12 resultados para Global Functioning Evaluation GFE, Obesity.
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Para alm das variveis clnicas e sociodemogrficas existem concerteza importantes componentes individuais que desempenham um contributo importante no nvel de insight apresentado por cada pessoa doente, por exemplo, o nvel de inteligncia, personalidade, cultura, experincias passadas, memria, etc. A natureza clnica, emocional e/ou intelectual do termo ajuda-nos a compreender a complexidade da dificuldade que existe na sua traduo e, inclusive, na sua compreenso. Da que as definies atribudas ao conceito sejam muito distintas e variem consoante a formao terica do autor/investigador. Pretende-se, a partir dessa identificao/compreenso, promover a qualidade de vida destas pessoas atravs do desenvolvimento de novas aprendizagens que possibilitem uma cooperao activa. igualmente fundamental ir ao encontro das capacidade intactas de maneira a possibilitar a aquisio de novos(s) comportamento(s) que tenham um impacte positivo nas queixas, sinais, sintomas, incapacidade e disfuncionalidade apresentados pelo/a utente. Uma vez que a prpria conceptualizao do termo traduzir aquilo que se pretende avaliar,ser efectuada uma reflexo detalhada acerca dos instrumentos e definies que tm sido mais utilizadas para explorar o insight nas psicoses.Procurei, no meu trabalho de investigao, realar e promover a importncia que cada sujeito, alvo de interveno, desempenha ao longo do seu processo de recuperao e na preveno de recadas. No seguimento dos objectivos acima descritos, para alm da reviso terica efectuada ao fenmeno em termos de conceptualizao e estudos desenvolvidos na rea de investigao, foi,neste estudo, realizada a contribuio para a validao do instrumento Assessment of Insight in Psychosis: a re-standartization of a New Scale de Markov & Berrios (2003).O fenmeno de insight escolhido pela Insight Scale, relata menos as mudanas vividas em relao doena mental, e mais a actual conscincia e articulao de tais mudanas. Tendo como base uma abordagem psicopedaggica, o fenmeno do insight aqui explorado assentou numa perspectiva reabilitativa, actual e multidimensional, que fosse para alm das dimenses clnicas tradicionais. Neste sentido apresentada uma escala original, intitulada Escala de Avaliao do Insight e Identificao das Necessidades em Pessoas com Psicose, bem como um modelo de interveno psicopedaggico breve, assente nos pressupostos descritos ao longo do trabalho.-----------------------------------------ABSTRACT: The importance of insight in people with mental illnesses was first studied in psychiatry, in the first decades of the 20th century, by people as important as Lewis (1934) and Jaspers (1959). However, this field of investigation was left unexplored for many years. Only in the last decade has this phenomenon become the object of numerous scientific investigations, having been given special attention by its investigators. For this reason a significant number of instruments for evalauting insight in psychotic disorders were developed. Since then many papers have been published, which has allowed for a more in depth knowledge on the subject. Therefore, in recent years, the concept of insight has been developed in an attempt to clarify its compexity. A once dichotomic phenomenon, described in terms of presence or absence, became considered multidimensional, which made the identification of different levels of insight and different dimensions possible. Current concepts categorize insight into five dimensions: the awareness of the patient in relation to his/her mental illness, the awareness of the patient in relation to the social consequences of his/her illness, the awareness of the need for treatment, the awareness of the symptoms and the explanation of those symptoms in relation to the illness. The lack of insight in psychiatry, in general terms, and as this phenomenon has been described, the lack of awareness of having a mental illness, represents one of the most common symptoms of schizophrenia and affects a big part of the population that suffer from this illness. It is estimated that bewteen 50 and 80 per cent of patients with schizophrenia do not believe that they are ill, which, consequently has a big impact in the process of adherence to treatment. It is still not possible, however, to identify all the factors that determine the lack of insight in schizophrenics. There are psychological, social and cultural influences that almost certainly play their role in the lack of insight registered in this pathology.Since the impact of scizophrenia is felt in many aspects of the individuals life, its effective treatment should be directed at various levels, including the improvement of insight. One of the objectives of this study is to explore the relationship between the level of insight in psychosis and the clinical and sociodemographic variables, the psychopathology and its global functioning. As well as the clinical and sociodemographic variables, there are of course important individual components that contribute to the level of insight seen in each patient, for example, their level of inteligence, personality, culture, past experiences, memory, etc. The clinical, emotional and/or intelectual nature of the term helps us understand the difficulty that lies in its interpretation as well as in its comprehension. Therefore, the definitions attributed to the term are very different and vary according to the theoretical training of the investigator. It is intended, from this identification/understanding, to promote the quality of life of these people through the development of new findings that might enable an active cooperation. It is equally fundamental to observe their unimpaired capacities in order to enable the acquisition of new behaviour(s) that have a positive impact on the complaints, signs, symptoms, incapacity and disfunctioning seen in the patient.As the actual comprehension of the term explains what we intend to evaluate, a detailed reflection is made on the instruments and definitions that have been used the most to explore insight in psychosis.In this investigation I tried to underline and promote the importance that each subject, undergoing medical intervention, plays during his/her process of recovery and prevention of relapses. Considering the above mentioned objectives, as well as a theoretical review of the phenomenon in terms of conceptualization and investigative studies developed, this study contributed to the validation of the instrument.The insight phenomenon chosen by the Insight Scale, records less changes experienced in relation to the mental illness and more actual awareness and articulation of these changes. Based on a psychopedagogical approach, the insight phenomenon explored here settled on a rehabilitation, current and multidimensional perspective that would go beyond the traditional clinical dimensions. For this reason an original scale entitled Insight Evaluation Scale and Need Identification in Psychosis Patients is presented, as well as a psychopedagogical intervention model soon to be used with admitted patients based on the presuppositions described in this study.
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RESUMO: Fizemos uma anlise da evoluo do conceito de estigma, das suas correlaes e das suas consequncias e analismos os instrumentos psicomtricos utilizados para estudar experincias pessoais de estigma. Revimos os principais estudos de investigao sobre estigma em Portugal. Revimos, igualmente, os estudos relevantes utilizando o Consumer Experiences of Stigma Questionnaire (CESQ) e as propriedades psicomtricas j documentadas. O nosso estudo teve como objetivos: explorar as experincias de estigma numa amostra portuguesa de pessoas com perturbao mental grave e contribuir para a documentao das propriedades psicomtricas do Consumer Experiences of Stigma Questionnaire e para a validao da sua verso portuguesa. Fizemos um estudo transversal, descritivo e analtico, recolhemos dados sociodemogrficos e clnicos e medimos as experincias de estigma e o funcionamento global. A frequncia das respostas da seco de estigma foi semelhante dos restantes estudos utilizando a CESQ. A frequncia das respostas na seco de discriminao foi ligeiramente inferior reportada noutros estudos. Verificmos a existncia de uma associao entre a pontuao da subescala de discriminao, o sexo masculino e o facto de se viver na comunidade. A pontuao da subescala de discriminao est tambm correlacionada de forma positiva com o funcionamento global. Os alfas de Cronbach para a CESQ e para as suas subescalas foram considerados bons. Os coeficientes de correlao intraclasse foram igualmente considerados igualmente bons. Utilizando tcnicas de anlise fatorial, verificmos que a maior parte dos itens da CESQ se enquadrava em dois fatores, correspondendo sensivelmente s subescalas definidas previamente. Conclumos que o presente estudo explorou com sucesso a questo do estigma em Portugal, contribuindo em simultneo para a validao do Consumer Experiences of Stigma Questionnaire.--------------ABSTRACT: We reviewed the evolution of concept of stigma, its correlates and consequences, and analysed psychometric instruments that were used to study personal experiences of stigma. We provided an insight over research of stigma in Portugal. We reviewed relevant studies that use Consumer Experiences of Stigma Questionnaire and documented psychometric properties of this instrument. Our study aimed both to explore experiences of stigma in a Portuguese sample of people with severe mental illness and to contribute to the assessment of the psychometric properties of Consumer Experiences of Stigma Questionnaire and to the validation of its Portuguese translation. We performed a cross sectional descriptive and analytic study, collected socio-demographic data and measured experiences of stigma and global functioning. Frequency of responses regarding stigma section of CESQ matched previous studies using that scale. Frequency of responses in discrimination section was slightly lower than previously reported studies. We found an association between the discrimination score of CESQ and both male gender and living in the community. The discrimination score also positively correlated with global functioning. Cronbach alphas for CESQ and its subscales were good. Intraclass correlation coefficients for CESQ and stigma subscale were also good. Using factor analysis we found most of the items in CESQ would fit 2 factors, grossly corresponding to the previously defined subscales. We conclude that this study successfully explored stigma in Portugal, contributing in simultaneous to the validation of Consumer Experiences Questionnaire.
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Dissertation to obtain a Masters Degree in Chemical and Biochemical Engineering
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RESUMO- Introduo: A obesidade e a Sndrome Metablica (SM) so atualmente um importante problema de sade pblica, com prevalncias crescentes, que se acompanham tambm por aumento da prevalncia de Diabetes Mellitus (DM).Estudos prvios demonstram associao destas entidades com o aumento de risco de eventos cardiovasculares, em particular a DM. A SM tem sido uma entidade muito debatida nos ltimos anos, com aparecimento de diversas definies, contribuindo para resultados dspares no que diz respeito influncia da SM nas doenas cardiovasculares. Tambm tm sido descritas variaes tnicas e regionais. Para alm de alguns estudos epidemiolgicos na populao geral, a informao relativamente sua influncia na presena de doena cardiovascular desconhecida em Portugal, em particular em populaes com suspeita de doena coronria. Objetivos - Esclarecimento de questes relacionadas com a prevalncia de SM e a sua influncia na evoluo de doena ateroclertica arterial por avaliao de uma populao com suspeita de doena coronria. Populao e Mtodos - Estudo observacional, transversal, com incluso prospetiva de indivduos admitidos letivamente para realizao de angiografia coronria por suspeita de doena coronria, tendo sido tambm efetuadas anlises laboratoriais e ecografia carotidea para avaliao da espessura intima-mdia carotidea (EIMc) e da presena de placas carotdeas. Efetuou-se avaliao dos parmetros demogrficos, antropomtricos, determinao do perfil lipdico, glicmia e insulinmia. Os exames angiogrficos foram analisados por anlise quantitativa semi-automtica. Foram excludos indivduos com antecedentes conhecidos de doena cardaca. Resultados - Incluram-se 300 doentes, com idade mdia de 64 9 anos, 59% do gnero masculino. A prevalncia de SM de acordo com a definio da AHA/NHLBI foi 48,4% (ajustada para idade e gnero da populao portuguesa) e a prevalncia de DM foi 14,8% (ajustada). A concordncia global das trs definies mais recentes de SM foi de apenas 43%. A prevalncia de SM aumenta com a idade e tambm mais elevada no gnero feminino. O componente mais frequente foi a hipertenso arterial, seguido pela obesidade abdominal, a elevao da glicmia e por fim as alteraes dos triglicridos e do colesterol HDL. Por outro lado, a presena de doena coronria significativa (leses 50%) ocorreu em apenas 51,3% dos doentes, sendo ainda mais baixa no gnero feminino. Demonstrou-se tambm uma baixa capacidade preditiva para doena coronria dos testes no invasivos clssicos, em particular no gnero feminino. A prevalncia de doena coronria significativa foi idntica nos indivduos com SM comparativamente com indivduos sem alteraes metablicas (46,3% vs. 48,2%, respectivamente), sendo mais elevado nos diabticos (65,2%). Os fatores predizentes independentes de doena coronria significativa foram a idade, o gnero masculino, a elevao da glicmia e dos triglicridos. Pelo contrrio, o ndice de Massa Corporal (IMC) mostrou uma associao protetora relativamente presena de doena coronria. A SM no fator predizente de doena coronria. Relativamente s dimenses dos vasos coronrios, o IMC correlaciona-se positivamente e a glicmia / DM correlacionam-se negativamente. A EIMc aumenta com o aumento da idade e no gnero masculino. A EIMc foi intermdia nos doentes com SM (0,88 0,31 mm) comparativamente com os doentes diabticos (0,97 0,34 mm) e os indivduos Normais (0,85 0,34 mm). Os fatores predizentes independentes de EIMc foram a idade, o gnero masculino, o colesterol HDL e a insulinmia. A EIMc permite predizer com uma acuidade moderada a presena de doena coronria significativa (AUC 0,638), em particular no gnero feminino, sendo um fator predizente independente de presena de doena coronria (OR 2,35, IC 95% 1,04-5,33. p=0,04). Apesar de no se correlacionar com o nmero de vasos coronrios com doena, correlacionou-se com a gravidade da doena (pelo score de Gensini). A insulinmia e o ndice HOMA aumentam diretamente com a idade e com o IMC, sendo contudo sobreponveis em ambos os gneros. Os fatores predizentes de ndice HOMA (resistncia insulina) foram o IMC, bem como os restantes componentes de SM, estando o ndice HOMA relacionado com a presena de SM e o nmero dos seus componentes presentes. O limiar para resistncia insulina foi de 2,66 e para SM foi 2,41. Ao contrrio das restantes definies de SM, a definio da AHA/NHLBI no predizente da presena de DM no gnero masculino. A associao da resistncia insulina com doena coronria foi limiar (OR 1,13, IC 95% 1,00-1,28, p=0,045). Concluses - Numa populao com suspeita de doena coronria, a prevalncia de SM muito elevada (superior a 50%), sendo a prevalncia de DM de 23%. Tambm a obesidade e o excesso de peso foram extremamente prevalentes nesta populao. A concordncia entre definies de SM baixa. A hipertenso arterial e a obesidade abdominal so os componentes mais frequentes de SM, sendo menos prevalentes as alteraes lipdicas. Pelo contrrio, a presena de doena coronria significativa foi muito baixa, em particular nas mulheres. A SM no se associou presena de doena coronria significativa, estando esta mais dependente das alteraes do metabolismo glicdico e dos triglicridos, bem como de outros fatores de risco no modificveis, nomeadamente a idade e o gnero. A EIMc da cartida comum e a presena de placas carotdeas mais elevada nos indivduos diabticos, estando tambm ligeiramente aumentada nos doentes com SM, sendo os fatores predizentes de EIMc apenas a idade, o gnero, a hiperinsulinmia bem como os nveis baixos de colesterol HDL. A utilizao da avaliao da EIMc na estratificao de risco pr-angiografia coronria, poder ser til no gnero feminino. A hiperinsulinmia e o ndice HOMA (ndice de resistncia insulina), esto relacionados com o IMC e consequentemente com a presena de obesidade, embora tambm se correlacione de forma independente com os outros componentes de SM. A resistncia insulina associou-se presena de SM. Relativamente capacidade preditiva da coexistncia com DM, verificou-se associao com a definio da NCEP-ATP III e da IDF, contudo, a definio da AHA/NHLBI s foi predizente de DMnas mulheres. -------------ABSTRACT - Introduction: Obesity and Metabolic Syndrome (MS) are a major public health problem, with increasing prevalence, that follows the increase in diabetes prevalence. Previous studies showed an association of both entities with increased cardiovascular risk, particularly diabetes. MS has been debated in the last few years, with several definitions and different results when analysed the influence of MS on cardiovascular diseases. There are also some regional and ethnical variations. Beyond general population epidemiological studies, information about the influence on cardiovascular disease in Portugal is unknown, particularly in patients with suspected coronary disease. Objectives- To clarify several questions regarding the prevalence of MS and the influence in arterial atherosclerotic disease by evaluation of a population with suspected coronary artery disease. Population and Methods- Observational, cross-sectional study with prospective inclusion of individuals admitted electively for coronary angiography with suspicion of coronary artery disease. All individuals also performed laboratorial evaluation and carotid ultrasound to evaluate carotid intima-media thickness (cIMT) and carotid plaques. We also evaluated demographic, anthropometric parameters, lipid profile, blood glucose and blood insulin. Angiographic data was obtained by semi-automated quantitation. Individuals with previously known cardiac history were excluded from the study. Results- We included 300 individuals with a mean age of 64 9 years, 59% males. MS prevalence according to AHA/NHLBI definition was 48.4% (adjusted for age and gender of the Portuguese population) and the adjusted prevalence of diabetes was 14.8%. Global agreement between the more recent three definitions of MS was only 43%. MS prevalence increases with age and is also higher in women. The most frequent components were hypertension and abdominal obesity, followed by elevated glucose and triglicerides and low HDL-cholesterol. Significant coronary artery disease (stenosis 50%) was present in only 51.3% of patients, being lower in females. Non-invasive tests also had a low predictive capacity, particularly in females. The prevalence of significant coronary disease was identical in patients with MS compared with normal metabolism individuals (46.3% vs. 48.2%, respectively), being higher in diabetics (65.2%). Independent predictive factors for coronary disease were age, male gender, high blood glucose and triglycerides. On the contrary, Body Mass Index (BMI) was a protective factor for coronary disease. MS wasnt a predictor of coronary disease. BMI showed a positive correlation with coronary vessel diameter and glucose /diabetes had a negative correlation. CIMT increased with age and was higher in males. CIMT was intermediate in patients with MS (0.88 0.31 mm) when compared to diabetic patients (0.97 0.34 mm) and Normal individuals (0.85 0.34 mm). Independent predictors for cIMT were age, male gender, HDL-cholesterol and insulin. CIMT had a moderate predictive accuracy for coronary disease (AUC 0,638), particularly in females and is an independent predictor of the presence of significant coronary disease (OR 2.35, 95% CI 1.04-5.33. p=0.04). Although it did not correlate with the number of diseased coronary arteries, it correlated with coronary disease severity by the Gensini score. Insulin and HOMA index increase directly with age and BMI, but were identical in both genders. Predictive factors for HOMA index (insulin resistance) were BMI as well as the other MS components. HOMA index is related to MS and the number of its components. The cut-off for insulin resistance was 2.66 and for MS 2.41. Unlike other MS definitions, AHA/NHLBI definition is not a predictor of diabetes in males. There was a borderline association between insulin resistance and coronary disease (OR 1.13, 95% CI 1.00-1.28, p=0.045). Conclusions - In a population of patients with suspected coronary disease, MS prevalence is extremely high (above 50%) with a diabetes prevalence of 23%. Also obesity and overweight are very prevalent in this population. Global agreement between MS definitions is however low. Hypertension and abdominal obesity are the most frequent components, with a lower prevalence of lipid abnormalities. Coronary disease prevalence was low, particularly in women. MS wasnt associated with coronary disease. Coronary disease was related to glucose and triglycerides, as well as with other non-modifiable factors such as age and gender. CIMT and carotid plaques are increased in diabetic patients, and also slightly elevated in patients with MS, but cIMT independent predictors were age, male gender, insulin and HDLcholesterol. CIMT can be useful in risk stratification before coronary angiography particularly in women. Elevated insulin and HOMA index (an insulin resistance index) are related with BMI and consequently with obesity, and it was also correlated with other MS components. Insulin resistance was associated with MS. The presence of diabetes was associated with the presence of MS by NCEP-ATP III and IDF definitions; however, AHA/NHLBI definition was only predictive of diabetes in females.
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RESUMO: De acordo com o estado da arte, existem intervenes psicofarmacolgicas, psicolgicas e psicossocias, com evidncia cientfica dos seus resultados, no tratamento de pessoas com esquizofrenia e perturbao esquizoafectiva. No entanto, muitos destes doentes, no procuram ajuda dos servios de sade mental, no recebem os referidos cuidados ou no so detectados nem seguidos por estes. Esta realidade levou ao desenvolvimento de programas integrados, intervenes e estudos mais especficos, nomeadamente para tentar ultrapassar os obstculos na acessibilidade aos cuidados de sade e na continuidade de seguimento destes doentes. No conjunto das dificuldades apuradas, as questes da exequibilidade (feasibility) e da implementao, tm tido particular relevo na literatura cientfica recente, bem como a melhor forma de vencer as respectivas barreiras e adaptar essas intervenes s varias realidades, culturas e recursos. Objectivos: Objectivos gerais:1) Avaliar a exequibilidade e a implementao inicial de um programa de cuidados integrados, para pessoas com esquizofrenia ou perturbao esquizoafectiva, no contexto clnico das equipas de sade mental comunitrias de um departamento de psiquiatria do Servio Nacional de Sade, em Portugal, com os recursos materiais e humanos existentes; 2) Avaliar o impacto deste programa, nestes doentes e na respectiva prestao de cuidados de sade mental. Metodologia. Elabormos um programa de cuidados integrados (Programa Integrar) com base no modelo clnico de case management, com seguimento mantido e integrado. Cada doente passou a ter um terapeuta de referncia, um plano individual de cuidados e manteve o seguimento com o seu psiquiatra assistente. Foram seleccionadas intervenes, nomeadamente, psicoeducativas, familiares, estratgias para lidar com os sintomas e a doena, preveno de recadas e intervenes para melhorar o funcionamento social e ocupacional. A estas intervenes foi sempre associado o tratamento psicofarmacolgico. O estudo delineado incluiu dois componentes: avaliao da exequibilidade e implementao inicial do programa de cuidados integrados (componente A) e avaliao do impacto deste programa (componente B), atravs de um estudo de interveno, prospectivo, naturalista, no aleatorizado e no ontrolado. A amostra do estudo resultou das sucessivas referenciaes, para o Programa Integrar, de pessoas com os diagnsticos de esquizofrenia ou perturbao esquizoafectiva, seguidas nas cinco equipas de sade mental comunitrias do Departamento de Psiquiatria do Centro Hospitalar de Lisboa Ocidental, com uma rea assistencial correspondente a uma populao de, aproximadamente, 400 000 pessoas. Definimos etapas, estratgias, parmetros e indicadores para o estudo da exequibilidade do programa. Efectumos a monitorizao e a avaliao de tarefas, procedimentos e intervenes recomendadas aos terapeutas de referncia. Realizmos duas avaliaes, uma no incio do programa e outra aps um ano de interveno. Foram avaliadas as seguintes dimenses (com indicao do acrnimo do instrumento de avaliao utilizado entre parntesis): psicopatologia (BPRS), depresso (MADRS), necessidades (CAN), incapacidade (DAS), actividade social e ocupacional (SOFAS), atitude em relao medicao (DAI), insight (SAI), qualidade de vida (WHOQOL-S) e satisfao (POCS). Resultados: Dos 146 doentes que foram includos no estudo, 97 (66%) eram do sexo masculino e 49 (34%) do sexo feminino, com uma idade mdia de 36 anos. Destes oentes,116 (79,4%)tinham o diagnstico (ICD10) de esquizofrenia e 30 (20,6%) de perturbao esquizoafectiva. Os restantes dados sociodemogrficos eram tpicos de populaes afins em servios de sade mental nacionais. Do total de doentes (146) que iniciaram o estudo, 26 (18%) abandonaram o seguimento neste programa. Para o componente A da investigao (estudo de exequibilidade) salientamos: exerceram funes a totalidade (15) dos terapeutas de referncia que receberam formao, 76 % efectuaram o nmero mnimo recomendado de sesses / ano por doente (18), 44,9 fizeram o nmero mnimo de sesses familiares pretendido ( 3). Nas intervenes mais especficas foram atingidos os objectivos em mais de 75% dos doentes, excepo das intervenes domicilirias (19,4%), preveno do abuso de substncias (45,4%) e do risco de suicdio (34,3%). O plano individual de cuidados foi realizado em 98 % dos doentes e em 38,9 % dos casos ocorreu a participao da famlia. Neste plano, a mdia de objectivos definidos foi de 5 e a mdia de objectivos atingidos correspondeu a 3 (p= 0,001). Na primeira avaliao, estavam a frequentar estruturas de reabilitao psicossocial 42 doentes (28,8%) e,12 meses aps, esse nmero passou para 80 (74,1%).Tambm aumentou o nmero de doentes com actividade profissional a tempo completo, de 8 (7,4%) para 18 (16,7%). No componente B do estudo (avaliao do impacto do programa), em termos de psicopatologia, e para as pontuaes mdias globais do BPRS, ocorreu uma diminuio entre a primeira e a segunda avaliao (p=0,001), tal como nas subescalas: sintomas positivos (p=0,003), sintomas negativos (p=0,002), sintomas de mania (p=0,002) e sintomas de depresso/ansiedade (p=0,001). Na avaliao da depresso (p= 0,001) e da incapacidade (p=0,003), as diferenas foram significativas e favorveis. O mesmo no sucedeu na atitude em relao medicao (p=0,690) nem na escala de avaliao do insight (p=0,079). Em relao ao funcionamento social e ocupacional, qualidade de vida e satisfao dos doentes, ocorreu uma melhoria significativa da primeira para a segunda avaliao As necessidades sem resposta mais frequentes, na primeira avaliao, corresponderam aos itens: actividades dirias, contactos sociais, relaes ntimas, relacionamento sexual, benefcios sociais, sintomas psicticos, sofrimento psicolgico, informao sobre a doena / tratamento e gesto/problemas de dinheiro. Para todos estes ltimos nove itens, verificou-se uma diferena estatisticamente significativa, entre a primeira e a segunda avaliao, com diminuio destas necessidades, excepto nas relaes ntimas, relacionamento sexual e nos problemas de dinheiro. Na distribuio dos trs estados de necessidades, para todos os itens, diminuram as necessidades sem resposta e as necessidades com resposta parcial e aumentaram as situaes em que deixaram de se verificar necessidades relevantes. Dos resultados obtidos para outros indicadores clnicos e de utilizao dos cuidados, ser importante referir que na comparao do ano anterior com o ano em que decorreu o programa, o nmero de doentes da amostra internados diminuiu 64,1%, bem como a mdia do nmero de internamentos (p=0,001). Em relao durao dos internamentos, no ano anterior ao programa, os 39 doentes internados, tiveram um total de dias de internamento de 1522, sendo que, no ano do programa, para os 14 doentes internados, o total foi de 523 dias. Em termos absolutos, ocorreu uma reduo de 999 dias (menos 65,6% dias). Tambm se verificou uma diminuio de 45,6 % de recadas (p=0,001).Discusso e concluses A exequibilidade do programa de cuidados integrados permitiu a aplicao do modelo clnico de case management, com seguimento mantido e integrado, atravs do qual cada doente passou a ter um terapeuta de referncia assim como, em 98% casos, um plano individual de cuidados. As famlias continuaram a ser o principal suporte para os doentes, mas surgiram dificuldades quando se pretendeu uma participao mais activa destas no tratamento.A diminuio do nmero e da durao dos internamentos constituram importantes resultados com implicaes no s em termos clnicos mas tambm econmicos. Os valores obtidos, para as diferentes variveis, tambm sugerem o impacto favorvel do Programa Integrar a nvel da psicopatologia, das necessidades, da incapacidade, do funcionamento social e ocupacional, da qualidade de vida e da satisfao dos doentes. O mesmo no sucedeu para o insight e para a mudana de atitudes dos doentes em relao medicao, resultados que devem ser igualmente considerados em futuros reajustamentos deste programa ou no desenvolvimento de novos programas. Como principais concluses podemos referir que: 1) Foi possvel a exequibilidade de um programa de cuidados integrados inovador e a implementao inicial desse programa, para doentes com esquizofrenia ou perturbao esquizoafectiva, com os recursos humanos e materiais existentes, no contexto clnico das equipas de sade mental comunitrias, de um departamento de psiquiatria e sade mental, em Portugal; 2) Na avaliao do impacto do programa, os resultados obtidos indiciam potencialidades de aplicao, deste programa de cuidados integrados, com vista melhoria clnica e psicossocial destes doentes. Devem ser realizados estudos de replicao, ou complementares presente investigao, no entanto, os dados obtidos so encorajadores para o desenvolvimento de programas similares, a nvel nacional e internacional, que possam beneficiar um grupo mais alargado de doentes.------------ABSTRACT: Although there are psychological and psychosocial interventions well supported by scientific evidence, which show benefit when combined with psychopharmacological treatments, we know that a significant number of people with schizophrenia or schizoaffective disorders, do not seek help from mental health services, do not receive the care mentioned and are not detected or followed-up by them. This reality led to the development of integrated programs, interventions and more specific studies, to try to overcome the obstacles in the accessibility to the health services and on the follow-up of these patients. Amongst the barriers identified, feasibility and implementation of those programs have been of special relevance in recent scientific literature, as well as the best way to overcome such difficulties and adapt the interventions to the various realities, cultures and resources. Objectives: General objectives were defined: 1) Assessment of the feasibility and initial implementation of an integrated care program, for people with schizophrenia or schizoaffective disorder, in the clinical setting of community mental health teams, in a psychiatric department from the national health service in Portugal; 2) Impact evaluation of the integrated care program, for these patients and their mental health care delivery. Methods: We drew up an integrated care program (Program Integrar) based on the clinical case management model, with continuous and integrated follow-up. Each patient got one case manager, an individual care plan and kept the same psychiatrist. Were selected the appropriated interventions, namely: psycho-educative, family-based interventions, strategies for dealing with the symptoms and the disorder, relapse prevention and interventions to improve social and occupational functioning. These interventions were always associated with psychopharmacological treatment. The investigation was outline with two parts: assessment of the feasibility and initial implementation of the Program Integrar (part A of the study) and impact evaluation of the program (part B of the study). We designed a naturalistic, prospective, intervention study, non-randomized and without control group. Our chosen sample was made with successive referrals of patients with the diagnosis of schizophrenia or schizoaffective disorder, followedup in one of the five community mental health teams of the Psychiatric Department of Centro Hospitalar Lisboa Ocidental, with a catchment area for a population of about 400 000 people. Different stages, strategies, criteria and indicators for studying the feasibility of the program and its implementation were set and the tasks, procedures and recommended interventions of the case managers were monitored and evaluated. We did two assessments with an interval of one year and we evaluated the following dimensions (the acronym of the assessment instrument used in brackets): psychopathology (BPRS), depression (MADRS), needs (CAN), disability (DAS), social and occupational functioning (SOFAS), attitude toward medication (DAI), insight (SAI), quality of life (WHOQOL-S) and satisfaction (POCS). Results: Of the 146 patients who started the study, 97 (66%) were male and 49 (34%) females with a mean age of 36 years. Of these, 116 (79,4%) were diagnosed (ICD10) with schizophrenia and 30 (20,6%) with schizoaffective disorder. The other socio-demographic data were typical of populations within Portuguese mental health services. Of all patients (146), who started the program, 26 (18%) of patients left the program (program dropout rate). Of the regarding part A of the study, which focused on feasibility, the following is of note: all professionals who had been trained for this purpose (15) acted as case manager, 76% did the recommended minimum number of sessions / year per patient (18) and 44,9% did the minimum number of family sessions desired ( 3). For the more specific interventions the parameters set out were met for more than 75% of patients, with the exception of domiciliar interventions (19.4%), prevention of substance abuse (45.4%) and suicide risk prevention(34.3%). The individual care plan was done for 98% of patients and in 38,9% of cases this involved family participation. For this plan the mean objectives defined were 5 and in average was achieved 3 (p=0,001). On the first assessment, 42 patients (28.8%) were attending psychosocial rehabilitation structures and 12 months later that number rose up to 80 (74,1%). Regarding their employment status, in the first assessment 8 (7,4%) were in full time employment and in the second evaluation the number rise to 18 (16,7%). For part B of the study (impact program evaluation), in terms of psychopathology, global mean scores for the BPRS, decreased (p=0,001), as did the four sub scales: positive symptoms (p=0,003); negative symptoms (p=0,002); manic symptoms (p=0,002) and symptoms of depression/anxiety (p=0,001). Both in the evaluation of depression (p=0,001), as in the assessment of disability (p=0,003), the differences were significant. However, this was not the case with attitudes towards medication (p=0,690) and with insight evaluation (p=0,079). In relation to social and occupational functioning, quality of life and patient satisfaction there was a statistically significant improvement from the first to the second assessment. The most commonly unmet needs in the first assessment were daily activities, social contacts, intimate relationships, sexual relations, social benefits, psychotic symptoms,psychological distress, information about the disorder / treatment and money problems money management. Of these, in the second assessment, all of those nine unmet needs showed significant improvement, excepted intimate relationships, sexual relations and Money problems / money management. In the distribution of the three states of needs for all items, it happened a decreased in unmet needs and partially met needs and increased in the situations where relevant needs were no longer found. For other clinical indicators it is important to note, when we compared the year prior to this program and the year after, there were fewer hospitalizations (reduction of 64,1% of admissions) and in the mean number of admissions (p=0,001). Regarding the length of hospitalization in the year prior to the program, the 39 patients admitted had a total of 1522 hospital days, and in the year of the program for the 14 hospitalized patients, the total was 523 days. In absolute terms, there was a reduction of 999 days (65,6%). There was also a 45,6% reduction of relapses (p = 0,001). Discussion and Conclusions: The feasibility of the integrated care program allowed the application of the clinical case management model, with continuous follow-up. Each patient got a case manager and in 98% of the cases they also got an individual plan of care. Families continued to be the main support for patients but, difficulties occurred when it was claimed a more active participation. The decrease in the number and duration of admissions were important findings with implications not only in clinical terms but also in economic field. The achieved results for the different variables can also indicate the favorable impact of this program, at the level of psychopathology, needs, disability, social and occupationa functioning, quality of life and patient satisfaction. The same did not happen for the evaluation of insight and in the changes of attitudes towards medication. These data should also be considered for future readjustments of this program and for the developing of new programs.Finally, the two-overview conclusions are: 1) It was possible the feasibility of an integrated care program and initial implementation of this innovative program, for patients with schizophrenia or schizoaffective disorder, with the human and material resources available in the clinical context of the community mental health teams, in a psychiatry and mental health department of the national health service in Portugal; 2) In assessing the impact of the program, the results suggest potential application of this integrated care program, to improve clinical state and psychosocial variables for these patients. There should be done studies to replicate these results, however the results obtained are promising for the development of similar programs at nationally and internationally level, that could benefit a wider group of patients.
Sade Mental em meio prisional : avaliao de necessidades de cuidados em reclusos com perturbao mental
Resumo:
RESUMO: A populao prisional constituda por indivduos geralmente sujeitos a alguma forma de excluso social e que apresentam problemas de sade fsica e mental mais frequentes do que na populao em geral. A prevalncia mais elevada de perturbaes mentais e de suicdio nos reclusos, em relao populao civil, consensual e est demonstrada em numerosos estudos internacionais. O abuso/dependncia de substncias, a depresso, as psicoses e a perturbao anti-social de personalidade so as perturbaes mais comuns na populao prisional. As perturbaes mentais so importantes factores de risco de suicdio, de vitimizao, de reincidncia e de reentrada no sistema prisional. Assim sendo, o grupo de reclusos com perturbao mental constitui um grupo de risco relevante. A avaliao de necessidades de cuidados foi iniciada no Reino Unido como um mtodo para o planeamento, medio dos resultados e financiamento dos cuidados de sade. Para esta avaliao foram desenvolvidos instrumentos que avaliam as necessidades em diversos domnios (clnicos e sociais) para aplicao aos utentes, cuidadores e profissionais. At aos anos noventa, a avaliao de necessidades no contexto prisional incidia especialmente nas necessidades de segurana dos servios, segundo a perspectiva dos profissionais. Contudo, a partir do relatrio Reed (1992), sobre a situao dos reclusos com perturbao mental, verificou-se uma abordagem mais abrangente, que inclua a avaliao das necessidades de cuidados dos reclusos. Embora as necessidades dos reclusos com perturbao mental paream ser similares s dos doentes psiquitricos em geral, existem diferenas em determinados domnios como a comorbilidade do eixo II, o abuso de substncias e o risco de violncia. Por este motivo, as necessidades de cuidados de sade mental dos reclusos so elevadas e frequentemente no se encontram satisfeitas. De forma a incluir estas especificidades foi desenvolvida a verso forense do Camberwell Assessment of Need (CAN), designada por CAN - Forensic Version (CANFOR). Actualmente existe um consenso generalizado entre as instituies internacionais do dever de proporcionar aos reclusos cuidados de sade, de preveno e de tratamento, equivalentes aos cuidados disponveis para a populao civil - o princpio da equivalncia de cuidados. A presente investigao pretendeu caracterizar e avaliar as necessidades de cuidados dos reclusos acompanhados nos servios de psiquiatria prisionais na rea da Grande Lisboa (internamento no Servio de Psiquiatria do Hospital Prisional de S. Joo de Deus (HPSJD) e consultas nos Estabelecimentos Prisionais (EP) de Caxias e de Tires). De modo a estabelecer uma comparao com sujeitos civis foi seleccionada uma amostra de convenincia de pacientes acompanhados num departamento de psiquiatria da mesma regio, segundo um emparelhamento por sexo, escalo etrio, e por diagnstico, num perodo de 3 meses. Realizou-se um estudo de tipo observacional, transversal e comparativo. Aplicaram-se os seguintes instrumentos de avaliao: questionrio especfico, Brief Psychiatric Rating Scale 4.0, Mini International Neuropsychiatric Interview 5.0.0, Global Assessment Functioning, CAN-R e CANFOR-R. No perodo do estudo (12 meses) foram assistidos 149 reclusos, dos quais, 35 (23,5%) no cumpriram os critrios de incluso. A amostra final de reclusos (PRs) (n=114) foi constituda por 79 homens (69,3%) e 35 mulheres (30,7%), dos quais 77 eram condenados (67,5%) e 37 (32,5%) encontravam-se detidos preventivamente. A amostra final de participantes civis (PCs) foi constituda por 121 indivduos, dos quais 76 eram homens (62,8%) e 45 eram mulheres (37,2%).A amostra final de participantes civis (PCs) foi constituda por 121 indivduos, dos quais 76 eram homens (62,8%) e 45 eram mulheres (37,2%). Relativamente aos PRs, o diagnstico mais frequente foi a Perturbao Anti-social da Personalidade (57,9%), seguida pela Depresso Major (56,1%). A maioria (53,5%) apresentava trs ou mais categorias diagnsticas. Aproximadamente um tero dos PRs (30%) pontuou o nvel elevado de risco de suicdio. A probabilidade deste risco aumentava, significativamente, nos portadores de Depresso Major, de um maior nvel de psicopatologia e de uma condenao actual. Perto de metade dos PRs (47,4%) possua duas ou mais condenaes prvias e mais de metade estavam envolvidos em crimes contra pessoas (53,5%). A probabilidade de condenaes mltiplas foi significativamente superior nos portadores de Perturbao Antisocial da Personalidade e nos reclusos com maior nmero de necessidades totais. Entre os PRs dos dois sexos, as principais diferenas significativas residiram na maior frequncia de consumo de substncias e no maior nmero de necessidades de cuidados nosatisfeitas nos homens versus mulheres. A comparao entre os PRs, antes da deteno, e os PCs mostrou que os primeiros possuam menor escolaridade, menos medicao psiquitrica, mas mais emprego e mais consumos de substncias ilcitas. A Perturbao Anti-social da Personalidade (OR=26,4; IC95%: 10,7-64,9), a Perturbao Ps-stress Traumtico (OR=15,0; IC95%: 3,5-65,4), a Dependncia/Abuso de Substncias (OR=8,5; IC95%: 4,2-17,6) a Depresso Major (OR=2,6; IC95%: 1,5-4,4) e o Risco de Suicdio Elevado (OR=2,6; IC95%: 1,4-5,0) foram significativamente mais frequentes nos PRs versus PCs. Relativamente avaliao de necessidades de cuidados, os PRs mostraram maior nmero de necessidades no-satisfeitas e maior necessidade de ajuda profissional, em relao aos PCs. Embora diversas necessidades no-satisfeitas possam resultar da condio de recluso, outras, em domnios da sade fsica, da segurana do prprio e dos consumos txicos, podero indicar que os PRs recebem um nvel de cuidados inferior ao necessrio, em comparao com os PCs. Os PRs apresentaram patologia mental, predominantemente no-psictica e elevado risco de suicdio/auto-agresso, associado a depresso, necessidades de cuidados e uma pena de priso. Possuam, numa frequncia elevada, caractersticas, consistentemente, associadas reincidncia criminal (personalidade anti-social, consumos txicos, condenaes anteriores), pelo que se justifica um especial acompanhamento deste grupo, no perodo pr e ps-libertao. A comparao de necessidades de cuidados no contexto civil e prisional indica um maior nvel de necessidades e um menor nvel de cuidados recebidos pelos PRs, em relao aos PCs. O princpio da equivalncia de cuidados poder estar comprometido nos indivduos reclusos com perturbao mental. A utilizao do CANFOR foi fcil e poder contribuir para um melhor planeamento, oferta e avaliao de resultados ao nvel individual. Os PRs e PCs revelaram caractersticas clnicas e de necessidades muito diferentes entre si, pelo que, os reclusos com perturbao mental devero ser assistidos em servios de sade mental preparados para abordar as suas especificidades.---------------ABSTRACT: The prison population is generally made up of individuals who are usually subject to some sort of social exclusion and who show physical and mental problems more frequently than the general population. Various international studies have found higher rates of mental disturbances and suicide within the prison population. The most common mental disturbances found are substance abuse or dependency, depression, psychosis, and anti-social personality disturbance. Such mental disturbances are important factors in suicide, victimization, delinquency recurrence, and the risk of reentry into prison. As a result, prison inmates with mental disturbances are a relevant at risk group. Assessment of needs of care first started in the United Kingdom as a method of care planning, results measuring and finance health care. The method involved the development of certain measuring instruments to be used by patients, caregivers and professionals in order to evaluate needs in various domains (clinical and social). Until the nineties, the assessment of needs of care in a prison context focused mainly on the services security needs. However, after the Reed (1992) report on mentally disturbed inmates, a much wider approach was considered, which included evaluation of the inmates needs of care. However similar mentally disturbed prison inmates needs may appear to those of other psychiatric patients, there are some differences in particular domains, namely, co-morbidity of Axis II, substance abuse and the risk of violence. For this reason, inmates mental health care needs are high and very often not met. In order to include these specificities, a forensic version of the Camberwell assessment of need (CAN,) designated CAN Forensic version (CANFOR) was developed. There is now generalized consensus among international institutions of the duty under the equivalent health care principle to provide inmates with preventative health care and treatment, that are equivalent to the care available to the civil population. This investigation aims to characterize and assess the health care provision of prison inmates admitted to Lisbons Psychiatric Prison ward - the Psychiatric Ward of So Joo de Deus Hospital (HPSJD) - and inmates in the Caxias and Tires Prison Establishments (EP) undertaking outpatient treatment. In order to establish a comparison between prison and civilian patients, a convenience sample was selected from civilian patients being treated in a psychiatric ward in the same geographical area. This sample was paired by gender, age group and diagnosis during a three month period. The study was observational, transversal and comparative. The following measuring instruments were used: a purpose-built questionnaire, Brief Psychiatric Rating Scale 4.0, Mini International Neuropsychiatric Interview 5.0.0, Global Assessment Functioning Scale, CAN-R and CANFOR-R. During the research period (12 months), 149 inmates received care, of whom 35 (23.5%) did not comply with the prerequisite criteria of this study. The final sample of inmates (PRs) (n=114) comprised 79 men (69.3%) and 35 (30.7%) women, of whom 77 (67.5%) were convicted prisoners and 37 (32.5%) were in preventive custody. The final sample for Civilian Participants (PCs) was made up of 121 individuals, of whom 76 (62.8%) were men and 45 (37.2%) were women. The most common diagnosis among the PRs was Anti-Social Personality Disorder (57.9%), followed by Major Depression (56.1%). More than half of the subjects in the sample (53.5%) showed three or more diagnostic categories. Approximately one third (30%) of the PRs showed a high level of suicide risk. The probability of this risk was significantly higher among Major Depression patients, those showing a higher level of psychopathology and those with a current conviction. Almost half of the PRs (47.4%) had been given two or more prior convictions and more than half (53.5%) were involved in crimes against people. The probability of multiple convictions was significantly higher among inmates with Anti-Social Personality Disorder and in those with more total needs. With regard to gender, the main significant difference among the PRs was that men were found to have a higher frequency of substance use and a greater number of unsatisfied caring needs than women. Comparison between the PRs prior to detention and PCs revealed that the former held lower educational qualifications and received less psychiatric medication, but had higher levels of employment and showed greater consumption of illicit substances. In addition Anti-Social Personality Disorder (OR=26.4; IC 95%: 10.7-64.9), Post-Stress Traumatic Disturbance (OR=15.0; IC 95%: 3.5-65.4), Substance Dependency/Abuse (OR=8.5; IC 95%: 4.2-17.6), Major Depression (OR=2.6; IC 95%: 1.5-4.4), and High Suicide Risk (OR=2.6; IC 95%: 1.4-5.0) were significantly more frequent amongst PRs than PCs. The results for needs assessment revealed that the PRs showed higher levels of unmet needs and a greater need for professional help in comparison with the PCs. Although various unmet needs may result from the inmates condition, other needs - in particular those regarding physical health, personal security and toxic substance use - suggest that the care given to PRs may be inadequate in comparison with that given to PCs. This implies that the principle of equivalent health care for PRs with mental illnesses may not be upheld. Furthermore, the mental morbidity results of the PRs indicated that they suffer predominantly from non-psychotic and high suicide/self inflicted aggression risk associated with depression, caring needs and a prison sentence. They also often showed characteristics that are consistently associated with criminal recidivism (Anti-social Personality, use of toxic substances, prior convictions). This result justifies that there should be special follow-up for this group in the pre- and after release period. The use of CANFOR proved to be simple and the application delay was acceptable. No difficulties were encountered in the understanding of its categories by its users. As a result, itcould contribute towards better planning, supply and assessment of results at an individual level. Given that the PRs and PCs revealed different clinical and needs characteristics, it is recommended that inmates with mental disturbances should be assisted in mental health services that are adequately prepared to address their specificities.
Resumo:
RESUMO: Apesar de toda a evoluo farmacolgica e de meios complementares de diagnstico possvel nos ltimos anos, o enfarte agudo do miocrdio e a morte sbita continuam a ser a primeira manifestao da aterosclerose coronria para muitos doentes, que estavam previamente assintomticos. Os exames complementares de diagnstico tradicionalmente usados para avaliar a presena de doena coronria, baseiamse na documentao de isqumia do miocrdio e por este motivo a sua positividade depende da presena de leses coronrias obstrutivas. As leses coronrias no obstrutivas esto tambm frequentemente implicadas no desenvolvimento de eventos coronrios. Apesar de o risco absoluto de instabilizao por placa ser superior para as leses mais volumosas e obstrutivas, estas so menos prevalentes do que as placas no obstrutivas e assim, por questes probabilsticas, os eventos coronrios resultam com frequncia da rotura ou eroso destas ltimas. Estudos recentes de imagiologia intracoronria avanada forneceram evidncia de que apesar de ser possvel identificar algumas caractersticas de vulnerabilidade em placas associadas ao desenvolvimento subsequente de eventos coronrios, a sua sensibilidade e especificidade muito baixa para aplicao clnica. Mais do que o risco associado a uma placa em particular, para o doente poder ser mais importante o risco global da sua rvore coronria reflexo da soma das probabilidade de todas as suas leses, sendo que quanto maior for a carga aterosclertica maior ser o seu risco. A angio TC cardaca a mais recente tcnica de imagem no invasiva para o estudo da doena coronria e surgiu nos ltimos anos fruto de importantes avanos na tecnologia de TC multidetectores. Estes avanos, permitiram uma progressiva melhoria da resoluo espacial e temporal, contribuindo para a melhoria da qualidade dos exames, bem como uma significativa reduo da dose de radiao. A par desta evoluo tecnolgica, foi aumentando a experincia e gerada mais evidncia cientfica, tornando a angio TC cardaca cada vez mais robusta na avaliao da doena coronria e aumentando a sua aplicabilidade clnica. Mais recentemente apareceram vrios trabalhos que validaram o seu valor prognstico, assinalando a sua chegada idade adulta. Para alm de permitir excluir a presena de doena coronria e de identificar a presena de estenoses significativas, a angio TC cardaca permite identificar a presena de leses coronrias no obstrutivas, caracterstica impar desta tcnica como modalidade de imagem no invasiva. Ao permitir identificar a totalidade das leses aterosclerticas (obstrutivas e no obstrutivas), a 18 angio TC cardaca poder fornecer uma quantificao da carga aterosclertica coronria total, podendo essa identificao ser til na estratificao dos indivduos em risco de eventos coronrios. Neste trabalho foi possvel identificar preditores demogrficos e clnicos de uma elevada carga aterosclertica coronria documentada pela angioTC cardaca, embora o seu poder discriminativo tenha sido relativamente modesto, mesmo quando agrupados em scores clnicos. Entre os vrios scores, o desempenho foi um pouco melhor para o score de risco cardiovascular Heartscore. Estas limitaes espelham a dificuldade de prever apenas com base em variveis clnicas, mesmo quando agrupadas em scores, a presena e extenso da doena coronria. Um dos factores de risco clssicos, a obesidade, parece ter uma relao paradoxal com a carga aterosclertica, o que pode justificar algumas limitaes da estimativa com base em scores clnicos. A diabetes mellitus, por outro lado, foi um dos preditores clnicos mais importantes, funcionando como modelo de doena coronria mais avanada, til para avaliar o desempenho dos diferentes ndices de carga aterosclertica. Dada a elevada prevalncia de placas aterosclerticas identificveis por angio TC na rvore coronria, torna-se importante desenvolver ferramentas que permitam quantificar a carga aterosclertica e assim identificar os indivduos que podero eventualmente beneficiar de medidas de preveno mais intensivas. Com este objectivo, foi desenvolvido um ndice de carga aterosclertica que rene a informao global acerca da localizao, do grau de estenose e do tipo de placa, obtida pela angio TC cardaca, o CT--LeSc. Este score poder vir a ser uma ferramenta til para quantificao da carga aterosclertica coronria, sendo de esperar que possa traduzir a informao prognstica da angio TC cardaca. Por fim, o conceito de rvore coronria vulnervel poder ser mais importante do que o da placa vulnervel e a sua identificao pela angio TC cardaca poder ser importante numa estratgia de preveno mais avanada. Esta poder permitir personalizar as medidas de preveno primria, doseando melhor a sua intensidade em funo da carga aterosclertica, podendo esta vir a constituir uma das mais importantes indicaes da angio TC cardaca no futuro.---------------- ABSTRACT Despite the significant advances made possible in recent years in the field of pharmacology and diagnostic tests, acute yocardial infarction and sudden cardiac death remain the first manifestation of coronary atherosclerosis in a significant proportion of patients, as many were previously asymptomatic. Traditionally, the diagnostic exams employed for the evaluation of possible coronary artery disease are based on the documentation of myocardial ischemia and, in this way, they are linked to the presence of obstructive coronary stenosis. Nonobstructive coronary lesions are also frequently involved in the development of coronary events. Although the absolute risk of becoming unstable per plaque is higher for more obstructive and higher burden plaques, these are much less frequent than nonobstructive lesions and therefore, in terms of probability for the patient, coronary events are often the result of rupture or erosion of the latter ones. Recent advanced intracoronary imaging studies provided evidence that although it is possible to identify some features of vulnerability in plaques associated with subsequente development of coronary events, the sensitivity and sensibility are very limited for clinical application. More important than the individual risk associated with a certain plaque, for the patient it might be more important the global risk of the total coronary tree, as reflected by the sum of the diferent probabilities of all the lesions, since the higher the coronary Atherosclerotic burden, the higher the risk for the patient. Cardiac CT or Coronary CT angiography is still a young modality. It is the most recente noninvasive imaging modality in the study of coronary artery disease and its development was possible due to important advances in multidetector CT technology. These allowed significant improvements in temporal and spatial resolution, leading to better image quality and also some impressive reductions in radiation dose. At the same time, the increasing experience with this technique lead to a growing body of scientific evidence, making cardiac CT a robust imaging tool for the evaluation of coronary artery disease and increased its clinical indications. More recently, several publications documented its prognostic value, marking the transition of cardiac CT to adulthood. Besides being able to exclude the presence of coronary artery disease and of obstructive lesions, Cardiac CT allows also the identification of nonobstructive lesions, making this a unique tool in the field of noninvasive imaging modalities. By evaluating both obstructive and nonobstructive lesions, cardiac CT can provide for the quantification of total coronary atherosclerotic burden, and this can be useful to stratify the risk of future coronary events. In the present work, it was possible to identify significant demographic and clinical predictors of a high coronary atherosclerotic burden as assessed by cardiac CT, but with modest odds ratios, even when the individual variables were gathered in clinical scores. Among these diferent clinical scores, the performance was better for the Heartscore, a cardiovascular risk score. This modest performance underline the limitations on predicting the presence and severity of coronary disease based only on clinical variables, even when optimized together in risk scores, One of the classical risk factors, obesity, had in fact a paradoxical relation with coronary atherosclerotic burden and might explain some of the limitations of the clinical models. On the opposite, diabetes mellitus was one of the strongest clinical predictors, and was considered to be a model of more advanced coronary disease, useful to evaluate the performance of diferent plaque burden scores. In face of the high prevalence of plaques that can be identified in the coronary tree of patients undergoing cardiac CT, it is of utmost importance to develop tools to quantify the total coronary atherosclerotic burden providing the identification of patients that could eventually benefit from more intensive preventive measures. This was the rational for the development of a coronary atherosclerotic burden score, reflecting the comprehensive information on localization, degree of stenosis and plaque composition provided by cardiac CT the CT-LeSc. This score may become a useful tool to quantify total coronary atherosclerotic burden and is expected to convey the strong prognostic information of cardiac CT. Lastly, the concept of vulnerable coronary tree might become more important than the concept of the vulnerable plaque and his assessment by cardiac CT Might become important in a more advance primary prevention strategy. This Could lead to a more custom-made primary prevention, tailoring the intensity of preventive measures to the atherosclerotic burden and this might become one of the most important indications of cardiac CT In the near future.
Resumo:
RESUMO: Introduo. O cancro de bexiga uma patologia comum que representa o 6 e o 5 cancro mais incidente em Portugal e na Itlia, respetivamente. Em mais de metade dos casos ocorre reincidncia durante o primeiro ano, requerendo acompanhamento clnico ao longo da vida. A instilao intravesical de Bacillus Calmette-Gurin (BCG) (uma estirpe atenuada do Mycobacterium bovis) representa uma imunoterapia eficaz no combate ao cancro de bexiga, no entanto, muitos aspetos da interao de BCG com as clulas tumorais bem como com as clulas do sistema imunitrio permanecem por desvendar. As clulas tumorais de bexiga expressam frequentemente as formas sialiladas dos antignios de Thomsen-Friedenreich (TF), i.e., sialil-T (sT) e sialil-Tn (sTn). Contudo ainda se desconhece o significado da sua expresso na malignidade tumoral e se afeta a eficcia da teraputica BCG. Objetivo do estudo. Investigar o papel dos antignios sT e sTn no fentipo maligno de clulas de cancro de bexiga bem como na resposta mediada pelo sistema imunitrio terapia com BCG. Metodologia. Para tal, foram utilizadas as linhas celulares de cancro da bexiga HT1376 e MCR, geneticamente modificadas por transduo com vetores codificantes para as sialiltransferases ST3GAL1 ou ST6GALNAC1, de forma a expressar homogeneamente os antignios sT ou sTn respetivamente. Estes modelos celulares foram estudados aps confronto com BCG. O nvel de BCG internalizado foi avaliado por citometria de fluxo. O perfil global de expresso gentica dos modelos celulares antes e aps incubao com BCG foi analisado pela tecnologia de microarray. O perfil de citocinas secretadas pelos modelos celulares aps incubao com BCG, bem como de macrfagos estimulados pelo secretoma de clulas de cancro de bexiga que por sua vez foram estimuladas previamente por BCG, foi estudado pelo sistema multiplex de imuno-esferas. Resultados. A anlise do transcritoma dos modelos celulares revelou que grupos de genes envolvidos em funes especficas foram modulados em paralelo nos dois modelos celulares, aps transduo, independentemente da sialiltransferase expressa. Ou seja, em clulas que expressavam a sialiltransferase ST3GAL1 ou ST6GALNAC1, os genes envolvidos na regulao da segregao cromossmica e na reparao do DNA foram consistentemente regulados negativamente. Genes descritos na literatura como marcadores para o cancro de bexiga foram tambm modulados. A incubao com BCG resultou numa tendncia ao aumento da expresso de genes relevantes na preservao e estabilidade genmica e menor malignidade, no entanto, apenas em clulas que expressavam sT ou sTn. Entre as dez citocinas testadas, apenas a IL-6 e IL-8 foram expressas pelas linhas celulares de cancro da bexiga, com induo destas aps estimulao com BCG, e principalmente em clulas que expressavam ST3GAL1 ou ST6GALNAC1. Em macrfagos, citocinas inflamatrias, tais como IL-1, IL-6 e TNF, e a citocina anti-inflamatria IL-10, foram induzidas apenas pelo secretoma de clulas de cancro da bexiga confrontadas com BCG, com maior relevncia quando estas expressavam ST3GAL1 ou ST6GALNAC1, prevendo a estimulao de macrfagos semelhantes aos de tipo M1 e uma melhor resposta terapia com BCG. Concluses. O efeito geral da expresso destas sialiltransferases e dos produtos enzimticos sT ou sTn nas clulas de cancro de bexiga conduz a um fentipo de maior malignidade. Contudo, a maior avidez de estas na produo de citocinas inflamatrias aps confronto com BCG, bem como a maior capacidade de estimulao de macrfagos, predir uma resposta terapia com BCG mais eficaz em tumores que expressem os antignios de TF sialilados. Tais concluses so totalmente concordantes com os nossos mais recentes dados clnicos obtidos em colaborao, que mostram que em doentes com cancro de bexiga que expressam sTn respondem melhor a terapia BCG. ----------ABSTRACT: Background. Bladder cancer is a common malignancy representing the 6th and the 5th most incident cancer in Portugal and in Italy, respectively. More than half of the cases relapse within one year, requiring though a lifelong follow-up. Intravesical instillation of Bacillus Calmette-Gurin (BCG) (an attenuated strain of Mycobacterium bovis) represents an effective immunotherapy of bladder cancer, although many aspects of the interaction of BCG with cancer cells and host immune cells remain obscure. Bladder cancer cells often express the sialylated forms of the Thomsen-Friedenreich (TF), i.e., sialil-T (sT) e sialil-Tn (sTn). However, its still unknown the sense of such expression in tumour malignancy and in the BCG therapy efficacy. Aim of the study. To investigate the role of the sT and sTn antigens on the malignant phenotype of bladder cancer cells and the immune mediated response to BCG therapy. Experimental. We have utilized populations of the bladder cancer cell lines HT1376 and MCR, genetically modified by transduction with the sialyltransferases ST3GAL1 or ST6GALNAC1 to express homogeneously sT or sTn antigens. The level of BCG internalized was assessed by flow cytometry. The whole gene expression profile of BCG-challenged or unchallenged bladder cancer cell lines was studied by microarray technology. The profile of cytokines secreted by BCG-challenged bladder cancer cells and that of macrophages challenged by the secretome of BCG-challenged bladder cancer cells was studied by multiplex immune-beads assay. Results. Transcriptome analysis of the sialyltransferase-transduced cells revealed that groups of genes involved in specific functions were regulated in parallel in the two cell lines, regardless the sialyltransferase expressed. Namely, in sialyltransferase-expressing cells, genes involved in the proper chromosomal segregation and in the DNA repair were consistently down-regulated, while genes reported in literature as markers for bladder cancer were modulated. BCG-challenging induced a tendency to up-regulation of the genes preserving genomic stability and reducing malignancy, but only in cells expressing either sT or sTn. Among the ten cytokines tested, only IL-6 and IL-8 were expressed by bladder cancer cell lines and up-regulated by BCG-challenging, mainly in sialyltransferases-expressing cells. In macrophages, inflammatory cytokines, such as IL-1, IL-6 and TNF, and the antinflammatory IL-10 were induced only by the secretome of BCG-challenged bladder cancer cells, particularly when expressing either sialyltransferase, predicting the stimulation of M1-like macrophages and a better response to BCG therapy. Conclusions. The general effect of the expression of the two sialyltransferases and their products in the bladder cancer cells is toward a more malignant phenotype. However, the stronger ability of sialyltransferase expressing cells to produce inflammatory cytokines upon BCG-challenging and to stimulate macrophages predicts a more effective response to BCG in tumours expressing the sialylated TF antigens. This is fully consistent with our recent clinical data obtained in collaboration, showing that patients with bladder cancer expressing sTn respond better to BCG therapy.
Resumo:
Domestication of plants and plant breeding have dramatically eroded the allelic variations of crop species which led to an increasing susceptibility of crop plants to environmental stresses, diseases and pests. Drought is a major environmental stress factor that affects the growth and development of plants so the selection of tolerant genotypes becomes increasingly important with respect to the predicted effects of global warming. In this study, several genotypes of Spelt (Triticum aestivum var. spelta) were tested under low water supply in soil with the aim of to find Spelt genotypes more resistant than wheat to these conditions, and select them so that in future may be used to improve wheat crops. Morphological analyses were performed and mineral and enzymatic analyses and also dry matter production were calculated. Our results suggests that the genotypes Sp53, Sp96, Sp912, Sp757 and Sp804 are a potential ones to use in breeding programs to improve wheat production. Under drought, these genotypes had growth efficiency of 38%, 45%, 64%, 37%, and 31% respectively and also showed higher biomass than modern wheat and were also mineralogical richer. The genotypes Sp96 and Sp912 showed highest activity of all antioxidants enzymes tested. This work proves that Spelt is a good wheat to continue to study in order to improve wheat crops in dry areas and consequently increase the quality of life and health of the populations living in those areas.
Resumo:
RESUMO: A estrutura demogrfica portuguesa marcada por baixas taxas de natalidade e mortalidade, onde a populao idosa representa uma fatia cada vez mais representativa, fruto de uma maior longevidade. A incidncia do cancro, na sua generalidade, maior precisamente nessa classe etria. A par de outras doenas igualmente lesivas (e.g. cardiovasculares, degenerativas) cuja incidncia aumenta com a idade, o cancro merece relevo. Estudos epidemiolgicos apresentam o cancro como lder mundial na mortalidade. Em pases desenvolvidos, o seu peso representa 25% do nmero total de bitos, percentagem essa que mais que duplica noutros pases. A obesidade, a baixa ingesto de frutas e vegetais, o sedentarismo, o consumo de tabaco e a ingesto de lcool, configuram-se como cinco dos fatores de risco presentes em 30% das mortes diagnosticadas por cancro. A nvel mundial e, em particular no Sul de Portugal, os cancros do estmago, recto e clon apresentam elevadas taxas de incidncia e de mortalidade. Do ponto de vista estritamente econmico, o cancro a doena que mais recursos consome enquanto que do ponto de vista fsico e psicolgico uma doena que no limita o seu raio de ao ao doente. O cancro , portanto, uma doena sempre atual e cada vez mais presente, pois reflete os hbitos e o ambiente de uma sociedade, no obstante as caractersticas intrnsecas a cada indivduo. A adoo de metodologia estatstica aplicada modelao de dados oncolgicos , sobretudo, valiosa e pertinente quando a informao oriunda de Registos de Cancro de Base Populacional (RCBP). A pertinncia justificada pelo fato destes registos permitirem aferir numa populao especfica, o risco desta sofrer e/ou vir a sofrer de uma dada neoplasia. O peso que as neoplasias do estmago, clon e recto assumem foi um dos elementos que motivou o presente estudo que tem por objetivo analisar tendncias, projees, sobrevivncias relativas e a distribuio espacial destas neoplasias. Foram considerados neste estudo todos os casos diagnosticados no perodo 1998-2006, pelo RCBP da regio sul de Portugal (ROR-Sul). O estudo descritivo inicial das taxas de incidncia e da tendncia em cada uma das referidas neoplasias teve como base uma nica varivel temporal - o ano de diagnstico - tambm designada por perodo. Todavia, uma metodologia que contemple apenas uma nica varivel temporal limitativa. No cancro, para alm do perodo, a idade data do diagnstico e a coorte de nascimento, so variveis temporais que podero prestar um contributo adicional na caracterizao das taxas de incidncia. A relevncia assumida por estas variveis temporais justificou a sua incluso numaclasse de modelos designada por modelos Idade-Perodo-Coorte (Age-Period-Cohort models - APC), utilizada na modelao das taxas de incidncia para as neoplasias em estudo. Os referidos modelos permitem ultrapassar o problema de relaes no lineares e/ou de mudanas sbitas na tendncia linear das taxas. Nos modelos APC foram consideradas a abordagem clssica e a abordagem com recurso a funes suavizadoras. A modelao das taxas foi estratificada por sexo. Foram ainda estudados os respectivos submodelos (apenas com uma ou duas variveis temporais). Conhecido o comportamento das taxas de incidncia, uma questo subsequente prende-se com a sua projeo em perodos futuros. Porm, o efeito de mudanas estruturais na populao, ao qual Portugal no alheio, altera substancialmente o nmero esperado de casos futuros com cancro. Estimativas da incidncia de cancro a nvel mundial obtidas a partir de projees demogrficas apontam para um aumento de 25% dos casos de cancro nas prximas duas dcadas. Embora a projeo da incidncia esteja associada a alguma incerteza, as projees auxiliam no planeamento de polticas de sade para a afetao de recursos e permitem a avaliao de cenrios e de intervenes que tenham como objetivo a reduo do impacto do cancro. O desconhecimento de projees da taxa de incidncia destas neoplasias na rea abrangida pelo ROR-Sul, levou utilizao de modelos de projeo que diferem entre si quanto sua estrutura, linearidade (ou no) dos seus coeficientes e comportamento das taxas na srie histrica de dados (e.g. crescente, decrescente ou estvel). Os referidos modelos pautaram-se por duas abordagens: (i)modelos lineares no que concerne ao tempo e (ii) extrapolao de efeitos temporais identificados pelos modelos APC para perodos futuros. Foi feita a projeo das taxas de incidncia para os anos de 2007 a 2010 tendo em conta o gnero, idade e neoplasia. ainda apresentada uma estimativa do impacto econmico destas neoplasias no perodo de projeo. Uma questo pertinente e habitual no contexto clnico e a que o presente estudo pretende dar resposta, reside em saber qual a contribuio da neoplasia em si para a sobrevivncia do doente. Nesse sentido, a mortalidade por causa especfica habitualmente utilizada para estimar a mortalidade atribuvel apenas ao cancro em estudo. Porm, existem muitas situaes em que a causa de morte desconhecida e, mesmo que esta informao esteja disponvel atravs dos certificados de bito, no fcil distinguir os casos em que a principal causa de morte devida ao cancro. A sobrevivncia relativa surge como uma medida objetiva que no necessita do conhecimento da causa especfica da morte para o seu clculo e dar-nos- uma estimativa da probabilidade de sobrevivncia caso o cancro em anlise, num cenrio hipottico, seja a nica causa de morte. Desconhecida a principal causa de morte nos casos diagnosticados com cancro no registo ROR-Sul, foi determinada a sobrevivncia relativa para cada uma das neoplasias em estudo, para um perodo de follow-up de 5 anos, tendo em conta o sexo, a idade e cada uma das regies que constituem o registo. Foi adotada uma anlise por perodo e as abordagens convencional e por modelos. No eplogo deste estudo, analisada a influncia da variabilidade espao-temporal nas taxas de incidncia. O longo perodo de latncia das doenas oncolgicas, a dificuldade em identificar mudanas sbitas no comportamento das taxas, populaes com dimenso e riscos reduzidos, so alguns dos elementos que dificultam a anlise da variao temporal das taxas. Nalguns casos, estas variaes podem ser reflexo de flutuaes aleatrias. O efeito da componente temporal aferida pelos modelos APC d-nos um retrato incompleto da incidncia do cancro. A etiologia desta doena, quando conhecida, est associada com alguma frequncia a fatores de risco tais como condies socioeconmicas, hbitos alimentares e estilo de vida, atividade profissional, localizao geogrfica e componente gentica. O contributo, dos fatores de risco , por vezes, determinante e no deve ser ignorado. Surge, assim, a necessidade em complementar o estudo temporal das taxas com uma abordagem de cariz espacial. Assim, procurar-se- aferir se as variaes nas taxas de incidncia observadas entre os concelhos inseridos na rea do registo ROR-Sul poderiam ser explicadas quer pela variabilidade temporal e geogrfica quer por fatores socioeconmicos ou, ainda, pelos desiguais estilos de vida. Foram utilizados os Modelos Bayesianos Hierrquicos Espao-Temporais com o objetivo de identificar tendncias espao-temporais nas taxas de incidncia bem como quantificar alguns fatores de risco ajustados influncia simultnea da regio e do tempo. Os resultados obtidos pela implementao de todas estas metodologias considera-se ser uma mais valia para o conhecimento destas neoplasias em Portugal.------------ABSTRACT: mortality rates, with the elderly being an increasingly representative sector of the population, mainly due to greater longevity. The incidence of cancer, in general, is greater precisely in that age group. Alongside with other equally damaging diseases (e.g. cardiovascular,degenerative), whose incidence rates increases with age, cancer is of special note. In epidemiological studies, cancer is the global leader in mortality. In developed countries its weight represents 25% of the total number of deaths, with this percentage being doubled in other countries. Obesity, a reduce consumption of fruit and vegetables, physical inactivity, smoking and alcohol consumption, are the five risk factors present in 30% of deaths due to cancer. Globally, and in particular in the South of Portugal, the stomach, rectum and colon cancer have high incidence and mortality rates. From a strictly economic perspective, cancer is the disease that consumes more resources, while from a physical and psychological point of view, it is a disease that is not limited to the patient. Cancer is therefore na up to date disease and one of increased importance, since it reflects the habits and the environment of a society, regardless the intrinsic characteristics of each individual. The adoption of statistical methodology applied to cancer data modelling is especially valuable and relevant when the information comes from population-based cancer registries (PBCR). In such cases, these registries allow for the assessment of the risk and the suffering associated to a given neoplasm in a specific population. The weight that stomach, colon and rectum cancers assume in Portugal was one of the motivations of the present study, that focus on analyzing trends, projections, relative survival and spatial distribution of these neoplasms. The data considered in this study, are all cases diagnosed between 1998 and 2006, by the PBCR of Portugal, ROR-Sul.Only year of diagnosis, also called period, was the only time variable considered in the initial descriptive analysis of the incidence rates and trends for each of the three neoplasms considered. However, a methodology that only considers one single time variable will probably fall short on the conclusions that could be drawn from the data under study. In cancer, apart from the variable period, the age at diagnosis and the birth cohort are also temporal variables and may provide an additional contribution to the characterization of the incidence. The relevance assumed by these temporal variables justified its inclusion in a class of models called Age-Period-Cohort models (APC). This class of models was used for the analysis of the incidence rates of the three cancers under study. APC models allow to model nonlinearity and/or sudden changes in linear relationships of rate trends. Two approaches of APC models were considered: the classical and the one using smoothing functions. The models were stratified by gender and, when justified, further studies explored other sub-models where only one or two temporal variables were considered. After the analysis of the incidence rates, a subsequent goal is related to their projections in future periods. Although the effect of structural changes in the population, of which Portugal is not oblivious, may substantially change the expected number of future cancer cases, the results of these projections could help planning health policies with the proper allocation of resources, allowing for the evaluation of scenarios and interventions that aim to reduce the impact of cancer in a population. Worth noting that cancer incidence worldwide obtained from demographic projections point out to an increase of 25% of cancer cases in the next two decades. The lack of projections of incidence rates of the three cancers under study in the area covered by ROR-Sul, led us to use a variety of forecasting models that differ in the nature and structure. For example, linearity or nonlinearity in their coefficients and the trend of the incidence rates in historical data series (e.g. increasing, decreasing or stable).The models followed two approaches: (i) linear models regarding time and (ii) extrapolation of temporal effects identified by the APC models for future periods. The study provide incidence rates projections and the numbers of newly diagnosed cases for the year, 2007 to 2010, taking into account gender, age and the type of cancer. In addition, an estimate of the economic impact of these neoplasms is presented for the projection period considered. This research also try to address a relevant and common clinical question in these type of studies, regarding the contribution of the type of cancer to the patient survival. In such studies, the primary cause of death is commonly used to estimate the mortality specifically due to the cancer. However, there are many situations in which the cause of death is unknown, or, even if this information is available through the death certificates, it is not easy to distinguish the cases where the primary cause of death is the cancer. With this in mind, the relative survival is an alternative measure that does not need the knowledge of the specific cause of death to be calculated. This estimate will represent the survival probability in the hypothetical scenario of a certain cancer be the only cause of death. For the patients with unknown cause of death that were diagnosed with cancer in the ROR-Sul, the relative survival was calculated for each of the cancers under study, for a follow-up period of 5 years, considering gender, age and each one of the regions that are part the registry. A period analysis was undertaken, considering both the conventional and the model approaches. In final part of this study, we analyzed the influence of space-time variability in the incidence rates. The long latency period of oncologic diseases, the difficulty in identifying subtle changes in the rates behavior, populations of reduced size and low risk are some of the elements that can be a challenge in the analysis of temporal variations in rates, that, in some cases, can reflect simple random fluctuations. The effect of the temporal component measured by the APC models gives an incomplete picture of the cancer incidence. The etiology of this disease, when known, is frequently associated to risk factors such as socioeconomic conditions, eating habits and lifestyle, occupation, geographic location and genetic component. The "contribution"of such risk factors is sometimes decisive in the evolution of the disease and should not be ignored. Therefore, there was the need to consider an additional approach in this study, one of spatial nature, addressing the fact that changes in incidence rates observed in the ROR-Sul area, could be explained either by temporal and geographical variability or by unequal socio-economic or lifestyle factors. Thus, Bayesian hierarchical space-time models were used with the purpose of identifying space-time trends in incidence rates together with the the analysis of the effect of the risk factors considered in the study. The results obtained and the implementation of all these methodologies are considered to be an added value to the knowledge of these neoplasms in Portugal.
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RESUMO: A hipertenso arterial (HA) uma patologia altamente prevalente, embora claramente subdiagnosticada, em doentes com sndrome de apneia obstrutiva do sono (SAOS). Estas duas patologias apresentam uma estreita relao e a monitorizao ambulatria da presso arterial (MAPA), por um perodo de 24 horas, parece ser o mtodo mais preciso para o diagnstico de hipertenso em doentes com SAOS. No entanto, esta ferramenta de diagnstico para alm de ser dispendiosa e envolver um nmero acrescido de meios tcnicos e humanos, mais morosa e, por conseguinte, no utilizada por rotina no contexto do diagnstico da SAOS. Por outro lado, apesar da aplicao de presso positiva contnua nas vias areas (CPAP Continous Positive Airway Pressure) ser considerada a teraputica de eleio para os doentes com SAOS, o seu efeito no abaixamento da presso arterial (PA) parece ser modesto, exigindo, por conseguinte, a implementao concomitante de teraputica anti-hipertensora. Acontece que so escassos os dados relativos aos regimes de frmacos anti-hipertensores utilizados em doentes com SAOS e, acresce ainda que, as guidelines teraputicas para o tratamento farmacolgico da HA, neste grupo particular de doentes, permanecem, at ao momento, inexistentes. A utilizao de modelos animais de hipxia crnica intermitente (CIH), que mimetizam a HA observada em doentes com SAOS, revela-se extremamente importante, uma vez que se torna imperativo identificar frmacos que promovam um controle adequado da PA neste grupo de doentes. No entanto, estudos concebidos com o intuito de investigar o efeito anti-hipertensor dos frmacos neste modelo animal revelam-se insuficientes e, por outro lado, os escassos estudos que testaram frmacos anti-hipertensores neste modelo no foram desenhados para responder a questes de natureza farmacolgica. Acresce ainda que se torna imprescindvel garantir a escolha de um mtodo para administrao destes frmacos que seja no invasivo e que minimize o stress do animal. Embora a gavagem seja uma tcnica indiscutivelmente eficaz e amplamente utilizada para a administrao diria de frmacos a animais de laboratrio, ela compreende uma sequncia de procedimentos geradores de stress para os animais e, que podem por conseguinte, constituir um vis na interpretao dos resultados obtidos. O objectivo global da presente investigao translacional foi contribuir para a identificao de frmacos anti-hipertensores mais efectivos para o tratamento da HT nos indivduos com SAOS e investigar mecanismos subjacentes aos efeitos sistmicos associadas SAOS bem como a sua modulao por frmacos anti-hipertensores. Os objectivos especficos foram: em primeiro lugar,encontrar novos critrios, baseados nas medidas antropomtricas, que permitam a identificao de doentes com suspeita de SAOS, que erroneamente se auto-classifiquem como nohipertensos, e desta forma promover um uso mais criterioso do MAPA; em segundo lugar, investigar a existncia de uma hipottica associao entre os esquemas de frmacos antihipertensores e o controle da PA (antes e aps a adaptao de CPAP) em doentes com SAOS em terceiro lugar, avaliar a eficcia do carvedilol (CVD), um frmaco bloqueador -adrenrgico no selectivo com actividade antagonista 1 intrnseca e propriedades anti-oxidantes num modelo animal de hipertenso induzida pela CIH; em quarto lugar, explorar os efeitos da CIH sobre o perfil farmacocintico do CVD; e, em quinto lugar, investigar um mtodo alternativo gavagem para a administrao crnica de frmacos anti-hipertensores a animais de laboratrio. Com este intuito, na primeira fase deste projecto, fizemos uso de uma amostra com um nmero aprecivel de doentes com SAOS (n=369), que acorreram, pela primeira vez, consulta de Patologia do Sono do CHLN e que foram submetidos a um estudo polissonogrfico do sono, MAPA e que preencheram um questionrio que contemplava a obteno de informao relativa ao perfil da medicao anti-hipertensora em curso. Numa segunda fase, utilizmos um modelo experimental de HT no rato induzida por um paradigma de CIH. Do nosso trabalho resultaram os seguintes resultados principais: em primeiro lugar, o ndice de massa corporal (IMC) e o permetro do pescoo (PP) foram identificados como preditores independentes de auto-classificao errnea da HA em doentes com suspeita de SAOS; em segundo lugar, no encontramos qualquer associao com significado estatstico entre os vrios esquemas de frmacos anti-hipertensores bem como o nmero de frmacos includos nesse esquemas, e o controle da PA (antes e depois da adaptao do CPAP); em terceiro lugar, apesar das doses de 10, 30 e 50 mg/kg de carvedilol terem promovido uma reduo significativa da frequncia cardaca, no foi observado qualquer decrscimo na PA no nosso modelo animal; em quarto lugar, as razes S/(R+S) dos enantimeros do CVD nos animais expostos CIH e a condies de normxia revelaram-se diferentes; e, em quinto lugar, a administrao oral voluntria mostrou ser um mtodo eficaz para a administrao diria controlada de frmacos anti-hipertensores e que independente da manipulao e conteno do animal. Em concluso, os resultados obtidos atravs do estudo clnico revelaram que o controle da PA, antes e aps a adaptao do CPAP, em doentes com SAOS independente, quer do esquema de frmacos anti-hipertensores, quer do nmero de frmacos includos num determinado esquema. Os nossos resultados salientam ainda a falta de validade da chamada self-reported hypertension e sugerem que em todos os doentes com suspeita de SAOS, com HA no diagnosticada e com um IMC e um PP acima de 27 kg/m2 e 39 cm, respectivamente, a confirmao do diagnstico de HA dever ser realizada atravs da MAPA, ao invs de outros mtodos que com maior frequncia so utilizados com este propsito. Os resultados obtidos no modelo animal de HA induzida pela CIH sugerem que o bloqueio do sistema nervoso simptico, juntamente com os supostos efeitos pleiotrpicos do CVD, no parece ser a estratgia mais adequada para reverter este tipo particular de hipertenso e indicam que as alteraes farmacocinticas induzidas pela CIH no ratio S/(R+S) no justificam a falta de eficcia anti-hipertensora do CVD observada neste modelo animal. Por ltimo, os resultados do presente trabalho suportam ainda a viabilidade da utilizao da administrao oral voluntria, em alternativa gavagem, para a administrao crnica de uma dose fixa de frmacos anti-hipertensores.---------------------------- ABSTRACT: Hypertension (HT) is a highly prevalent condition, although under diagnosed, in patients with obstructive sleep apnea (OSA). These conditions are closely related and 24-hour ambulatory blood pressure monitoring (ABPM) seems to be the most accurate measurement for diagnosing hypertension in OSA. However, this diagnostic tool is expensive and time-consuming and, therefore, not routinely used. On the other hand, although continuous positive airway pressure (CPAP) is considered the gold standard treatment for symptomatic OSA, its lowering effect on blood pressure (BP) seems to be modest and, therefore, concomitant antihypertensive therapy is still required. Data on antihypertensive drug regimens in patients with OSA are scarce and specific therapeutic guidelines for the pharmacological treatment of hypertension in these patients remain absent. The use of animal models of CIH, which mimic the HT observed in patients with OSA, is extremely important since it is imperative to identify preferred compounds for an adequate BP control in this group of patients. However, studies aimed at investigating the antihypertensive effect of antihypertensive drugs in this animal model are insufficient, and most reports on CIH animal models in which drugs have been tested were not designed to respond to pharmacological issues. Moreover, when testing antihypertensive drugs (AHDs) it becomes crucial to ensure the selection of a non-invasive and stress-free method for drug delivery. Although gavage is effective and a widely performed technique for daily dosing in laboratory rodents, it comprises a sequence of potentially stressful procedures for laboratory animals that may constitute bias for the experimental results. The overall goal of the present translational research was to contribute to identify more effective AHDs for the treatment of hypertension in patients with OSA and investigate underlying mechanisms of systemic effects associated with OSA, as well as its modulation by AHDs. The specific aims were: first, to find new predictors based on anthropometric measures to identify patients that misclassify themselves as non-hypertensive, and thereby promote the selective use of ABPM; second, to investigate a hypothetical association between ongoing antihypertensive regimens and BP control rates in patients with OSA, before and after CPAP adaptation; third, to determine, in a rat model of CIH-induced hypertension, the efficacy of carvedilol (CVD), a nonselective beta-blocker with intrinsic anti-1-adrenergic activity and antioxidant properties; fourth, to explore the effects of CIH on the pharmacokinetics profile of CVD and fifth, to investigate an alternative method to gavage, for chronic administration of AHDs to laboratory rats. For that, in the first phase of this project, we used a sizeable sample of patients with OSA (n=369), that attended a first visit at Centro Hospitalar Lisboa Norte, EPE Sleep Unit, and underwent overnight polysomnography, 24-h ABPM and filled a questionnaire that included ongoing antihypertensive medication profile registration. In the second phase, a rat experimental model of HT induced by a paradigm of CIH that simulates OSA was used. The main findings of this work were: first, body mass index (BMI) and neck circumference (NC) were identified as independent predictors of hypertension misclassification in patients suspected of OSA; second, in patients with OSA, BP control is independent of both the antihypertensive regimen and the number of antihypertensive drugs, either before or after CPAP adaptation; third, although the doses of 10, 30 and 50 mg/Kg of CVD promoted a significant reduction in heart rate, no decrease in mean arterial pressure was observed; fourth, the S/(R+S) ratios of CVD enantiomers, between rats exposed to CIH and normoxic conditions, were different and fifth, voluntary ingestion proved to be an effective method for a controlled daily dose administration, with a define timetable, that is independent of handling and restraint procedures. In conclusion, the clinical study showed that BP control in OSA patients is independent of both the antihypertensive regimen and the number of antihypertensive drugs. Additionally, our results highlight the lack of validity of self-reported hypertension and suggest that all patients suspected of OSA with undiagnosed hypertension and with a BMI and NC above 27 Kg/m2 and 39 cm should be screened for hypertension, through ABPM. The results attained in the rat model of HT related to CIH suggest that the blockade of the sympathetic nervous system together with the putative pleiotropic effects of carvedilol is not able to revert hypertension induced by CIH and point out that the pharmacokinetic changes induced by CIH on S/(R+S) ratio are not apparently responsible for the lack of efficacy of carvedilol in reversing this particular type of hypertension. Finally, the results here presented support the use of voluntary oral administration as a viable alternative to gavage for chronic administration of a fixed dose of AHDs.
Resumo:
With GS Strategy 2025 BASF Business Services GmbH was formed to centrally steer all IT related topics of BASF group. Thus, a global charging system has to be designed, which complies to international transfer price regulations and the strategy of BASF SE. This work project develops a charging system with a following evaluation. The direct charging system benefits from its cost transparency upsides but comes with a higher administrative effort due to volume-based charging. In contrast, the indirect charging system convinces because of easy handling, which is the result of the application of suitable allocation keys. Regarding the complex group structure of BASF SE with more than 300 legal entities in 80 countries, the lower administrative effort of the indirect charging system outweighs the benefits of the direct charging model and should be used by BASF group.
