Good handling practice of parenterally administered medicines in neonatal intensive care units - position paper of an interdisciplinary working group.

This position paper, developed by an interdisciplinary expert group of neonatologists, paediatric infectious disease physicians, clinical pharmacists and specialists for the prevention and control of nosocomial infections, describes the "Good handling practice of medicines parenterally administered to patients on NICUs". It takes equal account of patient safety and the specialties of neonatal intensive care regarding feasibility and proportionality. The overall concept is perceived as a "learning system", in which open communication within the health-care team relating to medication errors and critical incidents enables continuous development and improvement to ensure patient safety. In our opinion, pharmacists, who are responsible for the supply of ready-to-administer parenteral medicinal products for neonatal intensive care patients, as well as the hygiene staff responsible on site are integral parts of the interdisciplinary treatment team. Risks of the current clinical practice of parenteral treatment of NICU patients are discussed in detail and recommendations for safety-relevant procedures are given.

[Standardized concentrations for continuous infusion-results of a nationwide survey in German intensive care units]. / Standardkonzentrationen für Dauerinfusionen ­ Ergebnisse einer bundesweiten Befragung auf deutschen Erwachsenenintensivstationen.

BACKGROUND: Continuous infusion of numerous parenteral medications is common practice in intensive care units (ICU). In contrast to some countries, there is a lack of clearly defined standardized concentrations in Germany, especially for high-risk medications designated for infusion therapy. OBJECTIVES: The goal was to collect representative data of standardized concentrations commonly used for continuous infusion in German ICUs. Results should be used to draft nationwide recommendations for standardized continuous infusions. MATERIALS AND METHODS: To determine the nationwide acceptance and preference for medications designated for continuous infusion, a questionnaire was developed and sent to the directors of 1816 ICUs in Germany. The questionnaire comprised suggestions of 59 medicinal products with 73 concentrations. In addition, participants could make their own proposals on medications and concentrations preferably used. Evaluation was performed with SurveyMonkey® and Microsoft® Excel®. RESULTS: A total of 312 (17%) ICUs answered the survey. Data analyses indicate a very high acceptance rate for rate-controlled continuous infusion with standardized concentrations. More than 90% (50%) of participating physicians routinely use the top 10 (top 25) medicines listed for continuous infusion. For most medicines, one concentration could be identified. CONCLUSIONS: Our survey results generate a suitable basis for a nationwide list with standardized concentrations of medicines intended for continuous infusion (usually 50 mL). Publication of such a list by the corresponding expert committees is likely to be met with broad acceptance and implementation into clinical practice can be expected.

[Process for the Implementation of Evidence-Based Parenteral Nutrition in German Perinatal Centres - Outcomes of a Multidisciplinary Network]. / Prozess zur Implementierung Evidenzbasierter Parenteraler Ernährung in Deutschen Perinatalzentren ­ Ergebnisse eines Multidisziplinären Netzwerks.

INTRODUCTION: Parenteral nutrition, usually indicated for preterm infants with a birthweight<1500 g and sick newborns, enables the supply with critical nutrients. As a high degree of therapy safety is required, a European guideline provides recommendations for safe therapy procedures. The present project aimed to evaluate the implementation of the European guideline in German perinatal centers and to identify possible barriers that impede its implementation. A further goal was to develop solution approaches to overcome possible barriers. METHODS AND RESULTS: A multidisciplinary cooperation conducted an online survey questioning the current implementation procedures of the European guideline among pediatricians and hospital pharmacists. Results show barriers in the provisioning process of parenteral nutrition that hinder a guideline-compliant implementation in practice. Based on results of this survey, an expert network developed an interactive toolkit with simplified guideline recommendations, guideline-compliant advice for practice, best-practice examples, forms, and handouts. It seeks to encourage critical reflection of routine processes and provides concrete solutions to overcome barriers in practice. CONCLUSION: The current procedures related to parenteral nutrition deviate from guideline recommendations. The developed toolkit provides practice-oriented support aiming to enhance the guideline-compliant implementation of parenteral nutrition in perinatal centers.

Impact of Air Conditioning Systems on the Outdoor Thermal Environment during Summer in Berlin, Germany.

This study investigates the effect of anthropogenic heat emissions from air conditioning systems (AC) on air temperature and AC energy consumption in Berlin, Germany. We conduct simulations applying the model system CCLM/DCEP-BEM, a coupled system of the mesoscale climate model COSMO-CLM (CCLM) and the urban Double Canyon Effect Parameterization scheme with a building energy model (DCEP-BEM), for a summer period of 2018. The DCEP-BEM model is designed to explicitly compute the anthropogenic heat emissions from urban buildings and the heat flux transfer between buildings and the atmosphere. We investigate two locations where the AC outdoor units are installed: either on the wall of a building (VerAC) or on the rooftop of a building (HorAC). AC waste heat emissions considerably increase the near-surface air temperature. Compared to a reference scenario without AC systems, the VerAC scenario with a target indoor temperature of 22 ∘ C results in a temperature increase of up to 0 . 6 K . The increase is more pronounced during the night and for urban areas. The effect of HorAC on air temperature is overall smaller than in VerAC. With the target indoor temperature of 22 ∘ C , an urban site's daily average AC energy consumption per floor area of a room is 9 . 1 W / m 2 , which is 35% more than that of a suburban site. This energy-saving results from the urban heat island effect and different building parameters between both sits. The maximum AC energy consumption occurs in the afternoon. When the target indoor temperature rises, the AC energy consumption decreases at a rate of about 16% per 2 K change in indoor temperature. The nighttime near-surface temperature in VerAC scenarios shows a declining trend ( 0 . 06 K per 2 K change) with increasing target indoor temperature. This feature is not obvious in HorAC scenarios which further confirms that HorAC has a smaller impact on near-surface air temperature.

On the influence of density and morphology on the Urban Heat Island intensity.

The canopy layer urban heat island (UHI) effect, as manifested by elevated near-surface air temperatures in urban areas, exposes urban dwellers to additional heat stress in many cities, specially during heat waves. We simulate the urban climate of various generated cities under the same weather conditions. For mono-centric cities, we propose a linear combination of logarithmic city area and logarithmic gross building volume, which also captures the influence of building density. By studying various city shapes, we generalise and propose a reduced form to estimate UHI intensities based only on the structure of urban sites, as well as their relative distances. We conclude that in addition to the size, the UHI intensity of a city is directly related to the density and an amplifying effect that urban sites have on each other. Our approach can serve as a UHI rule of thumb for the comparison of urban development scenarios.

Accuracy of self-monitoring: does experience, ability or case difficulty matter?

CONTEXT: The ability to self-monitor one's performance in clinical settings is a critical determinant of safe and effective practice. Various studies have shown this form of self-regulation to be more trustworthy than aggregate judgements (i.e. self-assessments) of one's capacity in a given domain. However, little is known regarding what cues inform learners' self-monitoring, which limits an informed exploration of interventions that might facilitate improvements in self-monitoring capacity. The purpose of this study is to understand the influence of characteristics of the individual (e.g. ability) and characteristics of the problem (e.g. case difficulty) on the accuracy of self-monitoring by medical students. METHODS: In a cross-sectional study, 283 medical students from 5 years of study completed a computer-based clinical reasoning exercise. Confidence ratings were collected after completing each of six cases and the accuracy of self-monitoring was considered to be a function of confidence when the eventual answer was correct relative to when the eventual answer was incorrect. The magnitude of that difference was then explored as a function of year of seniority, gender, case difficulty and overall aptitude. RESULTS: Students demonstrated accurate self-monitoring by virtue of giving higher confidence ratings (57.3%) and taking a shorter time to work through cases (25.6 seconds) when their answers were correct relative to when they were wrong (41.8% and 52.0 seconds, respectively; p< 0.001 and d > 0.5 in both instances). Self-monitoring indices were related to student seniority and case difficulty, but not to overall ability or student gender. CONCLUSIONS: This study suggests that the accuracy of self-monitoring is context specific, being heavily influenced by the struggles students experience with a particular case rather than reflecting a generic ability to know when one is right or wrong. That said, the apparent capacity to self-monitor increases developmentally because increasing experience provides a greater likelihood of success with presented problems.

A combined 3D-SIM/SMLM approach allows centriole proteins to be localized with a precision of ∼4-5 nm.

Centrioles are small barrel-shaped structures that form centrosomes and cilia [1]. Centrioles assemble around a central cartwheel comprising the Sas-6 and Ana2/STIL proteins. The amino termini of nine Sas-6 dimers form a central hub of ∼12 nm radius from which nine dimer spokes radiate, placing the Sas-6 carboxyl termini at the outer edge of the ∼60 nm radius cartwheel [2]. Several centriole proteins are distributed in a toroid around the cartwheel, and super-resolution light microscopy studies have measured the average radii of these ∼100-200 nm radius toroids with a 'precision' - or standard deviation (s.d. or 1σ) - of ±âˆ¼10-40 nm. The organization of Ana2/STIL within the cartwheel, however, has not been resolvable. Here, we develop methods to calculate the average toroidal radius of centriolar proteins in the ∼20-60 nm range with a s.d. of just ±âˆ¼4-5 nm, revealing that the amino and carboxyl termini of Ana2 are located in the outer cartwheel region.

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation.

Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications. Here, we determined that neonatal NET-inhibitory factor (nNIF) is an inhibitor of NET formation in umbilical cord blood. In human neonatal and adult neutrophils, nNIF inhibits key terminal events in NET formation, including peptidyl arginine deiminase 4 (PAD4) activity, neutrophil nuclear histone citrullination, and nuclear decondensation. We also identified additional nNIF-related peptides (NRPs) that inhibit NET formation. nNIFs and NRPs blocked NET formation induced by pathogens, microbial toxins, and pharmacologic agonists in vitro and in mouse models of infection and systemic inflammation, and they improved mortality in murine models of systemic inflammation, which are associated with NET-induced collateral tissue injury. The identification of NRPs as neutrophil modulators that selectively interrupt NET generation at critical steps suggests their potential as therapeutic agents. Furthermore, our results indicate that nNIF may be an important regulator of NET formation in fetal and neonatal inflammation.

A tour through the transcriptional landscape of platelets.

The RNA code found within a platelet and alterations of that code continue to shed light onto the mechanistic underpinnings of platelet function and dysfunction. It is now known that features of messenger RNA (mRNA) in platelets mirror those of nucleated cells. This review serves as a tour guide for readers interested in developing a greater understanding of platelet mRNA. The tour provides an in-depth and interactive examination of platelet mRNA, especially in the context of next-generation RNA sequencing. At the end of the expedition, the reader will have a better grasp of the topography of platelet mRNA and how it impacts platelet function in health and disease.

Stress and development in Dictyostelium discoideum: the involvement of the catalytic calcineurin A subunit.

Calcium signaling is one of the most important signaling-pathways in all eukaryotes. One important target activated by an increased intracellular calcium concentration via calmodulin is the protein phosphatase calcineurin, which is composed of a catalytic subunit (calcineurin A) and a regulatory subunit (calcineurin B). The importance of calcium and calcineurin for the differentiation and development of the social amoeba Dictyostelium discoideum has already been shown by pharmacological approaches. However, so far only a RNAi-silenced calcineurin B mutant has been investigated on a molecular level. Here, we describe the construction and phenotypic investigation of a RNAi-silenced calcineurin A mutant. Phenotypic aberrations during development resemble those produced by silencing of calcineurin B with ectopic tip formation of the fruiting bodies. Additionally, we tested the response of the mutants under various stress conditions in liquid culture as well as during development. Both, calcineurin A and B RNAi-mutants, are hypersensitive during development towards cation stress. Besides its role in development, calcineurin is thus also involved in the stress response in D. discoideum. Further, our data imply that many functions of calcineurin are conserved among the eukaryotes.

Staphylococcus aureus α-toxin triggers the synthesis of B-cell lymphoma 3 by human platelets.

The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced α(IIb)ß(3)-dependent aggregation (EC(50) 2.98 µg/mL ± 0.64 µg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcusaureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis.

A review of Health Technology Assessment (HTA) recommendations for drug therapies issued between 2007 and 2009 and their impact on policymaking processes in Poland.

OBJECTIVE: The primary objective of this study was to critically review and analyze the Polish Health Technology Assessment (AHTAPol) agency's health technology drug recommendations (HTA activity), in order to ascertain to what extent HTA findings have been incorporated into national drug reimbursement decisions (HTA impact). METHODOLOGY: HTA recommendations issued between 2007 and 2009 were studied. Positive recommendations were classified into three categories: recommendations with major restrictions; minor restrictions; and without restrictions. Definitions of clinical and non-clinical reasons were drawn ups for negative recommendations. The study examined how many different drug technologies assessed by AHTAPol were included in reimbursement lists. RESULTS: In terms of HTA activity, 63 negative and 83 positive HTA recommendations were issued. While clinical arguments were the most prevalent reason for negative HTA recommendations, major restrictions were most common in the positive guidance group. In terms of HTA impact, the results revealed 30 drugs with positive HTA recommendations and four with negative HTA recommendations were included on the reimbursement lists. CONCLUSIONS: Most of AHTAPol's recommendations have a positive outcome for the drug being appraised. The study revealed room for further enhancement of HTA impact. Three key areas that need future attention were identified: consistency, credibility; and pragmatism.

Communication and social competencies in medical education in German-speaking countries: the Basel consensus statement. Results of a Delphi survey.

OBJECTIVE: To propose a comprehensive set of competencies and educational objectives for communication and social competencies in undergraduate medical education and to support the nationwide implementation of these issues in all medical schools. METHODS: Thirty experts from different medical and psychosocial disciplines participated in a 2-day workshop using the Nominal Group Technique (NGT) to develop an initial set of educational objectives. These were refined, structured, and rated according to their importance by means of a two-step Delphi Survey involving additional experts in medical education. RESULTS: The initial workshop resulted in 188 educational objectives assigned to 26 different topics. After the Delphi Survey, 131 objectives remained, assigned to 19 different topics. Some objectives that could be assigned to more than one topic were subsumed under a new more general category. CONCLUSION: The described consensus process proved successful as one method to develop a set of educational objectives. PRACTICAL IMPLICATIONS: The Basel consensus statement can be used to orientate curriculum reform and development in medical education.

The direct thrombin inhibitor argatroban effectively prevents cardiac catheter thrombosis in vitro.

The direct thrombin inhibitor argatroban offers some significant advantages over unfractionated heparin (UFH) and is recommended as an alternative anticoagulant during percutaneous coronary interventions (PCI). The impact of argatroban on cardiac catheter thrombosis--a severe potential complication of PCI--has not been systematically studied yet. The aim of the present study was to test in vitro the hypothesis that argatroban is equivalent to the more established anticoagulants UFH and enoxaparin in preventing catheter thrombus formation. Blood pretreated with the anticoagulants of interest was continuously circulated through a guiding catheter by using a roller pump for a maximum experimental period of 60 minutes. In an alternate model, coagulation was mechanically induced by a magnetic stirrer. Coagulation parameters, overall thrombus weight and electron microscopic features (deposits of platelets and fibrin on the catheter surface) were quantified as endpoints. Argatroban (administered as bolus or continuous infusion), UFH (bolus), and enoxaparin (bolus) significantly reduced catheter thrombus formation compared to untreated controls. Here, neither overall thrombus weight nor platelet/fibrin deposition was different among the specific anticoagulants. Declining ACT (activated clotting time) levels--which were found in the argatroban bolus group--could be prevented by continuous infusion. In magnetic stirrer-induced coagulation, thrombus weight was lower following bolus treatment with UFH and enoxaparin compared to argatroban. These data suggest that the potential for argatroban in preventing catheter thrombosis is comparable to that of UFH and enoxaparin. However, the anticoagulatory efficacy varied, depending on the model of coagulation activation, which demonstrates the necessity for specific testing.

Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves. Results of an in-vitro study.

Prevention of valve thrombosis in patients after prosthetic mechanical heart valve replacement and heparin-induced thrombocytopenia (HIT) is still an open issue. The aim of the present in-vitro study was to investigate the efficacy of argatroban and bivalirudin in comparison to unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves. Blood (230 ml) from healthy young male volunteers was anticoagulated either by UFH, argatroban bolus, argatroban bolus plus continuous infusion, bivalirudin bolus, or bivalirudin bolus plus continuous infusion. Valve prostheses were placed in a newly developed in-vitro thrombosis tester and exposed to the anticoagulated blood samples. To quantify the thrombi, electron microscopy was performed, and each valve was weighed before and after the experiment. Mean thrombus weight in group 1 (UFH) was 117 + 93 mg, in group 2 (argatroban bolus) 722 + 428 mg, in group 3 (bivalirudin bolus) 758 + 323 mg, in group 4 (argatroban bolus plus continuous infusion) 162 + 98 mg, and in group 5 (bivalirudin bolus plus continuous infusion) 166 + 141 mg (p-value <0.001). Electron microscopy showed increased rates of thrombus formation in groups 2 and 3. Argatroban and bivalirudin were as effective as UFH in preventing thrombus formation on valve prostheses in our in-vitro investigation when they were administered continuously. We hypothesise that continuous infusion of argatroban or bivalirudin are optimal treatment options for patients with HIT after mechanical heart valve replacement for adapting oral to parenteral anticoagulation or vice versa.

Assessment of spatial anatomical knowledge with a 'three-dimensional multiple choice test' (3D-MC).

BACKGROUND: Text only multiple choice questions (MCQs) are often inadequate to assess anatomical and histological knowledge and may encourage students to memorize abstract textbook knowledge. An alternative are the "spotters" or "tag tests" well-known in North American and British anatomy. However, the psychometric properties of this assessment have only been reported in one study for a format using short answer questions. AIMS: To describe the implementation and feasibility of a multiple choice "tag test" (3D-MC) using prosected specimens, histological slides, models and radiographs; to report the psychometric properties and students' acceptance of the 3D-MC; to compare it with a traditional multiple choice format. RESULTS: The administration of the 3D-MC did not pose any major problems. The 3D-MC was significantly easier (mean scores 75% vs. 64%) than traditional MCQs. The estimated correlation (corrected for attenuation) between the two MCQ formats was r = 0.814. Reliability for the 3D-MC was. 665 for 30 items. Student acceptance was very high. CONCLUSIONS: The 3D-MC is a feasible, reliable and well-accepted test of anatomical knowledge. Further research should investigate if the higher cost as compared to MCQs using photographs is justified by the assessment of different knowledge and abilities as compared to MCQs using photographs.

Comparison of bivalirudin, enoxaparin, and unfractionated heparin in preventing cardiac catheter thrombosis. Results of an in-vitro study.

Bivalirudin, a direct thrombin inhibitor binds specifically and reversibly to both fibrin-bound and unbound thrombin. Bivalirudin is approved for use as an anticoagulant in patients undergoing percutaneous coronary intervention. The OASIS-5 trial presented a significant increase in cardiac catheter thrombosis for the pentasaccharid fondaparinux compared to enoxaparin. Catheter thrombosis has never been reported in any trial using bivalirudin. Our study compared the development of catheter thrombosis for bivalirudin, enoxaparin, and unfractionated heparin in a controlled in-vitro environment. Ten healthy male volunteers were pretreated with aspirin 500 mg 2 hours before venesection of 50 ml of blood. The seven groups of anticoagulant combinations tested were: UFH, UFH + eptifibatide, enoxaparin, enoxaparin + eptifibatide, bivalirudin bolus, bivalirudin + eptifibatide, bivalirudin bolus + continuous infusion. The blood/anticoagulant mix continuously circulated through a cardiac guiding catheter for 60 minutes or until the catheter became blocked with thrombus. Thrombus development was assessed by weighing each catheter before and after the procedure. Electron microscopy was used to quantify the degree of erythrocyte, platelet and fibrin deposition. Following anticoagulation with bolus dose bivalirudin, the catheter was invariably occluded with thrombus after 33 minutes of circulation. However, a continuous infusion of Bivalirudin prevented the development of occlusive catheter thrombosis. In the bolus bivalirudin group the mean thrombus weight was significantly greater than in all other groups (p-value < 0.01 in all analyses). Bivalirudin given as a bolus was not sufficient to prevent cardiac catheter thrombosis in our in-vitro study. However, a continuous infusion of bivalirudin had similar anti-thrombotic efficacy compared to other treatment strategies.

Serine protease inhibitor nafamostat given before reperfusion reduces inflammatory myocardial injury by complement and neutrophil inhibition.

Animal data strongly support a role for inflammation in myocardial ischemia reperfusion injury. Attempts at cardioprotection by immunomodulation (such as with the specific C5 antibody pexelizumab) in humans have been disappointing. We hypothesized that a broader spectrum antiinflammatory agent might yield successful cardioprotection. The serine protease inhibitor nafamostat (FUT-175), which is already in clinical use, is a potent antiinflammatory synthetic serine protease inhibitor with anticomplement activity that we tested in a well-established rabbit model of 1 hour of myocardial ischemia followed by 3 hours of reperfusion. Compared to vehicle-treated animals, nafamostat (1 mg/kg of body weight) administered 5 minutes before reperfusion significantly reduced myocardial injury assessed by plasma creatine kinase activity (38.1 +/- 6.0 versus 57.9 +/- 3.7I U/g protein; P < 0.05) and myocardial necrosis (23.6 +/- 3.1% versus 35.7 +/- 1.0%; P < 0.05) as well as myocardial leukocyte accumulation (P < 0.05). In parallel in vitro studies, Nafamostat was a significantly more potent broad spectrum complement suppressor than C1 inhibitor. Nafamostat appears to have capability as an inhibitor of both complement pathways and as a broad-spectrum antiinflammatory agent by virtue of its serine protease inhibition. Administration of nafamostat before myocardial reperfusion after ischemia produced significant, dose-dependent cardioprotection. Reduced leukocyte accumulation and complement activity seem involved in the mechanism of this cardioprotective effect.

A situational judgement test of professional behaviour: development and validation.

AIMS: To describe the development of a single best answer multiple choice situational judgement test (SJT) to assess medical students' ability to judge professional behaviour; to present results of an expert validation of the SJT; to describe experiences with two different validation formats. METHODS: Based on educational objectives and work situations concerning professional behaviour, a SJT with 17 vignettes and 35 questions was developed. Best answers were developed according to available evidence. Forty-four experts validated the answers using either a rank order or a rating scale. RESULTS: For sixteen questions in the rating group, thirteen questions in the ranking group and twelve questions in both groups more than two thirds of the experts agreed on a best answer. In the ranking group some experts found it difficult to commit themselves to a single best answer as instructed. In the rating group some experts did not mark any of the proposed answer options as adequate. DISCUSSION: The definition of the construct of and experts for professional behaviour remain a challenge. Both validation scales have advantages and disadvantages. The two thirds criterion is somewhat arbitrary and lower or higher agreement may be acceptable or necessary depending on the purpose of the assessment.

In-vitro comparison of fondaparinux, unfractionated heparin, and enoxaparin in preventing cardiac catheter-associated thrombus.

BACKGROUND: The Organization to Assess Strategies in Acute Ischemic Syndromes trials showed that fondaparinux (fonda) is at least as effective and safe as unfractionated heparin (UFH) and enoxaparin (enoxa) in acute coronary syndromes. Unexpectedly, there was an increase in catheter-related thrombus formation during percutaneous coronary interventions in fonda-treated patients. METHODS: Ten healthy male volunteers were pretreated with aspirin 500 mg 2 h before venesection of 50 ml of blood. Eight groups of anticoagulant (combinations) were tested and volunteers donated blood eight times, thus, acting as their own controls. The groups were UFH, UFH+eptifibatide, enoxa, enoxa+eptifibatide, fonda, fonda+eptifibatide, fonda+(half-therapeutic) UFH, and fonda+eptifibatide+(half-therapeutic) UFH. The blood/anticoagulant mix was kept at 37 degrees C and continuously circulated through a guiding catheter for 60 min or until the catheter became blocked with thrombus. Thrombus development was assessed by weighing each catheter before and after the procedure. Electron microscopy of the catheter lining was used to quantify the degree of erythrocyte and fibrin deposition. RESULTS: Despite fonda anticoagulation, catheters were invariably occluded by thrombus before the 60 min perfusion period had elapsed. Thrombotic catheter occlusion occurred even with higher fonda concentrations and combined fonda/eptifibatide use. All other combinations (including fonda and half-therapeutic UFH) ensured catheter patency for 60 min. Furthermore, thrombus weight and the cell/fibrinogen counts were significantly increased in fonda and fonda+eptifibatide compared with other treatment groups. CONCLUSION: Treatment with fonda, even in combination with eptifibatide, was not sufficient to prevent cardiac catheter thrombus development in our in-vitro study. However, the combination of fonda with 'half' therapeutic dosages of UFH were as efficient as other treatment strategies in preventing thrombus formation.