Thesis (Ph.D.)--University of Melbourne, Dept. of Opthalmology, 2007. / Typescript. SAFE Strategy refers to Surgery for trichiasis, Antibiotics for active infection, Facial cleanliness and Environmental improvements. Includes bibliographical references (leaves 233-253). Also available electronically: http://eprints.unimelb.edu.au/archive/00003844.

This diploma thesis on the theme:"The implementation of the International Health Regulations, 2005 in Czech Republic.", is divided into theoretical and practical part.The theoretical part focuses on the International Health Regulations 2005 capacity required, and the measures proposed in the Czech Republic. It describes the history of the International Health Regulations and the implementation of International Health Regulations 2005, in Czech Republic.I also deal, in this part of thesis, about highly contagious diseases.Data processing research for this study was collected in the district of Český Krumlov. The research was conducted by a qualitative method.The sample consisted of 8 respondents.The aim of the study was to determine whether practitioners know how to proceed in case of a patient with a highly contagious disease in their office.This diploma thesis could serve as a source of information, whether the Czech Republic meet the requirements formulated by the World Health Organization in the International Health Regulations 2005.

Submitted by Alexandre Sousa (alexandre.sousa@incqs.fiocruz.br) on 2015-04-10T14:28:00Z No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) / Approved for entry into archive by Alexandre Sousa (alexandre.sousa@incqs.fiocruz.br) on 2015-04-10T14:28:16Z (GMT) No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) / Approved for entry into archive by Alexandre Sousa (alexandre.sousa@incqs.fiocruz.br) on 2015-04-10T14:28:30Z (GMT) No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) / Made available in DSpace on 2015-04-10T14:28:30Z (GMT). No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) Previous issue date: 2015 / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde / O sistema público de saúde no Brasil ainda não supre completamente as necessidades básicas de saúde da população. Considerando a necessidade de ampliar o atendimento à saúde da população e disponibilizar opções de medicina tradicional e práticas complementares, o governo brasileiro criou políticas e programas de saúde pública para incentivar o uso de plantas medicinais e medicamentos fitoterápicos. Assim, plantas medicinais reconhecidamente eficazes vêm sendo utilizadas no atendimento das necessidades básicas de saúde da população para a cura de uma variedade doenças e sintomas. Grande parte da população brasileira utiliza plantas medicinais, incluindo pacientes de faixas etárias e grupos de risco diversos, e que muitas vezes residem em locais em precárias condições de saneamento básico. Portanto, as plantas medicinais devem ser produtos de qualidade garantida, para que seu uso seja seguro e não possua riscos à saúde dos consumidores. Neste estudo, 15 amostras de plantas medicinais das espécies Baccharis trimera, Bauhinia forficata e Tabebuia avellanedae, de lotes diferentes e de 4 marcas, compradas na cidade do Rio de Janeiro, foram avaliadas quanto à qualidade microbiológica. A análise consistiu na quantificação dos microrganismos viáveis e na pesquisa de patógenos presentes nas amostras. A escolha dos limites de contaminação microbiana e dos patógenos a serem pesquisados foi realizada com base nas possíveis formas de preparo e uso de plantas medicinais. Foi realizada a quantificação de bactérias aeróbias, bactérias Gram-negativas bile tolerantes e bolores e leveduras viáveis, e a pesquisa dos outros patógenos Escherichia coli, espécies de Salmonella, espécies de Shigella, Pseudomonas aeruginosa, Staphylococcus aureus e Candida albicans. As plantas medicinais analisadas apresentavam contaminação bacteriana e fúngica variável, onde 93,3% possuía carga de contaminação microbiana acima dos limites de contaminação permitidos para bactérias aeróbias e bolores e leveduras. Adicionalmente, foi identificada a contaminação pelos patógenos S. aureus, P. aeruginosa, E. coli e bactérias Gram negativasbile tolerantes em 20%, 20%, 46,6% e 100% das amostras, respectivamente. Nenhuma das amostras de plantas medicinais apresentou qualidade sanitária suficiente para ser aprovada para o uso (100% de reprovação), constituindo um problema para a saúde pública, visto que um produto terapêutico contaminado é disponibilizado para uma população que já se encontra enferma, e demonstrando a necessidade de um melhor controle e regulamentação para estes produtos. / The public health system in Brazil does not yet supplies completely the population basic needs for health. Considering the necessity to expand the health care and to provide traditional and complementary medicine options, the brazilian government created public health politics and programs to encourage the use of medicinal plants and phytotherapic drugs. Thus, medicinal plants admittedly effective have been used for the care of the population’s basic needs, to heal a variety of diseases and symptoms. A large portion of the brazilian population use medicinal plants, including a diversity of age and risk group patients, whose many times resides in places with precarious sanitary conditions. Therefore, medicinal plants need to be assured quality products, to be used safely and not bring risks to the user’s health. In this study, 15 medicinal plants samples of Baccharis trimera, Bauhinia forficata and Tabebuia avellanedae species, all from different batches from 4 brands, bought in the city of Rio de Janeiro, were evaluated about their microbiological contamination. The assay consisted in the quantification of viable microorganisms and in the search of pathogens present in the samples. The choosing of the microbiologic contamination limits and the pathogens to be searched was made based on the possible preparation methods and use of medicinal plants. Quantification of viable aerobic bacteria, bile tolerant Gram negative bacteria and yeasts and molds, and search of the others pathogens Escherichia coli, Salmonella species, Shigella species, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans were executed. The medicinal plants samples analyzed had variable bacterial and fungal contamination, where 93,3% had microbial contamination load above the allowed contamination limits for aerobical bacteria and yeasts and molds. Additionally, contamination by S. aureus, P. aeruginosa, E. coli, and bile tolerant Gram negative bacteria were identified in 20%, 20%, 46,6% and 100% of samples, respectively. No samples of medicinal plants had enough sanitary quality to be approved to use (100% disapproval), constituting a public health problem, since a highly contaminated therapeutic product is made available to a population who already is diseased, showing the need of better control and regulation to these products.

Made available in DSpace on 2016-12-23T13:54:30Z (GMT). No. of bitstreams: 1 Regina Furbino Villefort Rocha.pdf: 5172514 bytes, checksum: a4a9d38bcac502c5c9c1fe6298995e29 (MD5) Previous issue date: 2012-07-04 / Ameloblastomas são tumores odontogênicos (TOs) de origem epitelial e etiologia desconhecida. Porém, estudos recentes identificaram alterações moleculares associadas ao desenvolvimento e progressão dos TOs, dentre elas as móleculas de adesão celular E-caderina e beta catenina. Objetivos: realizar um levantamento epidemiológico dos casos de ameloblastomas pertencentes ao arquivo do Serviço de Anatomia Patológica da Universidade Federal do Espírito Santo (SAPB-UFES), analisar suas características histopatológicas e a expressão de beta catenina nas diferentes variantes de ameloblastomas. Método: estudo retrospectivo dos casos de ameloblastomas registrados no SAPB-UFES, no período compreendido entre março de 2004 e dezembro de 2010. Foram coletados dados sociodemográficos, clinicorradiográficos, dados sobre acesso, diagnóstico, tratamento e seguimento desses pacientes. As análises histopatológicas foram baseadas nos critérios de Vickers e Gorlin, Waldron e El-Mofty e da Organização Mundial da Saúde. Para análise imuno-histoquímica foi utilizada a técnica indireta de imuno-peroxidase, com anticorpo primário anti beta catenina monoclonal de camundongo. Foram avaliados a intensidade e a localização da marcação. Para análise semiquantitativa foram adotados os escores: negativo, postividade focal, positividade variável e uniformidade positiva. Resultados: foram encontrados 13 ameloblastomas, classificados histopatologicamente como sólidos (06), unicísticos (03) e desmoplásicos (03). Todos foram imunomarcados. A intensidade de marcação variou de fraca a forte (1 a 3). A média de marcação variou de 10,82% a 13,38% no núcleo; de 39,93% a 47,61% na membrana; e de 90,01% a 98,53% no citoplasma. Entretanto não foi encontrada diferença significante de expressão de beta catenina entre os três diferentes tipos de ameloblastomas. Conclusão: os resultados epidemiológicos foram semelhantes a outros estudos. A expressão citoplasmática de beta catenina evidencia o acúmulo da mesma no citoplasma e sugere alteração na via de sinalização de Wnt. Por outro lado, a redução da expressão na membrana sugere alteração na adesão celular / Ameloblastomas are odontogenic tumors (OTs) derived from epithelium which etiology remains unknown. However, recent studies have identified molecular changes associated with the development and progression of OTs, including cell adhesion molecules like E-cadherin and beta-catenin. Objectives: to conduct an epidemiological investigation of ameloblastomas cases from files of the Anatomical Pathology Service at Federal University of Espírito Santo (SAPB-UFES), analyze their histopathological features and the expression of beta-catenin in different variants of ameloblastomas. Methods: a retrospective study of ameloblastomas registered at SAPB-UFES between March 2004 and December 2010. Sociodemographic, clinical and imaginological data were collected, as well as data about access, diagnosis, treatment and follow up of these patients. The histopathological analyzes were based on Vickers and Gorlin, Waldron and El-Mofty and the World Health Organization criteria. Primary antibody anti beta-catenin mouse monoclonal and indirect immuno-peroxidase technique was employed for immunohistochemical analysis. Intensity and location of the immunostaining were analysed. For semiquantitative analysis the scores were: negative, focal, variable and uniformity positivity. Results: there were 13 ameloblastomas, histopathologically classified as solid (06), unicystic (03) and desmoplastic (03). All of them were immunostained. The intensity of immunostaining ranged from weak to strong (1-3). The mean of immunostaining ranged from 10.82% to 13.38% in the nucleus; from 39.93% to 47.61% in the membrane; and from 90.01% to 98.53% in the cytoplasm. However, there was no significant difference in expression of beta-catenin between three different types of ameloblastomas. Conclusion: The results were similar to other epidemiological studies. The cytoplasmic expression of beta-catenin shows accumulation in the cytoplasm and suggests changes in the Wnt signaling pathway. Moreover, the reduction of membrane expression suggests changes in cell adhesion

Introdução O Transtorno de Déficit de Atenção/hiperatividade (TDAH) tem sido muito estudado, mas informações econômicas referentes ao seu tratamento com o metilfenidato de liberação imediata (MFD-LI) ainda necessitam ser exploradas. Grande parte da população mundial, principalmente aqueles que vivem em países em desenvolvimento, utiliza essa formulação como principal escolha para o tratamento do TDAH. Esses países, por sua condição financeira, necessitam informações de análises econômicas para administrar de forma eficiente os recursos públicos destinados aos setores da saúde. Objetivos Avaliar a eficácia do MFD-LI através de estudos com tempo superior a 12 semanas, e realizar uma análise econômica para o tratamento do TDAH com MFD-LI para crianças e adolescentes brasileiros. Método O estudo foi planejado em cinco etapas: 1) estimativa de custo do não tratamento do TDAH para o Brasil, e estimativa de economia com tratamento com MFD-LI; 2) revisão sistemática da literatura nas principais bases de dados internacionais onde se buscaram estudos abertos com tratamento do TDAH com MFD-LI por tempo igual ou superior a 12 semanas; também foram feitas metanálises e uma metaregressão 3) estudo naturalístico para obterem-se dados de uma amostra brasileira referentes a probabilidades de uso e sucesso com tratamento com MFD-LI por 12 semanas, e estimar os utilities desses indivíduos; 4) painel Delphi com especialistas em TDAH no Brasil; 5) estudo de custo-efetividade para o tratamento do TDAH com MFD-LI no Brasil, utilizando um Modelo de Markov. A perspectiva adotada será a do sistema público de saúde brasileiro como pagador. Resultados Os resultados principais encontrados para cada uma das etapas foram: 1) a estimativa de custos anuais com o TDAH não tratado no Brasil foi de R$ 1.594 bilhões/ano, e da quantia que poderia ser economizada se tratado, R$ 1 bilhão/ano. 2) na revisão sistemática da literatura, de 4.498 resumos, sete foram incluídos para compor a metanálise. O tempo de tratamento variou entre 13 e 104 semanas. O efeito agregado para desatenção e hiperatividade medida pelos pais, respectivamente, foi 0.96 (95%CI 0.60 - 1.32) e 1.12 (95%CI 0.85 - 1.39), e pelos professores 0.98 (95%CI 0.09 - 1.86) e 1.25 (95% CI 0.7 - 1.81). A metaregressão não mostrou associação entre as variáveis idade, qualidade do artigo e tempo de tratamento com heterogeneidade. 3) no estudo naturalístico, de 171 pacientes avaliados, 73 forneceram informações para o baseline, e 56 para a 12a semana de tratamento com MFD-LI. Os utilities para um paciente com TDAH não tratado (baseline) foram 0.69 (crianças) e 0.66 (adolescentes), e estimaram-se ganhos entre 0.09 a 0.10 utilities/mês, se tratados adequadamente. 4) no painel Delphi, de 26 especialistas, 14 responderam o questionário online, e foi estimado que a probabilidade dos pacientes não tratados se manterem sintomáticos na 12a semana seria de 91%, e 9% a probabilidade de melhora espontânea; 5) no estudo de custo-efetividade, para o caso base, estimou-se que o Incremental Cost Effectiveness Ratio (ICER) seja I$9,103/QALY (Quality Adjusted Life Years) para crianças e I$11,883/QALY para adolescentes em um horizonte temporal de 06 anos. Para os cenários mais desfavoráveis, os ICERS mais elevados foram I$95,164/QALY para 50% de sucesso com o tratamento, e I$15,000/QALY para 70% de adesão em um horizonte temporal de 06 anos. Conclusões O MFD-LI é um tratamento eficaz para crianças e adolescentes, por um período superior a 12 semanas. Entretanto, o Brasil pode estar aumentando os custos referentes à saúde por não estar fornecendo um tratamento eficaz e economicamente acessível para o TDAH. O tratamento mostrou ser uma opção custo-efetiva para crianças e adolescentes brasileiros, mesmo em cenários desfavoráveis para o tratamento. / Introduction Attention-Deficit/Hyperactivity Disorder (ADHD) is a well-known psychiatric disorder, but some economical aspects of the treatment with Methylphenidate Immediate-release (MPH -IR) still need to be explored. A large number of people around the world, most living in Low-Middle Income Countries (LMIC), use this formulation as the first choice for ADHD treatment. These countries, due to their financial condition, need information from health economic analyzes to efficiently manage the public resources allocated to the health sector. Objective To study the efficacy of MPH-IR reviewing studies conducted for more than 12 weeks long, and to perform an economic analysis for the treatment of ADHD with MPH-IR for Brazilian children. Method The study was planned in a five stages process: 1) to estimate the cost of untreated ADHD for Brazil, and to estimate the savings if MPH-IR were adequately provided; 2) systematic review of the literature to identify papers published where young patients with ADHD were treated with MPH-IR for more than 12 weeks, and to perform a meta-analysis and a meta-regression; 3) to conduct a naturalistic study with a Brazilian sample to collect the probabilities of use and success with the MPH-IR treatment for 12 weeks, and to estimate the utilities; 4) to perform a Delphi panel with ADHD Brazilian experts; 5) to conduct a cost-effectiveness analysis for the treatment of ADHD with MPH-IR in Brazil, using a Markov model. The perspective is the one of the Brazilian public health system as the payer. Results The main findings for each step were: 1) the estimated annual expenditures with untreated ADHD in Brazil were R$1.594billon/year, and the estimated amount that could be saved was R$1billion/year; 2) in the systematic review, from 4,498 abstracts, 7 studies were selected. The length of treatment ranged from 13 to 104 weeks. The aggregate effects for inattention and hyperactivity, according to parents evaluations were respectively 0.96 (95%CI 0.60 - 1.32) and 1.12 (95%CI 0.85 - 1.39), and for teachers 0.98 (95%CI 0.09 - 1.86) e 1.25 (95% CI 0.7 - 1.81). There was no evidence of association between heterogeneity and the variables, age, paper quality and length of treatment; 3) in the naturalistic study, from 171 patients assessed, 73 provided information in the baseline, and 56 in the 12th week of MPH-IR treatment. Utilities for an untreated ADHD patient (baseline) were 0.69 (children) and 0.66 (adolescents), and it was estimated a gain ranging from 0.09 to 0.10 utilities/month if subjects were properly treated; 4) in the Delphi Panel, 26 experts were addressed and 14 filled in the online questionnaire. It was estimated the probability of untreated patients to remain symptomatic on the 12th week to be 91%, and the probability of spontaneous improvement, 9%; 5) in the cost-effectiveness analysis, for the base case, it was estimated an Incremental Cost Effectiveness Ratio (ICER) of I$9,103/QALY (Quality Adjusted Life Years) for children and I$11,883/QALY for adolescents, in a time horizon of 6 years. The worst case scenarios were also tested, and the highest ICER were I$95,164/QALY when patient reached 50 % of success with the treatment, and I$15,000/QALY if only 70% of use was observed in a time horizon of 6 years. Conclusions MPH-IR is an efficacious treatment for ADHD children and adolescents for periods longer than 12 weeks. However, Brazil may be probably wasting money due to not provide an efficient and affordable treatment for ADHD such as the MPH-IR. The treatment proved to be cost-effective for children and adolescents living in Brazil, even when the worst case scenarios were tested.

Trauma de crânio leve (TCE leve) é definido como um déficit neurológico transitório que ocorre após um trauma incluindo história de náuseas, vômitos, cefaléia ou tontura acompanhada de alteração ou perda da consciência com duração inferior a 15 minutos, amnésia pós traumática e Escala de Coma de Glasgow entre 13 e 15. Apesar da alta taxa de sobrevida, pode cursar com alguma morbidade, principalmente nos três primeiros meses posteriores ao trauma e cerca de 18 % dos pacientes desenvolvem pelo menos uma síndrome psiquiátrica no primeiro ano após o acidente. O diagnóstico ainda é um desafio no sentido de minimizar-se gastos desnecessários com exames subsidiários entretanto, intervenções precoces podem evitar seqüelas. Nosso objetivo foi verificar o impacto do TCE leve na qualidade de vida de suas vítimas e diagnosticar as várias alterações neuropsicológicas que podem advir deste trauma. Esses alterações podem ser verificadas através de instrumentos de pesquisa. Inicialmente, foram avaliadas cinqüenta vítimas com TCE leve, atendidas no Hospital João XXIII, em Belo Horizonte - MG, as quais foram submetidas a dosagem de proteína S100B e tomografia de crânio (TCC) na admissão. Nessa fase, verificou-se que a proteína S100B tem valor preditivo negativo de 100%. Dezoito meses após o trauma, esses pacientes foram procurados em suas residências, quando foi lhes solicitado para que respondessem a quatro instrumentos de pesquisa [dois para diagnóstico de qualidade de vida (World Health Organization WHOQOL-100), e o Short Form-36 (SF-36), um para análise da presença de ansiedade e depressão (Escala Hospitalar de Ansiedade e Depressão (EHAD) e o Questionário de Sinais e Sintomas (QSS), baseado no Post Concussion Questionnaire] com o objetivo de pesquisar a presença de sinais e sintomas da síndrome pós-concussão. Também foram pesquisados aspectos sociodemográficos, como idade, escolaridade, estado civil, renda pessoal e origem desta renda. Os mesmos questionários foram preenchidos por um grupo de controle composto, necessariamente, por coabitantes dos pacientes, sem história de trauma craniano de qualquer gravidade e com idade a mais próxima possível da do paciente. Na avaliação pelo WHOQOL-100, pacientes apresentaram qualidade de vida inferior nos domínios nível de independência, ambiente e no total de domínios (p< 0,05). Na avaliação do SF-36, pacientes revelaram qualidade de vida inferior nos domínios capacidade funcional, vitalidade, saúde mental (p<0,001), dor, estado geral de saúde e aspectos mentais (p<0,05). Pacientes apresentaram mais ansiedade e estavam uma classe acima de seus controles pela EHAD. Pacientes referem ainda número maior de sinais e sintomas da síndrome pós-concussão do que seus respectivos controles. Não verificamos correlação entre a qualidade de vida, classificação na EHAD ou número de sinais e sintomas da SPC com as dosagens de proteína S100B ou com a presença de lesão na TCC realizadas na admissão / Mild head trauma (MHT) is defined as a transitory neurological deficit that happens after the trauma and includes a history of nausea, vomiting, headache or dizziness and loss or alteration of consciousness (less than 15 minutes), post-trauma amnesia, and Glasgow Coma Scale (GCS) at admission between 13 and 15. Despite the high survival rates, some morbidity has been observed in the three month period after this trauma. Approximately 18% of head trauma patients develop at least one psychiatric syndrome in the first year after the accident. The diagnostics difficulty and the risks of complications after the MHT continue to be a relevant problem at the emergency departments around the world. Limitations of active participation in daily life are alterations that influence life quality. Several of these alterations may be diagnosed through Interview Instruments. Our study was divided in two phases. In the first phase, 50 MHT patients admitted at Hospital João XXIII, Belo Horizonte-MG, Brazil, had protein S100B dosing and head CT taken at admission. Concentration values of S100B lower than 0.01 g/l were considered negative once this was the lowest value found in patients who did not show brain injuty signs in the CT scan. In that study it was found that protein S100B has 100% negative predictive value. In this second phase of the study, 18 months after the trauma, these patients were contacted at their homes and asked to answer four self- assessment questionnaires: two for quality of life diagnostic - World Health Organizations WHOQOL-100 and the Short Form-36 (SF36); one for the analysis of anxiety and depression - Hospital anxiety and depression scale-HADS; and one instrument developed by the author based on the Rivermead Post Concussion Questionnaire to evaluate the presence of post-concussion syndrome signs and symptoms. Several socio-demographic aspects were also analyzed, including income, source of income, means of transportation used, etc. The same questionnaires were filled by a control group formed necessarily by patients co-inhabitants, with no history of head trauma of any severity, and with closest age as possible to the patients. In the WHOQOL assessment patients showed a lower quality of life in the independence, environment, as well as in the total domains (p< 0,05). In the SF 36 assessment patients showed a lower quality of life in the functional capacity, vitality, and mental health domains (p<0,001); and also in pain, general health situation, and mental aspects (p<0,05). Patients showed more anxiety and, in the HADS Scale, showed at least a level higher, on average, than their controls. Patients also showed a higher number of post-concussion signs and symptoms than their respective controls. We did not find correlation between the later quality of life and protein S100B dosing at admission. We were not able to find correlation between the protein concentrations with the presence of brain lesions in the CCT scans taken at patients admission in the emergency department

By 2020, cancer mortality rates are estimated to increase by 180% in Arab countries, where breast cancer is the most common type of cancer. This thesis explores and evaluates the ‘asabiyya-driven structuration (the cohesive force of the group that gives it strength in facing its struggles for progressive reproduction) of cancer agents, government agents, and the World Health Organization agents for breast cancer prevention and early detection in the Arab region. The layers of the philosophical standing from Ibn Khaldûn’s concept of ‘asabiyya and the theoretical foundation of social systems theory, structuration theory, social network analysis, and social capital theory are peeled in order to explore and evaluate the context, constraints, social networks, autopoiesis, and social capital. Utilizing a qualitative research design, this thesis employs content analysis and in-depth interviews, as well as NVivo as a tool for analysis. Data is collected from 122 publications and knowledgeable informants employed by cancer agencies, ministries of health, and World Health Organization offices in Egypt, Jordan, Morocco, and Oman. The findings are divided into the contextual scope of responsibility and resources, the progressive and hierarchal constraining structure, the optimal and weak social networks, the strong and vulnerable shields of autopoiesis, and the presence and absence of social capital momentum, followed by a discussion on the the struggle for structuration against breast cancer. The findings demonstrate that countries with a national cancer control program witness local strengthening ‘asabiyya and ‘asabiyya-driven structuration, while those without a national cancer control program witness weakening local ‘asabiyya. Ultimately, this thesis proposes strategic recommendations to accelerate the regional ‘asabiyya-driven structuration of breast cancer.

Introdução O Transtorno de Déficit de Atenção/hiperatividade (TDAH) tem sido muito estudado, mas informações econômicas referentes ao seu tratamento com o metilfenidato de liberação imediata (MFD-LI) ainda necessitam ser exploradas. Grande parte da população mundial, principalmente aqueles que vivem em países em desenvolvimento, utiliza essa formulação como principal escolha para o tratamento do TDAH. Esses países, por sua condição financeira, necessitam informações de análises econômicas para administrar de forma eficiente os recursos públicos destinados aos setores da saúde. Objetivos Avaliar a eficácia do MFD-LI através de estudos com tempo superior a 12 semanas, e realizar uma análise econômica para o tratamento do TDAH com MFD-LI para crianças e adolescentes brasileiros. Método O estudo foi planejado em cinco etapas: 1) estimativa de custo do não tratamento do TDAH para o Brasil, e estimativa de economia com tratamento com MFD-LI; 2) revisão sistemática da literatura nas principais bases de dados internacionais onde se buscaram estudos abertos com tratamento do TDAH com MFD-LI por tempo igual ou superior a 12 semanas; também foram feitas metanálises e uma metaregressão 3) estudo naturalístico para obterem-se dados de uma amostra brasileira referentes a probabilidades de uso e sucesso com tratamento com MFD-LI por 12 semanas, e estimar os utilities desses indivíduos; 4) painel Delphi com especialistas em TDAH no Brasil; 5) estudo de custo-efetividade para o tratamento do TDAH com MFD-LI no Brasil, utilizando um Modelo de Markov. A perspectiva adotada será a do sistema público de saúde brasileiro como pagador. Resultados Os resultados principais encontrados para cada uma das etapas foram: 1) a estimativa de custos anuais com o TDAH não tratado no Brasil foi de R$ 1.594 bilhões/ano, e da quantia que poderia ser economizada se tratado, R$ 1 bilhão/ano. 2) na revisão sistemática da literatura, de 4.498 resumos, sete foram incluídos para compor a metanálise. O tempo de tratamento variou entre 13 e 104 semanas. O efeito agregado para desatenção e hiperatividade medida pelos pais, respectivamente, foi 0.96 (95%CI 0.60 - 1.32) e 1.12 (95%CI 0.85 - 1.39), e pelos professores 0.98 (95%CI 0.09 - 1.86) e 1.25 (95% CI 0.7 - 1.81). A metaregressão não mostrou associação entre as variáveis idade, qualidade do artigo e tempo de tratamento com heterogeneidade. 3) no estudo naturalístico, de 171 pacientes avaliados, 73 forneceram informações para o baseline, e 56 para a 12a semana de tratamento com MFD-LI. Os utilities para um paciente com TDAH não tratado (baseline) foram 0.69 (crianças) e 0.66 (adolescentes), e estimaram-se ganhos entre 0.09 a 0.10 utilities/mês, se tratados adequadamente. 4) no painel Delphi, de 26 especialistas, 14 responderam o questionário online, e foi estimado que a probabilidade dos pacientes não tratados se manterem sintomáticos na 12a semana seria de 91%, e 9% a probabilidade de melhora espontânea; 5) no estudo de custo-efetividade, para o caso base, estimou-se que o Incremental Cost Effectiveness Ratio (ICER) seja I$9,103/QALY (Quality Adjusted Life Years) para crianças e I$11,883/QALY para adolescentes em um horizonte temporal de 06 anos. Para os cenários mais desfavoráveis, os ICERS mais elevados foram I$95,164/QALY para 50% de sucesso com o tratamento, e I$15,000/QALY para 70% de adesão em um horizonte temporal de 06 anos. Conclusões O MFD-LI é um tratamento eficaz para crianças e adolescentes, por um período superior a 12 semanas. Entretanto, o Brasil pode estar aumentando os custos referentes à saúde por não estar fornecendo um tratamento eficaz e economicamente acessível para o TDAH. O tratamento mostrou ser uma opção custo-efetiva para crianças e adolescentes brasileiros, mesmo em cenários desfavoráveis para o tratamento. / Introduction Attention-Deficit/Hyperactivity Disorder (ADHD) is a well-known psychiatric disorder, but some economical aspects of the treatment with Methylphenidate Immediate-release (MPH -IR) still need to be explored. A large number of people around the world, most living in Low-Middle Income Countries (LMIC), use this formulation as the first choice for ADHD treatment. These countries, due to their financial condition, need information from health economic analyzes to efficiently manage the public resources allocated to the health sector. Objective To study the efficacy of MPH-IR reviewing studies conducted for more than 12 weeks long, and to perform an economic analysis for the treatment of ADHD with MPH-IR for Brazilian children. Method The study was planned in a five stages process: 1) to estimate the cost of untreated ADHD for Brazil, and to estimate the savings if MPH-IR were adequately provided; 2) systematic review of the literature to identify papers published where young patients with ADHD were treated with MPH-IR for more than 12 weeks, and to perform a meta-analysis and a meta-regression; 3) to conduct a naturalistic study with a Brazilian sample to collect the probabilities of use and success with the MPH-IR treatment for 12 weeks, and to estimate the utilities; 4) to perform a Delphi panel with ADHD Brazilian experts; 5) to conduct a cost-effectiveness analysis for the treatment of ADHD with MPH-IR in Brazil, using a Markov model. The perspective is the one of the Brazilian public health system as the payer. Results The main findings for each step were: 1) the estimated annual expenditures with untreated ADHD in Brazil were R$1.594billon/year, and the estimated amount that could be saved was R$1billion/year; 2) in the systematic review, from 4,498 abstracts, 7 studies were selected. The length of treatment ranged from 13 to 104 weeks. The aggregate effects for inattention and hyperactivity, according to parents evaluations were respectively 0.96 (95%CI 0.60 - 1.32) and 1.12 (95%CI 0.85 - 1.39), and for teachers 0.98 (95%CI 0.09 - 1.86) e 1.25 (95% CI 0.7 - 1.81). There was no evidence of association between heterogeneity and the variables, age, paper quality and length of treatment; 3) in the naturalistic study, from 171 patients assessed, 73 provided information in the baseline, and 56 in the 12th week of MPH-IR treatment. Utilities for an untreated ADHD patient (baseline) were 0.69 (children) and 0.66 (adolescents), and it was estimated a gain ranging from 0.09 to 0.10 utilities/month if subjects were properly treated; 4) in the Delphi Panel, 26 experts were addressed and 14 filled in the online questionnaire. It was estimated the probability of untreated patients to remain symptomatic on the 12th week to be 91%, and the probability of spontaneous improvement, 9%; 5) in the cost-effectiveness analysis, for the base case, it was estimated an Incremental Cost Effectiveness Ratio (ICER) of I$9,103/QALY (Quality Adjusted Life Years) for children and I$11,883/QALY for adolescents, in a time horizon of 6 years. The worst case scenarios were also tested, and the highest ICER were I$95,164/QALY when patient reached 50 % of success with the treatment, and I$15,000/QALY if only 70% of use was observed in a time horizon of 6 years. Conclusions MPH-IR is an efficacious treatment for ADHD children and adolescents for periods longer than 12 weeks. However, Brazil may be probably wasting money due to not provide an efficient and affordable treatment for ADHD such as the MPH-IR. The treatment proved to be cost-effective for children and adolescents living in Brazil, even when the worst case scenarios were tested.

Masters of Science / The aim of this study was to develop a Stock Control Assessment Tool for use in the public health care sector and then to apply it to identify problems in the stock control system. This would help authorities to optimize the system. The advantages experienced with such a dynamic Assessment Tool were many: The Tool was quick and easy to apply; it was user friendly; it provided an immediate SWOT analysis of a particular facility; it is in line with the SA NDP directives and it provides an indication of which structures are in place and whether they are functioning properly. Furthermore; it could determine the increase or decrease in performance of a facility (therefore identify trends within the functional status of a system) when data is collected over a period of time; and finally, it could also be used to prioritize drug policy directives. The following steps were established in the development of the Tool: A literature review of pharmaceutical stock control and Drug Supply Management was addressed to provide the background information for the motivation of this study and to identify the various elements that could influence stock control at a facility level. Observational studies were applied at selected private and public facilities to observe the impact of these identified stock control elements. An 'ideal' stock control system was then generated from the literature review and observational assessment. A structured questionnaire was developed and surveyed at these facilities to generate key areas of concern of a stock control system. A study and adaptation of the indicator methods used by the World Health Organization (WHO) to monitor drug use in health facilities resulted in the formulation of a practical Stock Control Assessment Tool based on 11 key indicators and a number of sub-indicators, all of which were objectively defined. The Tool was then applied at selected public facilities and the results were analyzed quantitatively, qualitatively and subjectively. Each of the indicators was then applied and results examined closely with a view to possible refinements of the indicator. The refinements were made and the Tool was re-applied at two selected facilities. These two facilities were randomly selected from the original six facilities included for the testing of the Tool. Final conclusions and specific recommendations were generated to improve the stock control systems at the selected public health care facilities.

Cette thèse examine l’apport du travail statistique à la normalisation de la vaccination en France, des années 1950 au milieu des années 1990, une période au cours de laquelle la vaccination a fait l’objet de peu de controverses. Au moyen d’opérations statistiques de rationalisation, de régulation et de justification, l’épidémiologie (entendue comme un ensemble de pratiques plutôt qu’une discipline universitaire autonome) a largement contribué à maintenir cet état de fait – un processus que je qualifie de routinisation. L’enquête est construite sur des archives issues de diverses institutions, nationales et internationales, ainsi que sur une série d’entretiens avec les principaux acteurs du domaine. Elle éclaire le rôle d’un groupe d’épidémiologistes associés au Centre international de l’enfance (1949-1999), qui mit en œuvre un programme de rationalisation et de simplification de la vaccination. Dans cette période coloniale et postcoloniale, l’Afrique subsaharienne était un de leurs terrains de prédilection : ils y réalisèrent de nombreux essais, simultanément à leurs activités métropolitaines. L’implication de l’OMS dans le domaine de la vaccination a conforté la dimension internationale de cette routinisation : les épidémiologistes français se sont appropriés des opérations statistiques popularisées par Genève. À la fin de la période considérée, la controverse de la vaccination contre l’hépatite B a perturbé cette routinisation et mis en évidence un écart croissant entre les logiques de l’épidémiologie et l’expérience des individus vaccinés. Cette recherche éclaire d’une lumière nouvelle la façon dont l’intervention de santé publique la plus courante a été normalisée et gouvernée par des nombres. / This dissertation studies the entanglement between statistical production and the normalization of immunization practices in France from the 1950s to the mid-1990s, a period during which immunization remained largely uncontroversial. By rationalizing, regulating, and justifying immunization, epidemiology (understood as a collection of practices, rather than a discrete academic discipline) has contributed greatly to this normalization – a process I term “routinization.” This research project is based on archival findings, both in France and internationally, as well as a series of interviews with significant actors in the field. It is primarily focused on a group of epidemiologists affiliated with the Centre international de l’enfance (French International Children’s Center, 1949-1999), whose mission was to rationalize and simplify immunization for children. Throughout the institution’s history, which overlaps with the late colonial period and the process of de-colonization, there is a significant engagement with Francophone Africa: numerous trials were carried out simultaneously in Sub-Saharan Africa and the Paris region. The transnational nature of this activity is also due, in part, to the involvement of the World Health Organization in matters of immunization – French epidemiologists appropriated calculations popularized on a global scale. At the end of the period in question, the Hepatitis B vaccine controversy disrupted the routinization process and shed light on the rising gap between the discourse and practice of epidemiology and the experience of vaccinated individuals. This study offers new insights into the role of numbers in the maintenance and governance of the most common public health intervention.