OBJETIVOS: O objetivo do estudo foi avaliar se a transfusão de hemácias no intraoperatório de cirurgia cardíaca com circulação extracorpórea está associada a complicações clínicas incluindo choque cardiogênico, arritmia, insuficiência renal aguda, isquemia miocárdica, choque séptico, necessidade de reintubação orotraqueal, acidente vascular cerebral ou mortalidade durante a internação hospitalar. DESENHO: Estudo clínico de coorte retrospectivo e unicêntrico com escore de propensão, realizado no Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. PACIENTES: Pacientes adultos submetidos à cirurgia cardíaca eletiva com circulação extracorpórea no período de janeiro de 2004 a dezembro de 2008. DESFECHO PRIMÁRIO: Complicações clínicas durante a internação hospitalar (choque cardiogênico, arritmia, insuficiência renal aguda, isquemia miocárdica, choque séptico, necessidade de reintubação orotraqueal, acidente vascular cerebral ou mortalidade hospitalar). DESFECHO SECUNDÁRIO: 1- Avaliar o efeito da transfusão de hemácias no intraoperatório no tempo livre de inotrópicos e vasopressores, tempo de ventilação mecânica e tempo de permanência na UTI e internação hospitalar. 2- Avaliar o efeito do número das unidades de hemácias transfundidas no intraoperatório na ocorrência de mortalidade hospitalar, choque cardiogênico, arritmia, isquemia miocárdica, choque séptico, acidente vascular cerebral e reintubação orotraqueal. 3- Avaliar o efeito da anemia à admissão e durante internação hospitalar na ocorrência de complicações pós-operatórias. INTERVENÇÃO: Não houve intervenção. RESULTADOS: Foram incluídos 2851 pacientes na análise final, dos quais 1471(51,6%) foram expostos a transfusão de hemácias e 1380 (48,4%) não receberam transfusão no intraoperatório. Os pacientes transfundidos apresentaram maior incidência das seguintes complicações: mortalidade (2,1% vs 0,4%, P < 0,001), insuficiência renal aguda (9,1% vs 3,9%, P<0,001), reintubação orotraqueal (3,8% vs 1,4%, P < 0,001) e choque séptico (2,2% vs 0,4%, P < 0,001). Os pacientes transfundidos também apresentaram maior tempo de internação hospitalar [16 dias (12-23) vs 13 dias (9-18), P < 0,001] e em unidade de terapia intensiva [3 dias (2-6) vs 2 dias (2-4), P < 0,001]. A concentração da hemoglobina menor que 9 g/dL ocorreu em 1847 pacientes (64,7%) durante a internação hospitalar e foi associada a maior risco de insuficiência renal aguda e de acidente vascular cerebral. O escore de propensão identificou 588 pacientes pareados em relação à exposição à transfusão, e essa análise demonstrou que a transfusão intraoperatória de hemácias não aumentou a ocorrência de complicações no período de internação hospitalar. Contudo a transfusão de 4 ou mais unidades de hemácias está associada a maior ocorrência de mortalidade hospitalar, choque cardiogênico e IRA, maior incidência de reintubação orotraqueal, choque séptico e AVC. Além de uma relação direta entre as unidades de hemácias transfundidas e a ocorrência de morte. CONCLUSÃO: Esse estudo observacional demonstrou que a anemia é frequentemente detectada no pós-operatório de cirurgia cardíaca, e está associada a maior incidência de complicações. Além disso, a transfusão de hemácias no intraoperatório não modifica a ocorrência das complicações pós-operatórias em pacientes submetidos a cirurgia cardíaca. No entanto a transfusão de 4 ou mais hemácias está associada a maior incidência de complicações clínicas, além de uma relação dose-dependente. Estratégias como detecção precoce de anemia e emprego de técnicas alternativas à transfusão no manejo devem ser estimuladas no ambiente perioperatório / OBJECTIVE: The objective of this study was to evaluate whether the transfusion of red blood cells in the intraoperative cardiac surgery with extracorporeal circulation is associated with complications after cardiac surgery. DESIGN: A retrospective cohort study with a propensity score analysis, performed at Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. PATIENTS: Adult patients undergoing elective cardiac surgery with cardiopulmonary bypass in the period of January to 2008 December. PRIMARY OUTCOME: Clinical complications during hospital stay (cardiogenic shock, arrhythmia, cardiogenic shock, acute kidney injury, myocardial ischemia, septic shock, tracheal reintubation, stroke or hospital mortality). SECONDARY OUTCOME: 1- Evaluate the effect of intraoperative red blood cell transfusion in inotropic and vasopressor free time, mechanical ventilation time, length of ICU stay and hospital stay. 2- Evaluate the effect of the number of units of transfused red blood cells intraoperatively on the occurrence of hospital mortality, cardiogenic shock, arrhythmia, myocardial ischemia, septic shock, stroke and orotracheal reintubation. 3- Evaluate the effect of anemia on admission and during hospitalization in the occurrence of postoperative complications. RESULTS: In the final analysis, 2851 patients were included. Of these patients, 1471(51.6%) were exposed to red blood cell transfusion (RBC) and 1380 (48.4%) were not exposed to RBC during intraoperative. Transfused patients had higher incidence of the following complications: mortality (2.1% vs. 0.4%, P < 0.001), acute kidney injury (9.1% vs. 3.9%, P < 0,001), tracheal reintubation (3.8% vs. 1.4%, P < 0.001) and septic shock (2.2% vs. 0.4%, P < 0.001). Transfused patients also had a longer length of hospital stay [16 days (12-23) vs. 13 days (9-18), P<0.001] and prolonged intensive care unit stay [3 days (2-6) vs. 2 days (2-4), P < 0.001]. Hemoglobin lower than 9 g/dL was found in 1847 patients (64.7%) during hospital stay and was associated to a higher risk of acute kidney injury and stroke. The propensity score identified 588 paired patients in relation to transfusion exposure, and this analysis demonstrated that intraoperative transfusion of red blood cells did not increase the occurrence of complications during hospitalization. However, transfusion of 4 or more units of red blood cells is associated with a higher occurrence of hospital mortality, cardiogenic shock and acute renal failure, a higher incidence of orotracheal reintubation, septic shock and stroke. In addition to a direct relationship between the units of transfused red blood cells and the occurrence of death. CONCLUSIONS: This observational study demonstrated that anemia is frequently detected in the postoperative period of cardiac surgery, and is associated with a higher incidence of complications. In addition, red blood cell transfusion in the intraoperative does not modify the occurrence of postoperative complications in patients undergoing cardiac surgery. However, transfusion of 4 or more erythrocytes is associated with a higher incidence of clinical complications, in addition to a dose-dependent relationship. Strategies such as early detection of anemia and use of alternative techniques to transfusion in management should be stimulated in the perioperative environment

Introdução: A obesidade é uma doença crônica de incidência global e crescente que se tornou nas últimas décadas um dos maiores problemas de saúde pública nas sociedades urbanas. A intervenção cirúrgica, ou cirurgia bariátrica, tem sido apontada como eficaz no tratamento das formas graves de obesidade e a derivação gástrica em Y de Roux (DGYR) é o tipo mais realizado no mundo e no Brasil. O acompanhamento contínuo de todos os indivíduos submetidos à DGYR por equipe multidisciplinar é recomendado por se tratar de uma cirurgia de grande porte com riscos de complicações em longo prazo, entre elas as deficiências nutricionais. Por isso, as consultas nutricionais pós-operatórias são um componente importante desse seguimento. Objetivos: Estimar a prevalência de adesão ao seguimento nutricional ambulatorial pós-cirurgia bariátrica e avaliar a associação dessa adesão com fatores selecionados em um grupo de obesos moderados com comorbidades e obesos mórbidos submetidos à DGYR. Métodos: Estudo de coorte retrospectiva utilizando-se dados de prontuários hospitalares de 241 adultos de ambos os sexos submetidos à derivação gástrica pelo Sistema Único de Saúde entre 2006 e 2008 no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Considerou-se aderente o indivíduo que compareceu a quatro ou mais consultas nutricionais nos 12 primeiros meses após a cirurgia. Para estimar a associação da adesão ao seguimento nutricional pós-cirúrgico com os fatores idade, sexo, estado conjugal, escolaridade, situação empregatícia, distância entre a residência e o hospital, estratégias para perda de peso no período pré-operatório, índice de massa corpórea (IMC) no précirúrgico imediato, presença de comorbidades e duração da internação após a cirurgia, foram calculadas as Razões de Prevalência (RP) e os intervalos de 95% de confiança (IC 95%); para a análise ajustada utilizou-se regressão múltipla de Poisson. Resultados: A população de estudo foi caracterizada pelo predomínio de mulheres (80,9%), pela média de idade de 44,4 anos (±11,6), pela média de IMC pré-operatório de 47,2kg/m2 (±6,16) e 78,4% dos participantes apresentaram uma ou mais comorbidades. Convivência com companheiro foi relatada por 51,5% da população, 41,9% referiram ter ensino fundamental incompleto como nível de escolaridade, 50,9% não possuíam atividade remunerada, 44,7% residiam à distância de até 16 km do hospital e 11,6% ficaram internados por seis ou mais dias após a cirurgia. A prevalência de adesão nessa população foi de 56,0% (IC 95% 49,7-62,3). A análise multivariada revelou que somente duração da internação maior ou igual a seis dias foi associada à adesão ao seguimento nutricional pós-cirúrgico (RP=1,46 IC 95% 1,15-1,86). Conclusões: A prevalência de adesão encontrada nesta população foi semelhante às dos estudos internacionais, mas menor do que a prevalência mínima de 75% recomendada para que o centro seja reconhecido como de excelência em cirurgia bariátrica. Os indivíduos que ficaram internados por mais tempo no pós-cirúrgico mostraram-se significantemente mais aderentes ao seguimento nutricional, podendo sugerir que o maior contato desses com a equipe multiprofissional pode ter contribuído para aumentar a percepção da gravidade da doença e da necessidade de cuidados contínuos com a saúde, e consequentemente ter levado à maior assiduidade às consultas ambulatoriais / Introduction: Obesity is a global chronic disease with increasing incidence during the past decades and has become one of the major public health problems in the urban societies. The surgical intervention, or bariatric surgery, has been considered as an effective treatment of the severe forms of obesity and the Roux-en-Y gastric bypass (RYGB) has been the commonest surgical procedure worldwide, including in Brazil. The long term outpatient postoperative follow up after bariatric surgery by a multidisciplinary team has been recommended to all individuals submitted to RYGB because it is a major surgery which can cause complications such as nutritional deficiencies. Therefore, nutritional assessment in the postoperative period is an important component of the follow up. Objectives: To estimate the prevalence of adherence to outpatient postoperative nutritional follow up after bariatric surgery and to analyze the association between adherence and selected factors in a group of moderately obese with comorbidities and morbidly obese adults who underwent RYGB. Methods: Retrospective cohort study using data from hospital records of 241 adults of both sexes who were submitted to RYGB by the Unified Health System between 2006 and 2008 at the Hospital das Clínicas - Medical School, University of São Paulo. It was considered adherent the individuals who attended four or more nutritional appointments in the first 12 months after surgery. To estimate the association between adherence to postoperative nutritional follow up and factors such us age, sex, marital status, education, employment status, distance between home and hospital, strategies for weight loss in the preoperative period, body mass index (BMI) in the immediate pre-surgical, presence of comorbidities and duration of hospitalization after surgery, were calculated the Prevalence Ratios (PR) and the 95% confidence intervals (95% CI); for the adjusted analysis, Poisson multiple regression was used. Results: The study population was characterized by the predominance of women (80.9%), the mean age of 44.4 years (±11.6), the mean of preoperative BMI of 47.2kg/m2 (±6.16) and 78.4% of participants presented one or more comorbidities. Living with partner was reported by 51.5% of the population, 41.9% had incomplete primary education level, 50.9% had no paid work, 44.7% lived at a distance of up to 16km to the hospital and 11.6% were hospitalized for six or more days after surgery. The prevalence ratio of adherence in this population was 56.0% (95% CI 49.7- 62.3). Multivariate analysis revealed that only length of hospital stay greater than or equal to six days was associated with adherence to nutritional follow up in the postoperative period (PR=1.46 95% CI 1.15-1.86). Conclusions: The prevalence of adherence found in this population was similar to those of international studies, but less than the minimum prevalence of 75% recommended for services to be recognized as a bariatric surgery center of excellence. Individuals who were hospitalized for longer than six days after surgery were significantly more adherent to the nutritional follow-up. This may have happened because they had longer contact with the multidisciplinary team which may have contributed to increase their perception of disease severity and the need for long term health care, and consequently, it may have led to higher assiduity to the nutritional appointments

Le cancer demeure en France un problème majeur de santé publique : Cette pathologie reste la principale cause de mortalité, avec près de 150 000 décès chaque année. Afin de lutter contre cette maladie, le plan cancer 2014-2019 a posé comme objectif de développer la recherche clinique, en incluant dès 2019 au moins 50 000 patients par an dans des essais thérapeutiques. La recherche clinique en oncologie est en plein essor depuis l’avènement de thérapies telles que les thérapies moléculaires ciblées ou l’immunothérapie. Le nombre de nouveaux médicaments en développement en oncologie a augmenté de façon exponentielle depuis les années 2000. Il en découle un accroissement important du nombre de publications d’études en oncologie. L’analyse d’une étude n’est possible que si son schéma expérimental, sa réalisation et ses conditions d’analyse sont clairement décrits dans l’article publié. Le reporting est le fait de décrire dans une publication toutes les actions, notamment d’ordre méthodologiques, réalisées au cours de l’étude. 5 revues systématiques de la littérature ont été réalisées afin d’analyser le reporting des articles d’études en oncologie. La première étude a objectivé que la littérature était pauvre en articles analysant le reporting des études observationnelles (2% des publications) et que le reporting intrinsèque des revues systématiques récentes portant sur le sujet était exhaustif (score OQSR moyen (2010-2014) = 10, écart-type =2). 826 articles d’études ont été analysés dans la deuxième revue systématique, dont 84.5% d’études observationnelles. Les reporting des variables et du critère de jugement principal étaient clairs, respectivement dans 100% et 85.2% des cas. Une discordance de reporting pour le test statistique principal utilisé, entre les parties Méthodes et Résultats, a été identifié dans 23 articles. La troisième revue systématique a mis un évidence un manque de données sur le reporting des essais de phase II en oncologie (13 articles) et 3 scores d’évaluation du reporting avaient été décrits : score OQS, score KMS et score d’index de qualité. 557 publications d’essais de phase II ont été étudiées dans la quatrième revue systématique. Le score de reporting KMS était égal à 0, 1, 2, 3 respectivement pour 3,9%, 21,4%, 48,5% et 26,2% articles. En analyse multivariée, les 3 variables associées à la valeur du score KMS étaient : Le reporting clair du design statistique (OR = 2.22; IC 95% [1.36-3.65] ; p <0.001), l’essai monocentrique (OR = 0.25 [0.09 – 0.74] ; p = 0.012) et l’analyse menée per protocole (OR = 0.48; IC 95% [0.32 -0.72] ; p <0.001). La dernière revue systématique a porté sur 557 articles d’essais de phase II. 182 des essais de phase II (32.7%) ont abouti à la réalisation d’un essai de phase III, dont 57 avaient un critère de jugement principal positif et statistiquement significatif. En conclusion, le reporting des études en oncologie reste perfectible. Les points d’optimisation relevés sont l’élaboration de recommandations de reporting spécifique aux essais de phase II en oncologie et l’adhésion de l’ensemble des journaux médicaux aux différentes recommandations de reporting / Cancer remains a major public health problem in France : This pathology is the leading cause of death, with nearly 150,000 deaths each year. In order to fight against this disease, the 2014-2019 French cancer plan set the goal of developing clinical research, including at least 50,000 patients per year in 2019 in therapeutic trials. Clinical research in oncology has been booming since the advent of therapies such as targeted molecular therapies or immunotherapy. The number of new drugs being developed in oncology has increased exponentially since the 2000s, resulting in a significant increase in the number of oncology study publications. The analysis of a study is possible only if its experimental design, its realization and its conditions of analysis are clearly described in the published article. Reporting is the process of describing in a publication all the actions, including methodological ones, carried out during the study. 5 systematic reviews were conducted to analyze the reporting of oncology study articles. The first study showed that the literature was poor in articles analyzing the reporting of observational studies (2% of publications) and that the intrinsic reporting of recent systematic reviews on the subject was exhaustive (average OQSR score (2010-2014) = 10, standard deviation = 2). 826 articles of study were analyzed in the second systematic review, 84.5% of which were observational studies. The reporting of the variables and the primary endpoint were clear in 100% and 85.2% of the cases, respectively. A reporting discrepancy for the main statistical test used, between the Methods and Results parts, was identified in 23 articles. The third systematic review revealed a lack of data on the reporting of phase II trials in oncology (13 articles) and 3 reporting evaluation scores were described: OQS, KMS and quality index score. 557 phase II trial publications were reviewed in the fourth systematic review. The KMS reporting score was 0, 1, 2, 3 respectively for 3.9%, 21.4%, 48.5% and 26.2% publications. In multivariate analysis, the 3 variables associated with the KMS score were : Reporting of a clear statistical design (OR = 2.22, 95% CI [1.36-3.65], p <0.001), the single-center trial (OR = 0.25 [0.09 - 0.74], p = 0.012) and per protocol analysis (OR = 0.48, 95% CI [0.32-0.72], p <0.001). The last systematic review focused on 557 Phase II trial articles. 182 Phase II trials (32.7%) resulted in a Phase III trial, of which 57 had a positive and statistically significant primary endpoint. In conclusion, reporting of studies in oncology remains perfectible. Optimization points identified are the development of specific reporting recommendations for phase II trials in oncology and the adherence of all medical journals to the various reporting recommendations

A variety of atherosclerosis and cardiovascular disease (ASCVD) phenotypes are tightly linked to changes in the cardiac energy metabolism that can lead to a loss of metabolic flexibility and to unfavorable clinical outcomes. We conducted an association analysis of 31 ASCVD phenotypes and 97 whole blood amino acids, acylcarnitines and derived ratios in the LIFE-Adult (n = 9646) and LIFE-Heart (n = 5860) studies, respectively. In addition to hundreds of significant associations, a total of 62 associations of six phenotypes were found in both studies. Positive associations of various amino acids and a range of acylcarnitines with decreasing cardiovascular health indicate disruptions in mitochondrial, as well as peroxisomal fatty acid oxidation. We complemented our metabolite association analyses with whole blood and peripheral blood mononuclear cell (PBMC) gene-expression analyses of fatty acid oxidation and ketone-body metabolism related genes. This revealed several differential expressions for the heart failure biomarker N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in peripheral blood mononuclear cell (PBMC) gene expression. Finally, we constructed and compared three prediction models of significant stenosis in the LIFE-Heart study using (1) traditional risk factors only, (2) the metabolite panel only and (3) a combined model. Area under the receiver operating characteristic curve (AUC) comparison of these three models shows an improved prediction accuracy for the combined metabolite and classical risk factor model (AUC = 0.78, 95%-CI: 0.76–0.80). In conclusion, we improved our understanding of metabolic implications of ASCVD phenotypes by observing associations with metabolite concentrations and gene expression of the mitochondrial and peroxisomal fatty acid oxidation. Additionally, we demonstrated the predictive potential of the metabolite profile to improve classification of patients with significant stenosis.

Introdução: A ocorrência de episódios depressivos e abuso ou dependência de álcool após um evento agudo de insuficiência coronariana pode representar um marcador independente de mau prognóstico. Portanto, investigamos a presença de sintomas depressivos, transtorno depressivo maior (TDM) e abuso ou dependência de álcool em uma subamostra de uma coorte prospectiva de Síndrome Coronariana Aguda (SCA), Estratégia de Registro de Insuficiência Coronariana Aguda (ERICO) em andamento no pronto-socorro do Hospital Universitário. Métodos: Foi realizado um estudo observacional em 146 participantes do estudo ERICO. A gravidade dos sintomas depressivos foi avaliada em três momentos: 1ª) na admissão hospitalar pelo Patient Health Questionnaire (PHQ-9 itens); 2º) 30 dias pós-SCA pelo PHQ-9, Inventário de Depressão de Beck (BDI) e Escala de Depressão de Hamilton (HDRS-21 itens); e 3º) 180 dias pós-SCA pelo PHQ-9 e BDI. O abuso e uso nocivo de álcool foram avaliados pelo AUDIT e CAGE em 30 e 180 dias pós-SCA. Resultados: Ao longo do estudo as frequências de sintomas depressivos variaram entre 40% e 60% e de TDM entre 28% e 33%. Na admissão hospitalar houve maior predominância de sintomas depressivos entre os homens (58%; p=0,03) e sedentários (72,1%; p=0,02), entretanto, TDM foi mais frequente na população feminina (55,1%; p < 0,001) com uma razão de chances [(RC) 4,5; intervalo de confiança IC 95% 1,85-10,98]. Após 30 dias do evento agudo constatou-se um maior risco de sintomas depressivos entre os tabagistas (RC 5,8; IC 95% 1,81-18,72) e diabéticos (RC 3,6; IC 95% 1,40-9,60). Os diabéticos também apresentaram (RC 3,5; IC 95% 1,39-8,71) para desenvolver TDM. No seguimento de 180 dias verificou-se que indivíduos com angina instável (AI) (RC 4, 46; IC 95% 1,39-14,32) e infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCST) (RC 3,40; IC 95% 1,30-8,87) apresentaram maior probabilidade de desenvolverem sintomas depressivos em relação aos indivíduos que apresentaram IAMSST. Os únicos fatores de risco que se mantiveram associados a um maior risco de sintomas depressivos após 180 dias foi o sexo feminino (RC 3,9; IC 95% 1,54-9,73) e o tabagismo (RC 5,34; IC 95% 1,64-17,44). Em relação à TDM, encontramos uma RC de 14 (IC 95% 2,94-67,51) para associação com tabagismo. Quanto ao abuso e uso nocivo de álcool as frequências variaram ao longo do estudo pelo AUDIT e CAGE entre 18,3% e 33,6%. Verificamos na populacão masculina uma frequência de 88,2% (p=0,001) e entre os tabagistas de 55,9% (p=0,003) e foi encontrada uma RC de 51,64 para população mais jovem (35-44 anos) e uma RC de 42,95 para tabagistas. Finalmente, não foi encontrada nenhuma associação entre abuso de álcool e depressão de acordo com os subtipos de SCA nos períodos analisados. Conclusão: A frequência de depressão variou entre 40% e 60% da admissão até 180 dias pós-SCA. Indivíduos que desenvolveram AI ou IAMCST, além de mulheres e tabagistas apresentaram maiores chances de desenvolver depressão ao longo do seguimento de 180 dias e indivíduos entre 35 e 44 anos e tabagistas apresentaram maior possibilidade de abusar do álcool / Introduction: The occurrence of depression and alcohol abuse or dependence after an acute coronary insufficiency may represent an independent marker of poor prognosis. Therefore, we investigated the presence of depressive symptoms, major depressive disorder (MDD) and alcohol abuse or dependence in a subsample of a prospective cohort of Acute Coronary Syndrome (ACS), Strategy of Registry of Acute Coronary Syndrome Study (ERICO study), which is still ongoing in the emergency room of the Hospital Universitário. Methods: We conducted an observational study in 146 participants of the ERICO study. The severity of depressive symptoms was evaluated in 3 moments: 1st) at the hospital admission using The Patient Health Questionnaire (PHQ-9 items); 2nd) 30 days post-ACS using the PHQ-9, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS -21 items), and 3rd) 180 days post -ACS through PHQ-9 and BDI. The abuse and harmful alcohol consumption were assessed by the AUDIT and the CAGE 30 and 180 days post-ACS. Results: Along the study, the frequencies of depressive symptoms ranged from 40% to 60% and MDD from 28% to 33%. At the hospital admission there was a higher prevalence of depressive symptoms among men (58%, p= 0.03) and sedentary patients (72.1%, p= 0.02), however, MDD was higher among women (55.1%, p < 0.001) with an increased risk of [odds ratio [(OR) 4.5; confidence interval CI 95% 1.85-10.98]. After 30 days of the acute event, we observed an increased risk of depressive symptoms among smokers (OR 5.8; CI 95%, 1.81-18.72) and among diabetics (OR 3.6; CI 95%, 1.40-9.60) the diabetics were also more likely to develop MDD (OR 3.5; IC 95% 1,39-8,71). At 180 days follow-up, individuals with unstable angina (UA) (OR 4.46; CI 95% 1.39-14.32) and ST elevation myocardial infarction (STEMI) (OR 3.40; CI 95% 1.30-8.87) were more likely to develop depressive symptoms compared with patients who had NSTEMI. The only two factors that remained associated with a higher risk of depressive symptoms after 180 days were female gender (OR 3.9; CI 95% 1.54-9.73) and smokers (OR 5.34; CI 95% 1.64-17.44). Regarding MDD we found an OR of 14 (CI 95% 2.9-67.51) for smokers. In relation to abuse and hazardous consumption of alcohol, the frequencies for CAGE and AUDIT ranged from 18.3% to 33.6% along the study. We found among the male population a frequency of 88.2% (p=0.001) and smokers 55.9% (p=0.003). We also found OR of 51.64 among younger (aged 35-44 years) and OR of 42.95 for smokers. Finally, no association between alcohol abuse and depression according to ACS subtypes was observed. Conclusion: The prevalence of depression post-ACS ranged from 40% to 60% during the follow-up (admission hospital to 180 days). Individuals who developed UA or STEMI, besides women and smokers were more likely to develop depression during follow-up of 180 days and individual aged between 35-44 years and smokers were more likely to abuse of alcohol

This thesis examines philosophical controversies surrounding the evaluation of medical treatments, with a focus on the evidential roles of randomised trials and mechanisms in Evidence-Based Medicine. Current 'best practice' usually involves excluding non-randomised trial evidence from systematic reviews in cases where randomised trials are available for inclusion in the reviews. The first paper challenges this practice and evaluates whether adding of evidence from non-randomised trials might improve the quality and precision of some systematic reviews. The second paper compares the alleged methodological benefits of randomised trials over observational studies for investigating treatment benefits. It suggests that claims about the superiority of well-conducted randomised controlled trials over well-conducted observational studies are justified, especially when results from the two methods are contradictory. The third paper argues that postulating the unpredictability paradox in systematic reviews when no detectable empirical differences can be found requires further justification. The fourth paper examines the problem of absence causation in the context of explaining causal mechanisms and argues that a recent solution (Barros 2013) is incomplete and requires further justification. Solving the problem by describing absences as causes of 'mechanism failure' fails to take into account the effects of absences that lead to vacillating levels of mechanism functionality (i.e. differences in effectiveness or efficiency). The fifth paper criticises literature that has emphasised functioning versus 'broken' or 'non-functioning' mechanisms emphasising that many diseases result from increased or decreased mechanism function, rather than complete loss of function. Mechanistic explanations must account for differences in the effectiveness of performed functions, yet current philosophical mechanistic explanations do not achieve this. The last paper argues that the standard of evidence embodied in the ICE theory of technological function (i.e. testimonial evidence and evidence of mechanisms) is too permissive for evaluating whether the proposed functions of medical technologies have been adequately assessed and correctly ascribed. It argues that high-quality evidence from clinical studies is necessary to justify functional ascriptions to health care technologies. / <p>QC 20150312</p>

Objective: To determine whether continuity of care (COC) reduces emergency department (ED) visits and/or readmission in adolescents with psychiatric disorders. Methods: A retrospective cohort of adolescents discharged with psychiatric disorder between April 1, 2002 and March 1, 2004 was identified using hospital administrative databases. Good COC was defined as at least one aftercare contact in 30 days. Confounding by patient characteristics was adjusted for by propensity-score-matching of good and poor COC adolescents. Cox PH was used to analyze time to outcome. Results: 48.77% of adolescents had good COC. 38.39% of adolescents had ED visit or readmission in the year post-discharge. Good COC increased risk of readmission (HR = 1.38 (1.14 – 1.66)), but not of ED visits (HR = 1.14 (0.95 – 1.37)). Conclusions: COC increased risk of readmission by 38% but did not increase risk of ED visits. These findings are contextualized. Implications to adolescent mental health service delivery are discussed.

Objective: To determine whether continuity of care (COC) reduces emergency department (ED) visits and/or readmission in adolescents with psychiatric disorders. Methods: A retrospective cohort of adolescents discharged with psychiatric disorder between April 1, 2002 and March 1, 2004 was identified using hospital administrative databases. Good COC was defined as at least one aftercare contact in 30 days. Confounding by patient characteristics was adjusted for by propensity-score-matching of good and poor COC adolescents. Cox PH was used to analyze time to outcome. Results: 48.77% of adolescents had good COC. 38.39% of adolescents had ED visit or readmission in the year post-discharge. Good COC increased risk of readmission (HR = 1.38 (1.14 – 1.66)), but not of ED visits (HR = 1.14 (0.95 – 1.37)). Conclusions: COC increased risk of readmission by 38% but did not increase risk of ED visits. These findings are contextualized. Implications to adolescent mental health service delivery are discussed.

Introdução: A ocorrência de episódios depressivos e abuso ou dependência de álcool após um evento agudo de insuficiência coronariana pode representar um marcador independente de mau prognóstico. Portanto, investigamos a presença de sintomas depressivos, transtorno depressivo maior (TDM) e abuso ou dependência de álcool em uma subamostra de uma coorte prospectiva de Síndrome Coronariana Aguda (SCA), Estratégia de Registro de Insuficiência Coronariana Aguda (ERICO) em andamento no pronto-socorro do Hospital Universitário. Métodos: Foi realizado um estudo observacional em 146 participantes do estudo ERICO. A gravidade dos sintomas depressivos foi avaliada em três momentos: 1ª) na admissão hospitalar pelo Patient Health Questionnaire (PHQ-9 itens); 2º) 30 dias pós-SCA pelo PHQ-9, Inventário de Depressão de Beck (BDI) e Escala de Depressão de Hamilton (HDRS-21 itens); e 3º) 180 dias pós-SCA pelo PHQ-9 e BDI. O abuso e uso nocivo de álcool foram avaliados pelo AUDIT e CAGE em 30 e 180 dias pós-SCA. Resultados: Ao longo do estudo as frequências de sintomas depressivos variaram entre 40% e 60% e de TDM entre 28% e 33%. Na admissão hospitalar houve maior predominância de sintomas depressivos entre os homens (58%; p=0,03) e sedentários (72,1%; p=0,02), entretanto, TDM foi mais frequente na população feminina (55,1%; p < 0,001) com uma razão de chances [(RC) 4,5; intervalo de confiança IC 95% 1,85-10,98]. Após 30 dias do evento agudo constatou-se um maior risco de sintomas depressivos entre os tabagistas (RC 5,8; IC 95% 1,81-18,72) e diabéticos (RC 3,6; IC 95% 1,40-9,60). Os diabéticos também apresentaram (RC 3,5; IC 95% 1,39-8,71) para desenvolver TDM. No seguimento de 180 dias verificou-se que indivíduos com angina instável (AI) (RC 4, 46; IC 95% 1,39-14,32) e infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCST) (RC 3,40; IC 95% 1,30-8,87) apresentaram maior probabilidade de desenvolverem sintomas depressivos em relação aos indivíduos que apresentaram IAMSST. Os únicos fatores de risco que se mantiveram associados a um maior risco de sintomas depressivos após 180 dias foi o sexo feminino (RC 3,9; IC 95% 1,54-9,73) e o tabagismo (RC 5,34; IC 95% 1,64-17,44). Em relação à TDM, encontramos uma RC de 14 (IC 95% 2,94-67,51) para associação com tabagismo. Quanto ao abuso e uso nocivo de álcool as frequências variaram ao longo do estudo pelo AUDIT e CAGE entre 18,3% e 33,6%. Verificamos na populacão masculina uma frequência de 88,2% (p=0,001) e entre os tabagistas de 55,9% (p=0,003) e foi encontrada uma RC de 51,64 para população mais jovem (35-44 anos) e uma RC de 42,95 para tabagistas. Finalmente, não foi encontrada nenhuma associação entre abuso de álcool e depressão de acordo com os subtipos de SCA nos períodos analisados. Conclusão: A frequência de depressão variou entre 40% e 60% da admissão até 180 dias pós-SCA. Indivíduos que desenvolveram AI ou IAMCST, além de mulheres e tabagistas apresentaram maiores chances de desenvolver depressão ao longo do seguimento de 180 dias e indivíduos entre 35 e 44 anos e tabagistas apresentaram maior possibilidade de abusar do álcool / Introduction: The occurrence of depression and alcohol abuse or dependence after an acute coronary insufficiency may represent an independent marker of poor prognosis. Therefore, we investigated the presence of depressive symptoms, major depressive disorder (MDD) and alcohol abuse or dependence in a subsample of a prospective cohort of Acute Coronary Syndrome (ACS), Strategy of Registry of Acute Coronary Syndrome Study (ERICO study), which is still ongoing in the emergency room of the Hospital Universitário. Methods: We conducted an observational study in 146 participants of the ERICO study. The severity of depressive symptoms was evaluated in 3 moments: 1st) at the hospital admission using The Patient Health Questionnaire (PHQ-9 items); 2nd) 30 days post-ACS using the PHQ-9, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS -21 items), and 3rd) 180 days post -ACS through PHQ-9 and BDI. The abuse and harmful alcohol consumption were assessed by the AUDIT and the CAGE 30 and 180 days post-ACS. Results: Along the study, the frequencies of depressive symptoms ranged from 40% to 60% and MDD from 28% to 33%. At the hospital admission there was a higher prevalence of depressive symptoms among men (58%, p= 0.03) and sedentary patients (72.1%, p= 0.02), however, MDD was higher among women (55.1%, p < 0.001) with an increased risk of [odds ratio [(OR) 4.5; confidence interval CI 95% 1.85-10.98]. After 30 days of the acute event, we observed an increased risk of depressive symptoms among smokers (OR 5.8; CI 95%, 1.81-18.72) and among diabetics (OR 3.6; CI 95%, 1.40-9.60) the diabetics were also more likely to develop MDD (OR 3.5; IC 95% 1,39-8,71). At 180 days follow-up, individuals with unstable angina (UA) (OR 4.46; CI 95% 1.39-14.32) and ST elevation myocardial infarction (STEMI) (OR 3.40; CI 95% 1.30-8.87) were more likely to develop depressive symptoms compared with patients who had NSTEMI. The only two factors that remained associated with a higher risk of depressive symptoms after 180 days were female gender (OR 3.9; CI 95% 1.54-9.73) and smokers (OR 5.34; CI 95% 1.64-17.44). Regarding MDD we found an OR of 14 (CI 95% 2.9-67.51) for smokers. In relation to abuse and hazardous consumption of alcohol, the frequencies for CAGE and AUDIT ranged from 18.3% to 33.6% along the study. We found among the male population a frequency of 88.2% (p=0.001) and smokers 55.9% (p=0.003). We also found OR of 51.64 among younger (aged 35-44 years) and OR of 42.95 for smokers. Finally, no association between alcohol abuse and depression according to ACS subtypes was observed. Conclusion: The prevalence of depression post-ACS ranged from 40% to 60% during the follow-up (admission hospital to 180 days). Individuals who developed UA or STEMI, besides women and smokers were more likely to develop depression during follow-up of 180 days and individual aged between 35-44 years and smokers were more likely to abuse of alcohol

Les rhumatismes inflammatoires juvéniles sont des maladies chroniques débutant avant l’âge de 16 ans. Comprennent des pathologies classées dans un continuum, allant de la dérégulation de l’immunité innée à la dérégulation de l‘immunité adaptative. L’arthrite juvénile idiopathique (AJI) reste la plus fréquemment diagnostiqué. Les options thérapeutiques se sont élargies à partir des années 2000 avec le développement des thérapies ciblées, les biothérapies, associés aux traitements standard utilisés en rhumatologie pédiatrique (ex : anti-inflammatoires non stéroïdiens, corticostéroïdes, méthotrexate, et autres immunosuppresseurs). L’objectif de ce travail de thèse était d’estimer la relation bénéfice-risque des biothérapies utilisés dans les rhumatismes inflammatoires juvéniles à partir des essais cliniques randomisés (ECR) et d’explorer la tolérance à long cours à partir des essais observationnels. Premièrement, en utilisant une approche méta-analitique, les données des ECR en double aveugle contre placebo ou en ouvert dans l’AJI ont été analysées pour modéliser la relation bénéfice-risque des biothérapies avec le bénéfice net. Pour cela, l’efficacité clinique, mesuré par un score composite clinique et biologique (ACRped30), a été confronté à la tolérance clinique pendant la phase randomisée des ECR. Le critère de tolérance était la survenue d’un évènement indésirable (EI) grave (EIG). La balance bénéfice-risque reste favorable pour les biothérapies. Cependant, ces résultats sont limités par le suivi de faible durée, qui peut sous-estimer l’incidence des EI. Deuxièmement, nous avons conduit une étude observationnelle pour étudier la tolérance à moyen et long-terme des biothérapies utilisant les EI et les EIG décrits dans une base de données multicentrique rétrospective. La sécurité globale des biothérapies a été acceptable chez les enfants atteints de rhumatismes inflammatoires. Nous avons observé une variation des EIG au cours du temps et que la prescription concomitante des immunosuppresseurs a représenté un risque indépendant pour la survenue des EI. Afin d’explorer ces éléments et connaître la tolérance au long-terme, une méta-analyse des études observationnelles a été fait. Nous avons utilisé les EIG pour étudier précisément la tolérance à court et à long terme / Juvenile inflammatory rheumatism is a chronic disease that begins before the age of 16. Includes conditions classified along a continuum, ranging from the deregulation of innate immunity to the deregulation of adaptive immunity. Juvenile idiopathic arthritis (JIA) remains the most frequently diagnosed disease. Therapeutic options have expanded since the 2000s with the development of targeted therapies: biological agents (BAs). They can be combined with standard treatments used in paediatric rheumatology (e.g. non-steroidal anti-inflammatory drugs, corticosteroids, methotrexate, and other immunosuppressive drugs). The objective of the work of this thesis was to model the benefit-risk balance of BAs used in JIA from randomized clinical trials (RCTs) and to explore long-term tolerance from observational trials. First, using a meta-analytical approach, the data from double-blind, placebo-controlled or open RCTs in JIA were analysed for modelling the benefit-risk balance of BAs. For this purpose, the efficacy measured by a composite clinical and biological score (ACRped30), was compared with clinical safety during the randomized phase of RCTs. Safety criterion was the occurrence of adverse events (AEs). The risk-benefit balance remains favourable for biotherapies. However, these results are limited by the short follow-up period, which may underestimate the incidence of AEs. Second, we conducted an observational study to investigate the medium- and long-term safety of biotherapies using AEs and serious AEs described in a retrospective multicentre database. The overall safety of biotherapies has been acceptable in children with inflammatory rheumatic diseases. We observed a variation in the SAEs over time and that the concomitant prescription of immunosuppressants represented an independent risk for the occurrence of AEs. In order to explore these elements and long-term safety, a meta-analysis of observational studies was conducted. We used the SAEs to study precisely the short and long-term tolerance