Objetivo: Este estudo objetivou avaliar a precisão de infusões de medicamentos em dois modelos de Bomba de Infusão (BI), de equipo específico do fabricante e de equipo universal, a concordância entre estes dois modelos e sua relação de custo e efetividade. Método: Foi realizado um ensaio clínico randomizado em pacientes internados em um hospital geral universitário de 740 leitos. As unidades de internação foram randomizadas através de sorteio simples para cada modelo de equipamento e os pacientes foram incluídos de acordo com indicação de uso de BI, conforme protocolo institucional. Os tipos de erros e reações adversas foram classificados por meio de algoritmos. Foi calculado o custo de cada sistema de bomba de infusão, pela vida útil da tecnologia. Resultados: Em 55 pacientes foram acompanhadas 310 infusões, 117 no grupo da bomba de infusão de equipo universal e 193 na bomba de infusão de equipo especifico. Houve semelhança (p=0,40) entre o tempo programado e o observado nas infusões por meio da bomba de equipo específico (-2,1 ± 19 min) e universal (0,08 ± 23 min). Percentualmente, também não foi observada diferença (p=0,70) entre a infusão por bomba de equipo específico (-0,15±3,8%) e universal (0,1±6,3%). Foram observados 14 (4,5%) erros de medicação, semelhantes (p=0,58) entre os tipos de BI. Os custos cumulativos entre os dois sistemas de bombas se equivaleram em 30 meses, sendo que após 11 anos, foram significativamente maiores para bomba de equipo específico em 184,29%. Conclusão: Ambos modelos de BI avaliadas mostraram-se igualmente seguras para administração EV de fármacos, sendo o modelo de equipo universal mais vantajoso economicamente ao longo da vida útil dos equipamentos. / Objective: This study aimed to evaluate the accuracy of drug infusion in two models of infusion pumps (IP), one with a specific IV set and other with universal IV set, the correlation between these two models and their relation of cost and effectiveness. Method: A randomized clinical trial was conducted in hospitalized patients in a university general hospital of 740 beds. The ward units were randomly chosen for each type of equipment, and patients were included according to indication for use of IP, based on institutional protocol. The types of errors and adverse reactions were classified by means of algorithms. The costs of each system for IP, was calculated considering the useful life of the technology. Results: 310 infusions were monitored: 117 in the universal infusion pump group and 193 in the specific equipment group, in 55 patients. The average difference between the scheduled time and the actual one in the infusions was -2.1 ± 19 min. and 0.08 ± 23 min. (p = 0.40) for the universal equipment and specific equipment, respectively, which means an average error of -0.15% ± 3.8% for the universal equipment and 0.10% ± 6.3% for the specific equipment, with no difference between the two types of pump. Fourteen (4.5%) medication errors were observed during the administration of medication, similar between the two types of IP. The cumulative costs between the two pump systems were equivalent in 30 months, and after 11 years the costs were meaningfully higher for the specific equipment pumps in 184,29 %. Conclusion: The infusion pumps do not show meaningful difference in accuracy between scheduled time and the actual one qualifying them as safe for the drugs observed. Cumulative costs were significantly distinct between both pieces of equipment.

Le recours aux prescriptions sans ou hors AMM, dû principalement au manque d’essais cliniques, est très largement répandu en pédiatrie en particulier chez le nouveau-né. Les prescriptions hors AMM constituent un facteur de risque dans la survenue des effets indésirables médicamenteux (EIM). La pharmacovigilance est indispensable mais insuffisante afin d’évaluer le rapport bénéfice/risque des traitements en particulier lorsque les prescriptions hors AMM sont fréquentes. En combinant plusieurs approches pharmacoépidémiologiques, méta-analytiques et pharmacométriques, ce travail de thèse a pour objectifs de décrire les prescriptions hors AMM en néonatologie et explorer des approches qui permettront d’aboutir à mieux estimer le rapport bénéfice/risque des médicaments pour les enfants. Nous avons confirmé que le taux de prescription hors AMM en néonatologie est important (46%). Même en absence de soins de réanimation, plus de deux tiers des nouveaux-nés reçoivent au moins un médicament hors AMM pendant leur hospitalisation. En utilisant une approche méta-analytique explorant le rapport bénéfice risque du fluconazole en néonatologie en fonction du risque de base dans chaque étude (taux d’infection <10%), nous avons montré que la prophylaxie ciblée sur le risque de base serait plus bénéfique que la prophylaxie systématique des infections fongiques invasives. Nos travaux en pharmacovigilance pédiatrique, ont montré que les deux méthodes de détection actives (collaboration entre pharmaciens et cliniciens et le « trigger tool »), utilisant les dossiers patients informatisés, sont faisables et plus efficaces que la notification spontanée / Many drugs used to treat children in hospitals are either not licensed for use in children or are prescribed outside the terms of their product license (off-label prescribing) because of the lack of clinical trials in this population, and practical difficulties to involve children in clinical research. Drugs used within the specifications of the product license should therefore be less likely to cause ADRs compared to drugs that are either unlicensed or off-label for use in children. With different approaches such as pharmacoepidemiologic, meta-analytic and pharmacometrics, we sought to improve the estimate of the benefit risk ratio of medicines used for treating children. Our observational prospective study in a neonatal unit demonstrated that the prescriptions of unlicensed or off-label drugs in neonatal unit is common (46%). We also used meta-analytic approach in order to estimate the benefit risk ratio of the prophylactic use of fluconazole as a function of the baseline risk. Our results suggest that “systematic fluconazole prophylaxis for all VLBW in NICUs is not warranted by the available evidence and should be adapted to the baseline risk. We also showed that active drug monitoring by using electronic patient files by targeting review chart with a trigger tool in neonates and with close collaboration between the pharmacovigilance center, pharmacologists, and clinicians was necessary and feasible for improving the detection of ADRs in children

L'évaluation des données de sécurité du médicament reste encore limitée dans les pays en voie de développement. La création du Centre National de Pharmacovigilance du Vietnam en 2009 a permis l'enregistrement des notifications spontanées d'effets indésirables (EIs) permettant une analyse quantitative et qualitative et de générer des éventuels signaux de pharmacovigilance. Les objectifs principaux de la thèse étaient : (i) décrire le système de pharmacovigilance vietnamien, et comparer les données à travers quelques exemples, au système de pharmacovigilance français, (ii) appliquer un ensemble d'approches pharmaco-épidémiologiques pour identifier les risques médicamenteux au Vietnam et (iii) améliorer la sous-notification des EIs. Nous introduisons pour la première fois, un bilan complet du système de pharmacovigilance vietnamien avec une série de suggestions pour les pays partageant le même contexte de ressources limitées. Quelques résultats et défis pour le développement durable du système ont également été discutés. Secondairement, nous avons utilisé les bases de données de pharmacovigilance vietnamienne et française pour comparer le profil de notification pour 2 types d'EIs : anaphylaxie et syndrome de Steven-Johnson et nécrolyse épidermique toxique (SSJ/NET) d'origine médicamenteuse. Nous avons généré les premiers signaux de pharmacovigilance vietnamienne : l'allopurinol, la carbamazépine, les médicaments traditionnels, la colchicine, l'acide valproïque et le méloxicam ont généré des signaux pour le SSJ/NET - déjà connus dans littérature. Par ailleurs, nous avons retrouvé des signaux significatifs pour le cefixime et le paracétamol. Pour l'anaphylaxie, nous avons identifié 4873 (13.2%) cas dans la base vietnamienne pendant la période 2010-2016 avec une tendance à l'augmentation au cours du temps. Les antibiotiques (notamment céphalosporines de 3ème génération) sont les causes principales de l'anaphylaxie médicamenteuse au Vietnam. De plus, des signaux pour certains médicaments comme l'alpha-chymotrypsine, l'amoxicilline/sulbactame et les solutions de glucose ou électrolytes peuvent être typiques pour les pays en voie de développement. Enfin, l'identification des EIs à partir des données de laboratoire de biologie de l'hôpital pourrait améliorer le taux de notification d'EI au Vietnam. [...] / The understanding and quantitative analysis in drug safety domain among developing countries remain still limited. The creation of the National Drug Information and Adverse Drug Reaction Monitoring Centre (NDIADRMC) of Vietnam in 2009 was a landmark for the pharmacovigilance activities in this country and allowed the registration of spontaneous adverse drug reaction (ADR) reports. The accumulation of National Pharmacovigilance Database of Vietnam (NPDV) requires a quantitative and qualitative analysis and generation of pharmacovigilance signals to better protect Vietnamese people's health. The main objectives of the thesis are: (i) describe the Vietnamese pharmacovigilance system, with the comparison to another developed pharmacovigilance system as a reference (France), (ii) apply a set of pharmacoepidemiological approaches to identify the specific drug-related risks, and (iii) improve the under-reporting issue in Vietnam. Firstly, we introduce a full-detailed overview of Vietnamese pharmacovigilance system with a series of lessons learned for the other countries sharing the similar limited-resource context. Some achievements and challenges for the sustainable development of the system were also equitably discussed. Secondly, we used the Vietnamese and French pharmacovigilance databases to compare the differences in characteristics of two types of ADR: anaphylaxis and Steven-Johnson's syndrome and toxic epidermal necrolysis (SJS/TEN) induced by medications. Next, we generated the first Vietnamese pharmacovigilance signals. The signals of drug-induced SJS/TEN were generated with allopurinol, carbamazepine, traditional or herbal drugs, colchicine, valproic acid and meloxicam which were similar to the other previously studies in literature. Furthermore, we also found the significant signals of cefixime and paracetamol. For drug-induced anaphylaxis, we identified 4873 (13.2%) cases in the Vietnamese database during the period 2010-2016 with an increasing trend over time. The antibiotics (especially the third-generation cephalosporins) were the main causes of drug-induced anaphylaxis in Vietnam. In addition, the signals were generated with several drugs such as alpha-chymotrypsin, amoxicillin/sulbactam and glucose or electrolyte solutions which were typical for the resource-restricted countries. On the other hand, the identification of ADR through the screening the laboratory test results could help to increase the ADR reporting rate in Vietnam. [...]

AIMS: The aims of this study were to determine the recording of drug sensitivities of elderly care home residents, to describe the nature of sensitivities and to identify and describe discrepancies in the documentation of drug sensitivity status in general practices, pharmacies and care homes. METHODS: A random sample of residents within a purposive sample of care homes (nursing and residential) was selected. A clinical pharmacist inspected the GP medical record, the medicines administration record, and the care home record for each resident to identify drug sensitivities and discrepancies between records and to describe the nature of the recorded sensitivities. RESULTS: The records of 121 residents in 31 care homes were studied. Thirty-one (26%) residents had at least one documented drug sensitivity in one of the sources inspected, with 48 sensitivities in total recorded. There was no description of the nature of the sensitivities recorded in 39/48 (81%) cases. The number of sensitivities recorded on the medicines administration record, care home record and the GP record were 3 (6%), 29 (60%) and 35 (73%), respectively. Only two sensitivities were simultaneously recorded on all three records. CONCLUSIONS: It was of concern that over 90% of drug sensitivities were not recorded on the medicines administration record which is the final checking document when administering medication. The reason for this was that the dispensing pharmacy was responsible for generating the medicines administration record; however, drug sensitivity status is seldom shared between the GP and the dispensing pharmacy. Printing sensitivities on prescriptions would help to resolve this.

Objetivo: Este estudo objetivou avaliar a precisão de infusões de medicamentos em dois modelos de Bomba de Infusão (BI), de equipo específico do fabricante e de equipo universal, a concordância entre estes dois modelos e sua relação de custo e efetividade. Método: Foi realizado um ensaio clínico randomizado em pacientes internados em um hospital geral universitário de 740 leitos. As unidades de internação foram randomizadas através de sorteio simples para cada modelo de equipamento e os pacientes foram incluídos de acordo com indicação de uso de BI, conforme protocolo institucional. Os tipos de erros e reações adversas foram classificados por meio de algoritmos. Foi calculado o custo de cada sistema de bomba de infusão, pela vida útil da tecnologia. Resultados: Em 55 pacientes foram acompanhadas 310 infusões, 117 no grupo da bomba de infusão de equipo universal e 193 na bomba de infusão de equipo especifico. Houve semelhança (p=0,40) entre o tempo programado e o observado nas infusões por meio da bomba de equipo específico (-2,1 ± 19 min) e universal (0,08 ± 23 min). Percentualmente, também não foi observada diferença (p=0,70) entre a infusão por bomba de equipo específico (-0,15±3,8%) e universal (0,1±6,3%). Foram observados 14 (4,5%) erros de medicação, semelhantes (p=0,58) entre os tipos de BI. Os custos cumulativos entre os dois sistemas de bombas se equivaleram em 30 meses, sendo que após 11 anos, foram significativamente maiores para bomba de equipo específico em 184,29%. Conclusão: Ambos modelos de BI avaliadas mostraram-se igualmente seguras para administração EV de fármacos, sendo o modelo de equipo universal mais vantajoso economicamente ao longo da vida útil dos equipamentos. / Objective: This study aimed to evaluate the accuracy of drug infusion in two models of infusion pumps (IP), one with a specific IV set and other with universal IV set, the correlation between these two models and their relation of cost and effectiveness. Method: A randomized clinical trial was conducted in hospitalized patients in a university general hospital of 740 beds. The ward units were randomly chosen for each type of equipment, and patients were included according to indication for use of IP, based on institutional protocol. The types of errors and adverse reactions were classified by means of algorithms. The costs of each system for IP, was calculated considering the useful life of the technology. Results: 310 infusions were monitored: 117 in the universal infusion pump group and 193 in the specific equipment group, in 55 patients. The average difference between the scheduled time and the actual one in the infusions was -2.1 ± 19 min. and 0.08 ± 23 min. (p = 0.40) for the universal equipment and specific equipment, respectively, which means an average error of -0.15% ± 3.8% for the universal equipment and 0.10% ± 6.3% for the specific equipment, with no difference between the two types of pump. Fourteen (4.5%) medication errors were observed during the administration of medication, similar between the two types of IP. The cumulative costs between the two pump systems were equivalent in 30 months, and after 11 years the costs were meaningfully higher for the specific equipment pumps in 184,29 %. Conclusion: The infusion pumps do not show meaningful difference in accuracy between scheduled time and the actual one qualifying them as safe for the drugs observed. Cumulative costs were significantly distinct between both pieces of equipment.

Os sistemas de farmacovigilância fundamentam as decisões sobre segurança no uso de medicamentos regulamentados por autoridades de saúde. Estudá-los e propor estratégias de melhorias contribuem para fortalecer os sistemas de saúde, aperfeiçoando a qualidade da assistência à saúde e assegurando a segurança do paciente e coletividade. A Tese objetivou analisar a evolução e desempenho do sistema brasileiro de farmacovigilância, denominado de SINAF, e as notificações dos pacientes com suspeitas de reações adversas a medicamentos (RAMs) registradas no Notivisa-medicamento no período de 2008 a 2013 e propor uma lista-referência de códigos da CID-10 para vigilância de RAMs e intoxicações medicamentosas (IMs). A Tese compreende seis artigos científicos organizados para publicação. No primeiro, uma revisão de escopo apresentou uma perspectiva histórica para caracterizar a evolução do SINAF e lacunas identificadas no processo, como a ausência de comissão de farmacovigilância que atenda aos requisitos mínimos de um sistema de farmacovigilância propostos pela Organização Mundial da Saúde. Os artigos 2, 3 e 4 analisaram características relacionadas com o desempenho do SINAF. O artigo 2 revelou que não há preferência digital da idade na base de dados das notificações de eventos adversos a medicamentos (EAMs) do Notivisa-medicamento. Mediante uma análise comparativa, o artigo 3 mostrou diferenças entre o formulário para notificação de EAMs utilizado no SINAF e de outros doze países latinoamericanos (Argentina, Bolívia, Chile, Colômbia, Costa Rica, Cuba, Guatemala, México, Panamá, Peru, Uruguai e Venezuela), sobretudo na quantidade de variáveis para preenchimento, podendo contribuir com a subnotificação de casos. No artigo 4 – um estudo de avaliação de sistemas de vigilância de saúde pública –, revelou que o desempenho do Notivisa-medicamento foi considerado satisfatório para três atributos (flexibilidade, validade e erro preditivo positivo) e deficitário para a maioria deles (simplicidade, aceitabilidade, representatividade, completude, consistência, oportunidade e clareza metodológica). O artigo 5, mediante estudo descritivo e retrospectivo, encontrou uma taxa de notificação de RAMs de 22,8/ 1 milhão de habitantes/ano. Trata-se de taxa bastante inferior a países de alta renda como Nova Zelândia, Suécia, Austrália e Suíça que possuem mais de 300 notificações por milhão, como em relação a países de média renda, como a África do Sul, com taxa de 77 por milhão de habitantes. A população feminina (60,5%) prevaleceu no total de pacientes (26.554), assim como, a raça/cor branca (58,1%). A idade variou de 0 a 112 anos (mediana = 46 anos). Quase 1/3 (32,5%) das suspeitas de RAMs ocorreram em populações vulneráveis (idosos e crianças). Foram avaliados 54.288 pares de medicamento-reação adversa, onde prevaleceram as reações adversas graves (59,2%), com destaque para as que resultaram em efeito clinicamente importante (83,1%). O estudo 6 propôs uma lista-referência com 691 códigos da CID-10, sendo 360 (52,1%) relacionados com RAMs e 331 (47,9%) com IMs. Um total de 511 (73,9%) códigos estão relacionados com casos de admissão hospitalar e/ou óbito. Os achados da Tese evidenciam a necessidade de mudanças em diferentes aspectos estudados do SINAF, como forma de contribuir na produção de informações completas, fidedignas e mais representativas sobre danos ocasionados por medicamentos comercializados no país. / The pharmacovigilance systems support the decisions on safety when using medications regulated by health authorities. Analyzing them and proposing improvement strategies are ways to make healthcare systems stronger, improving the quality of healthcare assistance, making sure the patient is safe and that the population is ensured. The dissertation was aimed at analyzing the evolution and performance of the Brazilian pharmacovigilance system, SINAF, and the notification of patients with suspected adverse drug reactions (ADRs) registered with the notification system NOTIVISA/medication from 2008 through 2013, as well as proposing a reference list of ICD-10 codes for surveillance of ADRs and intoxication due to medication (IDM). The dissertation is comprised of six scientific articles ready to be published. The first one, a scoping review, presents a historical perspective to demonstrate the development process of SINAF and the gaps identified during the process, such as the absence of a pharmacovigilance commission that complies with the minimum requirements of a pharmacovigilance system as proposed by World Health Organization. Articles 2, 3 and 4 presents an analysis of the performance-related characteristics of SINAF. Article 2 reveals that there is no digital age preference in the adverse drug events (ADEs) database belonging to NOTIVISA/medication. Using a comparative analysis, article 3 shows differences between the form for ADEs notification using SINAF and in other twelve Latin-American countries (Bolivia, Chile, Colombia, Costa Rica, Cuba, Guatemala, Mexico, Panama, Peru, Uruguay and Venezuela), highlighting the number of variables to complete, and it may collaborate with the sub-notification of cases. Article 4 – a study on the evaluation of public health surveillance systems over time – reveal that the performance of NOTIVISA/medication was considered satisfactory regarding three attributes (flexibility, validity and positive predictive error) and deficient regarding most of the others (simplicity, acceptability, representability, integrality, consistency, opportunity and methodological clarity). Article 5, by means of a descriptive and retrospective study, found an ADR notification rate of 22.8/million inhabitants/year. This is a much lower rate than in high income countries, such as New Zealand, Sweden, Australia and Switzerland, which have over 300 notifications per million, when compared against average income, such as South Africa, with a rate of 77/million inhabitants. Female population (60.5%) prevailed in the total number of patients (26,554), as well as white race/color (58.1%). Age was between 0 - 112 years old (median = 46 years). Almost 1/3 (32.5%) of the suspected ADRs occurred in vulnerable populations (elderly and children). 54,288 pairs of medication/adverse reactions were assessed. Severe adverse reactions prevailed (59.2%), and attention is drawn to those resulting in clinically important effect (83.1%). Study 6 proposes a reference list with 691 ICD-10 codes; 360 (52.1%) out of them are ADRs-related and 331 (47.9%) out of them are IDM. A total of 511 (73.9%) codes are related to cases of hospital admission and/or death. The dissertation findings prove the need of changes across different aspects in SINAF as a way to contribute to production of complete, reliable and representative information on damages caused by commercially available drugs in Brazil.

Objetivo: Este estudo objetivou avaliar a precisão de infusões de medicamentos em dois modelos de Bomba de Infusão (BI), de equipo específico do fabricante e de equipo universal, a concordância entre estes dois modelos e sua relação de custo e efetividade. Método: Foi realizado um ensaio clínico randomizado em pacientes internados em um hospital geral universitário de 740 leitos. As unidades de internação foram randomizadas através de sorteio simples para cada modelo de equipamento e os pacientes foram incluídos de acordo com indicação de uso de BI, conforme protocolo institucional. Os tipos de erros e reações adversas foram classificados por meio de algoritmos. Foi calculado o custo de cada sistema de bomba de infusão, pela vida útil da tecnologia. Resultados: Em 55 pacientes foram acompanhadas 310 infusões, 117 no grupo da bomba de infusão de equipo universal e 193 na bomba de infusão de equipo especifico. Houve semelhança (p=0,40) entre o tempo programado e o observado nas infusões por meio da bomba de equipo específico (-2,1 ± 19 min) e universal (0,08 ± 23 min). Percentualmente, também não foi observada diferença (p=0,70) entre a infusão por bomba de equipo específico (-0,15±3,8%) e universal (0,1±6,3%). Foram observados 14 (4,5%) erros de medicação, semelhantes (p=0,58) entre os tipos de BI. Os custos cumulativos entre os dois sistemas de bombas se equivaleram em 30 meses, sendo que após 11 anos, foram significativamente maiores para bomba de equipo específico em 184,29%. Conclusão: Ambos modelos de BI avaliadas mostraram-se igualmente seguras para administração EV de fármacos, sendo o modelo de equipo universal mais vantajoso economicamente ao longo da vida útil dos equipamentos. / Objective: This study aimed to evaluate the accuracy of drug infusion in two models of infusion pumps (IP), one with a specific IV set and other with universal IV set, the correlation between these two models and their relation of cost and effectiveness. Method: A randomized clinical trial was conducted in hospitalized patients in a university general hospital of 740 beds. The ward units were randomly chosen for each type of equipment, and patients were included according to indication for use of IP, based on institutional protocol. The types of errors and adverse reactions were classified by means of algorithms. The costs of each system for IP, was calculated considering the useful life of the technology. Results: 310 infusions were monitored: 117 in the universal infusion pump group and 193 in the specific equipment group, in 55 patients. The average difference between the scheduled time and the actual one in the infusions was -2.1 ± 19 min. and 0.08 ± 23 min. (p = 0.40) for the universal equipment and specific equipment, respectively, which means an average error of -0.15% ± 3.8% for the universal equipment and 0.10% ± 6.3% for the specific equipment, with no difference between the two types of pump. Fourteen (4.5%) medication errors were observed during the administration of medication, similar between the two types of IP. The cumulative costs between the two pump systems were equivalent in 30 months, and after 11 years the costs were meaningfully higher for the specific equipment pumps in 184,29 %. Conclusion: The infusion pumps do not show meaningful difference in accuracy between scheduled time and the actual one qualifying them as safe for the drugs observed. Cumulative costs were significantly distinct between both pieces of equipment.

Os sistemas de farmacovigilância fundamentam as decisões sobre segurança no uso de medicamentos regulamentados por autoridades de saúde. Estudá-los e propor estratégias de melhorias contribuem para fortalecer os sistemas de saúde, aperfeiçoando a qualidade da assistência à saúde e assegurando a segurança do paciente e coletividade. A Tese objetivou analisar a evolução e desempenho do sistema brasileiro de farmacovigilância, denominado de SINAF, e as notificações dos pacientes com suspeitas de reações adversas a medicamentos (RAMs) registradas no Notivisa-medicamento no período de 2008 a 2013 e propor uma lista-referência de códigos da CID-10 para vigilância de RAMs e intoxicações medicamentosas (IMs). A Tese compreende seis artigos científicos organizados para publicação. No primeiro, uma revisão de escopo apresentou uma perspectiva histórica para caracterizar a evolução do SINAF e lacunas identificadas no processo, como a ausência de comissão de farmacovigilância que atenda aos requisitos mínimos de um sistema de farmacovigilância propostos pela Organização Mundial da Saúde. Os artigos 2, 3 e 4 analisaram características relacionadas com o desempenho do SINAF. O artigo 2 revelou que não há preferência digital da idade na base de dados das notificações de eventos adversos a medicamentos (EAMs) do Notivisa-medicamento. Mediante uma análise comparativa, o artigo 3 mostrou diferenças entre o formulário para notificação de EAMs utilizado no SINAF e de outros doze países latinoamericanos (Argentina, Bolívia, Chile, Colômbia, Costa Rica, Cuba, Guatemala, México, Panamá, Peru, Uruguai e Venezuela), sobretudo na quantidade de variáveis para preenchimento, podendo contribuir com a subnotificação de casos. No artigo 4 – um estudo de avaliação de sistemas de vigilância de saúde pública –, revelou que o desempenho do Notivisa-medicamento foi considerado satisfatório para três atributos (flexibilidade, validade e erro preditivo positivo) e deficitário para a maioria deles (simplicidade, aceitabilidade, representatividade, completude, consistência, oportunidade e clareza metodológica). O artigo 5, mediante estudo descritivo e retrospectivo, encontrou uma taxa de notificação de RAMs de 22,8/ 1 milhão de habitantes/ano. Trata-se de taxa bastante inferior a países de alta renda como Nova Zelândia, Suécia, Austrália e Suíça que possuem mais de 300 notificações por milhão, como em relação a países de média renda, como a África do Sul, com taxa de 77 por milhão de habitantes. A população feminina (60,5%) prevaleceu no total de pacientes (26.554), assim como, a raça/cor branca (58,1%). A idade variou de 0 a 112 anos (mediana = 46 anos). Quase 1/3 (32,5%) das suspeitas de RAMs ocorreram em populações vulneráveis (idosos e crianças). Foram avaliados 54.288 pares de medicamento-reação adversa, onde prevaleceram as reações adversas graves (59,2%), com destaque para as que resultaram em efeito clinicamente importante (83,1%). O estudo 6 propôs uma lista-referência com 691 códigos da CID-10, sendo 360 (52,1%) relacionados com RAMs e 331 (47,9%) com IMs. Um total de 511 (73,9%) códigos estão relacionados com casos de admissão hospitalar e/ou óbito. Os achados da Tese evidenciam a necessidade de mudanças em diferentes aspectos estudados do SINAF, como forma de contribuir na produção de informações completas, fidedignas e mais representativas sobre danos ocasionados por medicamentos comercializados no país. / The pharmacovigilance systems support the decisions on safety when using medications regulated by health authorities. Analyzing them and proposing improvement strategies are ways to make healthcare systems stronger, improving the quality of healthcare assistance, making sure the patient is safe and that the population is ensured. The dissertation was aimed at analyzing the evolution and performance of the Brazilian pharmacovigilance system, SINAF, and the notification of patients with suspected adverse drug reactions (ADRs) registered with the notification system NOTIVISA/medication from 2008 through 2013, as well as proposing a reference list of ICD-10 codes for surveillance of ADRs and intoxication due to medication (IDM). The dissertation is comprised of six scientific articles ready to be published. The first one, a scoping review, presents a historical perspective to demonstrate the development process of SINAF and the gaps identified during the process, such as the absence of a pharmacovigilance commission that complies with the minimum requirements of a pharmacovigilance system as proposed by World Health Organization. Articles 2, 3 and 4 presents an analysis of the performance-related characteristics of SINAF. Article 2 reveals that there is no digital age preference in the adverse drug events (ADEs) database belonging to NOTIVISA/medication. Using a comparative analysis, article 3 shows differences between the form for ADEs notification using SINAF and in other twelve Latin-American countries (Bolivia, Chile, Colombia, Costa Rica, Cuba, Guatemala, Mexico, Panama, Peru, Uruguay and Venezuela), highlighting the number of variables to complete, and it may collaborate with the sub-notification of cases. Article 4 – a study on the evaluation of public health surveillance systems over time – reveal that the performance of NOTIVISA/medication was considered satisfactory regarding three attributes (flexibility, validity and positive predictive error) and deficient regarding most of the others (simplicity, acceptability, representability, integrality, consistency, opportunity and methodological clarity). Article 5, by means of a descriptive and retrospective study, found an ADR notification rate of 22.8/million inhabitants/year. This is a much lower rate than in high income countries, such as New Zealand, Sweden, Australia and Switzerland, which have over 300 notifications per million, when compared against average income, such as South Africa, with a rate of 77/million inhabitants. Female population (60.5%) prevailed in the total number of patients (26,554), as well as white race/color (58.1%). Age was between 0 - 112 years old (median = 46 years). Almost 1/3 (32.5%) of the suspected ADRs occurred in vulnerable populations (elderly and children). 54,288 pairs of medication/adverse reactions were assessed. Severe adverse reactions prevailed (59.2%), and attention is drawn to those resulting in clinically important effect (83.1%). Study 6 proposes a reference list with 691 ICD-10 codes; 360 (52.1%) out of them are ADRs-related and 331 (47.9%) out of them are IDM. A total of 511 (73.9%) codes are related to cases of hospital admission and/or death. The dissertation findings prove the need of changes across different aspects in SINAF as a way to contribute to production of complete, reliable and representative information on damages caused by commercially available drugs in Brazil.

Nesta pesquisa foram avaliados 186 idosos hospitalizados quanto ao aparecimento de reações adversas a medicamentos (RAM). Encontrou-se 199 RAM (1,07 por paciente). Para 11,3% dos idosos a RAM constituiu a causa da internação, para 17,2% estava presente à internação mas não como causa e 46,2% apresentaram RAM durante a hospitalização. As RAM sérias mais comuns foram a insuficiência renal aguda, a hipercalemia e a hipotensão postural. Concluiu-se que houve uma prevalência importante de RAM nesses pacientes, encontrando-se como fatores de risco significativos o número de diagnósticos, o número de medicamentos e o uso de medicamento inapropriado para idosos / The present study evaluated the prevalence of adverse drug reactions (ADR) among 186 hospitalized elderly. A total of 199 ADR were founded (1.07 per patient). For 11.3% of the patients the ADR was the cause of hospitalization, for 17.2% the ADR was present at hospitalization but not as the cause and for 46.2% it was presented during hospitalization. The most common serious ADR were acute renal insufficiency, hyperkalemia and postural hypotension. We concluded that a significant prevalence of ADR was found among that patients, with the number of diagnosis, the number of drugs and the use of a drug considered to be inappropriate as risk factors

Pharmacogivilance consists in carefully monitoring drugs in order to re-evaluate their risk for people’s health. The sooner the Adverse Drug Reactions are detected, the sooner one can act consequently. This thesis aims at discovering such reactions in electronical health records under the constraint of lacking annotated data, in order to replicate the scenario of the Regional Center for Pharmacovigilance of Nice. We investigate how in a semi-supervised learning design the unlabeled data can contribute to improve classification scores. Results suggest an excellent recall in discovering adverse reactions and possible classification improvements under specific data distribution. / Läkemedelsövervakningen består i kolla försiktigt läkemedlen så att utvärdera dem för samhällets hälsa. Ju tidigare de läkemedelsrelaterade biverkningarna upptäcks, desto tidigare man får handla dem. Detta exjobb söker att upptäcka de där läkemedelsrelaterade biverkningarnna inom elektroniska hälsopost med få datamärkningar, för att återskapa Nice regionalt läkemedelelsöveraknings-centrumets situationen. Vi undersöker hur en halvväglett lärande lösning kan hjälpa att förbättra klassificeringsresultat. Resultaten visar en god återställning med biverknings-upptäckning och möjliga förbättringar.