The transition of the European energy grid to renewable energy sources is increasing the demand for back-up capacity with high flexibility. Current fossil fuel plants are continuously being forced into part load operation, where they are limited by pollution regulations that dictate their minimum environmental load, MEL. The power plants need to shut down when they no longer can comply to pollution regulations, but shutting down means that they can't act as quick back-up for the energy grid. Thus the EU project Turbo-Reflex aims to retrofit existing power plants in order to improve MEL by extending it to lower loads and, by doing so, meeting some of the back-up capacity that is needed. One method of improving MEL in a gas turbine power plants is reducing the mass flow from the compressor to the combustor. This study aims to investigate the stability and performance changes in a compressor as a function of intermediate mass extraction through bleeding lines. The study was made using a 2D throughflow model of a 15 stage axial compressor. Three different bleeding lines, positioned along the length of the compressor, were used for flow reduction. A design of experiments was made to get a structured data collection, combining different configurations of bleeding levels through the three lines, with up to 20% flow reduction. The influence of lowering the ambient temperature was also studied. Results detail the aerodynamic influence of intermediate mass extraction. The loading at the last stage increases with flow reduction, as evaluated by the diffusion factor, and stator 15 becomes the highest aerodynamically loaded position in the compressor. The increased loading is significantly dependent on the bleeding configuration, where upstream extraction is advantageous. The compressor power requirement has the same behavior, where extracting upstream has a 10% advantage. However, bleeding reduces efficiency, and in this regard it is better to use a bleed line further downstream. This combines into a trade off between these three parameters that needs to be made by the operator. Lowering the ambient temperature changes the interplay between these parameters. These research's results are part of the TURBO-REFLEX project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 764545.

A terapia antiplaquetária dual, cada vez mais tem sido utilizada como uma forma de abordagem terapêutica em pacientes com doença arterial coronariana (DAC), e principalmente em portadores de stents farmacológicos. Drogas antiplaquetárias, quando associadas, aumentam o risco de sangramento, isto faz com que muitos profissionais recomendem a suspensão da medicação antes de qualquer procedimento cirúrgico odontológico, entretanto, a suspensão desta terapia expõe os pacientes portadores de stent coronariano à riscos adversos de eventos trombóticos. Por consequência, permanece desafiador e controverso o manejo odontológico cirúrgico de pacientes coronariopatas em uso de terapia antiplaquetária dual. Diante disso, foi realizado uma pesquisa clínica com o objetivo de avaliar quantitativamente o sangramento trans-operatório de extração dentária de pacientes em uso de terapia antiplaquetária dual (AAS + clopidogrel). Este estudo caso-controle, incluiu 38 pacientes com DAC sob terapia antiplaquetária dual com AAS e clopidogrel (grupo de estudo = GE) e 35 pacientes com doença cardiovascular sem nenhum uso de medicação antiplaquetária (grupo controle = GC), ambos com indicação de extração dentária. No dia do procedimento cirúrgico, foi realizado exame de hemograma completo, coagulograma e agregação plaquetária por turbidimetria, utilizando agonistas de adrenalina, adenosina difosfato e ácido araquidônico, no GC e pelo Verifynow no GE, e no, trans-operatório mensurada a quantidade de sangramento por meio da coleta de sangue aspirado. O GE demonstrou um sangramento mais intenso do que o GC, estatisticamente significante, com média de quantidade de sangramento 1,0 e 0,6 ml/min, respectivamente. Métodos hemostáticos locais foram suficientes para controlar o sangramento e em nenhum dos casos houve episódios de hemorragia no trans e/ou pós-operatório. A agregação plaquetária, no GC, apresentou características de hipoagregabilidade, sendo estatisticamente significante apenas o efeito da adrenalina na quantidade de sangramento ocorrido durante o procedimento cirúrgico (p-valor 0,018). No GE, a agregação plaquetária não demonstrou resultados estatísticos significantes, no entanto, foram encontrados 11 (28,94%) pacientes considerados resistentes à terapia com ácido acetilsalicílico com valores de ARU entre 550 a 700 e 12 (31,57%) pacientes considerados não respondedores ao clopidogrel, com valores de PRU acima de 230. De acordo com os nossos resultados, pacientes portadores de DAC, em uso de terapia antiplaquetária dual, AAS + clopidogrel, apresentam maior quantidade de sangramento, mas que pode ser controlado com medidas hemostáticas locais, não sendo necessária a suspensão da terapia antiplaquetária para extração de até três dentes. / Dual-antiplatelet therapy has been used as a therapeutic approach for patients with coronary artery disease (CAD), mainly for those bearing pharmacological stents. The association of antiplatelet a drug increases the risk of bleeding, and for that reason many professionals withdraw the medications prior to any dental surgical procedure. Though, when this therapy is discontinued, patients with coronary stent are exposed to adverse risks of thrombotic events. As a consequence, dental surgical management of patients with CAD and on dual-antiplatelet therapy remains challenging and controversial. On this basis, a clinical research was developed with the aim to evaluate the amount of bleeding that occurs during the intraoperative period of tooth extraction procedures in patients with CAD who are either undergoing dual-antiplatelet therapy (AAS + clopidogrel). This case-control study comprised 38 patients diagnosed with CAD and on dual-antiplatelet therapy, AAS and clopidogrel (study group = SG) and 35 patients with cardiovascular disease, but not on antiplatelet therapy (control group = CG), both requiring tooth extraction. A complete blood count, blood clotting test and platelet aggregation by turbidimetry using epinephrine agonists, adenosine diphosphate and arachidonic acid were carried out on the day of the operation in the CG and using the Verifynow in the SG. The amount of bleeding was measured during the intraoperative period by means of aspirated blood collection. The statistically significant mean volumes of bleeding were 1.0 e 0.6 mL/min for both SG and CG, respectively. The SG showed a more intense bleeding compared to the CG. Local hemostatic measures showed to suffice for controlling possible bleeding problems and in none of the procedures there were intra-operative and/ or post-operative bleeding episodes. Platelet aggregation, for the CG, demonstrated platelet hypoagregability, and only the epinephrine effect was statistically significant for the amount of bleeding during the surgical procedure (p-value 0.018). In the SG, platelet aggregation has not shown statistically significant values. Nonetheless, 11 patients (28.94%) were resistant to acetylsalicylic acid demonstrating ARU values between 550 and 700, 12 patients (31.57%) have not responded to clopidogrel therapy, and the PRU values were above 230. According to the results of this study, individuals with CAD and on dual-antiplatelet therapy (AAS + Clopidogrel), demonstrated a greater amount of bleeding, which can be minimized by using local haemeostatics and not suspending the antiplatelet drug for tooth extraction.

A terapia antiplaquetária dual, cada vez mais tem sido utilizada como uma forma de abordagem terapêutica em pacientes com doença arterial coronariana (DAC), e principalmente em portadores de stents farmacológicos. Drogas antiplaquetárias, quando associadas, aumentam o risco de sangramento, isto faz com que muitos profissionais recomendem a suspensão da medicação antes de qualquer procedimento cirúrgico odontológico, entretanto, a suspensão desta terapia expõe os pacientes portadores de stent coronariano à riscos adversos de eventos trombóticos. Por consequência, permanece desafiador e controverso o manejo odontológico cirúrgico de pacientes coronariopatas em uso de terapia antiplaquetária dual. Diante disso, foi realizado uma pesquisa clínica com o objetivo de avaliar quantitativamente o sangramento trans-operatório de extração dentária de pacientes em uso de terapia antiplaquetária dual (AAS + clopidogrel). Este estudo caso-controle, incluiu 38 pacientes com DAC sob terapia antiplaquetária dual com AAS e clopidogrel (grupo de estudo = GE) e 35 pacientes com doença cardiovascular sem nenhum uso de medicação antiplaquetária (grupo controle = GC), ambos com indicação de extração dentária. No dia do procedimento cirúrgico, foi realizado exame de hemograma completo, coagulograma e agregação plaquetária por turbidimetria, utilizando agonistas de adrenalina, adenosina difosfato e ácido araquidônico, no GC e pelo Verifynow no GE, e no, trans-operatório mensurada a quantidade de sangramento por meio da coleta de sangue aspirado. O GE demonstrou um sangramento mais intenso do que o GC, estatisticamente significante, com média de quantidade de sangramento 1,0 e 0,6 ml/min, respectivamente. Métodos hemostáticos locais foram suficientes para controlar o sangramento e em nenhum dos casos houve episódios de hemorragia no trans e/ou pós-operatório. A agregação plaquetária, no GC, apresentou características de hipoagregabilidade, sendo estatisticamente significante apenas o efeito da adrenalina na quantidade de sangramento ocorrido durante o procedimento cirúrgico (p-valor 0,018). No GE, a agregação plaquetária não demonstrou resultados estatísticos significantes, no entanto, foram encontrados 11 (28,94%) pacientes considerados resistentes à terapia com ácido acetilsalicílico com valores de ARU entre 550 a 700 e 12 (31,57%) pacientes considerados não respondedores ao clopidogrel, com valores de PRU acima de 230. De acordo com os nossos resultados, pacientes portadores de DAC, em uso de terapia antiplaquetária dual, AAS + clopidogrel, apresentam maior quantidade de sangramento, mas que pode ser controlado com medidas hemostáticas locais, não sendo necessária a suspensão da terapia antiplaquetária para extração de até três dentes. / Dual-antiplatelet therapy has been used as a therapeutic approach for patients with coronary artery disease (CAD), mainly for those bearing pharmacological stents. The association of antiplatelet a drug increases the risk of bleeding, and for that reason many professionals withdraw the medications prior to any dental surgical procedure. Though, when this therapy is discontinued, patients with coronary stent are exposed to adverse risks of thrombotic events. As a consequence, dental surgical management of patients with CAD and on dual-antiplatelet therapy remains challenging and controversial. On this basis, a clinical research was developed with the aim to evaluate the amount of bleeding that occurs during the intraoperative period of tooth extraction procedures in patients with CAD who are either undergoing dual-antiplatelet therapy (AAS + clopidogrel). This case-control study comprised 38 patients diagnosed with CAD and on dual-antiplatelet therapy, AAS and clopidogrel (study group = SG) and 35 patients with cardiovascular disease, but not on antiplatelet therapy (control group = CG), both requiring tooth extraction. A complete blood count, blood clotting test and platelet aggregation by turbidimetry using epinephrine agonists, adenosine diphosphate and arachidonic acid were carried out on the day of the operation in the CG and using the Verifynow in the SG. The amount of bleeding was measured during the intraoperative period by means of aspirated blood collection. The statistically significant mean volumes of bleeding were 1.0 e 0.6 mL/min for both SG and CG, respectively. The SG showed a more intense bleeding compared to the CG. Local hemostatic measures showed to suffice for controlling possible bleeding problems and in none of the procedures there were intra-operative and/ or post-operative bleeding episodes. Platelet aggregation, for the CG, demonstrated platelet hypoagregability, and only the epinephrine effect was statistically significant for the amount of bleeding during the surgical procedure (p-value 0.018). In the SG, platelet aggregation has not shown statistically significant values. Nonetheless, 11 patients (28.94%) were resistant to acetylsalicylic acid demonstrating ARU values between 550 and 700, 12 patients (31.57%) have not responded to clopidogrel therapy, and the PRU values were above 230. According to the results of this study, individuals with CAD and on dual-antiplatelet therapy (AAS + Clopidogrel), demonstrated a greater amount of bleeding, which can be minimized by using local haemeostatics and not suspending the antiplatelet drug for tooth extraction.

<p>Transcatheter Arterial Embolization (TAE) is a method in which a catheter is inserted into an artery under fluoroscopy guidance. By using material that creates a thrombus, inserted through the catheter, the artery can be occluded and the bleeding stopped.</p><p>Endoscopy is the treatment of choice in upper gastrointestinal (GI) bleeding, but 10% to 30% of patients rebleed and needs other treatment options. Post Partum Hemorrhage (PPH) may evolve rapidly and can become life threatening. Obstetrical treatment will manage most cases, but in some cases emergency surgery is needed and in the worst case hysterectomy.</p><p>The primary aim of this thesis was to evaluate the clinical usefulness, improve the TAE technique and compare the outcome of TAE with surgery used as “salvage therapy” in patients with upper GI bleeding. Evaluate TAE technique and the long-term effect on the menstrual cycle and fertility in severe PPH.</p><p>To evaluate the clinical usefulness 13 patients were treated with TAE after endoscopic treatment failure and 5 were treated for recurrent hemorrhage after emergency surgery. </p><p>The clinical outcome and mortality rate of 40 patients treated with TAE was compared with 51 patients treated with surgery of upper GI bleedings. </p><p>In 13 patients the ulcer was marked with placement of a metallic clip at endoscopy to be able to locate the exact site of the bleeding ulcer during the TAE procedure.</p><p>A retrospective study of 20 patients with severe PPH treated with bilateral TAE of the uterine artery was performed. </p><p>TAE was found to be effective and an alternative to emergency surgery for control of massive upper GI bleeding. The 30-day mortality was lower in the TAE group (3%) compared to the surgical group (14%). </p><p>By marking the bleeding ulcer at endoscopy using a metallic clip the site of bleeding could be identified on angiography without extravasation of contrast media.</p><p>No major impact on fertility or menstruation cycle was found in patients treated with TAE in PPH. TAE in PPH is safe and have no major long-term side effect. By using TAE in PPH hysterectomy can be avoided.</p>

Transcatheter Arterial Embolization (TAE) is a method in which a catheter is inserted into an artery under fluoroscopy guidance. By using material that creates a thrombus, inserted through the catheter, the artery can be occluded and the bleeding stopped. Endoscopy is the treatment of choice in upper gastrointestinal (GI) bleeding, but 10% to 30% of patients rebleed and needs other treatment options. Post Partum Hemorrhage (PPH) may evolve rapidly and can become life threatening. Obstetrical treatment will manage most cases, but in some cases emergency surgery is needed and in the worst case hysterectomy. The primary aim of this thesis was to evaluate the clinical usefulness, improve the TAE technique and compare the outcome of TAE with surgery used as “salvage therapy” in patients with upper GI bleeding. Evaluate TAE technique and the long-term effect on the menstrual cycle and fertility in severe PPH. To evaluate the clinical usefulness 13 patients were treated with TAE after endoscopic treatment failure and 5 were treated for recurrent hemorrhage after emergency surgery. The clinical outcome and mortality rate of 40 patients treated with TAE was compared with 51 patients treated with surgery of upper GI bleedings. In 13 patients the ulcer was marked with placement of a metallic clip at endoscopy to be able to locate the exact site of the bleeding ulcer during the TAE procedure. A retrospective study of 20 patients with severe PPH treated with bilateral TAE of the uterine artery was performed. TAE was found to be effective and an alternative to emergency surgery for control of massive upper GI bleeding. The 30-day mortality was lower in the TAE group (3%) compared to the surgical group (14%). By marking the bleeding ulcer at endoscopy using a metallic clip the site of bleeding could be identified on angiography without extravasation of contrast media. No major impact on fertility or menstruation cycle was found in patients treated with TAE in PPH. TAE in PPH is safe and have no major long-term side effect. By using TAE in PPH hysterectomy can be avoided.

Intraoperative Blutungskomplikationen sind bei der Versorgung von Patienten mit primärer rhegmatogener Netzhautablösung relativ selten. Bei den aufgetretenen Komplikationen handelte es sich fast ausschließlich um leichtere Blutungen, die intraoperativ gut zu beherrschen waren. Die Wahl der Antikoagulation hatte dabei keinen Einfluss auf die Wahrscheinlichkeit des Auftretens intraoperativer Blutungskomplikationen. Dies gilt sowohl für die Thrombozytenaggregationshemmer Acetylsalicylsäure und Clopidogrel als auch für die gerinnungshemmenden Substanzen Heparin und Phenprocoumon. Interessanterweise zeigte sich bei den mit Phenprocoumon behandelten Patienten keine Korrelation zwischen einem erniedrigten Quick-Wert und einer erhöhten intraoperativen Blutungsneigung. Bei den wenigen Patienten, bei denen es unter der Therapie mit Phenprocoumon zu einer Blutung während der Operation kam, lagen die Quick-Werte sogar eher im oberen Bereich. Wenn man nun bedenkt, dass es sich bei der rissbedingten Netzhautablösung um einen Notfall handelt und beim Zuwarten mit einer Progredienz der Ablösung zu rechnen ist, kann eine klare Empfehlung für die sofortige Operation trotz wirksamer Antikoagulation ausgesprochen werden. Untermauert wird dies noch durch die erhöhte Gefahr thromboembolischer Ereignisse, wenn eine indizierte Gerinnungshemmung perioperativ abgesetzt oder auf andere Substanzen umgestellt wird. Schließlich werden nur Patienten antikoaguliert, bei denen dies aufgrund von gravierenden Erkrankungen in der Vorgeschichte indiziert ist. Dazu gehören zum Beispiel abgelaufene tiefe Beinvenenthrombosen oder Embolien, Vorhofflimmern oder auch der Herzklappenersatz. Im Gegensatz zu den Ergebnissen für die Antikoagulation ergab sich eine Abhängigkeit der intraoperativen Blutungswahrscheinlichkeit von der Wahl des operativen Verfahrens. Die wenigsten Blutungen traten bei den rein eindellenden Operationen (Plomben und Cerclagen) auf. Bei den kombinierten Operationen (Plombe oder Cerclage in Kombination mit Pars plana Vitrektomie) lag die Komplikationsrate schon deutlich höher. Die höchste Rate intraoperativer Blutungskomplikationen zeigte sich bei den nicht-eindellenden Operationen (Pars plana Vitrektomien). Dabei war die Komplikationsrate bei den nicht-eindellenden Verfahren gegenüber den rein eindellenden Verfahren signifikant erhöht (p<0,001). Es kann also festgehalten werden, dass intraoperative Blutungen bei der Akutversorgung von Patienten mit rissbedingter Netzhautablösung selten sind und nicht im Zusammenhang mit der Einnahme von Gerinnungshemmern zu stehen scheinen. Die Wahl des Operationsverfahrens hingegen beeinflusst die Rate intraoperativer Blutungskomplikationen.

Abstract The global aims of this thesis were: to evaluate if an individualised dose strategy for enoxaparin, based on lean body weight and renal function, resulted in a reduction in the prevalence of bleeding and bruising events when compared to conventional dosing; to further understand the dose-exposure-response relationship for enoxaparin using population pharmacokinetic-pharmacodynamic (PKPD) modelling. This thesis comprises seven chapters: an introduction to the current knowledge and literature pertaining to low-molecular-weight heparins (LMWHs), in particular enoxaparin; five research chapters; and a discussion. Each of the five research chapters consists of a manuscript that has been published in, accepted or submitted for peer review in a scientific journal. Preceding each chapter is a synopsis of the important features of the publication. Supplementary information that supports the findings of the publication, but could not be included in the publication, is provided at the end of the chapter. Appendices relevant to each chapter are located at the end of the thesis. Chapter one is the introduction to this thesis. It commences with an overview of the LMWHs, their mechanism of action, customary uses, licensed doses and adverse effects. There is a brief introduction to renal function and body composition; physiological factors that influence the disposition of LMWHs. As much of this thesis is centred on defining the dose-exposure-response relationship for enoxaparin, there is a critique of the existing literature relevant to each segment of this relationship, namely: dose-exposure, exposure-response and dose-response. To conclude this chapter there is a review of pharmacostatistical models and population modelling, followed by an appraisal of population PK and PKPD models that have previously been developed for enoxaparin, including the two key publications that are critical to this thesis. These two papers were the first to fully describe the dose-exposure relationship for enoxaparin in subjects with renal impairment and obesity. It is from these studies that the individualised dosing strategy, explored throughout this thesis, was developed. The specific aims of the five research chapters are then stated. Chapter two describes a confirmatory, randomised controlled trial (RCT) to compare an individualised dose of enoxaparin to conventional, label based dosing. The RCT was conducted at a major tertiary teaching hospital over an 18 month period. The primary endpoint was the prevalence of overt bleeding events and the secondary endpoint a combination of bleeding or major bruising events. A time-to-bleeding event analysis (Kaplan-Meier) was used and markers of effectiveness such as mortality and readmission were assessed out to 30 days post recruitment. Bleeding and bruising data, along with anti-Xa (aXa)-concentrations were collected for use in additional research described in chapters four and five. Chapter three details the evolution, progression and contemporary knowledge of drug dosing based on body composition and focuses on dosing in obese subjects with cardiovascular disease. The concept of dose-individualisation is explored in this chapter with reference to the methods used to normalise drug exposure across the spectrum of body compositions. Subsequently, there is a review of body size descriptors, such as lean body weight, that are used to scale dosing in the obese. Enoxaparin is used as a motivating example, with reference to data presented in Chapter two of this thesis. There is also a discussion about the type of research designs that are required to maximise information about PK parameters. This chapter was published within a book chapter which was intended for clinical practitioners in the discipline of cardiology. Chapter four is focused on the development and evaluation of population PK and PKPD models to describe the time-course of effects for enoxaparin. A population PK model linked to a proportional-odds model was used to describe the severity of an adverse event as a function of exposure and demographic variables. The final model was used to explore the likely occurrence of bleeding and bruising events in patients with obesity and / or renal impairment dosed using either the individualised or conventional dose strategies from Chapter two. Chapter five describes a study that was undertaken to evaluate the ability of the individualised dosing strategy to achieve and maintain aXa-concentrations within the therapeutic range (500 to 1000 IU L-1), by comparison to conventional dosing. As the confirmatory study focused on the prevalence of adverse events there was no assessment of the therapeutic capability of the dose strategies however, as aXa-concentrations were collected using a sparse design during the confirmatory study, the two dose strategies could not be compared using observed data. Therefore, the population PK model developed in Chapter four was used to predict individual subject concentration-time profiles to 120 hours of enoxaparin therapy. The time spent in the therapeutic, supra-therapeutic and sub-therapeutic ranges was computed for each subject and the dosing strategies statistically compared. This study also allowed the evaluation of the results from Chapter two from a dose-exposure perspective. Chapter six of this thesis describes a survey. The aim of this survey was to gain an understanding of how dosing strategies of enoxaparin vary in four countries, investigate if clinicians are prescribing according to the Product label, and determine the methods used to dose-individualise enoxaparin. In doing so, individual hospitals in the international community will be able to compare, critique or benchmark their own strategies to peer hospitals, as well as the current literature. The publication arising from this survey would assist in the dissemination of knowledge gained from the earlier chapters of this thesis. Chapter seven is the final discussion and conclusions of the thesis along with prospects for future research.

Submitted by Maria Creuza Silva (mariakreuza@yahoo.com.br) on 2016-04-14T19:51:38Z No. of bitstreams: 1 Disse MP. Silvia Helena L. Rodrigues. 2015.pdf: 548263 bytes, checksum: 6d3ed80388e26635a912e50c92938c23 (MD5) / Approved for entry into archive by Maria Creuza Silva (mariakreuza@yahoo.com.br) on 2016-04-18T12:22:40Z (GMT) No. of bitstreams: 1 Disse MP. Silvia Helena L. Rodrigues. 2015.pdf: 548263 bytes, checksum: 6d3ed80388e26635a912e50c92938c23 (MD5) / Made available in DSpace on 2016-04-18T12:22:40Z (GMT). No. of bitstreams: 1 Disse MP. Silvia Helena L. Rodrigues. 2015.pdf: 548263 bytes, checksum: 6d3ed80388e26635a912e50c92938c23 (MD5) / As coagulopatias hereditárias são doenças hemorrágicas decorrentes da deficiência quantitativa/qualitativa de um ou mais fatores de coagulação sanguínea, sendo as hemofilias as mais importantes e frequentes. Os pacientes com hemofilia podem desenvolver anticorpos (inibidores) contra o fator deficiente, o que constitui em um desafio terapêutico. O tratamento das crises hemorrágicas em pacientes com inibidor é realizado com agentes bypassing. Este estudo é importante para se ampliar o conhecimento em base epidemiológica dos pacientes que utilizaram agentes bypassing possibilitando o aprimoramento da assistência prestada. Objetivo: Analisar o perfil de utilização dos agentes bypassing distribuídos pelo Ministério da Saúde durante os anos de 2012 e 2013. Metodologia: Trata-se de um estudo descritivo, transversal, de abordagem quantitativa, com base nos dados dos pacientes cadastrados no sistema Hemovida Web Coagulopatias, que utilizaram agentes bypassing nestes anos. Resultados: o perfil de utilização dos agentes bypassing é representado pelos pacientes na faixa etária até 29 anos (69,5%), ensino fundamental incompleto (23,8%), sexo masculino (83,8%), raça branca (43,6%), residentes na região sudeste (48,9%), com Hemofilia A (63%), forma grave da hemofilia (71%), presença de inibidor positiva (56,9%) e inibidor de altos títulos (60,5%). Embora tenha sido evidenciada a utilização off-label (2,8%) para o tratamento de coagulopatias não descritas na bula destes medicamentos. Considerações: Embora tenha sido evidenciado a utilização off-label, o perfil delineado está de acordo com os achados da literatura sobre os fatores associados ao desenvolvimento de inibidores, principal indicação de uso de agentes bypassing, e com as recomendações do Ministério da Saúde.

Introduction Prior to percutaneous coronary intervention (PCI) guidelines recommend that patients with ST- elevation myocardial infarction (STEMI) receive dual antiplatelet therapy (DAPT) consisting of P2Y12 inhibition and acetylsalicylic acid (aspirin). However, in rare occasions, patients admitted with STEMI as preliminary diagnosis require acute thoracic surgery and oral P2Y12 inhibitors increases the bleeding risk over several hours. Cangrelor is an intravenous reversible P2Y12 antagonist with normal platelet function returning within 60 minutes and might therefore be an attractive alternative to oral P2Y12 inhibition.Aim Firstly, to quantify P2Y12 pre-treatment with ticagrelor in patients undergoing acute thoracic surgery and the mortality and morbidity rate associated with DAPT prior to surgery. Secondly, to estimate cost-benefit differences between cangrelor and ticagrelor pre-treatment.Material and Methods A descriptive cohort study using retrospective data. The inclusion criteria were patients undergoing acute thoracic surgery (≤ 24 hours) between January 2015 and December 2017, in the catchment area of Örebro University Hospital. Patients were stratified into groups depending on whether they had received pre-treatment with DAPT or not before surgery. Statistical analyses were made in SPSS and Excel.Results A total of 50 patients were included. 8 patients received DAPT before surgery. There was no mortality in patients receiving DAPT but TIMI major bleeding was more frequent compared to the group with no pre-treatment. The DAPT group required numerically more units of platelets and plasma, however the result was not significant. Direct treatment costs for ticagrelor was 20.14 SEK (the dosage is 2 tablets) and cangrelor was 3 059 SEK.Conclusions DAPT pre-treatment with ticagrelor was not associated with increased mortality but TIMI major bleeding was more frequent compared to the group with no pre-treatment. Direct treatment costs with cangrelor was higher compared to ticagrelor treatment. Further studies, with larger study samples, are needed to investigate complications associated with P2Y12 pre-treatment in patients undergoing acute thoracic surgery.

Submitted by Simone Souza (simonecgsouza@hotmail.com) on 2017-08-24T15:17:13Z No. of bitstreams: 1 DISS_2014_Kelly de Gaiva Carmona.pdf: 1305192 bytes, checksum: 130a12e376106a20bfef053a6c7f3863 (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2017-08-24T15:22:01Z (GMT) No. of bitstreams: 1 DISS_2014_Kelly de Gaiva Carmona.pdf: 1305192 bytes, checksum: 130a12e376106a20bfef053a6c7f3863 (MD5) / Made available in DSpace on 2017-08-24T15:22:01Z (GMT). No. of bitstreams: 1 DISS_2014_Kelly de Gaiva Carmona.pdf: 1305192 bytes, checksum: 130a12e376106a20bfef053a6c7f3863 (MD5) Previous issue date: 2014-03-21 / A carne de pescado é um dos alimentos mais susceptíveis à deterioração por microrganismos. Por esse motivo, procurou-se verificar o efeito da sangria sobre a qualidade da carne do tambaqui armazenado em gelo (2:1) (0ºC ± 4ºC) por 29 dias. Para tanto, foram utilizados 90 exemplares (1,230 ± 0,80kg e 36,20 ± 7,10cm) do peixe em questão, sendo divididos em dois grupos: 45 exemplares sangrados e 45 exemplares não sangrados. Em intervalos de 2 a 3 dias, amostras foram retiradas para as análises microbiológicas e físico-químicas. Nos tempos estabelecidos realizou-se as análises de contagem total de microrganismos heterotróficos aeróbios mesófilos, aeróbios psicrotróficos, bactérias do gênero Aeromonas spp, contagem de bactérias da família Enterobacteriaceae, e análises físico-químicas de pH e BVT (Bases Voláteis Totais). Não houve efeito significativo (p>0,05) entre peixes sangrados e não sangrados em relação à quantificação de mesófilos e Aeromonas spp. No entanto, para a quantificação de psicrotróficos e Enterobactérias, e determinação do pH e BVT, o teste de comparação de médias Tukey foi significativo ao nível de 5%, sendo que o grupo de peixes sangrados apresentou resultados mais satisfatórios em relação a manutenção da qualidade da carne. / The fresh fish is one of the most susceptible food to deterioration by microorganisms. Therefore, one intended to verified the effect of the difference between fish bled and not bled on the meat quality of tambaqui stored on ice (0°C to 4°C) for 29 days. Therefore, 90 samples(1.230 ± 0.80 kg and 36.20 ± 7.10 cm) of the fish in question were divided into two groups: 45 samples were bled and 45 samples were not bled. Within 2 to 3 days, samples were taken for microbiological and physico-chemical analysis. In the established times held the analyzes of total count of aerobic heterotrophic mesophilic microorganisms, quantification of aerobic heterotrophic microorganisms psychrotrophic bacteria from Aeromonas, Enterobacteriaceae bacteria, and physico-chemical analysis of pH and TVB (total volatile bases). There was no significant effect (p> 0.05) between fish bled and not bled on meat quality for the quantification of BHAM and Aeromonas. However, for the quantification of BHAP and Enterobacteriaceae, and determination of pH and TVB, the comparison Tukey test was significant at the 5% level, and the group bled fish showed better results.