INTRODUÇÃO: A Tuberculose (TB) e a Síndrome da Imunodeficiência Adquirida (AIDS) são, individualmente, grandes ameaças à saúde pública. As epidemias de AIDS e TB são sinérgicas e criaram uma crise de grandes proporções e desafios para o manejo clínico dos doentes, serviços de saúde e órgãos governamentais. A infecção pelo Vírus da Imunodeficiência Humana (HIV) é um dos principais fatores de risco para TB. O tratamento de pacientes com HIV ou aids e TB requer o uso concomitante de medicamentos tuberculostáticos e antirretrovirais, e as dificuldades a serem superadas incluem alto número de comprimidos, adesão aos tratamentos, interações medicamentosas com possibilidade de sobreposição de efeitos tóxicos e síndrome de reconstituição imune inflamatória. Uma forma de prevenção da TB é o Tratamento Preventivo com Isoniazida (TPI) nos pacientes com Infecção Latente por Mycobacterium tuberculosis (ILMTb), para os quais taxas de adesão de 80% ou mais são adequadas. A baixa adesão ao TPI diminui a sua efetividade. Neste cenário, avaliar a adesão ao TPI é de grande importância. O Serviço de Farmácia pode ser um instrumento altamente eficiente para realizar esta avaliação, através do acompanhamento das taxas de dispensação de isoniazida (INH) prescrita como TPI. OBJETIVO: Avaliar a taxa de adesão ao TPI em sujeitos com HIV ou aids e ILMTb, através da dispensação de INH. MÉTODO: Foram incluídos sujeitos que apresentaram prescrição do medicamento INH no período de 01/07/2008 a 30/06/2011 na farmácia do Serviço de Extensão ao Atendimento de Pacientes HIV/Aids da Divisão de Moléstias Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (SEAP HIV/Aids). As informações sobre sexo, idade, acompanhamento médico, uso de antirretrovirais, doenças concomitantes, intercorrências, datas de início e término do TPI foram obtidas do prontuário e informações sobre prescrição e dispensação de INH foram obtidas do Sistema de Informações de Gerenciamento Hospitalar (SIGH). RESULTADOS: Foram incluídos na análise 161 sujeitos, 78,9% (127) do sexo masculino, com idade média de 46 anos, 84,5% (136) deles acompanhados por médicos assistentes, 92,5% (149) utilizavam drogas antirretrovirais, 77,6% (125) apresentavam doenças concomitantes e 12,4% (20) sofreram intercorrências durante o TPI. Observou-se aumento transitório de enzimas hepáticas que não justificava a suspensão do TPI. A taxa de adesão foi de 96%. A prescrição eletrônica da INH nem sempre acompanhou, temporalmente, as datas, registradas em prontuário, de início e fim do TPI. A análise de concomitância entre início e fim do TPI e a prescrição de INH foi realizada para 90% (146) dos sujeitos para os quais estas informações eram disponíveis. Para 8,7% (14) dos sujeitos a prescrição eletrônica foi posterior à data de início de TPI; para 56,2% (82) dos sujeitos a prescrição de INH ultrapassou a data de término do TPI no prontuário e para 17,1% (25) dos sujeitos a prescrição de INH foi encerrada antes do término do TPI no prontuário. Não foram observadas associações estatísticas significativas entre o desfecho e as variáveis de interesse. CONCLUSÃO: Adesão é um comportamento complexo, assim como sua avaliação. Identificamos elevada taxa de adesão ao TPI entre sujeitos que vivem com HIV/aids; a frequência de hepatotoxicidade foi baixa e, quando ocorreu, transitória. Salientamos o descompasso entre o projeto terapêutico de TPI, registrado em prontuário, e a sua concretização, através da prescrição da INH. A prescrição eletrônica é um instrumento concebido para elevar a qualidade e agilizar a assistência; entretanto, pode expor o paciente a prescrição inadequada. Para evitá-lo devem ser adotadas medidas de segurança que, sem dificultar a prescrição, possam aprimorá-la constantemente, conforme os protocolos de tratamento disponíveis e os conhecimentos atualizados / BACKGROUND: Tuberculosis (TB) and Acquired Immunodeficiency Syndrome (AIDS) are major threats to public health. The Aids and TB epidemics are synergistic, bring great challenges for the clinical management of patients, health services and governments. Infection with Human Immunodeficiency Virus (HIV) is a major risk for TB. The treatment of coinfected patients requires antituberculosis and antiretroviral drugs administered concomitantly. These patients are defied by the high number of tablets, adherence, drugs interactions, overlapping toxicities and immune reconstitution inflammatory syndrome. The isoniazid preventive therapy (IPT) is recommended to reduce the risk of TB in HIV/aids patients with Mycobacterium tuberculosis Latent Infection (MTbLI). Adherence rates of 80% or more are adequate. Low adherence to the IPT reduces its effectiveness. Assessing adherence to the IPT is of great importance in this setting, and the withdrawal of INH from the pharmacy can be used for this purpose. OBJECTIVE: To evaluate the adherence to the IPT in subjects with HIV/Aids and MTbLI, followed at Serviço de Extensão ao Atendimento de Pacientes HIV/ Aids (SEAP HIV/Aids), an HIV/aids outpatient clinic, through the withdrawal of INH from the pharmacy. METHODS: subjects with HIV/Aids and MTbLI who had a prescription of INH for IPT from 01/07/2008 to 30/06/2011 were included. Information about sex, age, medical conditions, antiretrovirals, comorbidities, IPT period, intercurrences during the IPT and withdrawal of INH from the pharmacy were retrieved from the medical files and the system of information and hospital management (SIGH). RESULTS: 161 subjects were included in the study, 78,9% (127) of them males, with a mean age of 46 years, 84,5 % (136) of them assisted by infectologists, 92,5% ( 149) taking antiretrovirals, 77,6% (125) with comorbidities and 12,4% (20) with intercurrences during the IPT; a low and transient increase of liver enzymes that not led to discontinuation of the IPT was observed. The adherence rate was 96%. The evaluation of concordance between the periods of ITP and prescription of INH was performed for 90% (146) of subjects for whom this information was available. The electronic prescription of INH was not coincident with the period of IPT registered in medical files for most subjects. To 8,7% (14) of the subjects the electronic prescription was made after the beginning of IPT, for 56,2% (82) of the subjects the prescription of INH exceeded the date of completion of the IPT and for 17,1% (25) of the subjects the prescription of INH ended before the end of the IPT registered in medical files. No statistically significant associations between the outcome and the variables of interest were observed. CONCLUSION: Adherence is a complex behavior, as well as their evaluation. We found a high adherence rate to IPT among HIV/Aids subjects with MTbLI, with a low and transient grade of hepatotoxicity. Although the electronic prescription is an instrument designed to improve the quality of the health care, it can expose patients to inappropriate prescription. To avoid this, security measures should be adopted, in order to improve it constantly, according to the protocols of treatment available and updated knowledge, without hampering medical prescription

Made available in DSpace on 2014-12-17T14:16:30Z (GMT). No. of bitstreams: 1 MarceloVPA_DISSERT.pdf: 3152615 bytes, checksum: 2a3513c0df769468fec98423bf2dba29 (MD5) Previous issue date: 2013-03-21 / Tuberculosis is a serious disease, but curable in practically 100% of new cases, since complied the principles of modern chemotherapy. Isoniazid (ISN), Rifampicin (RIF), Pyrazinamide (PYR) and Chloride Ethambutol (ETA) are considered first line drugs in the treatment of tuberculosis, by combining the highest level of efficiency with acceptable degree of toxicity. Concerning USP 33 - NF28 (2010) the chromatography analysis to 3 of 4 drugs (ISN, PYR and RIF) last in average 15 minutes and 10 minutes more to obtain the 4th drug (ETA) using a column and mobile phase mixture different, becoming its industrial application unfavorable. Thus, many studies have being carried out to minimize this problem. An alternative would use the UFLC, which is based with the same principles of HPLC, however it uses stationary phases with particles smaller than 2 ?m. Therefore, this study goals to develop and validate new analytical methods to determine simultaneously the drugs by HPLC/DAD and UFLC/DAD. For this, a analytical screening was carried out, which verified that is necessary a gradient of mobile phase system A (acetate buffer:methanol 94:6 v/v) and B (acetate buffer:acetonitrile 55:45 v/v). Furthermore, to the development and optimization of the method in HPLC and UFLC, with achievement of the values of system suitability into the criteria limits required for both techniques, the validations have began. Standard solutions and tablets test solutions were prepared and injected into HPLC and UFLC, containing 0.008 mg/mL ISN, 0.043 mg/mL PYR, 0.030 mg.mL-1 ETA and 0.016 mg/mL RIF. The validation of analytical methods for HPLC and UFLC was carried out with the determination of specificity/selectivity, analytical curve, linearity, precision, limits of detection and quantification, accuracy and robustness. The methods were adequate for determination of 4 drugs separately without interfered with the others. Precise, due to the fact of the methods demonstrated since with the days variation, besides the repeatability, the values were into the level required by the regular agency. Linear (R> 0,99), once the methods were capable to demonstrate results directly proportional to the concentration of the analyte sample, within of specified range. Accurate, once the methods were capable to present values of variation coefficient and recovery percentage into the required limits (98 to 102%). The methods showed LOD and LOQ very low showing the high sensitivity of the methods for the four drugs. The robustness of the methods were evaluate, facing the temperature and flow changes, where they showed robustness just with the preview conditions established of temperature and flow, abrupt changes may influence with the results of methods / A tuberculose ? uma doen?a grave, por?m cur?vel em praticamente 100% dos casos novos, desde que obedecidos os princ?pios da moderna quimioterapia. S?o considerados f?rmacos de 1? linha no tratamento ? tuberculose: isoniazida, pirazinamida, etambutol e rifampicina. De acordo com USP 33 - NF28 (2010) as an?lises cromatogr?ficas para 3 dos 4 f?rmacos (isoniazida, pirazinamida e rifampicina) duram em m?dia 15 minutos e mais 10 minutos para a obten??o do 4? f?rmaco (etambutol) utilizando outra coluna, com outra mistura de fase m?vel, tornando esta aplica??o na pr?tica industrial desfavor?vel. Uma das alternativas ? utilizar o CLUE, o qual baseia-se nos mesmos princ?pios da CLAE, por?m utiliza fases estacion?rias com part?culas menores que 2 ?m. Dessa forma pretende-se com o presente estudo desenvolver e validar novos m?todos anal?ticos para determina??o simult?nea de tuberculost?ticos por CLAE/DAD e CLUE/DAD. Para isto, foi realizado um screening anal?tico, o qual verificou que ? necess?rio um gradiente de sistema de fase m?vel A (tamp?o acetato:metanol 94:6 v/v) e B (tamp?o acetato:acetonitrila 55:45 v/v). Posteriormente, ao desenvolvimento e otimiza??o do m?todo em CLAE e CLUE com a obten??o dos valores de adequabilidade do sistema dentro dos limites de aceita??es vigente para ambos as t?cnicas, as valida??es deram-se in?cio. Solu??es padr?es e solu??es testes dos comprimidos foram preparadas e injetadas no CLAE e CLUE, contendo isoniazida, pirazinamida, etambutol e rifampicina nas concentra??es de 0,008, 0,043, 0,030 e 0,016 mg.mL-1, respectivamente. A valida??o dos m?todos anal?ticos foram realizadas para: especificidade / seletividade, intervalos da curva anal?tica, linearidade, limite de detec??o, limite de quantifica??o, exatid?o, precis?o (repetibilidade, precis?o intermedi?ria) e robustez. Os m?todos foram adequados para determina??o dos 4 f?rmacos separadamente sem interfer?ncia nos demais. Precisos, devido ao fato de que os m?todos demonstraram que mesmo com varia??o de dias, al?m da repetibilidade, os valores ficaram dentro da faixa preconizada na legisla??o vigente. Lineares (R > 0,99), ou seja, os m?todos foram capazes de demonstrar que os resultados obtidos eram diretamente proporcionais ? concentra??o do analito na amostra, dentro de um intervalo especificado. Exatos, uma vez que os m?todos foram capazes de apresentar valores de coeficiente de varia??o e porcentagem de recupera??o dentro dos limites exigidos (98 a 102%). Os m?todos mostraram LD e LQ com n?veis baixos demonstrando que os m?todos possuem elevada sensibilidade aos quarto f?rmacos. A robustez foi avaliada frente ?s altera??es de temperatura e fluxo, onde os m?todos demonstraram-se robustos apenas nas condi??es previamente estabelecidas de temperatura e fluxo, altera??es bruscas podem acarretar influ?ncia nos resultados dos m?todos

The research objectives were to describe the age and gender of adult HIV positive clients on ART who received IPT; the incidence of tuberculosis among clients that received IPT and the defaulter rate among those that were commenced on IPT. Quantitative non-experimental descriptive retrospective cohort study was undertaken to ascertain the incidence of tuberculosis among adult HIV positive clients who received IPT. 104 clinic records of HIV positive adult clients accessing care at Isithebe Clinic, iLembe-South Africa who were commenced on IPT between 01 July 2010 and 30 November 2011 were analysed. The study found that 66 of 104 (63.5%) study respondents completed the course of IPT and the majority of those that defaulted were due to poor quality of care. Gender was statistically found to have played a role on whether a patient completes IPT. None of the study respondents that completed IPT was diagnosed with TB disease. / Health Studies / M.A. (Public Health)

The research objectives were to describe the age and gender of adult HIV positive clients on ART who received IPT; the incidence of tuberculosis among clients that received IPT and the defaulter rate among those that were commenced on IPT. Quantitative non-experimental descriptive retrospective cohort study was undertaken to ascertain the incidence of tuberculosis among adult HIV positive clients who received IPT. 104 clinic records of HIV positive adult clients accessing care at Isithebe Clinic, iLembe-South Africa who were commenced on IPT between 01 July 2010 and 30 November 2011 were analysed. The study found that 66 of 104 (63.5%) study respondents completed the course of IPT and the majority of those that defaulted were due to poor quality of care. Gender was statistically found to have played a role on whether a patient completes IPT. None of the study respondents that completed IPT was diagnosed with TB disease. / Health Studies / M.P.H.

This study assessed healthcare providers’ knowledge, attitudes and practices towards IPT provision for people living with HIV (PLHIV) in Addis Ababa, the capital city of Ethiopia. A quantitative, descriptive, cross-sectional study design was used for the study and data was collected using a self-administered questionnaire from 104 clinicians working in ART clinics. The findings show that healthcare providers who participated in this study had a mean value of high knowledge, positive attitude and good practice towards IPT provision for PLHIV. Significant association was found between knowledge and attitude (P=0.000) but no significant associations were found between knowledge and practice, attitude and practice as well as between the type of facility (public/private) and level of practice. This implied that, the low level of IPT implementation in Addis Ababa doesn’t seem due to health care providers’ lack of knowledge and resistance to provide IPT for people living with HIV. As a result, the researcher recommends for further researches of other possible factors like; the reliability of IPT information/data management, drug supply and the leadership and governance of the health system that IPT program is a direct concern. / Health Studies / M. Public Health (with specialisation in Medical Informatics)

The purpose of this study was to investigate the Isoniazid preventive therapy (IPT) initiation amongst eligible HIV positive patients at health facilities in the Polokwane subdistrict to identify key features in the knowledge and practice of health professionals as well as available resources at the health facilities. A quantitative non-experimental, descriptive, cross-sectional design was used to describe the practice of IPT initiation in health facilities. Data were collected using a structured questionnaire with medical doctors, operational managers and registered nurses from the district’s 34 health care facilities. The census sample was 124. Data were captured and analysed using Statistical Package for the Social Sciences (SPSS) Version 24. The results showed that the health care professionals knew the policy and procedures for the implementation of IPT but lacked knowledge on patient screening. The findings further suggest that record keeping and data capturing was not implemented sufficiently. Resources at the facilities were found to be sufficient. / Health Studies / M. P. H.

Introduction: No Fixed-Dose Combination (FDC) formulations currently exist for pediatric tuberculosis (TB) treatment. Earlier work implemented, in the software NONMEM, a rational method for optimizing design and individualization of pediatric anti-TB FDC formulations based on patient body weight, but issues with parameter estimation, dosage strata heterogeneity and representative pharmacokinetics remained. Aim: To further develop the rational model-based methodology aiding the selection of appropriate FDC formulation designs and dosage regimens, in pediatric TB treatment. Materials and Methods: Optimization of the method with respect to the estimation of body weight breakpoints was sought. Heterogeneity of dosage groups with respect to treatment efficiency was sought to be improved. Recently published pediatric pharmacokinetic parameters were implemented and the model translated to MATLAB, where also the performance was evaluated by stochastic estimation and graphical visualization. Results: A logistic function was found better suited as an approximation of breakpoints. None of the estimation methods implemented in NONMEM were more suitable than the originally used FO method. Homogenization of dosage group treatment efficiency could not be solved. MATLAB translation was successful but required stochastic estimations and highlighted high densities of local minima. Representative pharmacokinetics were successfully implemented. Conclusions: NONMEM was found suboptimal for the task due to problems with discontinuities and heterogeneity, but a stepwise method with representative pharmacokinetics were successfully implemented. MATLAB showed more promise in the search for a method also addressing the heterogeneity issue.

This study assessed healthcare providers’ knowledge, attitudes and practices towards IPT provision for people living with HIV (PLHIV) in Addis Ababa, the capital city of Ethiopia. A quantitative, descriptive, cross-sectional study design was used for the study and data was collected using a self-administered questionnaire from 104 clinicians working in ART clinics. The findings show that healthcare providers who participated in this study had a mean value of high knowledge, positive attitude and good practice towards IPT provision for PLHIV. Significant association was found between knowledge and attitude (P=0.000) but no significant associations were found between knowledge and practice, attitude and practice as well as between the type of facility (public/private) and level of practice. This implied that, the low level of IPT implementation in Addis Ababa doesn’t seem due to health care providers’ lack of knowledge and resistance to provide IPT for people living with HIV. As a result, the researcher recommends for further researches of other possible factors like; the reliability of IPT information/data management, drug supply and the leadership and governance of the health system that IPT program is a direct concern. / Health Studies / M.A. (Public Health (with specialisation in Medical Informatics))