O aumento da proporção de idosos trouxe mudanças importantes no perfil de morbidade geral. Uma maior frequência de doenças crônicas faz com que a prescrição de medicamentos seja cada vez mais extensa e mais complexa nesta população. Estes aspectos, somados às variações farmacocinéticas e farmacodinâmicas relacionadas com a idade e à crescente medicalização, levam ao aumento do risco de problemas relacionados à farmacoterapia, tais como o uso de medicamentos potencialmente inapropriados (MPI) e correspondente aparecimento de reações adversas. Esta dissertação tem como objetivo avaliar o uso de MPI entre idosos brasileiros utilizando a Lista PRISCUS (2010). Os dados analisados são provenientes da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), de caráter transversal e amostra probabilística populacional em municípios brasileiros urbanos. Neste estudo, foram analisadas as informações obtidas com a população de idosos (60 anos ou mais) (N=9.019). A variável independente foram os medicamentos utilizados por idosos com 60 anos ou mais. As variáveis intervenientes foram sexo, idade, escolaridade, nível econômico e região geográfica. Também foram analisadas as variáveis presença de doença crônica e médico que trata doença crônica. Uma análise multivariável foi realizada para identificar os fatores para o uso de medicamentos inapropriados. Do total de idosos, 18,1% utilizaram no mínimo um medicamento considerado potencialmente inapropriado, independente de dose, sendo que o grupo de medicamentos para o sistema nervoso correspondeu a 45,8%, sendo a amitriptilina a mais prevalente. O uso de medicamentos inapropriados foi maior em mulheres (20,4%), idosos com 80 anos ou mais (22,2%), idosos com nenhuma escolaridade (21,5%), nível econômico C (18,6%), região Sul do Brasil (22,4%), idosos com doença crônica (DC) (21,8%) e que tratavam a DC com mais de um médico (28%). De acordo com a análise multivariável, a variável que se mostrou associada à maior probabilidade para o uso de medicamentos inapropriados foi o aumento do número de medicamentos. Idosos que utilizam maior número de medicamentos simultaneamente (polifarmácia) têm maior probabilidade de terapia inapropriada. Com o intenso processo de envelhecimento, a tendência é aumentar a utilização de medicamentos na população. Programas de atenção ao idoso devem constar como prioridade dos órgãos públicos de saúde. / The proportion of aged has increased causing important changes in the general morbidity profile. A higher frequency of chronic diseases makes medications prescription more and more extensive and complex in this population. These aspects, coupled with pharmacokinetic and pharmacodynamic variations related to age and increasing medicalization, lead to an increased risk of problems related to the use of medications, such as the use of potentially inappropriate medications (PIM) and corresponding adverse reactions. This dissertation aims at evaluating the use of PIM among Brazilian elders using the PRISCUS List (2010). The analyzed data came from the National Survey of Access, Use and Promotion of the Rational Use of Medicines (PNAUM, in Portuguese), of transversal character and population probabilistic sample in urban Brazilian municipalities. In this study, the information obtained with the elderly population (60 years or more) (N=9.019) was analyzed. The independent variable was the medication used by the 60 years old people or older. The intervening variables were sex, age, schooling, economic level and geographic region. Also, it were analyzed the presence of chronic disease and the doctor who treats chronic disease. A multivariate analysis was performed to identify the risk factors for the use of inappropriate medications. Of the total aged, 18.1% used at least one medication considered to be potentially inappropriate, regardless of dose, and the group of medications for the nervous system corresponded to 45.8%, with amitriptyline being the most prevalent. The use of inappropriate medications was higher in women (20.4%), 80 years old people or older (22.2%), aged with no schooling (21.5%), economic level C (18.6%), South region of Brazil (22.4%), aged with chronic disease (CD) (21.8%) and who treated CD with more than one physician (28%). According to the multivariate analysis, the variable that was shown to be associated with the greatest probability for the use of inappropriate medications was the increase in the number of medications. Aged who use more medications at the same time are more likely to have inappropriate therapy. With the intense process of aging, the tendency is to increase the use of medications by the population. Aged care programs should be a priority of public health agencies.

Introdução: Nos últimos anos, o consumo de medicamentos tem aumentado em todo o mundo e também no Brasil. Investigar este consumo numa determinada população é relevante para a gestão da política de medicamentos e o gerenciamento dos recursos em saúde, pois serve como ferramenta no planejamento de ações de prevenção e promoção de saúde. Objetivo: Descrever a prevalência e a tendência de consumo de medicamentos por intermédio da dispensação numa Farmácia Pública Municipal no período de oito anos. Metodologia: Trata-se de um estudo descritivo, retrospectivo, baseado em dados secundários obtidos por meio dos relatórios de dispensação de medicamentos do sistema informatizado da Farmácia Pública Municipal de Glorinha (RS) no período de 2008 a 2015. A população do estudo constitui-se de todos os usuários que tiveram pelo menos um medicamento da Relação Municipal de Medicamentos. As variáveis demográficas foram sexo e idade. Para fins de análise, os medicamentos foram categorizados no primeiro (Grupo Anatômico – GA), segundo (Grupo Terapêutico Principal – GTP) e quinto nível (Substância Química – SQ) da classificação Anatomical Therapeutic Chemical (ATC) e seu consumo analisado pela Dose Diária Definida (DDD) por 1.000 habitantes por dia. Resultados: A população do estudo foi 9.967 pessoas, sendo o maior percentual do sexo feminino (52,8%) e a faixa etária mais prevalente de 0 a 9 anos (16,2%). O consumo pelas mulheres é maior que os homens em todas as faixas etárias. Em relação ao consumo de medicamentos dispensados por usuário por ano: os GA mais prevalentes foram sistema nervoso (22,1%) e sistema cardiovascular (19,5%); os GTP mais prevalentes foram anti-inflamatórios e antirreumáticos (11,3%) e analgésicos (10,5%) e as SQ mais consumidas foram ibubrofeno (11,3%) e paracetamol (9,9%). Quanto à quantidade de unidades farmacêuticas dispensadas por ano: os GA mais prevalentes foram sistema (43,1%) e sistema nervoso (26,7%); os GTP mais prevalentes foram os agentes com ação no sistema renina-angiotensina (18,0%) e psicoanalépticos (10,8%) e as SQ mais consumidas foram captopril (8,9%) e enalapril (7,9%). Sobre o total da DDD (DDD/1.000 habitantes/dia): os GA de maior consumo foram os medicamentos do sistema cardiovascular (47,6%) e do sistema nervoso (15,3%); os GTP mais utilizados foram os medicamentos com ação no sistema renina-angiotensina (22,7%) e os diuréticos (10,3%) e as SQ mais utilizadas foram enalapril (14,7%) e omeprazol (9,6%). Dentre os medicamentos disponibilizados foi observado um maior decréscimo de dispensação nos seguintes grupos terapêuticos principais: ação no sistema renina-angiotensina (93,0%), na diabetes (82,4%) e os diuréticos (79,0%). Conclusões: Apesar da ampliação do acesso da população aos medicamentos pelas políticas públicas vigentes de Assistência Farmacêutica, a expressiva e crescente prevalência de consumo e a sua utilização de forma não racional causa preocupação. Dentro deste contexto, o profissional farmacêutico desempenha um papel relevante na compreensão e enfrentamento do problema e, desta forma, pode também contribuir na elaboração de estratégias para educação em saúde e para o uso racional de medicamentos na população por intermédio de estudos na área de Farmacoepidemiologia. / Introduction: In recent years, the consumption of medicinal products has increased worldwide and also in Brazil. Investigating this consumption in a given population is relevant for the management of health resources, as it serves as a tool in the planning of health preventive and promotion actions. Objectives: Describing the prevalence and trend of the consumption of medicinal products through the dispensing procedure at a Municipal Public Pharmacy over a period of eight years. Methodology: This is a descriptive, retrospective study, based on secondary data obtained through the reports of dispensing procedures of medicines from the computerized system of the Municipal Public Pharmacy in Glorinha (RS), from 2008 to 2015. The studied population consisted of all users who got at least one medication from the Municipal Medication List. Demographic variables were sex and age. For the purposes of analysis, the medicinal products were categorized in the first (Anatomical Group – AG), second (Therapeutic Subgroup – TS) and fifth level (Chemical Substance – CS) of the Anatomical Therapeutic Chemical (ATC) classification, and its consumption analyzed by the Defined Daily Dose DDD (1,000 inhabitants per day). Results: The studied population was 9,967 people, the highest percentage being female (52.8%) ant the most prevalent age group that of 0 to 9 years old (16.2%). Consumption by women is greater than men in all age groups. Respecting the consumption of medicines dispensed to users per year: the most prevalent AG were nervous system (22.1%) and cardiovascular system (19.5%); the most prevalent TS were antiinflammatory and antirheumatic (11.3%) and analgesics (10.5%), and the most commonly consumed CS were ibuprofen (11.3%), and acetaminophen (9.9%). Regarding the quantity of pharmaceutical units dispensed per year: the most prevalent AG were cardiovascular system (43.1%) and nervous system (26.7%); the most prevalent TS were agents action on the renin angiotensin system (18.0%) and psychoanalytics (10.8%), and the most commonly used CS were captopril (8.9%) and enalapril (7.9%). About the total DDD (DDD/1,000 inhabitants/day): the most consumed AG were the cardiovascular system medications (47.6%) and the nervous system (15.3%); the most used TS were the medicines with action in the renin angiotensin system (22.7%) and the diuretics (10.3%) and the most used CS were enalapril (14.7%) and omeprazole (9.6%). Among the medicinal products available, a greater decrease in the following main therapeutic groups was observed: action in the renin angiotensin system (93.0%), diabetes (82.4%) and diuretics (79.0%). Conclusions: Despite the increasing access of the population to medication by the current public policies of Pharmaceutical Assistance, the expressive and growing prevalence of consumption and its use of form non-rational causes concern. Within this context, the pharmacy professional plays a relevant role in understanding and coping with the problem and, in this way, can also contribute in the elaboration of strategies for health education and for the rational use of medicines in the population through studies in the area of Pharmacoepidemiology.

Os estudos da utilização de medicamentos refletem o que acontece com os medicamentos num ambiente com variáveis não-controladas, ao contrário do que acontece nos ensaios clínicos. Dessa forma, este estudo visa determinar o consumo de psicofármacos, contextualizando-o com o crescimento populacional no município de Ribeirão Preto - SP no período de 2008 a 2012, bem como descrever o principal grupo consumidor. Para isto, este estudo observacional analítico transversal foi conduzido por meio do levantamento do uso de psicofármacos por meio dos bancos de dados Hygia (banco de dados da Secretaria Municipal de Saúde de Ribeirão Preto). Os medicamentos utilizados foram classificados de acordo com a classificação Anatômica Terapêutico Química (ATC) e suas quantidades foram expressas em Doses Diárias Definidas (DDD) a cada 1.000 habitantes por dia (DHD) e em Dose Diária Prescrita (DDP). Exceto para a faixa etária de 0 a 9 anos, em que o consumo tanto de medicamentos no geral quanto de psicofármacos foi maior ou igual para os homens; nas demais faixas etárias observa-se o consumo igual ou maior para todos os medicamentos, sendo o aumento no consumo correlacionado com o aumento da idade das mulheres. Para a maioria dos psicofármacos nota-se uma diferença significativa quando o valor da DDP foi comparado ao da DDD. Quando a taxa de aumento no consumo dos psicofármacos foi comparada a taxa do crescimento populacional, apenas o crescimento no consumo do clonazepam e da sertralina superam o crescimento populacional. Dessa forma, nota-se a importância de estabelecer comparações dos resultados encontrados dos trabalhos que avaliem a utilização de medicamentos com outras variáveis, como no caso, a taxa de crescimento populacional, para se ter uma real dimensão do seu aumento. / The drug utilization studies reflect what happens to the drug in an environment with non-controlled variables, unlike what happens in clinical trials. Thus, this study aims to determine the consumption of psychotropic drugs, contextualizing it with the population growth in RibeirãoPreto - SP from 2008 to 2012, as well as describing the main consumer group. Therefore, this cross-sectional analytical observational study was conducted through survey of the use of psychotropic drugs through databases Hygia (the RibeirãoPreto\'s Municipal database). The drugs used were classified according to the Anatomical Therapeutic Chemical classification (ATC) and their amount were expressed in Defined Daily Dose (DDD) per 1000 inhabitants per day (DHD) and Prescribed Daily Dose (PDD). Except for the age group 0-9 years, when the demand for both drugs in general and of psychotropic drugs was higher than or equal to men; in other age groups was observed a consumption equal to or greater for all medicines, the increase in consumption related with the increasing of women\' age. For most psychotropic drugs a significant difference was noticed when the value of PDD was compared to DDD. When increase rate in the consumption of psychotropic drugs was compared the rate of population growth, only the growth in consumption of clonazepam and sertraline exceed population growth.In this way, the importance of comparisons of the founded results of studies were highlighted; assessing the use of medications with other variables, as in the case, the rate of population growth, to have a real size of its increase.

Introdução: O crescente aumento da população idosa faz aumentar a necessidade de recursos de saúde, entre eles o uso de medicamentos.Objetivo: Estudar os riscos de polifarmácia em idosos no município de São Paulo, Brasil. Métodos: Este estudo faz parte do projeto SABE – Saúde,Bem-estar e Envelhecimento – através de questionários por amostra em domicílios de 2143 idosos com 60 anos e mais composta por sorteio. Os dados finais foram ponderados e expandidos de modo que representem a população idosa no ano de 2000. A polifarmácia foi definida como o uso de quatro ou mais medicamentos, e utilizado o estudo de regressão logística por passos (IC 95%). Resultados: A média do número de medicamentos foi de 2,72 e a prevalência de polifarmácia de 31,5%. A polifarmácia foi mais prevalente em mulheres com 75 anos e mais (52,1%), religião espírita(51,2%), que declaram estado de saúde ruim (40,2%) e escolaridade acima de 12 anos (46,9%). Verificou-se que 71,1% adquirem medicamentos do próprio bolso, 15,95% se automedicam e a não adesão é devida ao custo (9,1%). Os riscos para polifarmácia foram mulheres (OR 2,2), idade acima de 75 anos (OR 1,5), consulta e internação em quatro meses (OR de 1,9 e 3,8) e problemas cardíacos (OR 3,8). Quanto ao medicamento impróprio a prevalência foi de 15,6%. Conclusão: Os riscos identificados na polifarmácia mostram uma necessidade de políticas públicas que visem promover o uso racional de medicamentos. / Introduction: The continuous growth of the elderly population increases the need for further health resources; amongst them is the use of drugs.Object: Study the risks’ Polypharmacy in the population of elderly people within the city of São Paulo, Brasil. Method: This study is part of the ‘SABE’ project – Health, Well-being and aging. This survey is carried out by using a sample questionnaire in the residence of 2143 people aged 60 and over. The final data are pondered and expanded to represent the population of elderly people in the year 2000. In order to analyze, polypharmacy was defined as four or more drugs, using the study of stepwise logistical regression (IC95%). Results: The average number of drug stays at 2,72, with a prevalence of polyfarmacy of 31,5%. Polyfarmacy is more prevalent amongst women aged 75 and over (52,1%); spiritualists (51,2%); those who claim poor self perceived health status (40,2%); those whose level of education is at least 12 years (46,9%). It has been observed that 71,1% use their own money to buy drugs; 15,9% practice self-medication; the cost of treatment being the cause of nonadherence (9,1%). Women are more at risk (OR 2,2), aged 75 and over (OR 1,5), visit to the physician and hospitalization within four months(OR from 1,9 to 3,8), cardiovascular conditions (OR 3,8). As for inappropriate use of medications, the prevalence is 15,6%. Conclusion: The identified risks in polypharmacy show a need for public policies that would promote a more rational use of medications.

Made available in DSpace on 2015-04-22T22:06:22Z (GMT). No. of bitstreams: 1 Bruna Monteiro.pdf: 1262834 bytes, checksum: bbc2c46a807ede6c1b0b2594cef83934 (MD5) Previous issue date: 2013-06-25 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Population aging is a global reality, due to the reduction in child mortality and fertility, increased life expectancy and technological advances in healthcare. On the other hand, elderly people have become largely dependent on drugs/medicine due to the increasing incidence of chronic diseases, which require prolonged and/or continuous treatment. Excessive and improper intake of medications may pose risks to the patient and is a concern for public health. The objective of this work was to identify the profile of drug use among elderly patients in the Centros de Atenção a Melhor Idade (CAIMI) in Manaus-AM. We conducted a descriptive observational study in which we interviewed 355 elderly patients in the three different units that provide unique and specialized care for elderly patients. Data on drug use in the past seven days was collected through a form, and these drugs were classified according to the Anatomical Therapeutic Chemical Classification System. To obtain information about drug interactions was used Micromedex® and inappropriate drugs were classified according to the update of the Beers Criteria conducted by the American Geriatrics Society. We then analysed the occurrence of polypharmacy, redundancy and self-medication. Among the most respondents, 83.1% were women, aged between 60 and 69 years (62.5%), married (43.7%) and had children (95.5%). The prevalence of drug use was 80.3% and was the most drugs were for cardiovascular system (43.7%). The prevalence of polypharmacy was 19.3%, being higher in women (78.9%), redundancy was observed in 14.7% and 13% of self-medication in the elderly. Potential drug interactions were observed in 42.5% of the users of drugs and medicines within the total, 122 (14.7%) were considered inappropriate for use in the elderly. Although with high standard of medication use were low prevalence of self-medication, polypharmacy, use redundant and inappropriate use of drugs was observed. Our study demonstrates positive results regarding the use of drugs, a specialized and exclusive health services for the elderly in combination with multidisciplinary care, can promote better quality of life and correct use of drugs associate with improved health care. / O envelhecimento populacional é uma realidade mundial, decorrente da redução da mortalidade infantil e da fecundidade, do aumento da expectativa de vida e dos avanços tecnológicos na área da saúde, o aumento da incidência de doenças crônico-degenerativas, as quais necessitam de tratamentos prolongados e/ou contínuos, o que torna os idosos grandes consumidores de medicamentos. O uso de medicamentos pode representar riscos ao paciente, principalmente se realizado de maneira inadequada, e por isso tornou-se uma preocupação para saúde pública. Assim, o objetivo deste trabalho foi identificar o perfil do uso de medicamentos entre idosos atendidos nos Centros de Atenção a Melhor Idade (CAIMI) em Manaus-AM. Realizou-se estudo descritivo-observacional de recorte temporal no qual foram entrevistados 355 pacientes idosos nas três unidades que fornecem serviço de atenção exclusivo e especializado para pacientes idosos. Os dados sobre os medicamentos utilizados nos últimos sete dias foram coletados por meio de um formulário, e estes medicamentos foram classificados de acordo com o Anatomical Therapeutical Chemical Classification System. Para obtenção de informações sobre interações medicamentosas foi utilizado o Micromedex® e os medicamentos inapropriados foram classificados de acordo com a atualização do Critério de Beers realizado pela American Geriatrics Society. Foram analisadas a ocorrência de polifarmácia, redundância e automedicação. Dentre os entrevistados, a maioria eram mulheres (83,1%), entre a faixa etária de 60 e 69 anos (62,5%), casados (43,7%) e possuíam filhos (95,5%). A prevalência do uso de medicamentos foi de 80,3% e os medicamentos mais consumidos foram os para sistema cardiovascular (43,7%). A prevalência de polifarmácia foi de 19,3%, sendo superior nas mulheres (78,9%), a redundância foi verificada em 14,7% e automedicação em 13% dos idosos. Possíveis interações medicamentosas foram verificadas em 42,5% dos usuários de medicamentos e dentre o total de medicamentos, 122 (14,7%) foram considerados inapropriados para uso em idosos. Embora com padrão elevado de uso de medicamentos foram baixas as prevalências de automedicação, polifarmácia, uso redundante e uso de medicamentos inapropriados. Os resultados positivos em relação ao uso dos medicamentos indica que os serviços de saúde especializados e exclusivos para os idosos, com atendimento multiprofissional, podem promover melhor qualidade de vida e uso correto dos medicamentos, em virtude do melhor atendimento e atenção à saúde.

Introdução - Os efeitos prejudiciais envolvendo medicamentos pela cres- cente população idosa impulsionaram pesquisas para desenvolvimento e aplicação de diversos métodos e instrumentos para identificar padrões inadequados de prescrição/ uso e problemas farmacoterapêuticos envolvendo este grupo populacional. Objetivo - Verificar a prevalência do uso de medicamentos potencialmente inapropriados listados nos Critérios de Beers 2003 pelas pessoas idosas de 60 anos ou mais do município de São Paulo, entrevistadas pelo Estudo SABE no ano de 2006. Métodos - Trata-se de um estudo transversal de base populacional, com utilização de dados secundários obtidos do Estudo SABE. A amostra constituída de 1258 idosos de 60 anos ou mais. Os dados finais foram ponderados e expandidos de modo a representar a população idosa no ano de 2006. Os medicamentos foram classificados de acordo com a Anatomical Therapeutic Chemical Classification System. Para análise dos dados utilizou-se o pacote estatístico Stata com realização de regressão logística. Considerou-se nível de significância de p<0,05. Resultados Verificou-se a prevalência de 28 por cento de uso de MPI entre os idosos. Na análise pelo modelo de regressão logística multivariada as variáveis associadas ao consumo de MPI foram polifarmácia (p = 0,001), comorbidade (p = 0,011) e sexo (p = 0,007); ajustadas por fragilidade, idade e dificuldade em ABVD. Este estudo identificou 41 medicamentos ou classes potencialmente inadequados segundo os Critérios de Beers sendo utilizados pelos idosos moradores de São Paulo em 2006. Ao se analisar os MPI agrupados por sistema ATC notou-se que o de maior prevalência foi o grupo com os medicamentos que atuam no sistema cardiovascular (11,1 por cento ). Conclusões Entre outros problemas, os idosos, em especial as idosas, têm ainda a dificuldade de conviver com várias doenças o que leva a complexidade da terapêutica, em geral com polifarmácia e uso de medicamentos inadequados fatores ratificados pelo presente estudo situação agravada pelo contexto de alteração da farmacocinética, farmacodinâmica e as alterações relacionadas à composição corporal e fisiologia da idade avançada. Sugere-se a elaboração de método baseado em critérios explícitos de avaliação do uso de medicamentos por idosos adaptada a realidade nacional, levando-se em conta os medicamentos disponíveis no país, a opinião dos especialistas brasileiros e a literatura baseada em evidências na área de utilização de medicamentos / Introduction - The damaging effects involving drugs boosted by the growing elderly population research for developing and implementing a variety of methods and tools to identify patterns of inappropriate prescribing / use and drug related problems involving this population group. Objective - To assess the prevalence of potentially inappropriate medications (PIM) listed in the 2003 Beers criteria for people aged 60 or more of São Paulo, interviewed by the SABE survey in 2006. Methods - This is a population-based crosssectional study, using secondary data obtained from the SABE survey. The sample consisted of 1258 elderly aged 60 years or more. The final data were weighted and expanded to represent the elderly population in 2006. The drugs were classified according to the Anatomical Therapeutic Chemical Classification System. For data analysis it was used the Stata® with performance of logistic regression. It was considered a significance level of p <0.05. Results - There was a prevalence of 28 per cent using MPI among the elderly. In the analysis by multivariate logistic regression model the variables associated with consumption of PIM were polypharmacy (p = 0.001), comorbidity (p = 0.011) and female gender (p = 0.007) adjusted for frailty, age and difficulty in ADL. This study identified 41 PIM or classes according to the Beers criteria being used by the elderly residents of Sao Paulo in 2006. When analyzing the PIM grouped by the ATC system was noted that the most prevalent was the group with drugs that act on the cardiovascular system (11.2 per cent ). Conclusion - Among other problems, the elderly, especially elderly women, still have the difficulty of living with various illnesses leading to the complexity of therapy, usually with polypharmacy and inappropriate drug use - factors that are ratified by this study - a situation exacerbated by the context of altered pharmacokinetics, pharmacodynamics and changes related to body composition and physiology of aging. We suggest the preparation method based on explicit criteria for evaluating the use of medications by elderly adapted for the national reality, taking into account the available drugs in the country, the opinions of Brazilian experts and evidence-based literature in the area of drug use

Submitted by Maria Aparecida (cidazen@gmail.com) on 2017-04-18T13:46:52Z No. of bitstreams: 1 Danielle Franca Furtado.pdf: 7455681 bytes, checksum: fc9fda3fdd2b6ae52059cbf214521deb (MD5) / Made available in DSpace on 2017-04-18T13:46:52Z (GMT). No. of bitstreams: 1 Danielle Franca Furtado.pdf: 7455681 bytes, checksum: fc9fda3fdd2b6ae52059cbf214521deb (MD5) Previous issue date: 2017-03-03 / Projeto BRISA, CNPQ, FAPEMA,FAPESP e PRONEX / To analyze the medication use and associated factors to antimicrobials use in children aged 13 to 35 months in the city of São Luis – MA. A descriptive, analytical and cross-seccional study was conducted using BRISA Cohort sample data at two moments: Stage of the birth from January to December 2010 and in the stage of the first follow-up from April 2011 to January 2013. The sample of this study was 3308 children aged 13 to 35 months. Descriptive analysis of socioeconomic, demographic and health variables was carried out. The medication use in the 15 days prior to the interview was classified by means of the Anatomical Therapeutic Chemical (ATC) and to analyze the factors associated with the use of antimicrobials the Poisson regression model with robust variance was adjusted with inclusion of the independent variables using the hierarchical approach. Of the children followed up, the use of at least one medication was 90.9%; at least one antimicrobial, considering antibacterial, antifungal, antiviral and antiparasitic drugs, was 23.8%. The medicines classified by the most used anatomic groups were: respiratory activity in 83.5%, followed by those in the nervous system 28.4%, by medicines of the alimentary tract and metabolism 23.5%, and anti-infectives of systemic use 10.5%. The factors associated with the use of antimicrobials after adjusted analysis were: Maternal perception about the child's health (Regular / Bad: PR = 1.37, p <0.001), post - birth morbidity (PR = 1.50, p <0.001) and time of breastfeeding (Suck between 3 and 6 months: PR = 1.34 p = 0.013). The high consumption of drugs reinforces the need to promote rational use for this age group, since the information about the effects of pharmacotherapy in the infant organism is limited. Factors associated with the use of antimicrobials point to the importance of these drugs in the health-disease process, allowing managers to better understand this process and the consequent implementation of actions directed at the health care of the child, with increased access to these medicines. Safe and appropriate to the specificities of infantile pharmacotherapy. / Para analisar o uso de medicamentos e os fatores associados ao uso de antimicrobianos em crianças de 13 a 35 meses no município de São Luís – MA um estudo descritivo, analítico, transversal foi conduzido, utilizando dados amostrais da Coorte BRISA, em dois momentos: na etapa do nascimento de janeiro a dezembro de 2010 e na etapa do primeiro seguimento de abril de 2011 a janeiro de 2013. A amostra deste estudo foi de 3308 crianças com idade de 13 a 35 meses. Realizada análise descritiva das variáveis socioeconômicas, demográficas e de saúde. O uso de medicamentos nos 15 dias anteriores à entrevista foi classificado por meio da Anatomical Therapeutic Chemical (ATC) e para analisar os fatores associados à utilização de antimicrobianos foi ajustado o modelo de regressão de Poisson com variância robusta com inclusão das variáveis independentes utilizando-se a abordagem hierarquizada. Das crianças acompanhadas, o uso de pelo menos um medicamento foi de 90,9%, já o uso de pelo menos um antimicrobiano, considerando antibacterianos, antifúngicos, antivirais e antiparasitários, foi de 23,8%. Os medicamentos classificados pelos grupos anatômicos mais utilizados foram: com ação no sistema respiratório 83,5%, seguidos pelos que atuam no sistema nervoso 28,4%, pelos medicamentos do trato alimentar e metabolismo 23,5% e antiinfecciosos de uso sistêmico 10,5%. Os fatores associados ao uso de antimicrobianos após análise ajustada foram: percepção da saúde da criança pela mãe (Regular/Ruim: RP=1,37, p<0,001), apresentar morbidade pós - nascimento (RP=1,50, p<0,001) e tempo de aleitamento materno (Mamar entre 3 a 6 meses: RP=1,34 p=0,013). O consumo elevado de medicamentos reforça a necessidade de promoção do uso racional para essa faixa etária, uma vez que são limitadas as informações a cerca dos efeitos da farmacoterapia no organismo infantil. Os fatores associados ao uso de antimicrobianos apontam a importância que esses medicamentos exercem no processo saúde-doença, permitindo aos gestores a melhor compreensão desse processo e a consequente realização de ações direcionadas à assistência à saúde da criança, com ampliação do acesso a esses medicamentos de forma segura e adequada às especificidades da farmacoterapia infantil.

En pharmaco-épidémiologie, la mesure de l’exposition médicamenteuse est fondamentale. Des données déclaratives recueillies par interrogatoire des sujets ou des données extraites des bases de remboursement de l’Assurance Maladie peuvent être utilisées. Les objectifs de ce travail étaient de comparer l’exposition mesurée à partir de ces deux sources de données et d’évaluer l’impact du choix de l’une ou l’autre source sur les mesures de risque dans les études étiologiques. Les travaux ont été conduits au sein de l’étude des Trois-Cités, cohorte de sujets âgés pour laquelle étaient disponibles des données déclaratives et de remboursement. La concordance entre les expositions issues des deux sources ou la validité de l’exposition issue de l’une par rapport à celle issue de l’autre ont été évaluées dans différents contextes. La survenue d’événements a été simulée dans la population et des études cas-témoins nichées ont été conduites pour évaluer l’association entre l’exposition issue de chaque source et chaque événement. Pour les médicaments cardiovasculaires, les mesures d’exposition étaient peu différentes entre les deux sources. L’impact du choix de l’une ou l’autre source sur les mesures d’association entre l’exposition et un événement était faible. Pour les benzodiazépines ou les anti-inflammatoires non stéroïdiens, des différences étaient observées entre les expositions issues des deux sources. Pour ces médicaments, l’association avec un événement pouvait varier selon la source utilisée. Pour des médicaments pris de manière irrégulière ou intermittente, le choix de la source de données pour la mesure de l’exposition peut donc être un élément déterminant. / In pharmacoepidemiology, assessment of drug exposure is fundamental. It can rely on data collected through patient interviews or extracted from healthcare insurance system databases recording reimbursement claims. This work aimed to compare drug exposure measured from these two data sources and to evaluate the impact of choosing one source or the other on risk estimates in etiological studies. It was conducted as part of the Three-City Study, a cohort of French elderly persons for which both interview and reimbursement data were available. Agreement between exposures measured from both sources or validity of exposure measured from one source with reference to that measured from the other were evaluated in different backgrounds. Simulated outcomes were generated in the study population and nested case-control studies were conducted in order to estimate the association between the drug exposure measured from each source and each simulated outcome. For cardiovascular system drugs, exposure measured from interview data was close to that measured from reimbursement data. The choice of one source or the other had few impact on the estimated associations between the exposure and an outcome. For benzodiazepines or non-steroidal anti-inflammatory drugs, exposure measured from both sources could differ. For these drugs, the association between the exposure measured from each source and an outcome could vary. For drugs that can be used irregularly or intermittently, the choice of the source of data for drug exposure assessment could thus be of great importance.

Ces travaux de thèse présentent une approche de pharmaco-épidémiologie explorant l'exposition médicamenteuse chez des patients atteints de lymphome tout au long de leur parcours de soin. L'utilisation des données du Système National d'Information Inter-régimes de l'Assurance Maladie (SNIIRAM) nous a permis de quantifier cette exposition médicamenteuse et de déterminer les facteurs associés dans le contexte de la vie réelle. Les travaux de recherche réalisés au cours de cette thèse répondaient à 3 objectifs. Dans un premier objectif, nous avons souhaité valider l'utilisation du SNIIRAM à des fins de recherche pour améliorer la robustesse des futures études menées sur le lymphome. Après avoir défini plusieurs algorithmes d'identification des cas incidents de lymphome, nous avons testé leur validité par confrontation aux données cliniques exhaustives du Registre des cancers du Tarn. Les paramètres de performance obtenus permettent de considérer les données disponibles dans le SNIIRAM comme un outil puissant pour mener des études pharmaco-épidémiologiques ou médico-économiques sur le Lymphome. Le second objectif était d'explorer l'existence d'une surconsommation de médicaments psychotropes au cours de la phase active de traitement par rapport à une population témoin, sous l'hypothèse d'une initiation accrue de ces médicaments pour pallier les complications psychologiques associées à la prise en charge du Lymphome. Par ailleurs, la chronicisation fréquemment observée de ce type de consommation peut conduire à terme à des complications potentiellement évitables. Pour répondre à cet objectif, nous avons réalisé une étude selon une approche " new-user design ", à partir d'une cohorte de patients incidents de lymphome identifiés dans les données du SNIIRAM à l'échelon régional. Nous avons observé un taux d'initiation supérieur au taux observé en population générale ou chez des patients atteints d'autres pathologies mettant en jeu le pronostic vital (infarctus du myocarde). En fonction de la classe thérapeutique étudiée, 20 à plus de 50% des patients restaient exposés de façon inappropriée (au-delà des recommandations) à ces médicaments. Le troisième objectif a donc été d'explorer les déterminants associés à une utilisation prolongée de médicaments psychotropes dans la phase de l'après-cancer à partir des données de l'Echantillon généraliste des bénéficiaires (EGB). [...] / This thesis presents a pharmacoepidemiology approach to describe drug utilization in lymphomas during their whole care pathway. The use of the French claims database (Système National d'Informations Inter-Régimes de l'Assurance Maladie (SNIIRAM)) allows to exhaustively quantify this drug utilization in real life conditions. This thesis consists of three mains objectives. First, we aimed to develop validated algorithms for the identification of incident cases of lymphoma. For the validation, we used data from a regional Cancer Registry as the gold standard. The purpose of this validation study was to enhance validity of future studies conducted on lymphomas in the SNIIRAM database. The results of this study associated to strengths of this database demonstrate that this approach is of great interest to conduct pharmacoepidemiological or medico-economic studies in lymphomas. Second, we aimed to estimate the incidence of use of psychotropic drugs during the active treatment phase of lymphoma in comparison with control groups. Indeed, the increased probability of developing anxio-depressive disorders after diagnosis could lead to an increased initiation of psychotropic drugs and a potential inappropriate chronic use of these drugs after initiation. Such inappropriate chronic use can unnecessarily expose patients to adverse event. For this aim, we conducted a new-user cohort study using data from the SNIIRAM database. The results of this study revealed that the initiation rate of these drugs is higher than in the general population or for life-threatening diseases such as myocardial infarction. Moreover, we observed an inappropriate prolonged use for a significant fraction of patients (20% to more than 50% according to therapeutic class). On the basis of these findings, the third objective was to identify factors associated with prolonged use of these drugs during survivorship. This study was conducted using data from the General Sample of Beneficiaries (EGB). [...]

Bien que les vaccins représentent une avancée majeure pour la santé publique, le risque d’effets secondaires constitue une menace réelle pour leur acceptation par le grand public et les professionnels de santé. La France se classe, d’ailleurs, comme le pays manifestant la plus grande défiance envers le vaccin. Cela s’est souvent traduit pas des couvertures vaccinales faibles. L’origine de cette perte de confiance est, entre autres, liée à la polémique intense autour du vaccin anti-hépatite B (HB) et le risque de sclérose en plaques dans les années 1990. Le but de cette thèse est d’évaluer le lien potentiel entre vaccination et démyélinisation, en considérant deux exemples : les vaccins anti-VHB et anti-papillomavirus (HPV). Une approche méthodologique, progressive, fondée sur les preuves a été utilisée pour les deux vaccins. La génération d’hypothèse a considéré la plausibilité biologique, les rapports de cas publiés, les analyses de disproportionnalité conduites dans le système américain de pharmacovigilance des vaccins (i.e., Vaccine Adverse Event Reporting System (VAERS)), et l’analyse des signaux détectés par la surveillance passive. Concernant la vaccination anti-VHB, des analyses attendu/observé ont également été menées à partir des cas confirmés rapportés à la pharmacovigilance française dans les années 1990. Des revues systématiques de toutes les études individuelles ayant évalué la plausibilité de l’association entre démyélinisation et les deux vaccins considérés ont été réalisées, tandis que des méta-analyses ont permis d’obtenir des estimations de risque « poolées » à partir des preuves accumulées à ce jour. Les résultats restent mitigés pour les deux vaccins. Pour la vaccination anti-VHB, une plausibilité biologique faible et indirecte, l’analyse du signal français détecté en 1996 qui a révélé une disjonction complète entre les populations cible et rejointe, ainsi que les résultats des analyses de disproportionnalité dans VAERS sont des éléments en faveur d’une possible association entre démyélinisation centrale et vaccin anti-VHB. Cependant, ni la méta-analyse, ni les analyses attendu/observé (bien que leurs conclusions puissent être renversées par un facteur modéré de sous-notification), n’ont fourni de résultat statistiquement significatif. En tout état de cause, si un risque en excès existait, il serait faible et ne concernerait que l’adulte. Les recommandations actuelles qui minimisent la probabilité d’exposition à l’âge adulte, sont donc plus que justifiées. Pour la vaccination anti-HPV, le risque de démyélinisation centrale semble, à ce jour, écarté. Néanmoins, un doute subsiste concernant un possible risque en excès pour le syndrome de Guillain et Barré. Il serait nécessaire de conduire d’autres études, rendues difficiles par la rareté de l’événement, estimée à 1 cas pour 1,000,000 doses vendues. En conclusion, une association forte avec un risque de démyélinisation semble à exclure pour les deux vaccins, rendant la balance bénéfice/risque largement positive pour ces produits, dès lors qu’ils sont utilisés dans leurs populations cibles. Dans ce contexte, une communication scientifique, indépendante et claire est la clé pour promouvoir les programmes de vaccination et créer la confiance et l’adhésion du grand public. Les décisions politiques ont aussi une lourde responsabilité. En effet, les suspensions des campagnes nationales de vaccination peuvent avoir des conséquences délétères à long terme. Le futur de la pharmacovigilance des vaccins pourrait résider dans la mise en place d’un réseau collaboratif entre le patient et son médecin, via l’utilisation de SMS et smartphones, comme cela existe déjà en Australie. En plus de collecter les effets secondaires des vaccins, cela représenterait une opportunité unique de placer le patient au coeur du système de surveillance, lui offrant une voix et contribuant à restaurer sa confiance envers les vaccins, et même envers les décideurs de santé publique. / While vaccines represent a great achievement for public health, the risk of adverse effects is a real threat for vaccine acceptability by both the population and healthcare professionals. France still ranks as the country having the highest vaccine defiance. This often turned into poor vaccination coverages. This origin of this mistrust in vaccines is probably related to the intense polemic around anti-hepatitis B (HB) vaccination and the risk of multiple sclerosis in the 1990’s. The main aim of this thesis was to assess the putative link between vaccination and demyelinating disorders by considering two examples: anti-HB and anti-papillomavirus (HPV) vaccines. For both vaccines, methods adopted a stepwise evidence-based approach. Hypothesis generation was based on evidence regarding the biological plausibility, the published case reports, the disproportionality analyses conducted in the US Vaccine Adverse Event Reporting System (VAERS) and the analysis of signals detected by spontaneous reporting systems, if any. For the research question centered on the anti-HB vaccination, observed-to-expected analyses based on all confirmed cases reported to the French pharmacovigilance in the 1990’s were also conducted. Systematic reviews of all individual studies having assessed the possible association between demyelination and either anti-HB or HPV vaccines were then conducted while meta-analyses brought pooled risk estimates of all evidence published so far. Results were non-conclusive for both vaccines. For anti-HB vaccination, several elements could give credence to an association with central demyelination: a weak and indirect biological plausibility, the analysis of the French signal detected in the 1990’s which revealed a complete disjunction between the target and the joint populations, and the results of the disproportionality analyses in VAERS. Nevertheless, neither the meta-analysis nor the observed-to-expected analyses (although might be easily reversed by a moderate degree of underreporting), provided statistically significant findings. If the excess risk actually existed, it would be weak and would be a concern for adults only. The current recommendations which are minimizing the probability of the French population to be exposed at an adult age, are therefore more than justified. For the anti-HPV vaccination, after reviewing all materials available, the risk of central demyelination seems, at this date, unlikely. Nevertheless, a doubt remains regarding a possible excess risk of Guillain Barré Syndrome (GBS) in the follow of an anti-HPV immunization. More specific studies would be needed, although the rarity of this event renders its evaluation difficult. From the studies already conducted, it was estimated that this excess risk, if any, would be lower than 1 per 1,000,000 doses sold. To conclude, a strong association with a risk of central demyelination can be ruled out for both vaccines, making the benefit and risk balances still largely positive for both products if used in their current target populations. In that context, an independent, clear and scientifically-based communication is the key element to promote vaccination programmes and to generate the confidence and adherence of the general population. Political decisions also carry a heavy responsibility in ensuring trust towards vaccination programmes, as the suspension of national immunization campaigns which could have long-lasting deleterious consequences. The future of vaccine pharmacovigilance could rely on the implementation of a collaborative GP-patient network-based solution using SMS and smartphones, as already experimented in Australia. While collecting potential adverse effects of vaccines, it would also be a unique opportunity to place the patients at the heart of the surveillance system, giving them a voice and potentially contributing to restore their confidence in vaccines and even, in the decision-makers in the field of public health.