Publications by authors named "Sibylle Kozek-Langenecker"

73 Publications

European Guidelines on perioperative venous thromboembolism prophylaxis: Executive summary.

Eur J Anaesthesiol 2018 02;35(2):77-83

From the Department of Anesthesia, Mother and Children's Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark (AA), Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (WA), Department of Anaesthesia and Critical Care, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK (AA), Department of Anaesthesia and Intensive Care, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, Hôpital de Bicêtre, UMRS 942, Paris, France (JD), Department of Anaesthesia and Pain Medicine, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada (DF), Sigmund Freud Private University and Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SKL), Department of Anaesthesiology and Critical Care Hospital Clinic, University of València, Spain (JL), Department of Obstetrics and Gynecology, Groupe hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France (JN), European Society of Anaesthesiology, Brussels, Belgium (MS), Department of Anaesthesia, Centre for Head and Orthopaedics, Rigshospitalet, University Hospital (JS), Section for Transfusion Medicine, Capitol Region Blood Bank, Copenhagen University Hospital, Copenhagen, Denmark (JS), Orthopaedic Surgery, University Hospital Saint Luc, Brussels, Belgium (ET), Orthopaedic Surgery, Aristotle University Medical School, Thessaloniki, Greece and Imperial College London Medical School, London, UK (ET), Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania (LV) and Department of Anaesthesia and Intensive Care, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France (CMS).

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http://dx.doi.org/10.1097/EJA.0000000000000729DOI Listing
February 2018

European guidelines on perioperative venous thromboembolism prophylaxis: Patients with preexisting coagulation disorders and after severe perioperative bleeding.

Eur J Anaesthesiol 2018 Feb;35(2):96-107

From the Department of Anaesthesia, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK (AA), Sigmund Freud Private University and Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SKL), Université catholique de Louvain, CHU UCLNamur, Namur Thrombosis and Hemostasis Center, Namur, Belgium (FM), Department of Clinical Haematology, Oxford University Hospitals, Oxford, UK (SP), and Division of Haematology, Haemostasis and Thrombosis Unit and Haemophilia Centre of Saint-Luc University Hospital, Bruxelles, Belgium (CH).

: In patients with inherited bleeding disorders undergoing surgery, we recommend assessment of individual risk for venous thromboembolism, taking into account the nature of the surgery and anaesthetic, type and severity of bleeding disorder, age, BMI, history of thrombosis, the presence of malignancy and other high-risk comorbidities. Venous thromboembolism risk should be balanced against the increased bleeding risk associated with anticoagulant use in patients with known bleeding disorders (Grade 1C). In these patients undergoing major surgery, we recommend against routine postoperative use of pharmacological thromboprophylaxis, especially for patients with haemophilia A and B (Grade 1B). Glomerular filtration rate should be assessed before initiation of each direct oral anticoagulant, and also at least once a year or more frequently as needed, such as postoperatively before the resumption of therapeutic direct oral anticoagulant administration, when it is suspected that renal function could decline or deteriorate (Grade 1C). Reduced dosages of low molecular weight heparins may be used relatively safely during transient severe (<50 × 10 l) thrombocytopaenia (Grade 2C). Monitoring of anti-Xa levels may be used to adjust the doses of low molecular weight heparin in patients with moderate or severe thrombocytopaenia (Grade 2C). The delay between major gastrointestinal bleeding and resuming warfarin should be at least 7 days (Grade 2C). For patients at a high risk of thromboembolism and with a high bleeding risk after surgery, we consider that administering a reduced dose of direct oral anticoagulant on the evening after surgery and on the following day (first postoperative day) after surgery is a good practice (Grade 2B).
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http://dx.doi.org/10.1097/EJA.0000000000000725DOI Listing
February 2018

European guidelines on perioperative venous thromboembolism prophylaxis: Surgery in the elderly.

Eur J Anaesthesiol 2018 02;35(2):116-122

From the Sigmund Freud Private University and Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SK-L), Department of Anaesthesiology, Aarhus University Hospital, Aarhus, Denmark (CF-E), Orthopaedic Surgery, University Hospital Saint Luc, Brussels, Belgium (ET), and Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania (GB).

: The risk for postoperative venous thromboembolism (VTE) is increased in patients aged more than 70 years and in elderly patients presenting with co-morbidities, for example cardiovascular disorders, malignancy or renal insufficiency. Therefore, risk stratification, correction of modifiable risks and sustained perioperative thromboprophylaxis are essential in this patient population. Timing and dosing of pharmacoprophylaxis may be adopted from the non-aged population. Direct oral anti-coagulants are effective and well tolerated in the elderly; statins may not replace pharmacological thromboprophylaxis. Early mobilisation and use of non-pharmacological means of thromboprophylaxis should be exploited. In elderly patients, we suggest identification of co-morbidities increasing the risk for VTE (e.g. congestive heart failure, pulmonary circulation disorder, renal failure, lymphoma, metastatic cancer, obesity, arthritis, post-menopausal oestrogen therapy) and correction if present (e.g. anaemia, coagulopathy) (Grade 2C). We suggest against bilateral knee replacement in elderly and frail patients (Grade 2C). We suggest timing and dosing of pharmacological VTE prophylaxis as in the non-aged population (Grade 2C). In elderly patients with renal failure, low-dose unfractionated heparin (UFH) may be used or weight-adjusted dosing of low molecular weight heparin (Grade 2C). In the elderly, we recommend careful prescription of postoperative VTE prophylaxis and early postoperative mobilisation (Grade 1C). We recommend multi-faceted interventions for VTE prophylaxis in elderly and frail patients, including pneumatic compression devices, low molecular weight heparin (and/or direct oral anti-coagulants after knee or hip replacement) (Grade 1C). : This article is part of the European guidelines on perioperative venous thromboembolism prophylaxis. For details concerning background, methods, and members of the ESA VTE Guidelines Task Force, please, refer to:Samama CM, Afshari A, for the ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35:73-76.A synopsis of all recommendations can be found in the following accompanying article: Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE Guidelines Task Force. European Guidelines on perioperative venous thromboembolism prophylaxis. Executive summary. Eur J Anaesthesiol 2018; 35:77-83.
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http://dx.doi.org/10.1097/EJA.0000000000000705DOI Listing
February 2018

Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016.

Eur J Anaesthesiol 2017 Jun;34(6):332-395

From the Department of Anaesthesiology & Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SAKL), Department of Anaesthesiology & Intensive Care, Glenfield Hospital, Leicester, United Kingdom (ABA), Department of Anaesthesiology, University Hospital of Copenhagen, Copenhagen, Denmark (AA, JS), Department of Anaesthesiology & Intensive Care, CHU De Grenoble Hôpital, Michallon, Grenoble, France (PA), Department of Anaesthesiology & Intensive Care, Hospital Universitario Rio Hortega, Valladolid, Spain (CA), Department of General Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania (GB), Department of Anaesthesiology & Intensive Care, University Hospital 'Federico II', Napoli, Italy (EDR), Department of Anaesthesiology, Boston Children's Hospital, Boston, Massachusetts, United States (DFa), Department of Anaesthesiology & Intensive Care, Emergency Institute for Cardiovascular Disease, Bucharest, Romania (DCF), Department of Anaesthesiology, University Hospital of Innsbruck, Innsbruck, Austria (DFr), Department of Anaesthesiology, Children's University Hospital Zurich, Zürich, Switzerland (TH), Department of Anaesthesiology & Intensive Care, Klinikum Straubing, Straubing, Germany (MJ), Department of Anaesthesiology & Pain Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands (MDL), Department of Anaesthesiology & Intensive Care, Hospital Clinico Universitario Valencia, Valencia, Spain (JVLP), Department of Anaesthesia, Royal Free Hospital, London, United Kingdom (SM), Department of Anaesthesiology & Intensive Care, General Hospital Linz, Linz, Austria (JM), Department of Anaesthesiology & Intensive Care, University Hospital of Szeged, Szeged, Hungary (ZLM), Department of Anaesthesiology & Intensive Care, Franziskus Hospital, Bielefeld, Germany (NRM), Department of Anaesthesiology & Intensive Care, Groupe Hospitalier Cochin, Paris, France (CMS), Department of Anaesthesiology, CHU Brugmann, Brussels, Belgium (PJFVDL), Department of Anaesthesiology, Herlev University Hospital, Herlev, Denmark (AJW), Department of Anaesthesiology, Ghent University Hospital, Ghent, Belgium (PWo, PWy) and Department of Anaesthesiology & Intensive Care, University Frankfurt/Main, Frankfurt am Main, Germany (KZ).

: The management of perioperative bleeding involves multiple assessments and strategies to ensure appropriate patient care. Initially, it is important to identify those patients with an increased risk of perioperative bleeding. Next, strategies should be employed to correct preoperative anaemia and to stabilise macrocirculation and microcirculation to optimise the patient's tolerance to bleeding. Finally, targeted interventions should be used to reduce intraoperative and postoperative bleeding, and so prevent subsequent morbidity and mortality. The objective of these updated guidelines is to provide healthcare professionals with an overview of the most recent evidence to help ensure improved clinical management of patients. For this update, electronic databases were searched without language restrictions from 2011 or 2012 (depending on the search) until 2015. These searches produced 18 334 articles. All articles were assessed and the existing 2013 guidelines were revised to take account of new evidence. This update includes revisions to existing recommendations with respect to the wording, or changes in the grade of recommendation, and also the addition of new recommendations. The final draft guideline was posted on the European Society of Anaesthesiology website for four weeks for review. All comments were collated and the guidelines were amended as appropriate. This publication reflects the output of this work.
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http://dx.doi.org/10.1097/EJA.0000000000000630DOI Listing
June 2017

Clinical guidelines: How can we improve adherence and implementation?

Eur J Anaesthesiol 2017 06;34(6):329-331

From the Department of Anesthesia, General Intensive Care, and Pain Management, Medical University of Vienna, Vienna (DMB); Department of General Anaesthesiology, Emergency and Intensive Care Medicine, Medical University of Graz, Graz, Austria (PGHM); Department of Intensive Care Medicine, St George's Healthcare NHS Trust, and St George's Hospital, St George's University of London, London, United Kingdom (AR); and Department of Anesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SAKL).

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http://dx.doi.org/10.1097/EJA.0000000000000603DOI Listing
June 2017

Point-of-Care Testing in Burn Patients.

Semin Thromb Hemost 2017 Jun 30;43(4):433-438. Epub 2017 Mar 30.

Division of General Anaesthesia and Intensive Care Medicine, Department of Anaesthesia, Critical Care and Pain Medicine, Medical University of Vienna, Vienna, Austria.

Severe burn injury has an impact on the coagulation system, but a unique definition regarding these changes is still missing. The results of conventional coagulation assays (CCAs) measured in daily clinical practice are often interpreted as coagulopathic, which implies a bleeding tendency. However, viscoelastic coagulation assays (VCA) like Rotational Thromboelastometry (ROTEM) and Thromboelastography (TEG) depict a hypercoagulable state. Therefore, hemostatic interventions should not be indicated according to deranged CCA results, but only in case of clinically relevant bleeding plus indicative VCA results. Massive blood loss mainly results from surgical excision of burn wounds. VCAs seem to be capable of guiding target-oriented coagulation management in this context. Owing to the increased thromboembolic risk, it appears rational to individualize pharmacologic venous thromboembolism prophylaxis by using sensitive laboratory tests and drug monitoring. Studies evaluating the use of new VCA test modifications are highly warranted and may substantially improve outcome in this difficult-to-treat patient population.
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http://dx.doi.org/10.1055/s-0037-1599155DOI Listing
June 2017

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

Anesth Analg 2017 04;124(4):1268-1276

From the *Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina; †Department of Anaesthesiology, RWTH Aachen University Hospital, Aachen, Germany; ‡Department of Surgical and General Critical Care Medicine, Medical University Innsbruck, Innsbruck, Austria; and §Department of Anesthesia and Intensive Care, Evangelical Hospital Vienna, Hans-Sachs-Gasse, Vienna, Austria.

Plasma products, including fresh frozen plasma, are administered extensively in a variety of settings from massive transfusion to vitamin K antagonist reversal. Despite the widespread use of plasma as a hemostatic agent in bleeding patients, its effect in comparison with other available choices of hemostatic therapies is unclear. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed Central, and databases of ongoing trials for randomized controlled trials that assessed the efficacy and/or safety of therapeutic plasma as an intervention to treat bleeding patients compared with other interventions or placebo. Of 1243 unique publications retrieved in our initial search, no randomized controlled trials were identified. Four nonrandomized studies described the effect of therapeutic plasma in bleeding patients; however, data gathered from these studies did not allow for comparison with other therapeutic interventions primarily as a result of the low number of patients and the use of different (or lack of) comparators. We identified two ongoing trials investigating the efficacy and safety of therapeutic plasma, respectively; however, no data have been released as yet. Although plasma is used extensively in the treatment of bleeding patients, evidence from randomized controlled trials comparing its effect with those of other therapeutic interventions is currently lacking.
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http://dx.doi.org/10.1213/ANE.0000000000001897DOI Listing
April 2017

The European Board of Anaesthesiology recommendations for safe medication practice: First update.

Eur J Anaesthesiol 2017 01;34(1):4-7

From the Department of Anaesthesia, Manchester Royal Infirmary, Manchester, UK (DW), Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway (GB), Department of Anaesthesiology and Intensive Medicine, P.J. Safarik University, Kosice, Slovakia (ST), Krompachy Agel Hospital, Krompachy (ST), Falck Zachranna a.s., Kosice, Slovakia (ST), Department of Anaesthesiology and Reanimatology, Pauls Stradins Clinical University Hospital, Riga, Latvia (IV), Department of Perioperative Medicine, Pain Therapy, RRS and ICU, Chieti University Hospital, Chieti, Italy (FP), Department of Anaesthesiology and Reanimation, Marmara University, Istanbul, Turkey (ZA), Département d'anesthésie-réanimation, Hôpital Bichat-Claude-Bernard, Paris, France (DL), Department of Anesthesiology, VU University Medical Center, Amsterdam, The Netherlands (SAL), Department of Anaesthesiology and Intensive Therapy, Medical University of Lodz, Poland (TG), Clinic of Anaesthesiology and Intensive Care, Vilnius University, Vilnius, Lithuania (JS), Department of Intensive Care, University Hospital, Carol Davila University of Medicine, Bucharest, Romania (EC), Department of Anaesthesiology, Perioperative Medicine and Intensive Care, J.E. Purkinje University, Masaryk Hospital, Usti nad Labem (VC), Department of Research and Development, Faculty of Medicine Hradec Kralove, Hradec Kralove, Czech Republic (VC), Department of Anaesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada (VC), Department of Anaesthesiology and Intensive Care Medicine, Lund University, Skåne University Hospital, Malmö, Sweden (JA), Department of Anaesthesiology and Intensive Care Medicine, Baerum Hospital, Oslo, Norway (JM-O), Department of Anaesthesia, Intensive Care and Pain Medicine, Mater Dei Hospital, Msida, Malta (CA), Clinical Department of Anaesthesiology and Intensive Therapy, University Clinical Center Ljubljana, Slovenia (AS), Sigmund Freud Private University Vienna and Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SK-L), Department of Anaesthesiology and Intensive Care, North Estonia Medical Centre, Tallinn, Estonia (IR).

These European Board of Anaesthesiology (EBA) recommendations for safe medication practice replace the first edition of the EBA recommendations published in 2011. They were updated because evidence from critical incident reporting systems continues to show that medication errors remain a major safety issue in anaesthesia, intensive care, emergency medicine and pain medicine, and there is an ongoing need for relevant up-to-date clinical guidance for practising anaesthesiologists. The recommendations are based on evidence wherever possible, with a focus on patient safety, and are primarily aimed at anaesthesiologists practising in Europe, although many will be applicable elsewhere. They emphasise the importance of correct labelling practice and the value of incident reporting so that lessons can be learned, risks reduced and a safety culture developed.
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http://dx.doi.org/10.1097/EJA.0000000000000531DOI Listing
January 2017

Intravenous fluids: should we go with the flow?

Crit Care 2015 18;19 Suppl 3:S2. Epub 2015 Dec 18.

Sensitive monitoring should be used when prescribing intravenous fluids for volume resuscitation. The extent and duration of tissue hypoperfusion determine the severity of cellular damage, which should be kept to a minimum with timely volume substitution. Optimizing the filling status to normovolaemia may boost the resuscitation success. Macrocirculatory pressure values are not sensitive in this indication. While the Surviving Sepsis Campaign guidelines focus on these conventional pressure parameters, the guidelines from the European Society of Anaesthesiology (ESA) on perioperative bleeding management recommend individualized care by monitoring the actual volume status and correcting hypovolaemia promptly if present. The motto is: 'give what is missing'. The credo of the ESA guidelines is to use management algorithms with predefined intervention triggers. Stop signals should help in avoiding hyper-resuscitation. The high-quality evidence-based S3 guidelines on volume therapy in adults have recently been prepared by 14 German scientific societies. Statements include, for example, repeated clinical inspection including turgor of the skin and mucosa. Adjunctive laboratory parameters such as central venous oxygen saturation, lactate, base excess and haematocrit should be considered. The S3 guidelines propose the use of flow-based and/or dynamic preload parameters for guiding volume therapy. Fluid challenges and/or the leg-raising test (autotransfusion) should be performed. The statement from the Co-ordination group for Mutual Recognition and Decentralized Procedures-Human informs healthcare professionals to consider applying individualized medicine and using sensitive monitoring to assess hypovolaemia. The authorities encourage a personalized goal-directed volume resuscitation technique.
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http://dx.doi.org/10.1186/cc14720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699083PMC
August 2016

A few of our favorite unconfirmed ideas.

Crit Care 2015 18;19 Suppl 3:S1. Epub 2015 Dec 18.

Medical practice is rooted in our dependence on the best available evidence from incremental scientific experimentation and rigorous clinical trials. Progress toward determining the true worth of ongoing practice or suggested innovations can be glacially slow when we insist on following the stepwise scientific pathway, and a prevailing but imperfect paradigm often proves difficult to challenge. Yet most experienced clinicians and clinical scientists harbor strong thoughts about how care could or should be improved, even if the existing evidence base is thin or lacking. One of our Future of Critical Care Medicine conference sessions encouraged sharing of novel ideas, each presented with what the speaker considers a defensible rationale. Our intent was to stimulate insightful thinking and free interchange, and perhaps to point in new directions toward lines of innovative theory and improved care of the critically ill. In what follows, a brief background outlines the rationale for each novel and deliberately provocative unconfirmed idea endorsed by the presenter.
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http://dx.doi.org/10.1186/cc14719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699060PMC
August 2016

Fluids and coagulation.

Curr Opin Crit Care 2015 Aug;21(4):285-91

aSigmund Freud Private University Vienna bDepartment of Anesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria.

Purpose Of Review: Infusion therapy is essential in intravascular hypovolaemia and extravascular fluid deficits. Crystalloidal fluids and colloidal volume replacement affect blood coagulation when infused intravenously. The question remains if this side-effect of infusion therapy is clinically relevant in patients with and without bleeding manifestations, and if fluid-induced coagulopathy is a risk factor for anaemia, blood transfusion, and mortality, and a driver for resource use and costs.

Recent Findings: Pathomechanisms of dilutional coagulopathy and evidence for its clinical relevance in perioperative and critically ill patients are reviewed. Furthermore, the article discusses medicolegal aspects.

Summary: The dose-dependent risk of dilutional coagulopathy differs between colloids (dextran > hetastarch > pentastarch > tetrastarch, gelatins > albumin). Risk awareness includes monitoring for early signs of side-effects. With rotational thromboelastometry/thrombelastography, the deterioration not only in clot strength but also in clot formation and in platelet interaction can be assessed. Fibrinogen concentrate administration may be considered in severe bleeding as well as relevant dilutional coagulopathy. Targeted doses of gelatins and tetrastarches seem to have no proven adverse effect on anaemia and allogeneic blood transfusions. Further studies are needed.
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http://dx.doi.org/10.1097/MCC.0000000000000219DOI Listing
August 2015

[Consensus statement: Stroke prevention in nonvalvular atrial fibrillation in special consideration of the new direct oral anticoagulants].

Wien Klin Wochenschr 2014 Dec 3;126(23-24):792-808. Epub 2014 Oct 3.

Klin. Abt. für Hämatologie u. Hämostaseologie, Univ.-Klin. f. Innere Medizin I, MedUni Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich,

The introduction of new direct oral anticoagulants has changed the treatment of nonvalvular atrial fibrillation. However, these changes are not yet fully reflected in current guidelines.This consensus statement, endorsed by six Austrian medical societies, provides guidance to current prophylactic approaches of thromboembolic events in nonvalvular atrial fibrillation on the basis of current evidence and published guidelines. Furthermore, some special subjects are treated, like changes in laboratory parameters and their interpretation under treatment with direct oral anticoagulants, treatment of bleedings, approach to operations, cardioversion and ablation, and specific neurological aspects. For a CHA2DS2-VASc-Score of ≥ 2, anticoagulation is recommended with a high level of evidence (1A). At the end of the consensus statement, recommendations for a number of specific patient subgroups can be found, in order to help treating physicians to arrive at appropriate therapeutic decisions.
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http://dx.doi.org/10.1007/s00508-014-0586-5DOI Listing
December 2014

Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry.

Thromb Res 2014 Oct 19;134(4):918-23. Epub 2014 Aug 19.

Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Routine drug monitoring is not required for the two novel direct factor Xa inhibitors apixaban and rivaroxaban. Rapidly available test results might be beneficial in case of bleeding or prior to urgent surgery.

Objectives: The aim of this study was to evaluate the applicability of the two rotational thrombelastometry (ROTEM®) -modifications Low-tissue factor activated ROTEM® (LowTF-ROTEM®) and Prothrombinase induced clotting time - activated ROTEM® (PiCT®-ROTEM®) for determination of apixaban and rivaroxaban in vitro and ex vivo.

Methods: Blood samples from 20 volunteers were spiked with apixaban / rivaroxaban to yield samples with ascending drug concentrations ranging from 50 - 400ng/mL. LowTF - and PiCT® modified ROTEM® tests and determination of the corresponding antifactor Xa activity were performed in duplicate in 280 samples. LowTF-ROTEM® tests were performed in samples from 20 patients on apixaban or rivaroxaban therapy and 20 controls.

Results: There was a strong correlation between apixaban / rivaroxaban plasma concentrations and the LowTF-ROTEM® parameters Clotting time (CT; spearman correlation coefficient (SCC) 0.81 and 0.81, respectively) and Time to maximum velocity (t,MaxVel; SCC: 0.81 and 0.80, resp.) and a low to moderate correlation for the PiCT®-ROTEM® parameters CT (SCC: 0.38 and 0.59, resp.) and t,MaxVel. (0.51 and 0.69, resp.) in the in vitro experiments. LowTF-ROTEM CT was significantly prolonged in patients on apxiaban or rivaroxaban therapy compared to controls.

Conclusions: LowTF-ROTEM® could be a valuable diagnostic tool for rapid determination of the effect of apixaban and rivaroxaban at the point of care.
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http://dx.doi.org/10.1016/j.thromres.2014.08.006DOI Listing
October 2014

[Perioperative anemia management: a systematic review and meta-analysis].

Wien Med Wochenschr 2014 Aug 29;164(15-16):330-41. Epub 2014 Aug 29.

Department für Klinische Epidemiologie und Evidenzbasierte Medizin, Donau-Universität Krems, Krems, Österreich,

Anemia is a risk factor for increased postoperative morbidity and mortality. International guidelines, therefore, recommend preoperative diagnostic work up and causal treatment of anemia. Iron therapy, however, is suspected to negatively affect disease progression in patients with cancer-associated anemia. The objective of our systematic review was to assess the efficacy and safety of perioperative diagnosis and causal therapy of anemia, and to determine the effect of iron supplement on disease progression of cancer.We systematically searched multiple electronic databases. Two persons independently reviewed abstracts and full-text articles. We rated the risk of bias using the Cochrane Risk of Bias Tool and assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Meta-Analyses were performed using the DerSimonian&Laird random effects method. Results indicate that preoperative therapy of anemia could reduce the need for blood transfusions (relative risk: 0,78; 95% confidence interval 0,61-1,02; number needed to treat: 6) For other patient-relevant outcomes the number of events were too small to detect clinically relevant differences. We could not find any evidence that iron supplements have an influence on the progression of tumors.
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http://dx.doi.org/10.1007/s10354-014-0293-xDOI Listing
August 2014

Coagulation and transfusion in the postoperative bleeding patient.

Curr Opin Crit Care 2014 Aug;20(4):460-6

Department of Anesthesia and Intensive Care, Evangelical Hospital Vienna, Hans-Sachs-Gasse, Vienna, Austria.

Purpose Of Review: Bleeding can be minimal, severe, life-threatening, or organ-threatening. Depending on the compensatory capacity of the patient, most bleeding events going beyond 20% blood volume may represent an emergency as well as a risk factor for anemia, transfusion, coagulopathy, and tissue hypoperfusion. All these factors are independent predictors for survival in postoperative critical care and are drivers for resource use and costs.

Recent Findings: A systematic literature search behind the guidelines from the European Society of Anesthesiology on the management of severe perioperative bleeding gives an up-to-date evidence-based summary of strategies intended to correct hemostasis, control bleeding, and increase patient safety. The current review discusses information, recommendations, and suggestions in the European Society of Anesthesiology guidelines, which appear applicable to the bleeding patient after the end of surgery.

Summary: Individualized coagulation management guided by viscoelastic tests and restrictive transfusion behavior are encouraged in clinical practice of critical care. Potential fields of research are multifold, for example, thromboembolic adverse effects of hemostatic interventions in the isochronic postoperative acute-phase response, transfusion restrictions by increasing postoperative tolerance to anemia and erythropoiesis, and implementation of guidelines and institutional algorithms.
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http://dx.doi.org/10.1097/MCC.0000000000000109DOI Listing
August 2014

Comments on perioperative fluid therapy with tetrastarch and gelatin in cardiac surgery--a prospective sequential analysis.

Crit Care Med 2014 Jul;42(7):e537-8

Department of General and Surgical Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria; Department of Anesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria; Department of General and Surgical Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria.

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http://dx.doi.org/10.1097/CCM.0000000000000283DOI Listing
July 2014

Perioperative management issues of direct oral anticoagulants.

Semin Hematol 2014 Apr 7;51(2):112-20. Epub 2014 Feb 7.

Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria. Electronic address:

The treatment repertoire of oral anticoagulation has changed dramatically over the past few years from one class of vitamin K1 antagonists to an increasing number of direct oral anticoagulants (DOACs). Clinicians are confronted with the problem of managing patients on novel agents in the critical setting before, during, and after surgery, where the risk of bleeding and thrombosis are increased simultaneously. Randomized clinical data are insufficient to date, but clinical exposure enlarges the body of experience. The following review considers perioperative management issues in various categories, including minor elective surgery, major elective surgery, and acute surgery. This review is a credo to personalized medicine where the patient's underlying thromboembolic risk status, the potential bleeding risk, or actual hemorrhagic manifestation determine the selection of multi-modal targeted management strategies.
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http://dx.doi.org/10.1053/j.seminhematol.2014.02.001DOI Listing
April 2014

[Prevention of venous thromboembolism in musculoskeletal surgery].

Wien Klin Wochenschr 2014 May 14;126(9-10):298-310. Epub 2014 May 14.

Klin. Abt. für Hämatologie und Hämostaseologie, Univ.-Klinik für Innere Medizin I, MedUni Wien, Wien, Österreich,

Musculoskeletal surgery is associated with a high risk of venous thrombosis and pulmonary embolism. The introduction of direct oral anticoagulants (DOAK) has broadened the possibilities for prevention of venous thromboembolism in the course of orthopedic and trauma surgery. Addressing this recent development, the Austrian Societies of Orthopedics and Orthopedic Surgery (ÖGO), Trauma Surgery (ÖGU), Hematology and Oncology (OeGHO) and of Anaesthesiology, Reanimation und Intensive Care Medicine (ÖGARI) have taken the initiative to create Austrian guidelines for the prevention of thromboembolism after total hip and knee replacement, hip fracture surgery, interventions at the spine and cases of minor orthopedic and traumatic surgery. Furthermore, the pharmacology of the DOAK and the pivotal trial data for each of the three currently available substances - apixaban, dabigatran, and rivaroxaban - are briefly presented. Separate chapters are dedicated to "anticoagulation and neuroaxial anesthesia" and "bridging".
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http://dx.doi.org/10.1007/s00508-014-0509-5DOI Listing
May 2014

Reply to: ESA guidelines on the management of severe perioperative bleeding.

Eur J Anaesthesiol 2014 Apr;31(4):241-3

From the Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Vienna, Austria (SAKL), Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (GI), Department of Anaesthesiology and Critical Care Medicine, Franziskus Hospital Bielefeld, Bielefeld, Germany (NRM), Department of Anaesthesia, Mother and Children's Section, Juliane Marie Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark and Department of Pediatric and Neonatal Intensive Care Service, Geneva University Hospital, Geneva, Switzerland (AA).

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http://dx.doi.org/10.1097/EJA.0000000000000029DOI Listing
April 2014

Management of dabigatran-induced bleeding: expert statement.

Wien Klin Wochenschr 2013 Nov 12;125(21-22):721-9. Epub 2013 Nov 12.

Department of Anesthesia and Intensive Care, Medical University Innsbruck, Innsbruck, Austria.

The interdisciplinary group of experts has compiled a clinical guidance for manifest dabigatran-induced haemorrhage and envisaged invasive interventions on patients under dabigatran. It recommends an escalation of treatment measures as summarized in a pocket guide (see electronic supplementary material online and insert in the print issue).
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http://dx.doi.org/10.1007/s00508-013-0430-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838590PMC
November 2013

Intravenous nonopioid analgesic drugs in chronic low back pain patients on chronic opioid treatment: a crossover, randomised, double-blinded, placebo-controlled study.

Eur J Anaesthesiol 2014 Jan;31(1):35-40

From the Department of Anaesthesia, Intensive Care and Pain Management (LW, MZ, GA, GS), Department of Physical Medicine and Rehabilitation, Medical University Vienna (TP-S), Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna (SK-L), Vienna, Austria.

Background: Addition of nonopioid analgesic drugs reduces pain and opioid requirements in acute low back pain. In noncancer chronic low back pain (CLBP), the efficacy of a combined regimen to reduce breakthrough pain has not been proven so far.

Objective: Evaluation of the effects of intravenous (i.v.) nonopioid analgesic drugs on pain intensity and lumbar mobility in CLBP patients on chronic opioid therapy.

Design: Randomised, placebo-controlled, double blinded, crossover study.

Setting: Vienna General Hospital, Austria, from December 2002 to May 2004.

Patients: Thirty-six adults with CLBP on chronic opioid therapy. Inclusion criteria are as follows: American Society of Anesthesiologists' physical status less than 3, visual analogue scale (VAS) more than 4 and no known allergy to any of the used drugs.

Intervention: After written informed consent and VAS assessment, any oral nonopioid analgesic drug (NSAIDs, metamizol, paracetamol) was replaced by placebo 10 days before the first test infusion as a washout period. Coanalgesics (anticonvulsants, antidepressants) were maintained. Each patient received randomly four i.v. test infusions of diclofenac 75 mg (and orphenadrine 30 mg), parecoxib 40 mg, paracetamol 1 g and isotonic saline. A washout time of 72 h was allowed between each infusion.

Main Outcome Measures: Primary outcome was as follows: VAS pain intensity (0 to 100 mm) at inclusion, before and within 30 min after infusion. Secondary outcomes were as follows: Roland-Morris questionnaire, McGill pain questionnaire and a test panel of physical functioning for spinal mobility, muscular endurance, balance and coordination. The differences in means of the above assessments among the groups were analysed.

Results: We found an improvement in VAS from the day of inclusion to the day of each appointment. We observed no improvement in pain intensity (VAS) or in any of the physical functioning tests immediately before versus after administration of the four i.v. drugs. Reductions in sensory, affective and cognitive dimensions of the McGill pain questionnaire were statistically significant in the diclofenac group. A trend of McGill pain questionnaire improvement existed in the other groups.

Conclusion: The present data show that the anticipation of an i.v. infusion of nonopioid analgesic drug improves VAS significantly, probably through expectation-related mechanisms. However, single dose i.v. infusions of nonopioid analgesic drugs fail to improve pain intensity and spinal mobility in CLBP patients on chronic opioid treatment, even immediately after the infusion.
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http://dx.doi.org/10.1097/EJA.0b013e328365ae28DOI Listing
January 2014

Outcome criteria such as massive transfusion are inadequate for matching and result in questionable conclusions.

J Trauma Acute Care Surg 2013 Oct;75(4):744-5

Tem International GmbH, Munich, Germany Department of Anaesthesiology and Intensive Care Medicine, University Hospital Essen University Duisburg-Essen Essen, Germany Department of Anaesthesia and Intensive Care Evangelical Hospital Vienna Vienna, Austria Institute of Anaesthesiology University and University Hospital Zurich Zurich, Switzerland.

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http://dx.doi.org/10.1097/01.ta.0000436142.47256.32DOI Listing
October 2013

Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement.

Crit Care 2013 Jul 26;17(4):R166. Epub 2013 Jul 26.

Introduction: Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses.

Methods: We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy.

Results: Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4).

Conclusions: The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.
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http://dx.doi.org/10.1186/cc12845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056523PMC
July 2013

[Periprocedual management of vitamin K antagonist's with low molecular weight heparins during invasive procedures--Consensus of experts].

Wien Klin Wochenschr 2013 Jul;125(13-14):412-20

AKH Wien, Univ.-Klinik für Innere Medizin I, Währinger Gürtel 18–20, 1090 Wien, Österreich.

Interruption of an ongoing therapy with vitamin K antagonists (VKAs) is necessary in almost all patients undergoing major surgery. The purpose of the following expert recommendations is to provide easy to use guidance for the periprocedural management of patients on VKAs based on current evidence from the literature. Management of anticoagulation during the time of interruption of VKAs is based on balancing the thromboembolic (TE) risk of underlying conditions against the bleeding risk of the surgical procedure. VKAs should be stopped 3–7days prior to surgery. Low molecular weight heparin (LMWH) is used to cover (“bridge”) the progressive pre-operative loss of anticoagulation and the slow post-operative onset of anticoagulant activity of VKAs. Patients with high risk of TE should receive a therapeutic dose of LMWH, patients with a moderate risk of TE should receive half of this dose. Patients with a low risk of TE do not need bridging therapy with LMWH. In case of an uneventful postoperative course, patients with a therapeutic pre-operative dose should be treated post-operatively with the same dose, starting on day 4 in case of major surgery and on day 2 in case of minor procedures. Patients with a half-therapeutic preoperative dose should be treated post-operatively with the same dose, starting on day 3 in case of major surgery and on day 1 in case of minor procedures. Therapy with VKAs should be re-instituted on the second post-operative day based on the preoperative dosage. Procedure-related post-operative thromboprophylaxis should be given irrespective of these recommendations on days without “bridging” anticoagulation.
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http://dx.doi.org/10.1007/s00508-013-0390-7DOI Listing
July 2013

Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology.

Eur J Anaesthesiol 2013 Jun;30(6):270-382

Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Austria.

The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient's tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.
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http://dx.doi.org/10.1097/EJA.0b013e32835f4d5bDOI Listing
June 2013

Ecarin modified rotational thrombelastometry: a point-of-care applicable alternative to monitor the direct thrombin inhibitor argatroban.

Wien Klin Wochenschr 2013 Mar 26;125(5-6):156-9. Epub 2013 Feb 26.

Department of Anaesthesiology, General Intensive Care and Pain Control, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Purpose: Adequate monitoring of the effect of the direct thrombin inhibitor argatroban may facilitate individualized dosing and perioperative management of anticoagulation. Ecarin Clotting Time is proposed for this purpose, but has the major disadvantage of limited availability. There is a point-of-care applicable ecarin-activated test modification for rotational thrombelastometry (ROTEM®) which is sensitive to direct thrombin inhibitors. The aim of the study was to evaluate the correlation between argatroban concentration and this ecarin modified thrombelastometry (EMT).

Methods: In this in vitro experiment, blood drawn from healthy volunteers was spiked with argatroban at clinically relevant concentrations and analyzed with ROTEM® using EMT. The main endpoint was the clotting time (CT).

Results: EMT-CT was prolonged with increasing argatroban concentrations (from 83.3 ± 6.7 s without argatroban to 743.5 ± 138.2 s at 2 μg/ml argatroban). The correlation between argatroban concentration and EMT-CT was high (r = 0.94) and statistically significant (p < 0.01).

Conclusion: These promising preclinical results mandate further clinical research to determine an EMT-CT target range regarding the clinical outcomes of thrombosis and bleeding.
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http://dx.doi.org/10.1007/s00508-013-0327-1DOI Listing
March 2013

Heparin-induced effects of prothrombin complex concentrates in thromboelastometry.

Wien Klin Wochenschr 2012 May 11;124(9-10):320-5. Epub 2012 May 11.

Department of Special Anesthesiology and Pain Management, General Intensive Care and Pain Control, Vienna Medical University, 1090, Vienna, Waehringer Guertel 18-20, Austria.

Background: Prothrombin complex concentrates (PCC) are currently used to treat congenital or acquired coagulation factor deficiency. In case of serious bleeding caused by new oral anticoagulant agents, reversing treatment with PCC is under debate. PCC preparations mostly contain heparin to prevent thromboembolic events. In factor VIII and IX deficient plasma, Takeyama et al. observed in vitro a heparin effect at appropriate concentrations of PCCs. The aim of the present experiment was to investigate the heparin effect of four factor-PCC at clinically relevant concentrations in whole blood. In an in vitro experiment, we compared the PCC preparation used in the experiments of Takeyama with a high heparin content to a new heparin-free PCC preparation.

Method: After ethics committee approval and written informed consent, the citrated whole blood was obtained from ten healthy volunteers. We tested heparin-containing Prothromplex(®) and heparin-free Cofact(®) at concentrations of 0.31, 0.63, and 1.25 IU/ml. Protamine was added to another set of samples (1:1 heparin:protamine). We used the NATEM test in the rotational thromboelastometer ROTEM(®).

Results: In the heparin PCC preparation, we observed a significant (p < 0.001) concentration-dependent prolongation in CT and CFT, even at the lowest concentration. MCF was also significantly reduced. The heparin effect was reversible by protamine. The heparin-free PCC did not affect the onset of coagulation. The interpretation of the alpha-angle showed no increased thrombus formation in heparin-free PCC preparation.

Conclusion: Our results extend the report of Takeyama et al. At clinically relevant PCC concentrations, the heparin effect was significant in thromboelastometry. The heparin content of PCCs should be considered in clinical routine.
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http://dx.doi.org/10.1007/s00508-012-0171-8DOI Listing
May 2012

Less blood loss with tetrastarch.

Intensive Care Med 2012 Jun 11;38(6):1078-9; author reply1080-1. Epub 2012 Apr 11.

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http://dx.doi.org/10.1007/s00134-012-2552-xDOI Listing
June 2012

[Primary immune thrombocytopenia in adults: diagnostics and treatment consensus statement of the Austrian Society of Hematology and Oncology (ÖGHO)].

Wien Klin Wochenschr 2012 Feb 3;124(3-4):111-23. Epub 2012 Mar 3.

Univ.-Klin. f. Innere Med. I, Med. Univ. Wien, Wien, Austria.

Immune Thrombocytopenia (ITP) is a rare and - in most patients - mild disease, but might be associated with severe or even life-threatening bleeding complications. The treatment of ITP has partly changed in recent years, due to new therapeutic options. International guidelines changed accordingly. This consensus statement by the Austrian Society of Hematology and Oncology (OEGHO) is not a new evaluation of the current evidence, but rather tries to discuss the available international guidelines and adapt them to the situation in Austria. The subject is primary ITP in adults only. Classification, epidemiology, clinical presentation and diagnostics of ITP, and especially the management of this disease, are discussed in detail. This includes current aspects of first, second, and third line therapies, splenectomy with its indications and contraindications, and the use of new therapeutic options like thrombopoetin receptor agonists (TRA).
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http://dx.doi.org/10.1007/s00508-012-0123-3DOI Listing
February 2012