 x 109/L, with normal leukocytes of 5.2 x 109/L). Creactive protein (157mg/l), lactate dehydrogenase (7вЂ™059 U/l) and liver enzymes (ALAT 155 U/l, ASAT 340 U/l) were elevated. Computed tomography indicated pleural and peritoneal effusions, whereas no enlargement of lymph nodes or hepatosplenomegaly were detectable. Blood, stool and urine cultures showed no growth. Bone marrow biopsy revealed slightly elevated megakaryopoiesis, whereas erythro- and myelopoiesis were considered normal. Small clusters of medium- to large-sized blastic cells were identified with slightly course nuclear chromatin and prominent nucleoli, exhibiting CD20, CD79a, Pax-5 and MUM-1 as well as lambda light chain restriction. There was no expression of CD138, cyclin D1, CD10, BCL-6, CD5, CD3 and the myeloid markers. These malignant lymphoid cells appeared вЂњalignedвЂќ and were found almost exclusively within the lumina of sinusoids of the bone marrow. These findings suggested the diagnosis of intravascular large B-cell lymphoma (IVLBCL). The patient was treated with six cycles of R-CHOP chemo-immunotherapy, and he was consolidated in first remission with R-BEAM high-dose chemotherapy conditioning and autologous stem cell transplantation (ASCT). Ten months after ASCT, the patient is in continuing first complete remission. Discussion: This case illustrates key features of this rare type of extra-nodal large B-cell lymphoma. With regards to the usually dismal prognosis of IVLBCL, such patients may benefit from early consolidation with ASCT in first complete remission. 196 P464 A rare case of association of primary cutaneous follicle centre lymphoma presenting as a giant tumor of the scalp and essential thrombocythaemia Yordanka Tirefort*, Xuan-Cuong Pham, Michael Bernimoulin, Crista Prins, Begonia Cortes, Yves Chalandon, Kaveh Samii University Hospital of Geneva (GenГЁve, CH) Introduction:The concomitant diagnosis of essential thrombocythemia(ET) and lymphoproliferative disorder(LPD) is extremely rare event.We describe exceptional case of primary cutaneous follicle center lymphoma(PCFCL) in patient presenting with giant tumor of the scalp and with concomitant ET.Case description:56-year-old man with unremarkable medical history developed multinodular mass on the scalp 19x16x4cm over 18 months.Skin biopsy showed dense infiltrate throughout the dermis and the subcutis consisted of large lymphocytes with focal nodular growth pattern,CD20+ and BCL6+,BCL2,IRF4,CD10 negatives.Staging procedures revealed only one suspicious spinal lymph node.According to ISCL/EORTC classification of cutaneous lymphomas, the diagnosis of PCFCL,stage T2bN1M0 was made.In parallel,laboratory investigations showed platelet count 772x10^9/L without other blood film anomalies,normal LDH values and no splenomegaly.The bone marrow(BM) biopsy found moderately hypercellular BM with marked proliferation of mature megakaryocytes with hyperlobulated nuclei,sometimes in loose clusters,without increase of reticulin fibres.The JAK2/V617F mutation was present and helped to exclude reactive thombocytosis.Because of the exceptional size of the tumor,its location and possible nodal involvement,the patient received systemic chemotherapy with 4 cycles of R-CHOP-21 followed by consolidation radiotherapy.After 2 courses of chemotherapy,there was 90% reduction of tumor mass.The patient was still in remission 18 months after last treatement.The chemotherapy received for PCFCL did not induce remission of the ET and the platelet count remained between 500x10^9/L and 600x10^9/L without any clinical feature.He was considered low risk ET and aspirin was started.Conclusion:PCFCL is cutaneous B-cell lymphoma with excellent prognosis.Despite the impressively large size of tumor,we observed spectacular response to treatment.This case is also exceptional in its concomitant presentation with ET.Although the outcome for both diseases was favourable in this case,coexistence of ET and LPD might raise concerns about long-term prognosis of these patients,due to the possibility of more aggressive natural history of either one or both of the hematologic malignancies.Local recurrences can occur in PCFCL.ET is considered a relatively benign disorder but the evolution may be influenced by hemorrhagic or thrombotic complications or by disease transformation.A long term follow-up is thus mandatory. 197 Autorenliste / Liste des Auteurs Name Programmnummer Abbal, Claire Abu Hussein, Nebal Acosta Martin, Adelina Aegerter, Jean-Philippe Aerne, Lea Aeschbacher, Stefanie Aeschlimann, Andre Aigner, Fabian Alatri, Adriano Alberio, Lorenzo Albert, Mathieu Allaz, Anne-FranГ§oise Allemann, Yves Althaus, Fabrice Ammann, Roland A. Amort, Jan Andrey, Diego Angelillo-Scherrer, Anne FM288 FM238, FM239, P386 P448 P305 P404 FM246, P337 P321 P359 P428 P459 P342 FM271, P307, P339, P408 FM256 FM230 P462 FM222, P328 P449 107, FM226, FM254, FM282, P452, P458 P321 FM292 FM230 P380 P377 P324, P325, P326 P449, P453 FM289, P450 FM226, FM254 FM257 P315, P423 FM274 P377, P379, P384, P405, P407 FM226, FM227, FM235, FM253, FM254, FM255, P323, P371, P452, P459 105 107, FM282 Angst, Felix Ansari, Marc Ansermet, Corine Antiochos, Panagiotis Applegate, William Arampatzis, Spyridon Araud, Tonguy Arn, Kornelius Aschwanden, Markus Aubert, Carole Aubry-Rozier, BГ©rengГЁre Auckenthaler, Anne Auer, Reto Aujesky, Drahomir Ayran, Christina Azevedo, Monica BГ¤chli, Esther Bachmann, Lucas Bachofner, Adrian Baerlocher, Gabriela Balabanov, Stefan Balestra, Gian-Marco Ballmer, Peter E. Banyai, Martin Banz, Yara Barbosa, Joana Bargetzi, Mario Baroudi, Mariem Barro, Javier Bassetti, Stefano Bastardot, FranГ§ois Batschwaroff, Marcus Battegay, Edouard Baudat, Dimitri Bauer, Douglas 198 P395, P409, P424, P429 P443 FM244 105 FM289 FM258 P399 FM226, FM254 P447, P463 P380 P455 P318 P313, P318 P360, P361, P363 P300 FM224 FM227, FM232, FM235, FM253, FM259, P299 P416 FM227, FM235, FM252, FM253, P377 Name Programmnummer Bauer, Sophie Baumgartner, Martin Beauverd, Yan Beer, Hans JГјrg P346 P343 FM228, FM292 FM226, FM234, FM254, FM279, P321, P431, P438 FM289 P432 FM236 P309 P414 FM286, P444 P463 P449, P453, P454 P414 FM292, P464 FM241 FM243 FM288 P410, P415 P419, P437 P346, P347, P456 FM249 P329 P294 P355 P440 FM275 P434 105 P446 FM222, P294 P311 FM272 P337 FM235 FM236 FM230, P306, P319, P320 FM228, FM280, P439, P458 P355 P396 P378 P458 P436 P330 FM250 P372 FM263 FM291 FM256 FM226, FM254 P435 FM257 P410 FM285 FM281, P450 FM242 P304 P370, P404, P417 P329 FM238 FM236, FM249 Bencze, Judit Bendjelid, Karim Bengough, Theresa Benkert, Pascal Benvenuti, Claudio Benz, Rudolf Berger, Martin D. Beris, Photis Bernasconi, Augusto Bernimoulin, Michael Berra, GrГ©gory Bertholet, Nicolas Berthon, CГ©line Besson, Marie Besson, Marius Betticher, Daniel Bhatt, Deepak L. Bingisser, Roland Bircher, Daniela BirkhГ¤user, FrГ©dГ©ric Biron, Christine Bischofberger, Gabriela Bitzenhofer-GrГјber, Michaela Blaney, Martha Bleckmann, Marion Bloemberg, Guido V. Blondon, Katherine Blozik, Eva Blum, Jonas Blum, Manuel BlГјmle, Anette Bodenmann, Patrick Boehlen, FranГ§oise Bohlender, JГјrgen BГ¶hm, Thomas Bonetti, Piero O. Bonfils, FranГ§oise Bonnabry, Pascal Bonvin, Raphael Bordet, Julie Bosshard, Stephan BГ¶ttcher, Steffen Bougeon, Sandrine Bouillet, Elise Bounameaux, Henri Bourgeois, Guy Bourron, Olivier Boyer, Celia Bradbeer, Peter Brand, Brigitte BrГ¤ndli, Otto Brausch, Anne Bregenzer, Thomas Breidthardt, Tobias Bridevaux, Pierre-Olivier Briel, Matthias 199 Name Programmnummer Brisset, Anne Broccoli, Vania Broers, Barbara Brun del Re, Claudia Bruzzese, Ornella Brylski, Lukas Bubenhofer, Manuel Bucher, Heiner C. Bucklar, Guido Budak, Kemal Budka, Herbert Buehlmann, Cyrill BГјla, Christophe Burdet, Luc Burgmann, Konstantin Burington, Bart Burkhard, Regula Burkhart, Andreas Burnand, Bernard Burnand, JГ©rГґme Burnier, Laurent Buschbeck, Christiane Buser, Andreas Butler, Javed Butsch, Raphael BГјttner, Franz 107 FM286 P318, P432 P398 FM291 P392 P301 FM249 P299 P358 FM223 P348 FM247, FM276, P420 P346 P351, P430 105 FM267 P395 FM250, P356, P411 P380 107 P350 P438, P445 P377 P303, P344 P373 Caballero, Marcelo Calanca, Luca Calmy, Alexandra Calzavarini, Sara Cappai, Milva Carballo, David Carballo, Sebastian Carrel, Thierry Casillas, Alejandra P459 P428 P437 107, FM282 P406 P379, P405, P407 FM241, P379, P405, P407 FM240 P306, P312, P313, P318, P319, P320, P356 FM280, FM292, P439 P349 P416 FM288 FM271, P307, P339, P408, P410 P346 FM288, FM292, P457, P461, P464 P456 P344 P440 FM285 FM243 FM274 FM288 FM238 FM292 P329, P389 P305 P347, P366 P433 FM244 FM233 P448, P449, P453 P357 Casini, Alessandro Caspar, Clemens Cavassini, Matthias Cayuela, Jean-Michel Cedraschi, Christine Chabanel, David Chalandon, Yves Chalandon, Yves Chaloupka, Karla Chambost, HervГ© Chan, George Cheng, Debbie Chevalley, Thierry Chevret, Sylvie Chhajed, Prashant Chigrinova, Ekaterina Christ-Crain, Mirjam Christin, Laurent Chuard, Christian Clair, Carole Classen, Regina Clerc, Olivier Clerici, Lorella Coattrenec, Yann 200 Name Programmnummer Coelho GraГ§a, Didia Cole, Nyree Collet, Tinh-Hai Compagnoni, Sergio Conen, David Conzelmann, Martin Cornuz, Jacques Cortes, Begonia Corti, Natascia Cozzi, Anna Craighero, Raffaella Crevoisier, Jean-Luc Crook, David William Cullati, StГ©phane Curatolo, Michele P448 FM285 FM227, FM235, FM250, FM253 P340, P402 FM246, P337 FM277, P394 FM226, FM235, FM227, FM253, FM254, P314, P379, P384, P420, P433 P464 P401, P424 FM286 P380 P390 P361 P311, P316 P415 D'Oiron, Roseline da Costa, Bruno Daali, Youssef Daeppen, Jean-Bernard Dantin, Carole Darbellay, Regis Darling, Katharine Dayer, Pierre de Jong, Cor de Moerloose, Philippe de Waal, Margot W.M. Degenhardt, Ewa Degiorgi, Adriana Dejung, Sarah Demann, DГ©sirГ©e Demarmels, Franziska Demertzis, Stefanos den Elzen, Wendy P.J. Desmeules, Jules Despotovic, Dragan Diaz, Carolina Dietrich, Pierre-Yves Diotte, Serge Dolan, G. Dolmans, Diana Dombret, HervГ© DoГ±ate, Carmen Dougoud-Chauvin, VГ©rГЁne Dreher, Rebecca Drexler, Beatrice Duek, Adrian Duong, Hong Dung Durieux-Paillard, Sophie DГјrr, Selina P440 FM235 P415 FM230 FM292 P449, P453 P416 P415, P436 P432 FM280, FM284, P439, P440 FM229 P301 FM231 P329 P389 P462 P414 FM229, FM252 P410, P415, P436 P396 P381 P461 P390 FM284 P316, P317 FM288 FM266 P347, P357 FM273 P329 FM265 FM245, FM262, P421 P437 P386, P388 Ebneter, Andreas Efe, Jana Egger, Martin Egloff, Michael Eichelberger, Markus Englberger, Lars Epiney, Manuella Erdmann, Andreas Erne, Paul P357 FM234 P297 FM226, FM254 P333 FM240 P306 P349 FM248 201 Name Programmnummer ErnГ©, Seiichi Ernst, Delphine Escher, Robert Escoffre-Barbe, Martine Etter, Laurence Etter, Marco Exadaktylos, Aristomenis Eyer, Stephan P361 FM291 P297 FM288 FM291 P364 P324, P325, P326 FM247 FГ¤h, Uta Favre-Bulle, TimothГ©e Favrod-Coune, Thierry Fellmann, Petra Fernandez, Jose Ferrari, Nicola Ferrari Pedrini, Petra Ferreira, Maria Fey, Maritn F. Fiedler, Georg Fischer, Roland Fischli, Stefan Fitting, Jean-William Flatz, Aline FonfrГЁde, MichГЁle Fontana, Enzo Fontana, Pierre Fontolliet, TimothГ© Ford, Ian Franceschi, Michael FranГ§ois, Anne Frank, Matthias Franzen, Daniel Frascarolo, Sylvain Frauchiger, Beat Frauenfelder, Thomas Frei, Remus Frey, Peter Fricker, M Friedl, AndrГЁe Frigerio, Susanna Fujimura, Yoshihiro Funk, Georg Furrer, Florian Fux, Christoph FM240 P416 P318 P455 107 P414 FM234 P334 FM268, FM270 P324, P326 P314, P433 FM251 FM238 P411 FM257 P357 P458 P307 FM252 P454 P318 FM277, P394 P295, P344 FM276 FM226, FM254, P427 FM290 P387 FM229, FM253 P301 P349 P363 P451 P324 P304 FM224 Gachoud, David Gagliano, Mariangela Gallardo, Cristina Gantenbein, Andreas GaramvГ¶lgyi, Esther Garavaglia, Barbara Garcia Martinez, Juan Garin, Nicolas Garnier, Antoine Gaspoz, Jean-Michel Geiser, Thomas Gemperli, Armin GemГјnden, Cornelia Gencer, Baris George, James N. Georgios, Georgiou P342, P406 P406 P460 P321 P456 FM286 P432 FM241 P406 FM227, FM235, FM253 FM238 FM227 P444 P377, P379, P384, P405, P407 P451 P454 202 Name Programmnummer Georgiou, Georgios Gerber, Bernhard Gerber, Martin Gerosa, Rahel Gerschheimer, Christiane Gerstel, Eric Geschwindner, Heike Gessler, Katharina GГ©taz, Laurent Gex, Gregoire Gigandet, Thierry GillГ©ry, Philippe Gilliot, GГ©raldine Gisler, Valentin Gloy, Viktoria Luise Gmel, Gerhard GГ¶ber, Volkhard Goede, Jeroen S. Goede, Jeroen Gold, Christina Gold, Gabriel Gonzenbach, Tobias Graber, Peter Graedel, Lena Graf, Christophe Graf, Lukas Grandjean, Anne-Pascale Green, Alexander Gregoriano, Claudia Griesser, Anne-Claude Griesshammer, Ines Griffin, John H Grisouard, Jean Grobholz, Rainer Grolimund, Eva Marianne Grouzmann, Eric Grueber, Maude GrГјter, Erwin Gubler, Jacques Guerry, FrГ©dГ©ric Guggiari, Celine Guida, Linda Guignard, Bertrand Gussekloo, Jacobijn Gut, Anne Gutmann, Marc Guyot, Sophie P449, P453 FM281, FM290, P444 P308 FM263 P452 FM228 FM261 P386 P306, P312, P313, P318 P457 P297 FM257 P406 P341 FM249 P433 FM240 P444 FM286, FM289 P358, P425 FM274, FM278 P332 P362 FM224 FM274 P442 FM292 P319, P320 FM239, P386 FM245, FM262, P421 P360, P361 107 FM265 P343 P389 P355, P397 P422 P338 FM222, P294, P328, P368, P369 P449, P453 FM247 P458 P436 FM229, FM252 P317 P376 FM230 Hagedorn, Christian Haimovici, Aladin Haldemann, Cornelia Haller, Christlieb Halter, JГ¶rg Hanns Ulrich, Zeilhofer Hans, Didier Hao-Shen, Hui Harris, Tamara Hartemann, AgnГЁs Hartmer, Ralf Haubitz, Sebastian P296 FM268 P360 P298 P445 P415 P315, P423 106 P377 FM257 P448 FM224, P389 203 Name Programmnummer Hauffe, Till HГ¤uptle, Pirmin Hayette, Sandrine Hayoz, Daniel Hediger, Emanuel HeikenwГ¤lder, Mathias Heim, Dominik Heinrich, Henriette Helbling, Arthur Henzen, Christoph Henzen, Silke Hermans, Cedric Herrmann, Francois Heuss, Ludwig Theodor Hiltbrunner, Sabine Hitz, Fabienne Hochstrasser, Denis Hoefflinghaus, Tobias Hoess, Claus Holbro, Andreas Holler, Thomas Holm, Niels Holzer, Barbara Hrachovinova, Ingrid Huber, Andreas Huber, Philippe Hudelson, Patricia Hug, Balthasar Hugli, Olivier Huguet, FranГ§oise Hunziker, Sabina Husmann, Marc P354, P358, P397 P376 FM288 P422, P460 P386 FM263 P445 P295 P301, P374, P381, P434 FM251, P389 P435 P440 FM271, FM274 P351, P430 FM283 FM224 P448 P409, P429 P389 P445 P308 P429 FM232, FM259 P451 P343 FM278 P311, P316, P419 P308, P309 FM230, P323, P416 FM288 FM258 FM226, FM254 Ifrah, Norbert Iglesias, Katia Iglesias-Rutishauser, Katia Imboden, Hans Imhof, Alexander Imhof, Beat A. Imoberdorf, Reinhard Irion, Olivier Jaeger, Kurt FM288 FM230, FM247, P356 P331 P355 P353, P418 FM266 P368, P372 P306 FM226 Jaff, Amir JГ¤ger, Kurt Jaisson, StГ©phane Jandus, Camilla Jandus, Peter Janot-Berthier, Anne-Sophie Jauslin, Daniel Jeker, Raphael Jent, Philipp Jesaimani, Ameena Joos Zellweger, Ladina JГ¶rg, Lukas JГ¶rg-Walther, Lukas Jotterand, Martine Juch, Heike Juillet, Christian Jukema, Wouter JГјni, Peter P380 FM254 FM257 P374 P374, P434 FM241 P376 P340, P378, P396 P371 P408, P410 FM238 P374 P381 P445 P350 P457 FM252 P379 204 Name Programmnummer Junod Perron, Noelle P316, P317 Kaelin, Rainer Kaiser, Cristoph Kaiser, Udo KГ¤lin, Marisa Kalogeropoulos, Andreas Kalu Olu, Kelechi Kamber, Christine KГ¤mpfen, Pascal Kana, Veronika Kaplan, Vladimir Karajkovic, Aida Karrer, Urs Kasenda, Benjamin Kashyap, Sangeeta R. Kathriner, Silvio Kaufmann, Theodor Kearney, Patricia Keller, Cornelia Keller, Dorothee Keller, Gabriela Keller, Katarzyna Keller, Pierre F. Kentouche, Karim Kerr, Eve Kerse, Ngaire Kherad, Omar Kindler, Vincent Klingenberg, Roland KneubГјhl, Agnes Knoebl, Paul Koch, Peter P. Kohler, Malcolm KГ¶nig, Vera Kopf, Manfred KГ¶ppel, Jan Kossovsky, Michel KrГ¤henmann-MГјller, Simone Kralovics, Robert Kramer, Naomi Esther Krattinger, Regina Kremer Hovinga, Johanna A. Krieg, Marc-Antoine Kriz, David Kubik, Rahel Kucher, Nils Kueng, Marc Kullak-Ublick, Gerd A. KГјng, Marc Kunz, Isabelle KГјnzi, Thomas Kupferschmidt, Hugo Kuss, Florian Kutz, Alexander Kwiatkowski, Maciej P327, P426 P390 P385 P424 P377 FM236 P446 FM255, P459 FM223 FM259 P435 FM222, P294, P328, P368, P372 FM236 FM249 P443 P310 FM229, FM252 P399 FM240 P372 P336 P384, P405, P407 FM283 FM227, FM235, FM253 FM229 P322 FM269, FM292 P379 P364 P451 FM281 FM238 P378 FM263 FM290 P307, P408 FM235 106 FM291 P299 FM283, FM285, P451 P315, P423 P385 FM234 FM226, FM254 P346, P456 P299, P401 P347 P425 P353 FM233 P328 P389 P343 Lafage, Marina Lambert, Jean-FranГ§ois LГ¤mmle, Bernhard FM288 FM287, FM288 FM226, FM254, FM283, FM285, P451, P452, P459, P462 205 Name Programmnummer Lamy, Olivier Landolt, Lea Lang, Marianne Langewitz, Wolf Lanz, Annika Laube, Marcus Laumonier, Thomas Lazzaro, Mario Leclair-Rezbach, ValГ©rie LГ©cureux, Estelle LefГЁbre - van de Fliert, Anne Leguay, Thibault Lehmann, Susanne Lehmann, Thomas Leib, Stefanie Leichtle, Alexander Leichtle, Georg Leiss, Waltraud Lepori, Mattia Lepretre, Stephane Lescuyer, Pierre Leuppi, JГ¶rg Daniel Levi, Sonia Levrat, Emmanuel LhГ©ritier, VГ©ronique Licht, Abraham Limacher, Andreas Limacher, Andreas Lindner, Gregor Lippuner, Nadine Liu, Kun Locca, Didier Lohmann, Christine Lohri, Andreas Looser, Renate Louis-Simonet, Martine Ludwig, Catherine Lundberg, Pontus LГјscher, Thomas Luthy, Christophe Lutz, Nina Lyko, Christina FM245, FM262, P315, P421 P409, P423 P414 FM258 FM277, P394 P348 FM269 FM231 P458 FM245, FM262, P421 FM229 FM288 P321 P442 FM246 P324, P325, P326 P325 FM226 FM231 FM288 P448 FM238, FM239, P386, P388 FM286 P456 FM288 P450 FM226, FM254, FM255 P323 P324, P325, P326 P298 106 P300 FM279 P376 106 P317 FM271 106, FM265 FM279, P379, P384, P405, P407, P438 FM271, P307, P339, P408, P410 P365 P366 Mach, FranГ§ois Macinetti, Marco Maier, Sabrina MaГ®tre, Fabienne Mallen, Christian D. Mancinetti, Marco Mandier, Jean-Luc Mansouri Taleghani, Magnus Manz, Markus Marcoz, NoГ©mie Margelli Hartmann, Daniela Markun, Stefan Marono, David Marques-Vidal, Pedro P379, P384, P405, P407 P422 FM238, FM239, P386, P388 P311 FM229 P460 P454 FM285, P451 FM263, FM264, FM289, FM290, P444 FM273 FM239 FM259 P329 FM237, FM260, P300, P334, P335, P375, P377 FM258 P325 P458 Marsch, Stephan Marti, Grischa Martin, Gabrielle 206 Name Programmnummer Martin, Ivan Martin, Pierre-Yves Martin, Yonas Martinuz, Marco Marx, Bea Masouridi-Levrat, Stavroula Mateiciuc, Simona Matter, Christian FM264 FM241 FM235 FM237, P375, P406 P414 FM292 FM273 FM226, FM254, FM279, P379, P384, P405, P407 FM266 P415 P294 FM288 FM225 FM223 P362 P428 FM229 P323, FM226, FM254, FM255, P452 FM287 P350 P370 P354, P397 P449, P453, P454 FM236 P373 P423 P329 P387 P448 P405, P407 P438 P300 FM257 FM238, FM239, P386, P388 FM232 FM249 P390 P414 P457 P420 P330, P331, P428 FM229, FM252 P345 P333 FM257 105 P329 P413 FM286 FM291 FM224 P442 P304 P304 P363 P308, P329, P389 P329 P401 P322 P300 Matthes, Thomas Matthey, Alain Maurer, Florian P. Maury, Sebastien MГ¤usezahl-Feuz, Mirjam Mauti, Laetitia Mayr, Sylvia Mazzolai, Lucia McCarthy, Vera MГ©an, Marie Medina, Pedro Meier, Christoph A. Meier, Silvan Meindl-Fridez, Claudine Menoud, Pierre-Alain Mertz, Dominik Mertz, Kirsten Metzger, Marie Meune, Christophe Meyenberger, Christa Meyer, Markus Meyer, Philippe Meyer, Sara Michel, Patrik Michel, Pierre-Louis Miedinger, David Minder, Christoph Mingrone, Geltrude Mitropoulou, Georgia Moccetti, Tiziano Mohamed, Rania Monod, StГ©fanie Monti, Matteo Mooijaart, Simon P. Moosmann, Peter Morales, Isabel Morel, Florence Morfeld, Dianne Mosimann, Tamina Motamed, Sandrine Muckenthaler, Martina Muehlematter, Dominique Mueller, Beat Muesser, Patricia MГјggler, Simon Andreas Muggli, David MГјller, Beatrice MГјller, Beat MГјller, Christian MГјller, Daniel MГјller, Halima Muller, Olivier 207 Name Programmnummer MГјller, Stefan Muller-Juge, Virginie MГјllhaupt, Beat MГјnzer, Thomas Muth, Christiane FM232 P311 P450 FM275 FM229 Nagler, Michael Nagy Hulliger, Monika Nair, Gayathri Nanchen, David Neerman-Arbez, Marguerite Nendaz, Mathieu Newman, Anne Ngyuen-Kim, Thi Dan Linh Nicolaus, Stefanie Niggemeier, Verena Nonnenmacher, Eveline Nordmann, Alain J. Novak, Urban Nowak, Albina Nsangu Mampasi, Mireille NГјbling, RГјdiger Nuredini, Shpendin Nussberger, JГјrg Nydegger, Urs P443 FM292, P457, P461 FM290 P379, P384, P405, P407 FM280, P439 FM228, P311, P316, P317 P377 FM290 P367 P344 FM277, P394 FM249 FM267 P329, P336 P382 P385 P398 P355 FM287 Odenike, Olatoyosi Ody, Christiane Oppliger Leibundgut, Elisabeth Osterwalder, Joseph Г–ttl, Tobias Ottman, Oliver 105 FM266 105 FM226, FM254 P376 105 Pabst, Thomas Pache, Basile Palan, Pakize Parlier, Valerie Paroz, Sophie Pasch, Andreas Passweg, Jakob Paul, Michaela Perger, Ludwig PГ©riard, Daniel Perrier, Arnaud Petersen, Jens Alexander Petrausch, Ulf Petriccioli, Nicole Petrig, Christophe Peyrani Dicastelnuovo, Paula Peytremann-Bridevaux, Isabelle Pfefferle, Maria Pfenninger, Max PfortmГјller, Carmen Pham, Xuan-Cuong Piallat, Marie Luce Pianta, Annalisa Piccinini, Elia Pichler, Werner Piguet, ValГ©rie Pilo, Paola Pireva, Agim P446, P447, P463 FM260, P335 P314, P420 P456 FM230, P319, P320 P352 P445 FM290 P299 P460 FM228, FM241, P436 P351 P296, P412 P322 P400 FM224 FM250, P356, P411 P312 P381 P326 P464 FM269 106 FM264 P374, P381, P434 P408, P410 FM222 FM256 208 Name Programmnummer Piso, Rein Jan Plate, Andreas Pletneva, Natalia Polchlopek, Karolina Pollock, Emily Polsfuss, Silke Popovic Sesartic, Bozana Porter, Sarah Portmann, Daniel Postert, Flann Benjamin Precup, Mihaela Preisig, Martin Prie, Nolwen Prince, Raja Prins, Crista Privitera, Daniela Pruvot, Etienne Pugin, Paul Pugliesi, Angela Pumpol, Katrin P360, P361 P403 P408 P461 P341 FM222 FM275 FM291 P369 P417 P456 P335, P423 FM291 FM282 P464 FM286 P331 P456 P339 P337 Quist-Paulsen, Petter P451 RГ¤ber, Lorenz Racine, Michael Radpour, Ramin Raffoux, Emmanuel Ramirez, Julio Randazzo, Marco Ranzi, Monica Rapin, NoГ©mie Rapiti, Elisa Rapold, Roland Raschle, Joelle RГ¤z, Hans-Ruedi Recker, Franz Reddy, Anita Reemts, Christoph Reeves, Scott Regard, Simon Regenass, Stephan Regoli, FranГ§ois Reiber, Claudine Reich, Oliver Reiner, CГ¤cilia Reiner, Martin Reinhart, Sophie A. Reinhart, Walter H. Renner, Christoph Reny, Jean-Luc Rettke, Horst Reuss, Daniel Rexhaj, Emrush Rieder, Jean-Pierre Riederer, Markus Rieke, Alexander Righini, Marc Rimoldi, Stefano Rincon Garriz, JosГ© Maria Rinderknecht Graf, Stefan Risch, Corina P379, P405, P407 FM282 FM263 FM288 FM224 P343 P414 P331 P339 FM272 P447 P338 P343 105 P308 P342 P322 FM223 P414 P401 FM272 FM223 P438 P441 P378, P402, P441 P296 FM228 FM261 P435 FM256 P318 P297 P396 FM226, FM254 FM256 FM269 FM281 FM287 209 Name Programmnummer Risch, Lorenz Risch, Martin Ritter, Christian Ritter, Simon Rochat, Mathilde Rochat, Philippe Rodak, Roksana Rodondi, Nicolas Roeth, Alexander Rogler, Gerhard Rollason, Victoria Roosnek, Eddy Rosegger, Paula Rosemann, Thomas Rosset, Nina Rothen, Claude Rothen, Madeleine Rotundo, Ida Luisa Rotzetter, Jeanine RovГі, Alicia RГјegg, Linda Russell, Audrey Russmann, Stefan Rutishauser, Jonas Rutishauser, Maya RГјtti, Markus F. FM246, FM287, P337 FM246, FM287, P337 FM277, P394 P350 P323 P427 FM259 FM226, FM227, FM229, FM235, FM252, FM253, FM254, P377, P379, P384, P405, P407 105 P302, P383 P410 FM292 P427 FM229 FM232 P310 P367, P398 FM286 P360 P445 P349 FM229 P299 P398 P332 FM234 Saber, Abdelmalek Safroneeva, Ekaterina Saitz, Richard Saller, Francois Samaras, Panagiotis Samer, Caroline Samet, Jeffrey Samii, Kaveh Sanches Rodrigues, Debora Sander, Tina Saner, Hugo Santambrogio, Paolo Sarasin, Francois Sartori, Claudio Satterfield, Suzanne Savoldelli, Geroges Schaer, Dominik Schafroth TГ¶rГ¶k, Salome Schai, Marcel Schaller, Monica Schanz, Urs SchГ¤tti, Gabriela Schatzmann, Sarah Schauer, Philip R. Scheidegger, Paul Scheidegger, Stephan Schelling, Martin Scherl, Alexander Scherrer, Urs Schers, Henk Schiemann, Uwe Schifferli, JГјrg FM278 P302, P383 FM243 107, FM282 P341 P436 FM243 P448, P449, P453, P464 107 FM242 FM240 FM286 FM274 FM256, P406 P377 P311 FM223, P344, P412 FM238 P435 FM283 FM290 FM232 P431 FM249 P349 FM234 P392 P448 FM256 FM229 P380 P308, P309 210 Name Programmnummer Schmidt, Helen Schmidt, JГјrgen Schmied, Christian Schneemann, Markus Schneider, Dominik Schneider, Martin Schnellmann, Yves Schneppenheim, Reinhard Schoen, Tobias Schoenenberger, Renate Schoepfer, Alain SchГ¶n, Tobias SchГ¶nenberger, Andreas SchГ¶nrath, Felix Schott, Peter Schoumans, Jacqueline Schuberth, Petra Schudel, Inge Maria Schuetz, Philipp Schulzki, Thomas Schutgens, Roger SchГјtz, Tobias Schved, Jean-FranГ§ois Schwarz, Christoph Schwarz, Urs Schwotzer, Rahel Scotti, Celeste Seematter-Bagnoud, Laurence Seiler, Daniel Semadeni, Gian-Marco Semmo, Nasser Senn, Nicolas Senn, Oliver Shapiro, Amy Shimizu, Takafumi Sibalic, Vladimir Siderow, Anelia Signorell, Ladina Simic, Sandra Singer, Gad Skoda, Radek Slahor, Lea Sleptsova, Marina Snyder, David So, Alexander Soltermann, Alex Sommer, Johanna Speidel, Victor Spitzer, Gary Sproedt, Julia Spycher-Elbes, Rachel Stahel, Rolf StГ¤hli, NoГ©mie Staritz, Peter Steffen, Christian Stegert, Mihaela Steiner, Simon Steiner, Urs Steinmann, Eva SteinrГјcken, Julia Stelzer, Teresa P321, P321 P385 P407 FM233, P303, P354, P397 P295 P393 FM278 P451 P337 FM248 P302, P383 FM246 FM248 P378 P418 FM291, P456 P296 P352 FM224, P308, P389 P402, P441 FM284 P361 P440 P324, P325, P326 P354, P397 P295, P450 FM264 FM276 P343 P387 P462 P314, P420 P401, P444 106 106, FM265 P435 P462 P396 P435 P349 106, FM265 FM251 P293 105 P315 P296 P317 P367 105 P328 P458 P296 P404 FM284 P364 FM236 P371 P434 P442 P362 P430 211 Name Programmnummer Stern, Martin Steveling, Esther Helen Stirnimann, Guido Stivala, Simona StГ¶ckli, Thomas Stoffel, Georg Stoll, Delphine Stott, David J. Streit, Sven Stuart, Monic Stuck, Anna Stucki, Stephanie Studer, Irene StГјrzebecher, Katja Suhm, Norbert Sulzer, Irmela Suna, Gonca Surial, Bernard Suter, Paolo P445 P386, P388 P309 FM279, P438 P400, P403 P435 P315, P423 FM229, FM252 FM253 105 FM254 FM230 FM223, P341 P373 FM277, P394 FM283 P431 P395, P424 FM242, FM248, P354, P359, P397 TaffГ©, Patrick Takizawa, Hitoshi Tamm, Michael Tavernier, Emmanuelle Tessitore, Elena Thalmann, George Theodoloz, MГ©lanie Thomann, Robert Thomas, Xavier Thommen, DГ©sirГ©e ThГ¶ne, Joachim Thurnheer, Robert Tichelli, AndrГ© Tirefort, Yordanka Tisljar, Kai Tomaszek, Sandra Tomonaga, Yuki Trachsel, Maria Tran Thang Ducommun, Nhu Nam Trelle, Sven Trobia, Massimo Trueb, Lionel Tsakiris, Dimitrios Tschan, Mario Tscherry, Georg Tsopra, Olga Tsybin, Yury Turk, Alexander FM250 FM264 FM238 FM288 FM228 P355 FM273 P389 FM288 P308 P425 FM238 P309, P445 FM292, P464 FM258 P296 FM236 P368, P399 P461 P452 FM231 FM230 P442 FM268, FM270 P424 FM292 P448 FM242 Uhlmann, Marc Ullmer, Elke FM245, FM262, P421 P373 Vader, John-Paul Vallelian, Florence Van der Vleuten, Cees Varcher, Monica Vaucher, Julien Vavricka, Stephan Verloo, Henk Verstovsek, Srdan Vieira, Margarida P379 P412 P316, P317 P419 P300 P302, P383 P334 105 P334 212 Name Programmnummer Virgini, Vanessa Vittinghoff, Eric Vogel, Daniel Vogel, Monique VГ¶geli, Alaadin Vogt, Pierre Vollenbroich, RenГ© Vollenweider, Peter von der Weid, Nicolas von Elm, Erik von Moos, Seraina von Overbeck, Jan Vu, Nu Viet Vuillemier, Pascal Waeber, Bernard Waeber, GГ©rard Wagner, Claudia Wagner, StГ©phanie Waldegg, Gabriel Wampfler, Julian Warner, Alex Weber-Mani, Ulrich Weder, Walter Weilenmann, Daniel Weiler, Stefan Weissenberger, Noemi Welker, Joris Westendorp, Rudi G.J. Wiemken, Timothy Lee Wijsman, Liselotte Windecker, Stefan Winkler, Annette Winter, Michael Wirth, Rahel Wolff, Hans Wuillemin, Walter Wymann, Monica FM229, FM235, FM252 P377 P371 FM283 P389 P379, P384, P405, P407 P391 FM260, P300, P335, P423 P458 FM236 P425 FM272 P311, P330 P415 FM247 FM237, FM245, FM260, P300, P331, P335, P375, P406, P423 FM259 P398 P297 FM270 FM229 P301 P296 P391 FM227, FM235, FM253 P308 P384 FM229, FM252 FM224 FM252 P379, P384, P405, P407 P398 FM243 P398 P306, P312, P313, P318, P319, P320 P443 FM225 Yalamanoglu, Ayla Yerly, Daniel You, John P353 P374 FM236 Zbinden, Reinhard Zechmann, Stefan Zellweger, Jean-Pierre Zellweger, Matthias Zimmerli, Lukas Zimmerli, Marius Zimmerli, Stefan Zimmerli, Werner Zimmermann, Heinz Zogg, Stefanie Zoller, Bernhard Zuber, Markus Zufferey, Pascal Zysset, Yvonne P298 FM234 P305 P340 FM227, FM232, FM253, FM259 FM258 P446 FM244, P389 P324 FM239, P388, P386 P350 P361 P315 FM277, P394 213 В