A avaliação do estado de saúde percebido tem sido um tema de pesquisa imprescindível na área da saúde, visto que seus resultados contribuem para definir tratamentos, avaliar custo/benefício do cuidado, além de reduzir as taxas de morbimortalidade. Os objetivos deste estudo foram: comparar a presença de sintomas, o estado de saúde percebido e o grau de severidade da depressão, segundo o diagnóstico da Síndrome Isquêmica Miocárdica Instável (SIMI): Infarto Agudo do Miocárdio (IAM) versus Angina Instável (AI); investigar a presença de possíveis relações entre o estado de saúde percebido e o grau de severidade da depressão nos dois grupos e analisar a variância da medida do estado de saúde percebido e do grau de severidade da depressão explicada por variáveis preditoras. Estudo descritivo, correlacional e transversal, desenvolvido na Unidade Coronariana e enfermarias da cardiologia de dois hospitais públicos do interior de São Paulo. Entrevistas individuais foram realizadas pela pesquisadora com a coleta de dados para caracterização sociodemográfica e clínica, questionário de sintomas associados à SIMI, avaliação do estado de saúde percebido (SF-36) e depressão (Inventário de Depressão de Beck). Os dados foram analisados utilizando o teste de associação (Qui-quadrado), teste t de Student para amostras independentes e o teste de correlação de Pearson. Foram construídos cinco modelos de regressão linear múltipla, a fim de se verificarem as porcentagens da variância que eram explicadas por cada uma das variáveis preditoras. O nível de significância adotado foi de 0,05. Participaram da investigação 253 pacientes, sendo 142 diagnosticados com IAM, com idade média de 55,8 anos e a maioria homens (74,6%). No grupo de AI (111 pacientes), a idade média foi de 60,6 anos, e a maioria também foi do sexo masculino (62,2%). Com relação ao estado de saúde percebido, pode-se observar que as melhores avaliações foram relatadas pelos pacientes que sofreram um IAM, assim como apresentaram menor grau de severidade de depressão do que quando comparados com pacientes com AI. Foram observadas correlações negativas entre o estado de saúde percebido e a depressão nos dois grupos de pacientes, sendo de forças fracas a forte no grupo de infartados e de moderadas a forte no grupo de angina, todas são estatisticamente significantes. Utilizando como variáveis preditoras o sexo, a idade, a presença de tratamentos prévios para doenças cardiovasculares e a manifestação da SIMI, foram obtidos valores de R2 ajustados de 0,138; 0,231; 0,129 e 0,117 para os domínios Aspectos Físicos, Capacidade Funcional, Dor e Aspectos Emocionais, respectivamente. A inclusão da medida de depressão e o uso de psicofármacos elevaram os valores para 0,251; 0,349; 0,259 e 0,263, todos são aumentos estatisticamente significantes. Com relação ao modelo construído para a depressão, utilizando as mesmas variáveis preditoras dos modelos anteriores, o R2 ajustado encontrado foi de 0,149. Conclui-se que os pacientes com AI apresentaram maior comprometimento em todos os domínios avaliados pelo SF-36, quando comparados com os pacientes com IAM, assim como reportaram maior grau de severidade de depressão. Além disso, pacientes com maior grau de depressão apresentaram piores avaliações do estado de saúde percebido. / Perceived health state assessment has been a fundamental research theme in health, as its results contribute to define treatments, assess the cost/benefit of care and reduce morbidity/mortality rates. This research aimed to: compare the presence of symptoms, the perceived health state and the severity degree of depression according to the diagnosis of Acute Coronary Syndrome (ACS): Acute Myocardial Infarction (AMI) versus Unstable Angina (UA); investigate the presence of possible relations between perceived health state and the severity degree of depression in the two groups and analyze the variance in the perceived health state and the severity degree of depression measure explained by predictive variables. Study descriptive, correlational and cross-sectional, developed at the Coronary Unit and cardiology wards of two public hospitals in the interior of São Paulo, Brazil. The researcher held individual interviews, collecting sociodemographic and clinical characterization data and applying a questionnaire on ACS-associated symptoms, an instrument to assess the perceived health state (SF-36) and depression (Beck Depression Inventory). Data were analyzed using the association test (Chi-square), Students t-test for independent samples and Pearsons correlation test. Five multiple linear regression models were constructed to verify the variance percentages explained by each of the predictive variables. The significance level was set at 0.05. Research participants were 253 patients, 142 of whom were diagnosed with AMI, with an average age of 55.8 years and mostly men (74.6%). In the UA group (111 patients), the average age was 60.6 years and patients were mostly male (62.2%) too. With regard to the perceived health state, the best assessments came from patients victims of AMI, who also presented minor severity degree of depression when compared with UA patients. Negative correlations were observed between perceived health state and the severity degree of depression in both patient groups, which were weak to strong in the infarction group and moderate to strong in the angina group, all statistically significant. Using gender, age, presence of previous treatments for cardiovascular diseases and ACS manifestations as predictive variables, adjusted R2 levels amounted to 0.138; 0.231; 0.129 and 0.117 for Physical Aspects, Functional Capacity, Pain and Emotional Aspects, respectively. The inclusion of the depression measure and the use of psychotropic drugs raised levels to 0.251; 0.349; 0.259 and 0.263, all statistically significant increases. With regard to the model constructed for depression, using the same predictive variables as in earlier models, the adjusted R2 was 0.149. In conclusion, all SF-36 domains were more committed among patients with UA than among patients with AMI. UA patients also reported higher severity degree of depression more frequently. Moreover, patients with higher severity degree of depression presented worse assessments of the perceived health state.

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2017-02-24T13:52:37Z No. of bitstreams: 1 tiagoamaschiodelima_dissert.pdf: 1551815 bytes, checksum: 306de498464b225cff49cd1ad34c1862 (MD5) / Made available in DSpace on 2017-02-24T13:52:37Z (GMT). No. of bitstreams: 1 tiagoamaschiodelima_dissert.pdf: 1551815 bytes, checksum: 306de498464b225cff49cd1ad34c1862 (MD5) Previous issue date: 2016-05-31 / Introduction: Despite the need, it is verified the use of high number of drugs in patients affected by Acute Coronary Syndrome, causing problems related to drugs, among them, the drug interactions representing serious problems, resulting in severe adverse events or inefficacy of drug therapy. Objectives: The aim of this study was to investigate the prescriptions for elderly diagnosed with acute coronary syndrome hospitalized in the clinical cardiology unit of a teaching hospital and to determine the rate of theoretical potential drug interactions present in prescriptions. Methods: Descriptive exploratory study with analysis of 607 medical prescriptions throughout the period of hospitalization of 119 elderly patients 60 years or older in the period from April to July 2014. We collected demographic data from the patients, the information related to prescription drugs and the prescription indicators. The computerized databases Micromedex, Drugs and Medscape were used to identify the drug interactions that were classified according to their intensity level, mechanism and documentation. Results: The average age was 71 ± 8 and 55% were male. It was identified the quantitative of 7266 prescription drugs and the average of 12 ± 3 drugs per prescription, minimum of three and maximum of 23 prescription drugs. The most prescribed therapeutic classes were antiplatelets, anticoagulants, analgesics and antilipemics. Acetylsalicylic acid, Atorvastatin, dipyrone, and clopidogrel were the most prescribed drugs. The oral administration and the tablets were the most used. Only 74% were prescribed in accordance with the generic nomenclature, most obeyed the hospital standardization list, and there was a low frequency of antimicrobial and controlled drugs. 10162 interactions were detected and distributed among 554 types of different combinations of prescribed drugs and 99% of prescriptions presented at least one and maximum of 53 interactions, being highlighted the prevalence of moderate and major, 64% and 25%, respectively. There was a correlation between the number of interactions and the number of prescription drugs and hospitalization time. Conclusions: The high rate of interactions present in the prescriptions of patients with Acute Coronary Syndrome emphasizes the importance of clinical pharmacists activities for the identification and management of interactions, and monitoring of patients through critical analysis based on evidence, contributing to the necessary medical interventions and achieves better therapeutic results. The information gathering on the profile of prescription performed by clinical pharmacists in partnership with the multidisciplinary health team contributes to the analysis of clinical and scientific data, optimization of pharmacotherapy, the reduction of pharmacotherapeutic results unfavorable and pharmacoeconomics in the health system. / Introdução: Verifica a utilização de elevado arsenal de medicamentos em pacientes hospitalizados acometidos por Síndrome Coronariana Aguda, que apesar da necessidade, acarreta problemas relacionados aos medicamentos, dentre eles, as interações medicamentosas representam sérios problemas, resultando em eventos adversos graves ou ineficácia da terapia medicamentosa. Objetivos: Investigar as prescrições para idosos com idade igual ou superior a 60 anos e com diagnóstico de Síndrome Coronariana Aguda, hospitalizados na unidade da Cardiologia Clínica de um hospital de ensino e identificar as interações medicamentosas potenciais teóricas presentes nas prescrições. Métodos: Estudo descritivo exploratório com análise de 607 prescrições médicas durante todo o período de hospitalização de 119 pacientes idosos no período de abril a julho de 2014. Foram coletados os dados demográficos dos pacientes, as informações relacionadas aos medicamentos prescritos, e os indicadores de prescrição. Foram utilizadas as bases de dados informatizadas Micromedex, Drugs e Medscape para identificação das interações medicamentosas que foram classificadas de acordo com seu nível de intensidade, mecanismo e documentação. Resultados: A média de idade foi 71 ± 8 e 55% eram do gênero masculino. Identificou-se o quantitativo de 7266 medicamentos prescritos e média de 12 ± 3 medicamentos por prescrição, mínima de três e máxima de 23 medicamentos prescritos. As classes terapêuticas mais prescritas foram antiplaquetários, anticoagulantes, antilipêmicos e analgésicos. Ácido Acetilsalicílico, atorvastatina, dipirona, e clopidogrel foram os fármacos mais prescritos. A via oral e a forma farmacêutica comprimido foram as mais utilizadas. 74% foram prescritos de acordo com a nomenclatura genérica, a maior parte obedeceu à lista de padronização do hospital, e houve baixa frequência de antimicrobianos e medicamentos controlados. Foram detectadas 10162 interações, distribuídas entre 554 tipos de combinações diferentes dentre os medicamentos prescritos, e 99% das prescrições apresentaram pelo menos uma e máximo de 53 interações, destacando-se a prevalência das moderadas e maiores, 64% e 25%, respectivamente. Houve correlação entre o número de interações e o número de medicamentos prescritos e o tempo de hospitalização. Conclusões: A elevada taxa de interações encontradas nas prescrições de pacientes com Síndrome Coronariana Aguda demonstra a importância da atuação de farmacêuticos clínicos para a identificação e manejo das interações, e monitoramento dos pacientes, através de análise crítica baseada em evidências, contribuindo para as intervenções médicas necessárias, e alcançar melhores resultados terapêuticos. O levantamento de informações sobre o perfil da prescrição realizado por farmacêuticos clínicos em parceria com a equipe multidisciplinar em saúde contribui para a análise de dados clínicos e científicos, a otimização da farmacoterapia, a redução de resultados terapêuticos desfavoráveis, e farmacoeconomia no sistema de saúde.

<p>Uvod: Kardiovaskularne bolesti predstavljaju vodeći uzrok obolevanja i umiranja savremenog čoveka i vodeći su javno-zdravstveni problem u svetu i kod nas. Brojna istraživanja sugeri&scaron;u da se mediteranski način ishrane povezuje sa smanjenjem rizika za nastanak i razvoj kardiovaskularnih bolesti i drugih masovnih nezaraznih bolesti kao i smanjenjem stope ukupnog mortaliteta. Cilj istraživanja: Utvrditi stepen pridržavanja mediteranskom načinu ishrane kod obolelih od akutnog koronarnog sindroma i kod osoba sa utvrđenim rizikom za nastanak kardiovaskularnih bolesti, upotrebom validovanog skora mediteranske ishrane &ndash; MedDiet skora. Takođe, cilj istraživanja je bio da se utvrdi da li postoji značajna razlika u vrednostima biohemijskih i kliničkih faktora rizika za razvoj kardiovaskularnih bolesti između dve posmatrane grupe ispitanika, kao i da se odredi granična vrednost MedDiet skora između poželjnog i rizičnog načina ishrane za nastanak akutnog koronarnog sindroma. Metod: Istraživanje je sprovedeno kao analitička studija preseka na uzorku od 294 ispitanika (146 žena i 148 mu&scaron;karaca), starosti od 30 do 82 godine. Istraživanje je sprovedeno u vremenskom periodu od 07.02.2016. godine do 16.03.2017. godine. Prvu grupu činili su ispitanici kod kojih je&nbsp; dijagnostikovan akutni koronarni sindrom, koji su hospitalizovani u Institutu za kardiovaskularne bolesti Vojvodine u Sremskoj Kamenici, dok su drugu grupu činili ispitanici kod kojih je utvrđeno prisustvo najmanje jednog faktora rizika za nastanak kardiovaskularnih bolesti, bez klinički manifestne koronarne bolesti, koji su se javili na pregled u Savetovali&scaron;te za pravilnu ishranu, Instituta za javno zdravlje Vojvodine u Novom Sadu. Kod svih učesnika u studiji izvr&scaron;ena su: antropometrijska merenja, merenje arterijskog krvnog pritiska, odgovarajuće biohemijske analize, EKG i anketiranje upotrebom posebno pripremljenog upitnika, u čijem sastavu se nalazio i MedDiet skor &ndash; validovan skor system za procenu stepena zastupljenosti mediteranskog načina ishrane kod pojedinca. Rezultati istraživanja: Srednja vrednost MedDiet skora ispitanika bez akutnog koronarnog sindroma bila je 27,48&plusmn;6,59, dok je srednja vrednost MedDiet skora ispitanika sa akutnim koronarnim sindromom bila 20,53&plusmn;4,01. Razlika srednjih vrednosti MedDiet skora između dve grupe ispitanika bila je statistički značajna (p=0,029). Ispitivanjem prediktivnih vrednosti pojedinih varijabli utvrđeno je da su MedDiet skor i glikemija na&scaron;te odlični markeri za akutni koronarni sindrom (AUROC=0,815, p&lt;0,0005 i AUROC=0,829, p&lt;0,0005, respektivno). Rezultati istraživanja su pokazali da konzumiranje pojedinih namirnica iz kategorija definisanih MedDiet skorom (voće, povrće, živinsko meso i maslinovo ulje) može doprineti smanjenju rizika za nastanak akutnog koronarnog sindroma. Konzumiranje crvenog mesa i mesnih prerađevina povećava rizik od pojave akutnog koronarnog sindroma. Utvrđena granična vrednost MedDiet skora iznosila je 22,5. Vrednosti MedDiet skora &le;22,5 predstavljaju faktor rizika za nastanak akutnog koronarnog sindroma, dok vrednosti MedDiet skora &gt;22,5 ukazuju na smanjen rizik za nastanak akutnog koronarnog sindroma. Multivarijantnom regresionom analizom pokazano je da na pojavu akutnog koronarnog sindroma utiču sledeći faktori rizika: godine starosti 1,063 (1,270-1,819), mu&scaron;ki pol 4,071 (1,901-8,719), pu&scaron;enje 3,067 (1,322-7,114), indeks telesne mase 0,902 (0,839-0,970), sistolni pritisak 1,020 (1,003-1,037), glikemija na&scaron;te 1,520 (1,025-1,101) i MedDiet skor 0,783 (0,722-0,849). Zaključak: Akutni koronarni sindrom predstavlja značajan javno-zdravstveni problem odraslog stanovni&scaron;tva u Republici Srbiji na &scaron;ta ukazuju visoke prevalencije u populaciji. Rezultati sprovedenog istraživanja pokazuju da je i diskretnim povećanjem unosa namirnica koje predstavljaju osnovu mediteranskog načina ishrane moguće postići značajne zdravstvene koristi. Ovi rezultati mogu predstavljati okvir za razvoj lokalnog skoring sistema ishrane prikladnog za nemediteransko područje, kao i modela za procenu rizika za nastanak akutnog koronarnog sindroma u na&scaron;oj populaciji.</p> / <p>Introduction: Cardiovascular diseases are the leading cause of morbidity and mortality of a modern society and are major public health problem in our country and also worldwide. Numerous studies suggest that the Mediterranean diet is associated with a reduction in the risk of developing cardiovascular diseases and other non-communicable diseases, as well as reduction in the overall mortality rate. Aim: To determine the degree of Mediterranean diet complience in subjects with acute coronary syndrome and subjects with an established risk for developing cardiovascular diseases, using validated Mediterranean diet score - MedDiet. Also, the aim of the study was to determine whether there is a significant difference in the values of the&nbsp; biochemical and clinical risk factors for the development of cardiovascular diseases between the two observed groups of subjects, and to determine the cut-off value of the MedDiet score between the favorable and unfavorable dietaty pattern for the development of acute coronary&nbsp; syndrome. Method: The study was conducted as an analytical cross-sectional study with enrollment of 294 subjects (146 women and 148 men), 30 to 82 years of age. The research was conducted during the period from 02/07/2016 until 03/16/2017. The first group of subjects consisted of patients diagnosed with acute coronary syndrome who were hospitalized at the Institute for Cardiovascular Diseases Vojvodina in Sremska Kamenica. The second group was comprised of subjects with established at least one major risk factor for the development of cardiovascular diseases but without clinically manifest coronary artery disease, who came to the medical examination of the Counseling Center for Proper Nutrition, Institute of Public Health of Vojvodina in Novi Sad. Among all participants in the study the following examinations were conducted: anthropometric measurements, arterial blood pressure measurements, appropriate biochemical analysis, ECG and surveys using a specially prepared questionnaire, which included MedDiet score - validated score system for assessing the degree of compliance with Mediterranean dietary pattern among subjects. Results of the study: The average value of the MedDiet score among subjects without acute coronary syndrome was 27.48 &plusmn; 6.59, while the average value of MedDiet score among subjects with acute coronary syndrome was 20.53 &plusmn; 4.01. The difference in MedDiet average values between the two groups of subjects was statistically significant (p = 0.029). By examining the predictive values of individual variables, it was shown that MedDiet score and fasting blood sugar were excellent markers for acute coronary syndrome (AUROC = 0.815, p&lt;0.0005 and AUROC = 0.829, p &lt;0.0005, respectively). The results of the study showed that the consumption of certain foods in the categories defined by MedDiet score (fruits, vegetables, poultry, and olive oil) can contribute to reduction of the risk for developing acute coronary syndrome. On the other hand, consuming red meat and meat products increased the risk of acute coronary syndrome. The established cut-off value for MedDiet score was 22.5. MedDiet score &le;22.5 practicaly indicated greater risk for the development of acute coronary syndrome, while MedDiet score&gt; 22.5 indicated reduced risk for the development of acute coronary syndrome. Multivariate regression analysis showed that acute coronary syndrome is affected by the following risk factors: age 1,063 (1,270-1,819), male gender 4,071 (1,901-8,719), smoking 3,067 (1,322-7,114), body mass index 0,902 (0.839-0.970 ), systolic blood pressure 1.020 (1.003-1.037), fasting blood sugar 1.520 (1.025-1.101) and MedDiet score 0.783 (0.722- 0.849). Conclusion: Acute coronary syndrome is a major public health problem in the adult population of the Republic of Serbia, as indicated by its high prevalence. The results of the conducted research show that discrete increase in food intakes of foods which represent the basis of the Mediterranean diet, can lead to significant health benefits. These results can represent a framework for the development of a local scoring system for a non-mediterranean area, and also for creation of risk assessment model for acute coronary syndrome in our population.</p>

A via de acesso arterial é um importante sítio de complicações após a realização de procedimentos coronários invasivos. Dentre as estratégias para a redução de complicações vasculares, encontra-se estabelecida a eficácia da técnica radial. Os dispositivos de oclusão vascular propiciam maior conforto ao paciente, reduzindo o tempo de hemostasia e repouso no leito. Entretanto, a inconsistência de dados comprovando sua segurança limita sua adoção rotineira como estratégia para redução de complicações vasculares, requerendo evidências de estudos randomizados com metodologia adequada. O objetivo deste estudo foi comparar a incidência de complicações no sítio de punção arterial entre a técnica radial e a técnica femoral com utilização de Angio-Seal em pacientes com síndrome coronariana aguda sem supradesnível do segmento ST submetidos à estratégia invasiva precoce. Trata-se de um ensaio clínico unicêntrico, de não inferioridade, no qual duzentos e quarenta pacientes foram randomizados para a técnica radial ou técnica femoral com utilização de Angio-Seal. O objetivo primário foi a ocorrência de complicações no sítio de punção arterial até 30 dias após o procedimento, incluindo sangramento grave, hematoma >= 5 cm, hematoma retroperitoneal, síndrome compartimental, pseudoaneurisma, fístula arteriovenosa, infecção, isquemia de membro, oclusão arterial, lesão de nervo adjacente ou necessidade de reparo vascular cirúrgico. Em relação às características demográficas e clínicas, houve diferença apenas quanto ao gênero, com presença maior de pacientes do sexo feminino no grupo radial (33,3% versus 20,0%, p=0,020). Não se observaram diferenças entre os grupos quanto ao diagnóstico de admissão, alterações isquêmicas presentes no eletrocardiograma, elevação de marcadores de necrose miocárdica ou escores de risco, bem como quanto à farmacoterapia antitrombótica adjunta e características da intervenção coronária percutânea. A hemostasia foi obtida na totalidade dos procedimentos do grupo radial com a utilização da pulseira compressora seletiva TR Band e em 95% dos procedimentos realizados pela técnica femoral com o Angio-Seal (p=0,029). Exceto pela maior incidência de oclusão arterial no grupo radial comparado ao femoral, não houve diferenças entre os demais desfechos analisados. Segundo o teste de não inferioridade para complicações na via de acesso arterial aos 30 dias, verificou-se que a utilização do Angio-Seal não produziu resultados inferiores ao acesso radial, considerando-se a margem de 15% (12,5% versus 13,3%, diferença -0,83%, IC 95% -9,31 - 7,65, p para não inferioridade <0,001). Os resultados principais deste estudo demonstram que, em uma população de pacientes com diagnóstico de síndrome coronariana aguda sem supradesnível do segmento ST, submetida à estratificação de risco invasiva, a utilização do dispositivo de oclusão vascular Angio-Seal confere ao procedimento efetivado pelo acesso femoral inferioridade na incidência de complicações no sítio de punção arterial aos 30 dias quando comparado ao acesso radial. / Arterial access is a major site of complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients decreasing hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using Angio-Seal for the incidence of arterial puncture site complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy. This study is a unicentric, non-inferiority clinical trial where two hundred and forty patients with non-ST-segment elevation acute coronary syndrome were randomized to either radial or femoral access using Angio-Seal. The primary outcome was the occurrence of complications at the arterial puncture site until 30 days after the procedure, including major bleeding, hematoma >= 5 cm, retroperitoneal hematoma, compartment syndrome, pseudoaneurysm, arteriovenous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgery repair. With respect to demographic and clinical characteristics, there were differences only in terms of gender, with greater presence of female patients in the radial group (33.3% versus 20.0%, p = 0.020). There were no differences between the groups regarding the diagnosis of admission, ischemic changes present in the electrocardiogram, elevation of myocardial necrosis markers or risk scores, as well as the adjunct antithrombotic pharmacotherapy and features of the percutaneous coronary intervention. Hemostasis was achieved in the entire radial group with the use of selective radial compressor TR Band and in 95% of the procedures performed by femoral technique with Angio-Seal (p = 0.029). Except for a higher incidence of arterial occlusion in the radial group compared to the femoral, there were no differences among the other outcomes analyzed. According to the non-inferiority test for arterial access site complications in 30 days, it was found that the use of Angio-Seal not produced results inferior to the radial approach, considering the margin of 15% (12.5% vs. 13.3%, difference -0.83%, 95% CI -9.31 - 7.65, p for noninferiority <0.001). The main results of this study demonstrated that in a population of patients diagnosed with non-ST segment elevation acute coronary syndrome, who underwent invasive risk stratification, the use of the Angio-Seal vascular closure device confers to the femoral approach noninferiority in the incidence of arterial puncture site complications at 30 days when compared to the radial approach.

Economic evaluations provide a tool to estimate costs and health consequences of competing medical technologies, ultimately to aid decision makers when deciding which medical technologies should be funded from available resources. Such decisions inevitably need to be taken under uncertainty and it is not clear how to approach them in health care decision-making. Recent work in economic evaluation has proposed an analytic framework where two related, but conceptually different decisions need to be considered: (1) should a medical technology be adopted given existing evidence; and (2) whether more evidence should be acquired to support the adoption decision in the future. The proposed analytic framework requires a decision-analytic model appropriately representing the clinical decision problem under consideration, a probabilistic analysis of this model in order to determine cost-effectiveness and characterise current decision uncertainty, and estimating the value of additional information from research to reduce decision uncertainty. The main aim of this thesis is to apply the analytic framework on three case studies concerning treatment strategies for cardiovascular disease in order to establish whether the treatment strategies should be adopted given current available information and if more information should be acquired to support the adoption decisions in the future. The implications for policy and methodology of utilising the analytic framework employed in the case studies are also discussed in this thesis. The results of the case studies show that a screening programme for abdominal aortic aneurysm in 65-year-old men is likely to be cost-effective in a Swedish setting and there appears to be little value in performing further research regarding this decision problem; an early interventional strategy in non-ST-elevation acute coronary syndrome is cost-effective for patients at intermediate to high risk of further cardiac events in a UK setting; endarterectomy in patients with an asymptomatic carotid artery stenosis is cost-effective for men around 73 years of age or younger in a Swedish setting and conducting further research regarding this decision problem is potentially worthwhile. Comparing the results of the present analyses with current clinical practice shows a need for changing clinical practice in Sweden regarding screening for abdominal aortic aneurysm and endarterectomy in patients with asymptomatic carotid artery stenosis. Furthermore, employing the analytic framework applied in the case studies can improve treatment guidelines and recommendations for further research. In particular, treatment guidelines ought to consider in which particular subgroups of patients an intervention is cost-effective. The case studies indicate that it is feasible to apply the analytic framework for economic evaluation of health care. Methodological development can improve the accuracy with which cost-effectiveness and value of information is estimated, but may also lead to comprehensive and complex evaluations. The nature of the decision problem should determine the level of comprehensiveness required for a particular evaluation.

Acute Coronary Syndrome (ACS) is common and associated with high mortality. Effective treatments are available but require prompt administration. Studies have consistently demonstrated that delays to treatment are common, with patient decision time accounting for most delay. Interventions aimed at reducing delay have had little success. Evidence suggests that psychological factors, in particular illness representations (Leventhal’s Commonsense Model of Self-Regulation (CS-SRM)) might be important in relation to patient decision time. This thesis describes a two-stage investigation, undertaken within NHS 24, exploring the content and timing of people’s initial presentations with possible symptoms of ACS. The first stage comprised a CS-SRM-guided content analysis of peoples’ initial symptom presentations. The second stage utilised the Illness Perception Questionnaire-revised (IPQ-R) to explore how illness representations relate to patient decision time. Results show that the components of illness representations accounted for 95% of participants’ initial presentations. The components most related to behaviour and outcome were volunteered least (cause, consequences, cure/control and coherence). Decision time for most participants (89%) was out-with the ideal and appraisal time accounted for most of the delay. Appraisal delay was shorter for those with fewer symptoms and high emotion. Illness delay was longer where the person making the call reported high treatment control. Interventions may need to raise awareness of the range of possible presentations and of the consequences associated with delay. Interventions should also provide guidance as to an appropriate time-limit for self-care. Individuals may benefit from being informed about how to respond to strong emotional responses. Interventions aimed at bystanders may need to differ from those for patients. People at high risk of ACS should be informed about how and when to access healthcare out-of-hours.

Les efforts investis pour diminuer les risques de développer un infarctus du myocarde sont nombreux. Aujourd’hui les médecins prennent connaissance des divers facteurs de risque connus prédisposant aux syndromes coronariens aigus (SCA) dans le but de prendre en charge les patients «à risque» [1]. Bien que le suivi rigoureux et le contrôle de certains facteurs de risque modifiables aient permis une meilleure gestion des cas de SCA, les cas d’infarctus persistent de manière encore trop fréquente dans le monde. Puisque d’importantes études ont démontré que les SCA pouvaient survenir sans même la présence des facteurs de risque conventionnels [2, 3], les chercheurs se sont penchés sur un autre mécanisme potentiellement responsable de l’avènement des SCA : l’inflammation. L’inflammation joue un rôle prépondérant dans l’initiation, la progression et les complications de l’athérosclérose [4, 5] mais aussi dans les situations post-infarctus [6, 7]. Au cours des dernières années, le contrôle du processus inflammatoire est devenu une cible de choix dans la prévention et le traitement des SCA. Cependant, malgré les efforts investis, aucun de ces traitements ne s’est avéré pleinement efficace dans l’atteinte du but ultime visé par une diminution de l’inflammation : la diminution de la mortalité. Le complément est un système complexe reconnu principalement pour son rôle primordial dans l’immunité [2]. Cependant, lorsqu’il est activé de manière inappropriée ou excessive, il peut être à l’origine de nombreux dommages cellulaires caractéristiques de plusieurs pathologies inflammatoires dont font partie les complications de l’athérosclérose et des événements post-infarctus. Le travail effectué dans le cadre de mon doctorat vise à établir les rôles physiopathologiques du complément dans les interactions de l’axe thrombose-inflammation caractéristiques des SCA dans le but ultime d’identifier des cibles thérapeutiques permettant le développement de nouvelles approches pour la prévention et le traitement de ces pathologies. Les principaux résultats obtenus durant mon cursus suggèrent d’abord que la voie alterne du complément peut représenter une cible thérapeutique de choix dans les maladies coronariennes aiguës puisque l’activation terminale du complément semble y être principalement causée par l’activation du cette voie. De faibles niveaux sériques de MBL (mannan-binding lectin) et une activation terminale négligeable du complément caractérisent plutôt la maladie coronarienne stable. En comparant l’activité relative de chacune des voies du complément chez des cohortes de patients traités ou non par un anticorps spécifique à la protéine C5 du complément (pexelizumab), un second volet démontre quant à lui qu’une inhibition de l’activation du C5 n’a pas d’effet bénéfique majeur sur l’inhibition de la formation du complexe sC5b-9 ou sur les événements cliniques subséquents. Par conséquent, nous avons exploré, à l’aide d’un modèle in vitro, les raisons de l’inefficacité du traitement. Les résultats révèlent que le blocage du C5 avec le pexelizumab inhibe la production de l’anaphylatoxine pro-inflammatoire C5a et du complexe terminal du complément sans toutefois avoir d’effet sur l’apoptose des cellules endothéliales produites induite par le sérum des patients atteints de STEMI. Finalement, une autre section stipule que l’atorvastatine diminue l’activation du complément induite par les plaquettes sanguines chez des patients hypercholestérolémiques, mettant en évidence l’importance du rôle de cette statine dans la réduction des effets délétères de l’activation du système du complément médié par les plaquettes. Ensemble, l’étude du rôle spécifique des différentes voies d’activation du complément dans des contextes pathologiques variés, l’analyse des effets d’une inhibition spécifique de la protéine C5 du complément dans la progression des SCA et la mise en évidence des interactions entre l’activation du complément et les plaquettes activées ont contribué au développement d’une meilleure connaissance des rôles physiopathologiques du complément dans la progression de la maladie coronarienne. / Many efforts have been made in lowering the risk of myocardial infarction in the general population. Most clinicians are knowledgeable of the several identified risk factors leading to the development of acute coronary syndromes (ACS), and in turn, insure a better follow-up for “at risk” patients [1]. Despite the fact that intensive efforts in controlling modifiable risk factors have led to a better management of new cases of ACS, myocardial infarction and its deleterious consequences are still a world plague. Because it as been shown that ACS can occur without the presence of traditional risk factors [3, 4], researchers have been interested in modifying new ACS biological pathways such as inflammation. Inflammation plays a key role in the initiation, progression, and complications of atherosclerosis [5, 6], but also in post-infarction situations [7, 8]. In the past years, inflammation markers have become important targets for the prevention and treatment of ACS. Despite intensive efforts, none of the yet tested drug was found to be effective in decreasing mortality. The complement system is mainly known for its fundamental role in innate and adaptive immunity [2]. However, excessive activation of the complement can lead to a significant number of deleterious effects such as inflammation, apoptosis, necrosis and cell lysis. Earlier findings have shown that complement is extensively activated in atherosclerotic lesions, particularly in vulnerable and ruptured plaques. The objective of my doctoral project was to establish the pathophysiological roles of complement in the axis inflammation-thrombosis of ACS with the ultimate goal of identifying new therapeutic targets leading to the development of new drugs for the prevention and treatment of these diseases. The main results obtained first suggest that the complement alternative pathway represents a potential therapeutic target in acute coronary disease since terminal complement activation occurs mainly by this specific pathway. Low MBL levels (mannan-binding lectin) in serum and negligible terminal complement activation rather characterize stable coronary artery disease. By comparing the relative activity of each pathway of the complement in patients treated or not by an antibody specific to the C5 protein of the complement (pexelizumab), other results show that an inhibition of C5 activation does not have a major beneficial effect on the inhibition of the sC5b-9 complex expression or on the subsequent clinical events. Consequently, we explored, using an in vitro model of endothelial cells, the reasons of this inefficiency. This work reveals that C5 inhibition by pexelizumab inhibits the production of the pro-inflammatory anaphylatoxin C5a and of the terminal complement complex without, however, effecting endothelial cell apoptosis induced by the serum of patients with STEMI. Finally, another section stipulates that atorvastatin decreases platelet-induced complement activation in hypercholesterolemic patients, highlighting the importance of statins in the reduction of the deleterious effects of platelets-induced complement activation. All together, the study of the specific role of the various pathways of complement activation in different pathological contexts, the analysis of the effects of a specific inhibition of the C5 complement protein in the progression of ACS and the highlighting of the interactions between complement and platelet activation contribute to the development of a better knowledge of the pathophysiological roles of the complement system in ACS.

p. 1-98 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-29T21:00:40Z No. of bitstreams: 1 77777777777777.pdf: 665283 bytes, checksum: 577f985d772a498c9f7d5bc8a10b4b25 (MD5) / Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-05-04T17:38:16Z (GMT) No. of bitstreams: 1 77777777777777.pdf: 665283 bytes, checksum: 577f985d772a498c9f7d5bc8a10b4b25 (MD5) / Made available in DSpace on 2013-05-04T17:38:16Z (GMT). No. of bitstreams: 1 77777777777777.pdf: 665283 bytes, checksum: 577f985d772a498c9f7d5bc8a10b4b25 (MD5) Previous issue date: 2010 / Dados epidemiológicos, experimentais e clínicos têm sugerido que a doença periodontal, especialmente a periodontite crônica, pode constituir um fator de risco para doenças cardiovasculares isquêmicas. A proposta deste estudo foi investigar a associação entre a doença periodontal e o infarto agudo do miocárdio (IAM) em indivíduos adultos. Uma revisão de literatura de estudos de caso-controle que estudaram essa associação foi sumarizada em uma meta-análise que demonstrou uma chance em dobro para ocorrência de desfechos cardiovasculares isquêmicos em presença da doença periodontal (OR = 2,52; IC 95%: [2.10 3.00], p< 0, 001). Uma estimativa próxima foi obtida por meio de um estudo de caso-controle com uma amostra de 621 indivíduos com 40 anos ou mais, que avaliou a chance de desenvolver o infarto agudo do miocárdio em portadores de doença periodontal do tipo periodontite. As co-variáveis investigadas foram: idade, sexo, raça/cor auto referida, nível de escolaridade, renda per capita, condição marital, prática de atividade física, hábito de fumar presente e passado, consumo de álcool, índice de massa corporal, nível glicêmico, colesterol total e frações, relação cintura-quadril, hipertensão arterial sistêmica. Os resultados encontrados mostraram que os portadores de doença periodontal tiveram uma chance quase em dobro de desenvolver infarto agudo do miocárdio em relação a indivíduos sem doença periodontal, mesmo após ajustar por hábito de fumar, nível de escolaridade, ocupação, diabetes e nível de HDL-colesterol tanto quando comparada a controles comunitários (ORajustada=1,89; IC 95%: [1,11- 3,28], p=0,018), quanto a controles hospitalares (ORajustada=1,92; IC 95% :[1,14-3,23], p=0,015). Ao se estimar a associação de periodontite crônica e níveis plasmáticos de proteína C-reativa em um sub-amostra (n=359), observou-se uma associação positiva e significante (ORajustada= 2,26; IC 95%: [1.30 - 3.93]), considerando também o efeito da idade, nível de escolaridade, sexo, gênero, hábito de fumar, HDL-colesterol e diabetes. Assim, no grupo estudado a exposição à DP aumentou a chance de ocorrência do IAM, bem com da proteína Creativa, independentemente de outros fatores, o que reafirma que a doença periodontal pode ser um marcardor ou um fator de risco para o aparecimento de alterações cardiovasculares isquêmicas, havendo necessidade de estudos adicionais para confirmação da relação causal entre elas. / Salvador

Introdução: O Sistema Manchester de Classificação de Risco tem como objetivo definir a prioridade clínica para atendimento médico de pacientes nos serviços de emergência. A avaliação de pacientes com suspeita de infarto agudo do miocárdio com sintomas típicos como a dor torácica realizada por meio do Sistema Manchester exige adequada sensibilidade e especificidade do sistema ao determinar a prioridade para atendimento médico. Objetivos: Os objetivos deste estudo foram integrar as melhores evidências disponíveis quanto a sensibilidade e especificidade do Sistema Manchester na classificação de pacientes com relação ao diagnóstico de síndrome coronariana aguda; estimar a sensibilidade e especificidade do Sistema Manchester na classificação de pacientes com dor torácica para a adequada priorização no que se refere ao diagnóstico de infarto agudo do miocárdio num hospital geral de ensino na cidade de São Paulo; e verificar associação entre o desempenho do Sistema Manchester na avaliação desses pacientes e variáveis selecionadas. Método: Este estudo foi desenvolvido em duas etapas, sendo a primeira uma revisão sistemática da literatura realizada segundo metodologia de revisões de acurácia de testes diagnósticos do Joanna Briggs Institute. Na segunda etapa do estudo foram estimadas a sensibilidade e a especificidade do Sistema Manchester na avaliação de pacientes com infarto agudo do miocárdio por meio de um estudo metodológico, transversal e retrospectivo. A sensibilidade e a especificidade do Sistema Manchester foram estimadas por meio da verificação da classificação estabelecida para pacientes com dor torácica que receberam ou não o diagnóstico médico de infarto agudo do miocárdio após a classificação. Resultados: Foram incluídos na revisão sistemática seis estudos com total de 54.176 participantes, todos de qualidade metodológica moderada, que apontaram valores de sensibilidade entre 70% e 80%. Dois estudos que apresentaram os dados necessários para o cálculo de especificidade, tiveram valores calculados de 59% e 97%. A amostra do estudo primário incluiu 10.087 episódios de classificação, sendo 52,3% de pacientes do sexo feminino com média de idade de 43,6 anos (DP=17,6). Do total de episódios, 139 tinham diagnóstico de infarto. A sensibilidade do Sistema Manchester foi de 44,6% e a especificidade foi de 91,3%. Houve associação estatisticamente significativa entre o desempenho do Sistema Manchester e a idade dos pacientes (p<0,001), com maior frequência de classificação incorreta nas faixas etárias mais altas. Não houve associação entre o sexo dos pacientes e o desempenho do Sistema Manchester. Conclusão: a recomendação para uso do Sistema Manchester na avaliação de pacientes no serviço de urgência em relação ao diagnóstico de síndrome coronariana aguda foi de grau B segundo graus de recomendação estabelecidos pelo Joanna Briggs Institute, o que remete a uma recomendação \"fraca\" para uma determinada estratégia de gestão da saúde. Essa conclusão decorre sobretudo da heterogeneidade dos critérios de inclusão e portanto das amostras dos estudos incluídos. Os resultados do estudo evidenciam a necessidade de se discutir formas de melhorar a sensibilidade desse sistema para a adequada priorização de pacientes com dor torácica. / Introduction: The Manchester Triage System aims to define the clinical priority of patients for medical care in the emergency department. The evaluation of patients with suspected acute myocardial infarction presenting typical symptoms such as chest pain using the Manchester Triage System requires proper sensitivity and specificity of the system in order to determine medical care priority. Objectives: The objectives of this study were: to integrate the best available evidence regarding the sensitivity and specificity of the Manchester Triage System in the evaluation of patients with the diagnose of acute coronary syndrome; to estimate the sensitivity and specificity of the Manchester Triage System in the classification of patients with chest pain to adequate prioritization in relation to the diagnose of acute myocardial infarction in a general teaching hospital in the city of São Paulo; to verify the association between the performance of the Manchester Triage System in the evaluation of these patients and selected variables. Methods: This study was developed in two stages, the first one consisted in a systematic review performed according to the methodology of diagnostic test accuracy systematic reviews from Joanna Briggs Institute. In the second stage of the study the sensitivity and specificity of the Manchester Triage System in the evaluation of patients with acute myocardial infarction were estimated though a methodological retrospective cross-sectional study. The sensitivity and specificity of the Manchester Triage System were estimated by verifying the classification of patients with chest pain who received or not the medical diagnosis of acute myocardial infarction. Results: The systematic review included six studies with a total of 54,176 participants, all of the studies with moderate methodological quality. The studies pointed sensitivity values from 70% to 80%. The specificity values calculated from two studies containing the necessary data were 59% and 97%. The sample of the performed primary study included 10,087 episodes of classification, 52.3% of the patients were females with average age of 43.58 years (SD=17.6). Of the total episodes, 139 had the diagnosis of infarction. The sensitivity of the Manchester Triage System was 44.6% and the specificity was 91.3%. There was statistically significant association between the performance of the Manchester Triage System and the age of the patients (p<0.001), with a higher frequency of incorrect classification in the older age groups. There was no observed association between the sex of the patients and the performance of the Manchester Triage System. Conclusion: Recommendation for the utilization of the Manchester Triage System in the evaluation of patients in emergency services to correct prioritization related to the diagnose of acute coronary syndrome was graded B according to the Joanna Briggs Institute grades of recommendation, which refers to a weak recommendation to a certain strategy for healthcare management. This finding is due to the heterogeneity of the inclusion criteria and therefore the samples of the included studies. The results of this study highlight the necessity of discussion about ways to improve the sensitivity of this system, for the adequate prioritization of patients with chest pain.

Acute coronary syndrome (ACS) is characterized by the occurrence of a set of signs and symptoms that are related to myocardial ischemia. Unstable angina (UA) and acute myocardial infarction with ST segment elevation (AMI-SST) and without ST segment elevation (AMI-SSST) comprise this syndrome. It stands out among the diseases that affect the cardiovascular system due to its high prevalence and its impact on mortality in the general population. Its formation occurs due to rupture or erosion of atheromatous plaque, producing progressive tissue ischemia. This ischemia may progress to necrosis of the cardiomyocytes and changes could be detected by laboratory biomarkers. The gold standard biomarkers for the diagnosis of myocardial necrosis are the cardiac troponins I (cTnI) or T (cTnT), which have nearly absolute myocardial specificity and clinical sensitivity, reflecting microscopic areas of myocardial necrosis. However, markers used for the detection of myocardial ischemia during the pre-infarction are potentially the most interesting because they offer the opportunity for early intervention to prevent progression of the infarction. Thus, a biomarker to detect myocardial ischemia in the absence of necrosis would add substantially to the current clinical tools. The main objectives of this study were: (a) to evaluate the binding of albumin to nickel in patients with suspected ACS and develop a laboratory method based on this property capable of detecting cardiac ischemia, (b) develop a test protocol on the binding of albumin to nickel adapted to the automated Cobas Mira, (c) to investigate the diagnostic features of this method in the diagnosis of ACS, and (d) compare the test results of albumin binding to nickel with the albumin cobalt- binding to investigate whether the type of metal used in the test interferes with the diagnostic features of the method. Patients with myocardial ischemia showed a reduction in the capacity of binding albumin to nickel. A test, which was adapted for the automated Cobas Mira, was developed to detect this change. The binding test of albumin to nickel showed a potential role in excluding the diagnosis of AMI and was effective in the diagnosis of ACS because of its significant negative and positive predictive values, respectively. The test using nickel showed a slightly higher skill in the diagnosis of ACS than the test using cobalt. Thus, we could conclude that the type of metal (nickel or cobalt) influences the characteristics of the diagnostic test. / A síndrome coronariana aguda (SCA) caracteriza-se pela ocorrência de um conjunto de sinais e sintomas que estão relacionados à isquemia miocárdica. A angina instável (AI) e o infarto agudo do miocárdio com elevação do segmento ST (IAM-SST) e sem elevação do segmento ST (IAM-SSST) compõem esta síndrome. Destaca-se dentre as doenças que acometem o sistema cardiovascular devido a sua alta prevalência e seu impacto sobre a mortalidade na população em geral. Sua formação ocorre devido à ruptura ou erosão da placa ateromatosa, produzindo isquemia progressiva tecidual, sendo que esta isquemia pode progredir para necrose dos cardiomiócitos, podendo as alterações serem detectadas por biomarcadores laboratoriais. Os biomarcadores padrão-ouro para o diagnóstico de necrose miocárdica são as troponinas cardíacas I (cTnI) ou T (cTnT), que tem quase absolutas especificidade miocárdica e sensibilidade clínica, refletindo zonas microscópicas de necrose miocárdica. No entanto, marcadores utilizados para detecção da isquemia miocárdica na fase pré-infarto são potencialmente os mais interessantes, pois oferecem a oportunidade de intervenção precoce para impedir a progressão do infarto. Desta forma, um biomarcador que realmente detecte isquemia miocárdica na ausência de necrose acrescentaria substancialmente às atuais ferramentas clínicas. Os objetivos principais deste estudo foram: (a) avaliar a ligação da albumina ao níquel em pacientes com suspeita de SCA e desenvolver um método laboratorial baseado nesta propriedade capaz de detectar a isquemia cardíaca; (b) desenvolver um protocolo do teste de ligação da albumina ao níquel adaptado ao sistema automatizado Cobas Mira; (c) investigar as características diagnósticas deste método no diagnóstico da SCA; (d) comparar os resultados obtidos no teste de ligação da albumina ao níquel com o teste de ligação da albumina ao cobalto a fim de investigar se o tipo de metal utilizado no ensaio interfere nas características diagnósticas do método. Os pacientes com isquemia do miocárdio apresentaram uma redução na capacidade de ligação da albumina ao níquel, sendo desenvolvido um teste capaz de detectar essa alteração, o qual foi adaptado para o sistema automatizado Cobas Mira. O teste de ligação da albumina ao níquel apresentou um potencial papel na exclusão diagnóstica do IAM e foi eficaz no diagnóstico da SCA em virtude de seus significativos valores preditivos negativo e positivo, respectivamente. O ensaio utilizando o níquel demonstrou uma habilidade discretamente superior no diagnóstico da SCA, do que o ensaio que utiliza o cobalto, o que permite concluir que o tipo de metal (níquel ou cobalto) influencia nas características diagnósticas do ensaio.