Bakgrund och problemformulering: Vård av kritiskt sjuka patienter på intensivvårdsavdelning (IVA) innefattar smärtbehandling, sedering och mekanisk ventilation. En lättare sedering och god smärtlindring eftersträvas vilket möjliggör tidig mobilisering och optimerar mekanisk ventilatoravvänjning. Merparten av patienter som vårdats på en IVA har någon form av minnen av den vård de erhållit där. Minnen av negativa upplevelser kan leda till Posttraumatic Stress Disorder (PTSD). Genom att identifiera eventuella brister i omvårdnaden av svårt sjuka patienter på IVA kan vårdkvaliteten förbättras och risken för framtida negativa psykologiska konsekvenser minskas. Syfte: Syftet med examensarbetet var att värdera och sammanställa publicerade forskningsresultat som beskriver svårt sjuka patienters upplevelser och erfarenheter av att vårdas på IVA. Metod: En systematisk litteraturöversikt valdes som sammanställer tio nyare publicerade studier inom aktuellt område. Inkluderade artiklar analyserades utifrån tematisk analysmetod. Resultat: Analysen resulterade i fyra kategorier med tillhörande subkategorier: Förlust av autonomi med subkategorier hjälplöshet och fysiskt obehag; Närhet till döden med subkategorierna dödsångest och lättnad att leva; Ökat trygghetsbehov med subkategorierna personalkompetens, beteende och attityd och närstående stöttande/störande, samt förankring i verkligheten med subkategorierna vårdmiljö och förvriden verklighetsuppfattning. Diskussion: Svårt sjuka patienter som vårdas på IVA upplever fortfarande fysiskt och psykiskt lidande, trots en mindre invasiva behandlingsmetoder, förbättrad smärtlindring och lättare sedering. / Background and problem formulation: The main care of critically ill patients at an Intensive Care Unit (ICU) includes pain-relief, sedation, and mechanical ventilation. Lighter sedation regimens and good pain management is strived for, which makes it easier for earlier mobilization and optimizes removal of mechanical ventilation. The majority of patients who have received treatment at an ICU have some kind of memory of the care they received there. Memories of negative experiences can lead to Post-traumatic Stress Disorder (PTSD). By identifying possible flaws in the care of critically ill patients at the ICU the quality of care can be improved and the risk of future psychological consequences can be lessened. Aim: This essay aimed to evaluate and compile published research results that describe the experiences of critically ill patients of being cared for at ICU. Method: A systematic literature review was chosen that summarizes ten recently published studies in the current field. Included articles were analyzed based on a thematic analysis method. Results: The analysis resulted in four categories with associated subcategories: Loss of autonomy with subcategories helplessness and physical discomfort; Proximity to death with the subcategories death anxiety and relief to live; Increased need for security with the subcategories staff competence, behavior and attitude and relatives supportive / disturbing, and Anchoring in reality with the subcategories care environment and distorted perception of reality. Discussion: Critically ill patients who are cared for at ICU still experience physical and mental suffering, despite less invasive treatment methods, improved pain relief and easier sedation.

Background: Critical Care Nurses have previously noted obstacles in caring for dying patients. Obstacles noted by nurses working in more urban settings have been reported. What is not known is the obstacles to providing end-of-life (EOL) care as perceived by nurses working in Critical Access Hospitals (CAHs). Objective: To determine the stories/experiences related to obstacles in providing EOL care as reported by nurses working in CAHs. Methods: This was an exploratory, cross-sectional study. Previous quantitative data has been reported. Documentation of the qualitative stories/experiences of nurses working in CAHs related to obstacles to providing EOL care for dying patients and their families. Results: Sixty-four CAH nurses provided 96 categorizable responses. Two major categories emerged related to either Family, Physician, & Ancillary staff issues or Nursing, Environment, Protocols, and Miscellaneous issues. Issues related to family behaviors included families insisting on futile care, disagreeing about DNR/DNI orders, issues with out-of-town family members, or even family members who suggested to the nurse to hasten the death of their family member. Physician behaviors related to providing false hope, dishonest communication, continuing futile treatments, or not ordering pain medications. Nursing issues included not having enough time to provide EOL care, already knowing the patient/family, or actions of compassion for the dying patient and family. Conclusion: Family issues continue to be obstacles to providing EOL care for nurses regardless of urban or rural setting. Physician behaviors are also consistent regardless of setting. Education of family members regarding issues with EOL care in ICUs is challenging because it is likely the families first experience with ICU terminology and technology. Further research into EOL care in CAHs is needed.

No description available.

A presente tese explora aspectos importantes do suporte nutricional, no paciente crítico: método e vias de administração da nutrição enteral, determinação do gasto energético, monitorização da adequação do suporte nutricional e seu efeito sobre os desfechos em curto e longo prazo. Em face da evidência de benefícios significativos, a nutrição enteral é recomendada como a primeira opção para a maioria dos pacientes, quando comparada à nutrição parenteral. É comum a intolerância gástrica associada ao uso de opióides, choque e vasopressores, o que reduz a entrega de energia e talvez aumente a incidência de pneumonia hospitalar. A subalimentação parece estar associada com consequências indesejáveis, que incluem o risco aumentado de infecção, o desmame da ventilação prolongada, o tempo de internação na UTI e as taxas elevadas de mortalidade, na UTI e no hospital. A determinação do gasto energético é alvo de debates, pois vários são os fatores que influenciam diretamente o gasto energético do paciente crítico. O método calorimetria indireta é apontado como o mais preciso para adequar o suporte nutricional, quando comparado com as equações preditivas. Vale destacar, porém, que ainda é necessária maior evidência clínica sobre a real influência da calorimetria indireta nos desfechos clínicos (Tempo em VM, tempo de UTI e mortalidade em UTI, mortalidade hospitalar). Os estudos avaliam os desfechos clínicos mais relevantes, em curto prazo, e há uma escassez de estudos que avaliam a qualidade de vida dos sobreviventes, em médio ou longo prazo. Para a realização da tese, foram desenvolvidos três estudos, um ensaio clínico randomizado, em que foi definida a incidência de pneumonia e avaliada a taxa de mortalidade na UTI, comparando a nutrição por sonda gástrica com a por sonda jejunal. Não encontramos diferença na taxa de pneumonia, quando é utilizada a sonda em posição gástrica ou jejunal. Não observamos diferenças na sobrevida na UTI e hospitalar. Em nossa revisão sistemática, analisamos quatro artigos da literatura sobre paciente crítico adulto e adequação do suporte nutricional guiado pela calorimetria indireta, de 1950 a maio de 2014. Não encontramos estudos suficientes para evidenciar o impacto da utilização da calorimetria indireta, como método de adequação do suporte nutricional sobre os desfechos clínicos. Realizamos estudo observacional, onde procuramos definir as relativas contribuições da adequação nutricional maior ou igual a 70%, em relação ao previsto nas primeiras 72 horas de internação na UTI, para os desfechos clínicos em curto e longo prazo (capacidade de realizar atividades da vida diária). Os pacientes que receberam um aporte calórico igual ou superior a 70%, nas primeiras 72 horas de internação, não apresentaram melhores desfechos em curto prazo (tempo em VM, tempo de UTI e mortalidade em UTI), bem como melhora da capacidade funcional em um ano. Esta tese se justifica por buscar melhor entendimento dos principais aspectos do suporte nutricional enteral, no paciente crítico, mecanicamente ventilado e submetido à terapia intensiva. Como aspectos da terapia nutricional, destacamos a importância de investigar evidências clínicas do impacto do suporte nutricional enteral sobre desfechos clínicos. / This thesis explores important aspects of nutritional support in critically ill patients: method and routes for enteral nutrition administration; determining energy expenditure; monitoring the optimal nutritional support and its effect on short- and long-term outcomes. Given the evidence of significant benefits, enteral nutrition is recommended as the first choice for most patients compared to parenteral nutrition. Gastric intolerance associated with opioid use, shock, and vasopressors is common, which reduces energy delivery and may increase the incidence of hospital-acquired pneumonia. Malnutrition appears to be associated with undesirable consequences, including increased risk of infection; weaning from prolonged ventilation; length of stay in ICU; and high mortality rates in ICU and hospital. Determining energy expenditure is subject to debate because several factors directly influence it for critically ill patients. The method of indirect calorimetry is pointed out as the most accurate for establishing adequate nutritional support compared with predictive equations. It is worth noting, however, that more clinical evidence is needed on the real influence of indirect calorimetry on clinical outcomes (length of ventilation; length of stay in ICU and mortality in ICU; hospital mortality). The studies evaluate the most relevant clinical outcomes in the short term, and there is shortage of works assessing survivors’ quality of life in the medium or long term. Three studies were developed for the thesis: a randomized clinical trial where the incidence of pneumonia was established and the mortality rate in ICU was evaluated, comparing nutrition by gastric gavage with a jejunal probe. No difference was found in the rate of pneumonia when using the gavage in gastric or jejunal position. No differences in survival in ICU and hospital were found. In our systematic review, we analyze four articles on critically ill adult patients and optimization of nutritional support guided by indirect calorimetry, from 1950 to May 2014. We did not find enough studies to show the impact of using indirect calorimetry for optimizing nutritional support on clinical outcomes. We conducted an observational study to define the relative contributions of nutritional optimization higher or equal to 70% relative to predictions in the first 72 hours of ICU admission for clinical outcomes in the short and long term (ability to perform daily activities). Patients who received caloric intake equal to or higher than 70% in the first 72 hours of admission did not show better outcomes in the short term (time under MV, ICU stay, and ICU mortality) as well as improved functional capacity within one year. This thesis is justified for seeking to improve understanding of the key aspects of enteral nutritional support in critically ill, mechanically ventilated patients who have underwent intensive therapy. Important aspects of nutrition therapy include investigating clinical evidence of the impact of enteral nutritional support on clinical outcomes.

Background: The safety of critically ill patients during inter-hospital transfer is recognised as a globally important issue. However, little evidence exists pertaining to the care provided by transfer nurses throughout the processes of inter-hospital transfer in rural community hospitals where there is a high risk of adverse clinical events occurring during transportation. Aim: The overall aim of the study was to explore transfer nurses' understanding of the delivery of quality of care during the transfer of critically ill patients from rural community hospitals to a tertiary regional hospital in Thailand. Design and Methods: The theory of symbolic interactionism (Blumer, 1986) and focused ethnography methodology were used. Data were collected using multiple qualitative methods including sixteen semi-structured interviews with transfer nurses, fourteen observations of critically ill patients' transfers from three rural community hospitals to a tertiary centre and twenty-three subsequent handover events and the analysis of transfer documents from four hospital settings (e.g. one regional hospital and three rural community hospitals) in Thailand. Translation from Thai into English and back translation into vernacular language was required. Inductive, thematic analysis was conducted to identify major themes by using qualitative data analysis software, NVivo 10 to assist data management during the analysis. Results: Five major themes emerged including (i) protective factors influencing safe transfer care, (ii) barrier factors influencing safe transfer care, (iii) behavioural patterns in transfer care processes, (iv) maintaining the health condition of the patients, and (v) overcoming adverse events. These particular themes elaborate the meaning of the quality and patient safety of transfer care, the provision of care for safe transfer care, and significant contextual factors that influence the quality of inter-hospital transfer care for critically ill patients. In addition, Donabedian's model (Donabedian, 1966, 1988) incorporated within the concept of context and culture was utilised to assist in conceptualising the framework for the quality of inter-hospital transfer care of critically ill patients in Thailand. Conclusion: The Donabedian model is useful as it is simple, but it does not include detail of the organisational context and culture as determinants of care quality. A conceptual framework for the quality of inter-hospital transfer care of critically ill patients in Thailand was therefore proposed. This study has expanded on current theoretical knowledge of the quality of inter-hospital transfer care by elaborating the patterns of thought and the behaviour of transfer nurses during provision of care throughout the processes of the inter-hospital transfer. It also highlights the limitations of organisational structure and the environment in which transfer work takes place, including issues on handover processes in hospital transfer care. The results can be useful to transfer nurses in that they facilitate greater understanding of the provision of better quality of care. They also help to inform hospital policy makers how to ensure safety of critically ill patients being transferred from community hospital settings.

Exposure to antibiotics is an important factor influencing the development of bacterial resistance.  In an era where very few new antibiotics are being developed, a strategy for the development of optimal dosing regimen and combination treatment that reduces the rate of resistance development and overcome existing resistance is of utmost importance. In addition, the optimal dosing in subpopulations is often not fully elucidated. The aim of this thesis was to develop pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PKPD) models that characterize the interaction of antibiotics with bacterial growth, killing and resistance over time, and can be applied to guide optimization of dosing regimens that enhance the efficacy of mono- and combination antibiotic therapy. A mechanism-based PKPD model that incorporates the growth, killing kinetics and adaptive resistance development in Escherichia coli against gentamicin was developed based on  in vitro time-kill curve data. After some adaptations, the model was successfully applied for similar data on colistin and meropenem alone, and in combination, on one wild type and one meropenem-resistant strain of Pseudomonas aeruginosa. The developed population PK model for colistin and its prodrug colistin methanesulfonate (CMS) in combination with the PKPD model showed the benefits for applying a loading dose for this drug. Simulations predicted the variability in bacteria kill to be larger between dosing occasions than between patients. A flat-fixed loading dose followed by an 8 or 12 hourly maintenance dose with infusion duration of up to 2 hours was shown to result in satisfactory bacterial kill under these conditions. Pharmacometric models that characterize the time-course of drug concentrations, bacterial growth, antibacterial killing and resistance development were successfully developed. Predictions illustrated how PKPD models based on in vitro data can be utilized to guide development of antibiotic dosing, with examples advocating regimens that (i) promote bacterial killing and reduce risk for toxicity in preterm and term newborn infants receiving gentamicin, (ii) achieve a fast initial bacterial killing and reduced resistance development of colistin in critically ill patients by application of a loading dose, and (iii) overcome existing meropenem resistance by combining colistin and meropenem

A presente tese explora aspectos importantes do suporte nutricional, no paciente crítico: método e vias de administração da nutrição enteral, determinação do gasto energético, monitorização da adequação do suporte nutricional e seu efeito sobre os desfechos em curto e longo prazo. Em face da evidência de benefícios significativos, a nutrição enteral é recomendada como a primeira opção para a maioria dos pacientes, quando comparada à nutrição parenteral. É comum a intolerância gástrica associada ao uso de opióides, choque e vasopressores, o que reduz a entrega de energia e talvez aumente a incidência de pneumonia hospitalar. A subalimentação parece estar associada com consequências indesejáveis, que incluem o risco aumentado de infecção, o desmame da ventilação prolongada, o tempo de internação na UTI e as taxas elevadas de mortalidade, na UTI e no hospital. A determinação do gasto energético é alvo de debates, pois vários são os fatores que influenciam diretamente o gasto energético do paciente crítico. O método calorimetria indireta é apontado como o mais preciso para adequar o suporte nutricional, quando comparado com as equações preditivas. Vale destacar, porém, que ainda é necessária maior evidência clínica sobre a real influência da calorimetria indireta nos desfechos clínicos (Tempo em VM, tempo de UTI e mortalidade em UTI, mortalidade hospitalar). Os estudos avaliam os desfechos clínicos mais relevantes, em curto prazo, e há uma escassez de estudos que avaliam a qualidade de vida dos sobreviventes, em médio ou longo prazo. Para a realização da tese, foram desenvolvidos três estudos, um ensaio clínico randomizado, em que foi definida a incidência de pneumonia e avaliada a taxa de mortalidade na UTI, comparando a nutrição por sonda gástrica com a por sonda jejunal. Não encontramos diferença na taxa de pneumonia, quando é utilizada a sonda em posição gástrica ou jejunal. Não observamos diferenças na sobrevida na UTI e hospitalar. Em nossa revisão sistemática, analisamos quatro artigos da literatura sobre paciente crítico adulto e adequação do suporte nutricional guiado pela calorimetria indireta, de 1950 a maio de 2014. Não encontramos estudos suficientes para evidenciar o impacto da utilização da calorimetria indireta, como método de adequação do suporte nutricional sobre os desfechos clínicos. Realizamos estudo observacional, onde procuramos definir as relativas contribuições da adequação nutricional maior ou igual a 70%, em relação ao previsto nas primeiras 72 horas de internação na UTI, para os desfechos clínicos em curto e longo prazo (capacidade de realizar atividades da vida diária). Os pacientes que receberam um aporte calórico igual ou superior a 70%, nas primeiras 72 horas de internação, não apresentaram melhores desfechos em curto prazo (tempo em VM, tempo de UTI e mortalidade em UTI), bem como melhora da capacidade funcional em um ano. Esta tese se justifica por buscar melhor entendimento dos principais aspectos do suporte nutricional enteral, no paciente crítico, mecanicamente ventilado e submetido à terapia intensiva. Como aspectos da terapia nutricional, destacamos a importância de investigar evidências clínicas do impacto do suporte nutricional enteral sobre desfechos clínicos. / This thesis explores important aspects of nutritional support in critically ill patients: method and routes for enteral nutrition administration; determining energy expenditure; monitoring the optimal nutritional support and its effect on short- and long-term outcomes. Given the evidence of significant benefits, enteral nutrition is recommended as the first choice for most patients compared to parenteral nutrition. Gastric intolerance associated with opioid use, shock, and vasopressors is common, which reduces energy delivery and may increase the incidence of hospital-acquired pneumonia. Malnutrition appears to be associated with undesirable consequences, including increased risk of infection; weaning from prolonged ventilation; length of stay in ICU; and high mortality rates in ICU and hospital. Determining energy expenditure is subject to debate because several factors directly influence it for critically ill patients. The method of indirect calorimetry is pointed out as the most accurate for establishing adequate nutritional support compared with predictive equations. It is worth noting, however, that more clinical evidence is needed on the real influence of indirect calorimetry on clinical outcomes (length of ventilation; length of stay in ICU and mortality in ICU; hospital mortality). The studies evaluate the most relevant clinical outcomes in the short term, and there is shortage of works assessing survivors’ quality of life in the medium or long term. Three studies were developed for the thesis: a randomized clinical trial where the incidence of pneumonia was established and the mortality rate in ICU was evaluated, comparing nutrition by gastric gavage with a jejunal probe. No difference was found in the rate of pneumonia when using the gavage in gastric or jejunal position. No differences in survival in ICU and hospital were found. In our systematic review, we analyze four articles on critically ill adult patients and optimization of nutritional support guided by indirect calorimetry, from 1950 to May 2014. We did not find enough studies to show the impact of using indirect calorimetry for optimizing nutritional support on clinical outcomes. We conducted an observational study to define the relative contributions of nutritional optimization higher or equal to 70% relative to predictions in the first 72 hours of ICU admission for clinical outcomes in the short and long term (ability to perform daily activities). Patients who received caloric intake equal to or higher than 70% in the first 72 hours of admission did not show better outcomes in the short term (time under MV, ICU stay, and ICU mortality) as well as improved functional capacity within one year. This thesis is justified for seeking to improve understanding of the key aspects of enteral nutritional support in critically ill, mechanically ventilated patients who have underwent intensive therapy. Important aspects of nutrition therapy include investigating clinical evidence of the impact of enteral nutritional support on clinical outcomes.

A presente tese explora aspectos importantes do suporte nutricional, no paciente crítico: método e vias de administração da nutrição enteral, determinação do gasto energético, monitorização da adequação do suporte nutricional e seu efeito sobre os desfechos em curto e longo prazo. Em face da evidência de benefícios significativos, a nutrição enteral é recomendada como a primeira opção para a maioria dos pacientes, quando comparada à nutrição parenteral. É comum a intolerância gástrica associada ao uso de opióides, choque e vasopressores, o que reduz a entrega de energia e talvez aumente a incidência de pneumonia hospitalar. A subalimentação parece estar associada com consequências indesejáveis, que incluem o risco aumentado de infecção, o desmame da ventilação prolongada, o tempo de internação na UTI e as taxas elevadas de mortalidade, na UTI e no hospital. A determinação do gasto energético é alvo de debates, pois vários são os fatores que influenciam diretamente o gasto energético do paciente crítico. O método calorimetria indireta é apontado como o mais preciso para adequar o suporte nutricional, quando comparado com as equações preditivas. Vale destacar, porém, que ainda é necessária maior evidência clínica sobre a real influência da calorimetria indireta nos desfechos clínicos (Tempo em VM, tempo de UTI e mortalidade em UTI, mortalidade hospitalar). Os estudos avaliam os desfechos clínicos mais relevantes, em curto prazo, e há uma escassez de estudos que avaliam a qualidade de vida dos sobreviventes, em médio ou longo prazo. Para a realização da tese, foram desenvolvidos três estudos, um ensaio clínico randomizado, em que foi definida a incidência de pneumonia e avaliada a taxa de mortalidade na UTI, comparando a nutrição por sonda gástrica com a por sonda jejunal. Não encontramos diferença na taxa de pneumonia, quando é utilizada a sonda em posição gástrica ou jejunal. Não observamos diferenças na sobrevida na UTI e hospitalar. Em nossa revisão sistemática, analisamos quatro artigos da literatura sobre paciente crítico adulto e adequação do suporte nutricional guiado pela calorimetria indireta, de 1950 a maio de 2014. Não encontramos estudos suficientes para evidenciar o impacto da utilização da calorimetria indireta, como método de adequação do suporte nutricional sobre os desfechos clínicos. Realizamos estudo observacional, onde procuramos definir as relativas contribuições da adequação nutricional maior ou igual a 70%, em relação ao previsto nas primeiras 72 horas de internação na UTI, para os desfechos clínicos em curto e longo prazo (capacidade de realizar atividades da vida diária). Os pacientes que receberam um aporte calórico igual ou superior a 70%, nas primeiras 72 horas de internação, não apresentaram melhores desfechos em curto prazo (tempo em VM, tempo de UTI e mortalidade em UTI), bem como melhora da capacidade funcional em um ano. Esta tese se justifica por buscar melhor entendimento dos principais aspectos do suporte nutricional enteral, no paciente crítico, mecanicamente ventilado e submetido à terapia intensiva. Como aspectos da terapia nutricional, destacamos a importância de investigar evidências clínicas do impacto do suporte nutricional enteral sobre desfechos clínicos. / This thesis explores important aspects of nutritional support in critically ill patients: method and routes for enteral nutrition administration; determining energy expenditure; monitoring the optimal nutritional support and its effect on short- and long-term outcomes. Given the evidence of significant benefits, enteral nutrition is recommended as the first choice for most patients compared to parenteral nutrition. Gastric intolerance associated with opioid use, shock, and vasopressors is common, which reduces energy delivery and may increase the incidence of hospital-acquired pneumonia. Malnutrition appears to be associated with undesirable consequences, including increased risk of infection; weaning from prolonged ventilation; length of stay in ICU; and high mortality rates in ICU and hospital. Determining energy expenditure is subject to debate because several factors directly influence it for critically ill patients. The method of indirect calorimetry is pointed out as the most accurate for establishing adequate nutritional support compared with predictive equations. It is worth noting, however, that more clinical evidence is needed on the real influence of indirect calorimetry on clinical outcomes (length of ventilation; length of stay in ICU and mortality in ICU; hospital mortality). The studies evaluate the most relevant clinical outcomes in the short term, and there is shortage of works assessing survivors’ quality of life in the medium or long term. Three studies were developed for the thesis: a randomized clinical trial where the incidence of pneumonia was established and the mortality rate in ICU was evaluated, comparing nutrition by gastric gavage with a jejunal probe. No difference was found in the rate of pneumonia when using the gavage in gastric or jejunal position. No differences in survival in ICU and hospital were found. In our systematic review, we analyze four articles on critically ill adult patients and optimization of nutritional support guided by indirect calorimetry, from 1950 to May 2014. We did not find enough studies to show the impact of using indirect calorimetry for optimizing nutritional support on clinical outcomes. We conducted an observational study to define the relative contributions of nutritional optimization higher or equal to 70% relative to predictions in the first 72 hours of ICU admission for clinical outcomes in the short and long term (ability to perform daily activities). Patients who received caloric intake equal to or higher than 70% in the first 72 hours of admission did not show better outcomes in the short term (time under MV, ICU stay, and ICU mortality) as well as improved functional capacity within one year. This thesis is justified for seeking to improve understanding of the key aspects of enteral nutritional support in critically ill, mechanically ventilated patients who have underwent intensive therapy. Important aspects of nutrition therapy include investigating clinical evidence of the impact of enteral nutritional support on clinical outcomes.

BACKGROUND:Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.METHODS:We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients".RESULTS:Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.CONCLUSION:Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Introdução: Há poucos estudos avaliando qualidade de vida relacionada à saúde (QVRS) e anos de vida ajustados para qualidade de vida (QALY) em pacientes com câncer que necessitam internação em unidades de terapia intensiva. O objetivo deste estudo foi avaliar sobrevida, QVRS e QALY durante o seguimento a longo prazo de pacientes com câncer internados em UTI. Métodos: Realizamos uma coorte prospectiva de pacientes com câncer admitidos em duas UTIs do estado de São Paulo. Coletamos dados na admissão da UTI, incluindo QVRS antes da doença aguda que motivou internação em UTI e no seguimento em 15 dias, 3 meses, 6 meses, 12 meses e 18 meses para avaliar a QVRS e status vital. Adicionalmente, o status vital foi avaliado em 24 meses. QVRS foi determinada com o questionário EQ-5D-3L. A sobrevida foi calculada com o estimador de Kaplan-Meier e o QALY com uma adaptação do estimador Zhao e Tsiatis. Resultados: Foram incluídos 792 pacientes. A média de idade foi 61,6±14,3 anos, 42,5% dos pacientes eram do sexo feminino e metade foi admitida após cirurgia eletiva. A média do escore SAPS3 foi 47,4±15.6. A probabilidade de sobreviver 12 e 18 meses foi 42.4% e 38.1%, respectivamente. A média do índice de utilidade da QVRS antes da internação na UTI foi 0,47±0,43, aos 15 dias pós-admissão a UTI 0,41±0,44, aos 3 meses 0,56±0,42, aos 6 meses 0,60±0,41, aos 12 meses 0,67±0,35 e aos 18 meses 0,67±0,35. A probabilidade de atingir 12 e 18 meses de vida ajustados para qualidade de vida foi de 30.1% e 19.1%, respectivamente. Houve diferenças estatisticamente significativas do tempo de sobrevida e QALY conforme as características de base consideradas (admissão após cirurgia eletiva, cirurgia de urgência ou clínica; SAPS3; extensão do câncer; status do câncer; cirurgia prévia; quimioterapia prévia; radioterapia prévia; capacidade funcional; e QVRS prévia). No entanto, apenas QVRS prévia e capacidade funcional foram associados a QVRS ao longo do seguimento de 18 meses. Conclusão: Em pacientes com câncer admitidos em UTI, a sobrevida, QVRS e QALY a longo prazo são limitados. Entretanto, há bastante variabilidade entre os pacientes nestes desfechos clínicos que é associada a características simples presentes na admissão à UTI e que podem auxiliar a equipe de saúde a avaliar o prognóstico / Introduction: Only few studies assessed health-related quality of life (HRQOL) and quality-adjusted life years (QALY) of cancer patients admitted to intensive care units (ICU). We aimed to assess the long-term HRQOL and QALY of cancer patients admitted to ICUs. Methods: We conducted a prospective cohort study of cancer patients admitted to two ICUs from the state of São Paulo, Brazil. We assessed the HRQOL with the EQ-5D-3L before ICU admission, 15 days, 3, 6, 12 and 18 months. In addition, the vital status was assessed at 24 months. Survival was calculated with the Kaplan-Meier estimator and QALY with the adapted Zhao and Tsiatis estimator. Results: The mean age of the subjects was 61.6 ± 14.3 years, 42.5% were female and half were admitted after elective surgery. The mean Simplified Acute Physiology Score (SAPS) 3 was 47.4 ± 15.6. Survival at 12 and 18 months was 42.4% and 38.1%, respectively. The mean EQ5D utility measure before admission to the ICU was 0.47±0.43, at 15 days it was 0.41±0.44, at 90 days 0.56±0.42, at 6 months 0.60±0.41, at 12 months 0.67±0.35 and at 18 months 0.67±0.35. The probabilities for attaining 12 and 18 months of quality-adjusted survival were 30.1% and 19.1%, respectively. There were statistically significant differences in survival time and QALYs according to all assessed baseline characteristics (ICU admission after elective surgery, emergency surgery or medical admission; SAPS3; cancer extension; cancer status; previous surgery; previous chemotherapy; previous radiotherapy; performance status; and previous HRQOL). Only the previous HRQOL and performance status were associated with the HRQOL during the 18-month follow-up. Conclusion: Long-term HRQOL, survival and QALY expectancy of cancer patients admitted to the ICU are limited. Nevertheless, these clinical outcomes exhibit wide variability among patients and are associated with simple characteristics present at the time of ICU admission, which may help healthcare professionals estimate patients\' prognose