Emerging multidrug-resistant tuberculosis (MDR/XDR-TB) has become a major public health problem, placing millions at risk. Further, nosocomial transmission of MDR/XDR-TB places both patients and healthcare workers at an even higher risk. Effective tuberculosis (TB) infection prevention and control (IPC) policies in high-risk settings must use evidence-based science and should be customized to the setting. However, the growing incidence of MDR/XDR-TB in some global settings raises questions about whether adequate healthcare-related TB IPC policies are in place and whether they are implemented effectively. The purpose of this systematic literature review was to catalogue healthcare-related TB IPC policy research conducted in high-prevalence settings and draw a picture of existing evidence-based TB IPC policies and their implementation, with a focus on preventing and controlling nosocomial transmission of MDR/XDR-TB. Two databases (PubMed and Embase) were searched from 1990 – 2013 and outputs were categorized by region/country, income, MDR/XDR-TB incidence, level of IC intervention, and time period. None of the 20 captured research studies were conducted in TB high-prevalence, low-income settings. Most (12/20) were implemented within the Pan American Health Organization region, followed by the African (4/20) and European (4, 20%) regions. Most studies reviewed (70%) were undertaken because of an outbreak and most (70%) were published between 1990 – 2000. This systematic literature review showed a gap in research on TB IPC policies addressing nosocomial transmission of MDR/XDR-TB in high-prevalence, low-income settings. TB IPC policy development and implementation should be routinely undertaken as a part of effective and efficient public health practice. Development of TB IPC global best practices should be guaranteed and a concerted effort to promote, distribute, train, and implement these TB IPC best practices in low-resource countries would help mitigate the growing incidence of MDR/XDR-TB worldwide.

Introdução: A epilepsia é uma das condições mais comuns na prática neurológica. Sua prevalência na população em geral é expressiva (cerca de 2%). Dentre esses pacientes, existem aqueles que são fármaco-resistentes, ou seja aqueles que não atingem controle de suas crises com dois fármacos adequados de maneira otimizada, os quais correspondem a cerca de 20-40%. Esses pacientes apresentam um controle inadequado de sua condição crônica e o tratamento a longo prazo torna-se insatisfatório e de alto custo, sem levar em consideração a redução da qualidade de vida do paciente, o impacto psicossocial, as incapacidades e o risco aumentado de morte. Somando-se a isso, existe o fato de eles, muitas vezes, necessitarem de cuidadores, geralmente familiares, os quais, por consequência, também deixam de produzir. Sendo assim, é imperativo que tratamentos alternativos custo-efetivos sejam disponibilizados para esses pacientes. A cirurgia da epilepsia é uma opção muito adequada para pacientes selecionados, uma vez que ela pode melhorar substancialmente a qualidade de vida dos pacientes, em muitos casos fazendo até mesmo com que o paciente fique livre de crises, além da redução dos custos à longo prazo. O grande problema é anterior à cirurgia: reside no fato de existir uma certa dificuldade em identificar e encaminhar esses pacientes para uma avaliação adequada, seja por desconhecimento por parte dos médicos em geral, seja pela escassez de recomendações formais. Objetivos: Avaliar uma ferramenta online para indicar pacientes candidatos à cirurgia da epilepsia, colaborando, assim com uma maior facilidade para fins de tomada de decisão clínica com uma melhor identificação destes pacientes. Métodos: Realizamos um estudo transversal avaliando a indicação cirúrgica de pacientes com epilepsia focal, conforme testagem de uma ferramenta online disponível para este fim. Este trabalho foi realizado com pacientes consecutivos que frequentaram o Ambulatório de Epilepsia do Serviço de Neurologia do Hospital de Clínicas de Porto Alegre, no período de janeiro a abril de 2014. Todos os pacientes incluídos no estudo apresentavam o diagnóstico de epilepsia e suas informações foram retiradas da revisão de seus prontuários através de um questionário padronizado respondido pelos pesquisadores. As informações que porventura não constavam registradas em prontuário foram coletadas durante a consulta de rotina. No total, foram avaliados 211 pacientes. Resultados: No nosso estudo, primeiramente realizamos uma análise de prevalência, encontrando um resultado de 56,9% de pacientes com indicação à avaliação cirúrgica. Além disso, realizamos uma avaliação das variáveis que contribuem para a indicação ou não do tratamento cirúrgico. Nessa etapa, encontramos a frequência das crises, o número de fármacos testados e a presença de efeitos colaterais como as variáveis com maior significância estatística para indicação ao tratamento cirúrgico. Conclusão: Acreditamos que este trabalho possui grande relevância clínica por se tratar de uma ferramenta que pode ajudar na tomada de decisão para fins de tratamento, beneficiando, assim, pacientes e possivelmente reduzindo custos do sistema de saúde a médio e longo prazo. / Background: Epilepsy is one of the most commons neurological conditions in practice. Its prevalence in the general population is significant (about 2%). Among these patients, there are those that are drug-resistant (those who do not achieve control of their seizures with two suitable drugs optimally), which correspond to about 20-40%. These patients have inadequate control of their chronic condition and long-term treatment becomes unsatisfactory and expensive, regardless of the reduced quality of life of patients, the psychosocial impact, disability and increased risk of death. In addition, the fact that they often need caregivers usually familiar, which, therefore, also fail to produce. It is therefore imperative that cost-effective alternative treatments are available for these patients. The epilepsy surgery is a suitable option for selected patients, since it can substantially improve the quality of life of patients, in many cases making even the patient seizure free, in addition to reducing costs in the long term. The big problem is before surgery: lies in the fact that there is some difficulty in identifying and referring these patients for proper evaluation, either by ignorance on the part of physicians in general, and the lack of formal recommendations. Objectives: Evaluate an online tool to nominate patients candidates for epilepsy surgery, thus contributing to a larger facility for the purposes of clinical decision-making with better identification of these patients. Methods: We conducted a cross-sectional study evaluating the surgical indication in patients with focal epilepsy, as testing of an online tool available for this purpose. This work was performed with consecutive outpatients attending at the Epilepsy Clinic of the Hospital de Clínicas de Porto Alegre, in the period of January-April 2014. All patients included in the study had a diagnosis of epilepsy and their information was taken from the review of their medical records using a standardized questionnaire answered by researchers. The informations who were not registered, were collected during a routine visit. In total, 211 patients were evaluated. Results: In our study, first we conducted a prevalence analysis, finding a result of 56.9% of patients referred for surgical evaluation. In addition, we conducted an evaluation of variables that contribute to the indication or not of surgical treatment. At this stage, we found the frequency of seizures, the number of tested drugs and the presence of side effects such as variables with greater statistical significance for indication for surgical treatment. Conclusion: We believe that this work has great clinical relevance because it is a tool that can help in decision making for treatment, thus benefiting patients and reducing health care costs in the medium and long term.

Base teórica: A epilepsia é uma doença neurológica crônica, que causa grande impacto na qualidade de vida dos pacientes afetados. Isto se deve a fatores psicossociais e outros associados à própria epilepsia, além dos efeitos adversos das medicações utilizadas no tratamento. Estima-se que o controle satisfatório das crises seja alcançado em apenas uma parte dos pacientes e, muitas vezes, às custas de efeitos adversos significativos, principalmente nos pacientes com epilepsia refratária. Devido à falta de padronização na definição de epilepsia refratária, que dificulta a sua identificação e o cuidado dos pacientes, em 2010 a ILAE (International League Against Epilepsy) propôs uma classificação para identificar pacientes controlado e não controlados e às custas de efeitos adversos ou não. Objetivo: O presente trabalho tem como objetivo aplicar os critérios de epilepsia fármaco-resistente, propostos pela ILAE em 2010, em pacientes com epilepsia em acompanhamento em um centro de referência e avaliar os efeitos adversos de medicações sobre a qualidade de vida, através da aplicação de questionários padronizados.Métodos: Foram incluídos 81 pacientes com diagnostico definido de epilepsia em acompanhamento em um centro terciário. Todos os pacientes tinham mais de 18 anos, estavam em uso de droga antiepiléptica em dose estável por pelo menos 3 meses, não foram diagnosticados com outras comorbidades clinicas ou psiquiátricas e não estavam em uso regular de nenhuma outra medicação que não o DAE. Os pacientes foram classificados em quatro grupos seguindo as orientações da ILAE: 1A (crises controladas, sem efeitos adversos); 2A (crises não controladas, sem efeitos adversos); 1B (crises controladas, com efeitos adversos), 2B (crises não controladas, com efeitos adversos). Na avaliação da qualidade de vida foi utilizado o questionário QOLIE-31 (Quality of life in epilepsy-31) e para auxiliar na avaliação da presença de efeitos adversos foi utilizada a escala LAEP (Liverpool adverse effects profile). Conclusão: Os pacientes dos grupos com pior controle de crises (2A e 2B) mostraram piores escores de qualidade de vida, enquanto que os grupos com controle de crises (1A e 1B) mostraram melhor qualidade de vida, independente da presença de efeitos adversos. A escala LAEP foi útil na avaliação de efeitos adversos por ajudar a diminuir a subjetividade desta avaliação. É conhecido da literatura que o controle de crises e a presença de efeitos adversos podem impactar negativamente na qualidade de vida dos pacientes com epilepsia. No nosso trabalho, a presença de efeitos adversos não foi um fator que influenciou na qualidade de vida, o que pode estar associado ao número das amostras. / Background: Epilepsy is a chronic neurological disease that causes a great impact in the quality of life of the patients. This is related not only due to psychosocial factors but also due to factors associated with the disease itself, as well as to the antiepileptic drugs adverse effects. It is estimated that the good seizure control will be achieved for only some patients and many times with significant adverse effects, mainly in patients with drug resistant epilepsy. Since there was no defined criteria for refractory epilepsy, making the identification and care of these patients more difficult, in 2010 the International League Against Epilepsy (ILAE) suggested a classification to identify patients with good seizure control or uncontrolled seizures, with or without adverse effects. Objectives: Our work aims to use the ILAE 2010 criteria to identify patients with drug resistant epilepsy in patients of a referral center and to evaluate their quality of life and the presence of antiepileptic drugs adverse effects. Methods: It was included 81 patients with a defined diagnosis of epilepsy, all patients were 18 years old or older, were using an antiepileptic drug in a stable dose for at least 3 months, did not have other clinical or psychiatric diagnosis and were not using any other medication than the antiepileptic drug. Patients were classified in four groups, according to ILAE guidelines: 1A (good seizure control, no adverse effects); 2A (no seizure control, no adverse effects); 1B (good seizure control, with adverse effects), 2B (no seizure control, with adverse effects). For the evaluation of quality of life it was used the QOLIE-31 (Quality of life in epilepsy-31) questionnaire and for the evaluation of adverse effects it was used the LAEP (Liverpool adverse effects profile) questionnaire. Conclusion: Patients from groups with poor seizure control (2A and 2B) showed worse scores for quality of life while patients from groups with good seizure control (1A and 2A) showed better scores, regardless the presence of adverse effects. The LAEP scale was useful for the evaluation of adverse effects, since it helped to decrease the subjectivity in the evaluation. It is known from literature that seizure control and adverse effects have a negative impact the quality of life in patients with epilepsy. In our study, we were not able to show that the presence of adverse effects influenced the quality of life, this may be associated with the sample size.

Les infections nosocomiales à bactéries multi-résistantes sont en constante augmentation en réanimation. Elles ont des conséquences individuelles et collectives majeures. La mortalité en réanimation et les prolongations des durées de séjour sont les deux principales conséquences individuelles connues à ce jour. Plusieurs facteurs confondants rendent l'interprétation des études difficiles, dont l'état sous jacent du patient, la virulence de la bactérie et l'adéquation thérapeutique. Mesurer la part de chacun de ces facteurs et préciser leur responsabilité respective est indispensable pour mobiliser les différents acteurs et améliorer le pronostic des patients en réanimation. Dans cette thèse nous avons souhaité approcher la réponse quant aux conséquences individuelles. A partir d'une base de données incluant des patients de réanimation, nous avons utilisé les méthodes statistiques les plus récentes et avons tenté de prendre en compte les différents facteurs confondants , pour répondre à trois questions précises que sont : la mortalité liée à une espèce bactérienne donnée, les facteurs associés à la mortalité des patients présentant un sepsis sévère ou choc septique en réanimation et les conséquences liées à l'isolement des patients infectés ou colonisés avec une bactérie multi-résistante. Nous montrons que (1) par l'intermédiaire d'une prolongation de la durée de séjour en réanimation, l'infection à Clostridium difficile augmente la pression de colonisation, sans pour autant avoir d'impact direct sur le décès. (2) que le pronostic des sepsis sévères et des chocs septiques dépend de l'adéquation de l'antibiothérapie et que les bactéries résistantes sont plus souvent traitées de manière inadéquate. (3) que l'isolement contact est associé non seulement à une augmentation attendue du risque de pneumonie nosocomiale a germe multi-résistants mais aussi à une augmentation du risque d'erreurs thérapeutiques et d'événements indésirables non infectieux. Cet impact délétère suggéré par des études en dehors de la réanimation doit être pris en compte lors de la mise en place des précautions contact en réanimation. / Nosocomial infections with multidrug-resistant bacteria are increasing in ICU. They have major individual and collective consequences. Mortality in the ICU and prolongation of length of stay are the two main individual consequences known to date. Several confounding factors make it difficult to interpret studies, including the patient's underlying condition, the virulence of bacteria and the adequacy of therapy. It is essential to measure the share of each of these factors and to clarify their respective responsibilities to mobilize the different actors and improve the prognosis of patients in intensive care. In this thesis, and drawing upon a database including ICU patients, we used the latest statistical methods and tried to take into account the various confounding factors to evaluate the individual consequences of multidrug-resistant bacteria in ICU. We sought to address three specific questions: mortality linked to specific bacterial species, factors associated with mortality in patients with severe sepsis or septic shock in intensive care unit, and the consequences of the isolation of patients infected or colonized with multidrug-resistant bacteria. We demonstrated that (1) because they are associated with a longer stay in intensive care unit, Clostridium difficile infections increase the pressure of colonization although they have no direct consequence on mortality; (2) the prognosis of sever sepsis or septic shock depends on the adequacy of the antibiotic therapy and that resistant bacteria are often inadequately treated; and (3) that isolation is not only associated with an expected increase in the risk of nosocomial pneumonia with multi-drug resistant pathogens strains but also with an increase in non-infectious adverse events.

Base teórica: A epilepsia é uma doença neurológica crônica, que causa grande impacto na qualidade de vida dos pacientes afetados. Isto se deve a fatores psicossociais e outros associados à própria epilepsia, além dos efeitos adversos das medicações utilizadas no tratamento. Estima-se que o controle satisfatório das crises seja alcançado em apenas uma parte dos pacientes e, muitas vezes, às custas de efeitos adversos significativos, principalmente nos pacientes com epilepsia refratária. Devido à falta de padronização na definição de epilepsia refratária, que dificulta a sua identificação e o cuidado dos pacientes, em 2010 a ILAE (International League Against Epilepsy) propôs uma classificação para identificar pacientes controlado e não controlados e às custas de efeitos adversos ou não. Objetivo: O presente trabalho tem como objetivo aplicar os critérios de epilepsia fármaco-resistente, propostos pela ILAE em 2010, em pacientes com epilepsia em acompanhamento em um centro de referência e avaliar os efeitos adversos de medicações sobre a qualidade de vida, através da aplicação de questionários padronizados.Métodos: Foram incluídos 81 pacientes com diagnostico definido de epilepsia em acompanhamento em um centro terciário. Todos os pacientes tinham mais de 18 anos, estavam em uso de droga antiepiléptica em dose estável por pelo menos 3 meses, não foram diagnosticados com outras comorbidades clinicas ou psiquiátricas e não estavam em uso regular de nenhuma outra medicação que não o DAE. Os pacientes foram classificados em quatro grupos seguindo as orientações da ILAE: 1A (crises controladas, sem efeitos adversos); 2A (crises não controladas, sem efeitos adversos); 1B (crises controladas, com efeitos adversos), 2B (crises não controladas, com efeitos adversos). Na avaliação da qualidade de vida foi utilizado o questionário QOLIE-31 (Quality of life in epilepsy-31) e para auxiliar na avaliação da presença de efeitos adversos foi utilizada a escala LAEP (Liverpool adverse effects profile). Conclusão: Os pacientes dos grupos com pior controle de crises (2A e 2B) mostraram piores escores de qualidade de vida, enquanto que os grupos com controle de crises (1A e 1B) mostraram melhor qualidade de vida, independente da presença de efeitos adversos. A escala LAEP foi útil na avaliação de efeitos adversos por ajudar a diminuir a subjetividade desta avaliação. É conhecido da literatura que o controle de crises e a presença de efeitos adversos podem impactar negativamente na qualidade de vida dos pacientes com epilepsia. No nosso trabalho, a presença de efeitos adversos não foi um fator que influenciou na qualidade de vida, o que pode estar associado ao número das amostras. / Background: Epilepsy is a chronic neurological disease that causes a great impact in the quality of life of the patients. This is related not only due to psychosocial factors but also due to factors associated with the disease itself, as well as to the antiepileptic drugs adverse effects. It is estimated that the good seizure control will be achieved for only some patients and many times with significant adverse effects, mainly in patients with drug resistant epilepsy. Since there was no defined criteria for refractory epilepsy, making the identification and care of these patients more difficult, in 2010 the International League Against Epilepsy (ILAE) suggested a classification to identify patients with good seizure control or uncontrolled seizures, with or without adverse effects. Objectives: Our work aims to use the ILAE 2010 criteria to identify patients with drug resistant epilepsy in patients of a referral center and to evaluate their quality of life and the presence of antiepileptic drugs adverse effects. Methods: It was included 81 patients with a defined diagnosis of epilepsy, all patients were 18 years old or older, were using an antiepileptic drug in a stable dose for at least 3 months, did not have other clinical or psychiatric diagnosis and were not using any other medication than the antiepileptic drug. Patients were classified in four groups, according to ILAE guidelines: 1A (good seizure control, no adverse effects); 2A (no seizure control, no adverse effects); 1B (good seizure control, with adverse effects), 2B (no seizure control, with adverse effects). For the evaluation of quality of life it was used the QOLIE-31 (Quality of life in epilepsy-31) questionnaire and for the evaluation of adverse effects it was used the LAEP (Liverpool adverse effects profile) questionnaire. Conclusion: Patients from groups with poor seizure control (2A and 2B) showed worse scores for quality of life while patients from groups with good seizure control (1A and 2A) showed better scores, regardless the presence of adverse effects. The LAEP scale was useful for the evaluation of adverse effects, since it helped to decrease the subjectivity in the evaluation. It is known from literature that seizure control and adverse effects have a negative impact the quality of life in patients with epilepsy. In our study, we were not able to show that the presence of adverse effects influenced the quality of life, this may be associated with the sample size.

Introdução: A epilepsia é uma das condições mais comuns na prática neurológica. Sua prevalência na população em geral é expressiva (cerca de 2%). Dentre esses pacientes, existem aqueles que são fármaco-resistentes, ou seja aqueles que não atingem controle de suas crises com dois fármacos adequados de maneira otimizada, os quais correspondem a cerca de 20-40%. Esses pacientes apresentam um controle inadequado de sua condição crônica e o tratamento a longo prazo torna-se insatisfatório e de alto custo, sem levar em consideração a redução da qualidade de vida do paciente, o impacto psicossocial, as incapacidades e o risco aumentado de morte. Somando-se a isso, existe o fato de eles, muitas vezes, necessitarem de cuidadores, geralmente familiares, os quais, por consequência, também deixam de produzir. Sendo assim, é imperativo que tratamentos alternativos custo-efetivos sejam disponibilizados para esses pacientes. A cirurgia da epilepsia é uma opção muito adequada para pacientes selecionados, uma vez que ela pode melhorar substancialmente a qualidade de vida dos pacientes, em muitos casos fazendo até mesmo com que o paciente fique livre de crises, além da redução dos custos à longo prazo. O grande problema é anterior à cirurgia: reside no fato de existir uma certa dificuldade em identificar e encaminhar esses pacientes para uma avaliação adequada, seja por desconhecimento por parte dos médicos em geral, seja pela escassez de recomendações formais. Objetivos: Avaliar uma ferramenta online para indicar pacientes candidatos à cirurgia da epilepsia, colaborando, assim com uma maior facilidade para fins de tomada de decisão clínica com uma melhor identificação destes pacientes. Métodos: Realizamos um estudo transversal avaliando a indicação cirúrgica de pacientes com epilepsia focal, conforme testagem de uma ferramenta online disponível para este fim. Este trabalho foi realizado com pacientes consecutivos que frequentaram o Ambulatório de Epilepsia do Serviço de Neurologia do Hospital de Clínicas de Porto Alegre, no período de janeiro a abril de 2014. Todos os pacientes incluídos no estudo apresentavam o diagnóstico de epilepsia e suas informações foram retiradas da revisão de seus prontuários através de um questionário padronizado respondido pelos pesquisadores. As informações que porventura não constavam registradas em prontuário foram coletadas durante a consulta de rotina. No total, foram avaliados 211 pacientes. Resultados: No nosso estudo, primeiramente realizamos uma análise de prevalência, encontrando um resultado de 56,9% de pacientes com indicação à avaliação cirúrgica. Além disso, realizamos uma avaliação das variáveis que contribuem para a indicação ou não do tratamento cirúrgico. Nessa etapa, encontramos a frequência das crises, o número de fármacos testados e a presença de efeitos colaterais como as variáveis com maior significância estatística para indicação ao tratamento cirúrgico. Conclusão: Acreditamos que este trabalho possui grande relevância clínica por se tratar de uma ferramenta que pode ajudar na tomada de decisão para fins de tratamento, beneficiando, assim, pacientes e possivelmente reduzindo custos do sistema de saúde a médio e longo prazo. / Background: Epilepsy is one of the most commons neurological conditions in practice. Its prevalence in the general population is significant (about 2%). Among these patients, there are those that are drug-resistant (those who do not achieve control of their seizures with two suitable drugs optimally), which correspond to about 20-40%. These patients have inadequate control of their chronic condition and long-term treatment becomes unsatisfactory and expensive, regardless of the reduced quality of life of patients, the psychosocial impact, disability and increased risk of death. In addition, the fact that they often need caregivers usually familiar, which, therefore, also fail to produce. It is therefore imperative that cost-effective alternative treatments are available for these patients. The epilepsy surgery is a suitable option for selected patients, since it can substantially improve the quality of life of patients, in many cases making even the patient seizure free, in addition to reducing costs in the long term. The big problem is before surgery: lies in the fact that there is some difficulty in identifying and referring these patients for proper evaluation, either by ignorance on the part of physicians in general, and the lack of formal recommendations. Objectives: Evaluate an online tool to nominate patients candidates for epilepsy surgery, thus contributing to a larger facility for the purposes of clinical decision-making with better identification of these patients. Methods: We conducted a cross-sectional study evaluating the surgical indication in patients with focal epilepsy, as testing of an online tool available for this purpose. This work was performed with consecutive outpatients attending at the Epilepsy Clinic of the Hospital de Clínicas de Porto Alegre, in the period of January-April 2014. All patients included in the study had a diagnosis of epilepsy and their information was taken from the review of their medical records using a standardized questionnaire answered by researchers. The informations who were not registered, were collected during a routine visit. In total, 211 patients were evaluated. Results: In our study, first we conducted a prevalence analysis, finding a result of 56.9% of patients referred for surgical evaluation. In addition, we conducted an evaluation of variables that contribute to the indication or not of surgical treatment. At this stage, we found the frequency of seizures, the number of tested drugs and the presence of side effects such as variables with greater statistical significance for indication for surgical treatment. Conclusion: We believe that this work has great clinical relevance because it is a tool that can help in decision making for treatment, thus benefiting patients and reducing health care costs in the medium and long term.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-08-26T18:01:43Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NILMA MEDTROP VD.pdf: 2060397 bytes, checksum: 801ad4896a8a5f3c544547167d27652d (MD5) / Made available in DSpace on 2016-08-26T18:01:43Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NILMA MEDTROP VD.pdf: 2060397 bytes, checksum: 801ad4896a8a5f3c544547167d27652d (MD5) Previous issue date: 2015-02-05 / A tuberculose (TB) é a doença mais comum da humanidade. Atualmente, a Organização Mundial de Saúde estimou nove milhões de novos casos e um milhão e meio de mortes decorrentes da doença. A rápida expansão da resistência aos fármacos antituberculose tem prejudicado o controle global da TB, constituindo um grave problema de Saúde Pública. No Brasil, a semelhença de outros países endêmicos, tem-se observado uma variabilidade na prevalência de resistência e no estado da Paraíba (PB) não há dados recentes e concisos. Dessarte, esse estudo objetivou verificar a prevalência de resistência do Mycobacterium tuberculosis aos fármacos do esquema de primeira linha do tratamento da TB utilizados no Brasil e a frequência de fatores de risco - sexo, idade, tratamento prévio e ingesta alcóolica - em pacientes adultos com diagnóstico de TB pulmonar resistente (TBP), atendidos em serviço de referência na PB durante o período de 01 de janeiro de 2003 a 31 de dezembro de 2013. Para obtenção dos dados, utilizou-se formulário padronizado, preenchido, retrospectivamente, a partir das informações contidas nos prontuários dos pacientes atendidos no período do estudo. Foram notificados 69 casos, com prevalência de 0,5%. Evidenciou-se 17,4% de mono, 14,5% de poli e 68,1% de multirresistência. A resistência à isoniazida (INH) mostrou-se importante, tanto isolada, quanto em associações; bem como e, principalmente, a TB multirresistente (TBMR). Perante os fatores de risco, o sexo masculino (73,9%), a faixa etária de 40 a 49 anos (46,4%), a realização de tratamento prévio (98,5%) e a ingesta alcóolica (57,4%) foram os de maior ocorrência. Todavia, não expressaram significância estatística no estudo realizado tendo a PB como cenário. O desfecho foi a cura para 44,9% dos casos; no entanto, o abandono ao tratamento foi considerável, principalmente para a TBP monorresistente (33,3%). As características sociodemográficas compreenderam: a cor da pele parda (68,5%), o estado civil casado (50,9%), o nível de instrução até o fundamental (67,3%) e a procedência do interior da PB (78,2%). Quanto à coinfecção com HIV/AIDS, ocorreu em 14,5%; no entanto, nesse grupo a TBMR, também, foi mais frequente. Desta feita, mais estudos são imprescindíveis no intuito de investigar genotipicamente a resistência da TB no estado da PB, visto que alguns estudos genéticos têm reportado mutações em cepas resistentes à rifampicina (RMP), estando associada a maior transmissibilidade e a resistência à INH tem sido associada com mutações de vários genes. Assim, correlacionando com outros estados e países a fim de colaborar com o enfrentamento da doença na busca do controle e cura extensiva a todos. Por outro lado, há necessidade de fortalecimento das ações do programa de controle da TB, tanto em nível estadual, quanto nos municípios. / Tuberculosis (TB) is the most common disease of humanity. Currently, the World Health Organization estimated nine million new cases and a million and a half deaths from the disease. The rapid spread of resistance to antituberculosis drugs has undermined the global TB control, constituting a serious public health problem. In Brazil, as other endemic countries, it has been observed variability in the prevalence of resistance and the state of Paraíba (PB) no recent and accurate data. Thus, this study aimed to determine the prevalence of resistance of the Mycobacterium tuberculosis to first-line drugs in TB treatment regimen used in the Brazil and frequency of risk factors - gender, age, prior treatment and alcoholic intake - in adults patients diagnosed with resistant pulmonary TB (PTB), treated on reference service in PB during the January 1, 2003 to December 31, 2013. To obtain the data, it used standardized form filled out retrospectively from the information contained in the medical records of patients seen during the study period. Were reported 69 cases, with a prevalence of 0.5%. Revealed a 17.4% to mono, 14.5% to poly and 68.1% to multidrug resistance. The isoniazid (INH) resistance was found to be important, both isolated, as in associations; as well as, and especially multidrug resistant TB (MDR-TB). In view of the risk factors, males (73.9%), the age group 40 -49 years (46.4%), the realization of previous treatment (98.5%) and alcoholic intake (57.4%) were the most frequent. However, did not express statistical significance in the study with the PB as a scenario. The outcome was the cure for 44.9% of cases; however, abandon to treatment was significant, particularly for mono resistant PTB (33.3%). The sociodemographic characteristics included: dark brown skin (68.5%), married status (50.9%), level of education up to primary (67.3%) and the origin from the interior of PB (78.2%). The co-infection with HIV/AIDS occurred in 14.5%; however, this group the MDR-TB also was more frequent. This time, more studies are essential in order to investigate genotypically the TB resistance in the state of PB, as some genetic studies have reported mutations in strains resistant to rifampicin (RMP) and are associated with increased transmissibility and INH resistance has been associated with mutations multiple genes. Thus, correlating with other states and countries to collaborate with coping with the disease in the search of control and extensive cure to all. On the other hand, there is need to strengthen the actions of the TB control program at the state level and in the municipalities.

A epilepsia é uma desordem cerebral definida por pelo menos duas crises não provocadas ocorrendo em um intervalo maior que 24 horas, uma crise não provocada e uma probabilidade de futuras crises similar ao risco de recorrência geral depois de duas crises não provocadas (pelo menos 60%) nos próximos 10 anos; ou o diagnóstico de uma síndrome epiléptica. Após o diagnóstico do tipo de epilepsia, existem situações em que o paciente não responde ao tratamento medicamentoso, apresentando pelo menos uma crise epiléptica por mês por um período mínimo de 2 anos. Se durante esse período, dois ou três diferentes fármacos antiepilépticos foram utilizados em monoterapia ou politerapia, e o paciente não obtém controle das crises, configura-se o quadro de epilepsia farmacorresistente. A intervenção cirúrgica é uma opção para essas crianças, atuando no controle das crises e, potencialmente no desenvolvimento neuropsicomotor. Neste estudo, avaliamos as variáveis clínicas como a idade de início da epilepsia, duração da epilepsia, frequência de crises, etiologia e a Escala de Comportamento Adaptativo de Vineland (ECAV) para caracterizar aspectos referentes aos domínios da comunicação, socialização, habilidades diárias e habilidades motoras, no período pré e pós-operatório de cirurgia de epilepsia. A nossa intenção foi determinar o impacto da cirurgia de epilepsia no desempenho dos pacientes nessas esferas avaliadas pela ECAV. Como resultados, encontramos que o grupo de participantes livre de crises após a cirurgia de epilepsia apresentou melhor desempenho cognitivo na segunda avaliação pós-operatória, quando comparado ao grupo que não teve controle de crises. A variável clínica duração da epilepsia influenciou a equivalência etária e as pontuações padrão da ECAV no período pré-operatório, sendo considerada determinante para o atraso neuropsicomotor dos pacientes submetidos à cirurgia de epilepsia. Quanto aos fatores preditivos de melhora das crises pós-operatórias, observou-se que Engel e cirurgia foram as variáveis consideradas significativas. A maioria dos pacientes (63,9%) na segunda avaliação pós-operatória ainda apresentou convulsões ou não obteve melhora. Nos achados da investigação sobre o impacto das crises em relação ao desenvolvimento neuropsicomotor na primeira avaliação 21,3 meses após a cirurgia, foi observado um ganho abaixo do esperado de apenas 4,4 meses na equivalência etária, não evidenciando melhora em curto prazo após a cirurgia, independente do controle de crises. Após 41,3 meses do procedimento cirúrgico os pacientes que apresentaram controle de crises tiveram ganhos adaptativos significativos de 15 meses na equivalência etária quando comparados com os que não apresentavam controle das crises. Nesses últimos pacientes, a equivalência etária permaneceu praticamente estável com um incremento de apenas 3 meses quando analisada as fases pré e pós - operatória / Epilepsy is a disease of the brain defined by at least two unprovoked seizures occurring 24 h apart, one unprovoked seizure and a probability of further seizures like the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years or diagnosis of an epilepsy syndrome. After epilepsy diagnosis, there are situations where patients do not respond to drug treatment, developing one seizure per month for a minimum of 2 years. If during this period two or three antiepileptic drugs different used as monotherapy or in combination, a condition known as drug-resistant epilepsy. Epilepsy surgery is an option for children with drug-resistant epilepsy acting on the seizure control seizures and, potentially on neuropsychomotor development. In this study, we evaluated clinical variables such as epilepsy age of onset, epilepsy duration, seizure frequency, etiology and adaptive behavior scale of Vineland to characterize aspects related to age equivalence through the domains of communication, socialization, daily skills and motor skills pre- and post-surgical period. Our intention was to determine the impact of epilepsy surgery on the performance of patients in these areas evaluated by Vineland. Thus, we found that the seizure free group participants showed better cognitive performance in the second evaluation, compared to the group that not seizure controlled. The clinical variable duration of epilepsy influenced the age equivalence and standard Vineland scores in the preoperative period, being considered determinant for the neuropsychomotor delay of patients submitted to epilepsy surgery. Regarding the predictive factors of improvement of postoperative crises, it was observed that Engel and surgery were the variables considered significant. The majority of the patients (63.9%) in the second postoperative evaluation still had seizures or did not improve. The findings of the research on the impact of crises on neuropsychomotor were that in the first evaluation 21.3 months after surgery there was a below-expected gain of only 4.4 months of age equivalence, not showing improvement in the short term after surgery, independent of control crisis. After 41.3 months of the surgical procedure, the patients presenting with seizure control had significant adaptive gains of 15 months when compared to those without seizure control. In the latter patients, the age equivalence remained practically stable with an increase of o preoperative only 3 months, analyzing the phases pre and postoperative evaluation

Magister Pharmaceuticae - MPharm / Tuberculosis and HIV are arguably South Africa’s largest and most important health issues. With drug-resistant strains of tuberculosis on the increase and little research on new drugs, there is an urgent need for research around the drugs presently available to ensure their optimal use and to minimise their sometimes serious and significant side effects. Treatment of drug-resistant tuberculosis is expensive and lengthy, and is complicated by a limited choice of drugs with lower efficacies and higher toxicities. Treatment is further complicated in patients with HIV due to several factors including drug interactions. While some authors suggest that HIV and malabsorption might be associated with poor clinical outcomes, other researchers have found no link. Patients may benefit from Therapeutic Drug Monitoring in order to ensure that their doses of antituberculosis drugs are reaching the required minimum effective concentrations, without attaining toxic levels in the plasma which may cause unpleasant side effects. There is little research concerning drug levels in HIV patients with TB in South Africa, let alone in patients with drug-resistant forms of tuberculosis, and there are no studies in this country that use Liquid Chromatography-Mass Spectrometry to investigate the plasma levels of pyrazinamide in patients with MDR-TB. This study aimed to investigate whether or not there is a difference in the pharmacokinetics of PZA in MDR-TB patients with HIV, and those without HIV infection. It also aimed to establish whether LC-MS could be used to study the levels of pyrazinamide in the plasma of patients with multidrug-resistant tuberculosis with and without concurrent HIV infection. The plasma levels of pyrazinamide in 32 MDR-TB patients (23 HIV negative and 9 HIV positive), were successfully 2 analysed using LC-MS, and the pharmacokinetics of PZA in these 2 populations was described. It was established that the Tmax of pyrazinamide was significantly higher in HIV-negative patients than in HIV-positive patients. Although there was a difference between the Ka in the two populations, this difference did not quite reach statistical significance. There were no statistically significant differences between HIV-negative and HIV-positive patients with regards to the other pharmacokinetic parameters investigated. Our findings established that there was little evidence to suggest that there is a difference between the pharmacokinetics of the antimycobacterial drug pyrazinamide in HIV-positive patients and that in HIV-negative patients. We were also able to successfully develop and validate an assay for the analysis of PZA in plasma using LC-MS, and this finding could be very valuable for further studies. Although our study failed to prove this, the possibility still exists that HIV-positive patients could exhibit altered kinetics of antiTB drugs and this has not been fully investigated in South Africa. The clinical impact of low plasma levels of antimycobacterial drugs is still largely unexplored and further research with larger sample sizes should be done in order to establish which factors may contribute to low plasma levels of anti-tuberculosis drugs in MDR-TB patients, and whether or not these low levels are increasing the risk of treatment failure or other poor clinical outcomes.

Thesis (MSc. (Medical Sciences)) -- University of Limpopo, 2015 / Introduction: Multidrug-resistant tuberculosis (MDR-TB) caused by resistance to at least rifampicin (RIF) and isoniazid (INH) drugs is a growing public health concern in South Africa. The detection of MDR-TB still relies on culture despite advancement in molecular diagnostic technology. Currently MTBDRplus and GeneXpert are the only available assays used in rapid diagnosis of MDR-TB using chromosomal mutations in drug target regions. Some strains are missed by these assays due to their limitation in mutational detection profile. Novel Seegene Anyplex assays simultaneously detect TB and resistance to RIF and INH using fifteen and six mutational probes, respectively within 3 hours. Limpopo Province has limited information on the circulating strains of TB. Aim: To determine drug-resistant Mycobacterium tuberculosis (M. tuberculosis) mutations using Anyplex™ MTB/NTM/MDR-TB real time assay and characterise the drug-resistant strains. Methods: We prospectively collected 204 clinical samples at Modimolle MDR-TB unit and retrospectively used 104 culture isolates from MRC laboratory in Pretoria. The MTBDRplus assay was used to screen for M. tuberculosis and drug resistant mutations to RIF and INH drugs. Anyplex™ MTB/NTM/MDR-TB assay was used for rapid detection of M. tuberculosis and drug resistance to RIF and INH within 3 hours. The discordance between phenotypic and genotypic assays was resolved by sequencing and the Anyplex™ resistant profiles were spoligotyped. Diagnostic data was collected from NHLS and MRC databases and analysed using the Microsoft excel and Epi Info version 3.5. Descriptive statistics (percentages and frequencies) were used to explain proportions. Results: The Anyplex™ MTB/NTM assay detected M. tuberculosis in 69/111(62%) and 100/104 (96%) of clinical and culture samples respectively. The sensitivities, specificity, PPV and NPV obtained for both RIF and INH resistance by Anyplex™ MDR-TB assay were 67%, 59%, 67%, 55% and 15%, 100%, 100% and 17%, respectively. Anyplex™ MTB/NTM/MDR-TB resolved 23/45 (51%) of discordant vi samples. Sequencing of remaining discordant isolates revealed L511P, L533P and D516Y mutations within rpoB gene. A novel R385W mutation within katG was also detected. Spoligotyping of Anyplex™ MDR-TB resistant clinical isolates revealed Euro American clade with 20% followed by 15% Manu2, 5% East African Indian, 5% H37Rv, 5% atypical and 50% were orphans. Conclusion: The novel Anyplex™ MTB/NTM/MDR-TB assay is a rapid and valid technique for detecting M. tuberculosis and most common mutations conferring resistance to RIF and INH. However further investigations are required, as the assay has a lower sensitivity as compared to already endorsed techniques. / National Research Foundation (NRF) and University of Limpopo TB Grant