A despeito de suas limitações, os dados do SIHSUS são os mais sistemáticos e abrangentes sobre as Reações Adversas e Intoxicações a medicamentos que provocam hospitalização. Eles demonstram a importância das ações de educação e investigação de casos do Programa Nacional de Farmacovigilância para possibilitar o diagnóstico mais acurado e superação do quadro atual de ocorrência desses agravos, além da possibilidade de o SIH/SUS ser utilizado sistematicamente como fonte de dados na detecção e análise dos problemas relacionados a medicamentos. No período de 1999 a 2007, foram emitidas 6.670.609 AIH (tipo 1), entre as quais 3.611 foram classificadas como internações devidas a RAM e 4.675 como Intoxicações, correspondendo, respectivamente, às taxas médias de 5,41 casos por 104 AIH e 7,2 casos por 104 AIH. Ocorreram 137 óbitos (3,79% das AIH) por RAM e 207 (4,43% das AIH) por Intoxicações na população internada. Tanto as RAM como as Intoxicações tiveram menor chance de levar ao óbito quando comparados às outras causas. Uma característica da distribuição dos RAM foi concentrar 62% das AIH nas faixas etárias de 20 a 59 anos de idade (grupo adulto). Nas Intoxicações merece destaque a elevada proporção de AIH na faixa etária de 0-4 anos (14,29%). As AIH registradas com causas básicas relacionados a RAM foram principalmente de pacientes do sexo masculino, já as Intoxicações foram principalmente de pacientes do sexo feminino. Em ambos tipos de agravos estes pacientes foram internados em hospitais que não faziam parte da Rede de Hospitais Sentinelas do Programa Nacional de Farmacovigilância. No entanto, a probabilidade destes hospitais registrarem as AIH com códigos CID-10 referentes às RAM é maior, o que ocorre provavelmente por estarem mais capacitados em diagnosticar este tipo de agravo. Porém este fato não foi observado para as Intoxicações. Os fármacos que causaram os agravos estudados são psicoativos. Este estudo apresentou algumas evidências sobre a distribuição da morbi-mortalidade provocada por medicamentos entre pacientes internados em hospitais conveniados ao SUS no período de 1999-2007, baseadas nas informações das AIH, que podem ser úteis ao Programa de Farmacovigilância no Estado do Rio de Janeiro. / Despite its limitations, the data SIHSUS are the most systematic and comprehensive on Adverse Reactions and Drug Poisonings causing hospitalization. They demonstrate the importance of these actions and investigation of cases of National Pharmacovigilance Programme to enable the most accurate and overcoming the current frame of event occurrences diagnosis, beyond the possibility of SIH / SUS be systematically used as a data source in the detection and analysis of drug-related problems. In the period 1999-2007, were issued 6,670,609 AIH (type 1), among which 3,611 were classified as hospitalizations due to poisoning as RAM and 4675, corresponding, respectively, at average rates of 5.41 cases per 104 AIH and 7.2 cases per 104 AIH. There were 137 deaths (3.79% of AIH) by RAM and 207 (4.43% of AIH) by poisoning in hospitalized population. Both the RAM as poisoning were less likely to cause death when compared to other causes. A characteristic distribution of RAM was concentrating 62% of AIH in the age groups 20-59 years of age (adult group). In Poisoning deserves the high proportion of AIH aged 0-4 years (14.29%). The AIH registered root causes related ADRs were mostly male patients, since the poisoning were mainly female patients. In both types of injuries these patients were admitted to hospitals that were not part of the Network of Sentinel Hospitals of the National Pharmacovigilance Programme. However, the likelihood of these hospitals register the AIH with ICD-10 codes related to RAM is higher, which is probably because they are better able to diagnose this type of offense. However this was not observed for the poisoning. The drugs that caused the diseases studied are psychoactive. This study presented some evidence on the distribution of morbidity and mortality caused by drugs among patients admitted to the SUS hospitals during the period 1999-2007, based on the information of AIH, which may be useful to Pharmacovigilance Programme in the State of Rio de Janeiro .

Objetivos: descrever incidência de eventos adversos medicamentosos em crianças sob terapia intensiva, avaliar fatores de riscos e métodos de detecção. Métodos: busca ativa em registros eletrônicos e em papel, utilizando parâmetros indicativos (gatilhos). A estatística envolveu modelos de regressão linear e logística. Resultados: Foram estudados 239 pacientes, com média de idade de 67,5 meses, em 1818 dias de internação. A média de internação foi de 7,6 dias. Houve 110 eventos adversos medicamentosos provados, prováveis e possíveis, em 84 pacientes (35,1%). Observamos 138 ocorrências de gatilhos. As principais classes de medicamentos envolvidas foram: antibióticos (n = 41), diuréticos (n = 24), anticonvulsivantes (n = 23), sedativos e analgésicos (n = 17) e corticóides (n = 18). O número de drogas foi a variável mais relacionada à ocorrência de EAM. Esta última também se correlacionou com o tempo de internação (P < 0,001). A ocorrência do evento pode estar implicada no aumento de 1,5 dia de internação para cada evento. A idade inferior a 48 meses mostrou ser um risco significativo para eventos, com OR de 1,84 (intervalo de confiança IC 95% - 1,07 - 3,15, P = 0,025). O número de drogas recebidas apresentou correlação com o número de eventos (P < 0,0001). A chance de apresentar pelo menos 1 evento elevou-se linearmente à medida que o paciente recebia mais drogas. Conclusões: o uso de múltiplas drogas e a baixa idade favorecem a ocorrência de EAM, que, por sua vez, podem estar implicados no aumento do tempo de internação em UTI. A busca ativa sistematiza a abordagem do problema / Objectives: To describe incidence of adverse drug events (ADE) in children under intensive care, to avaliate risk factors and detection methods. Methods: Active search of charts and electronic patient records using indicative parameters (\"triggers\"). The statistical analysis involved linear and logistic regression. Results: 239 patients with a mean age of 67.5 months representing 1818 days of PICU hospitalization were studied. The average PICU stay was 7.6 days. There were 110 proven, probable, and possible ADEs in 84 patients (35.1%). We observed 138 instances of triggers. The major classes of drugs associated with events were: antibiotics (n = 41), diuretics (n = 24), antiseizures (n = 23), sedatives and analgesics (n = 17), and steroids (n = 18). The number of drugs administered was most related to the occurrence of ADEs. This was also related to the length of stay (p < 0.001). The occurrence of an ADE may result in an increase in the length of stay by 1.5 days per event. Patient aged less than 48 months also proved to be at significant risk for ADEs, with an odds ratio of 1.84 (confidence interval - 95% CI - 1.07 to 3.15, p = 0.025). The number of drugs administered also correlated with the number of ADEs (p < 0.0001). The chance of having at least one ADE increased linearly as the patient was administered more drugs. Conclusions: The use of multiple drugs as well as lower patient age favor the occurrence of ADEs, which in turn may result in increasing the length of PICU hospitalization. Our active search provides a systematic approach to the problem

Introdução - Os medicamentos contribuem de forma significativa para melhorar a qualidade de vida das pessoas, mas não são isentos de riscos. Os erros envolvendo medicamentos têm recebido atenção dos profissionais, das instituições e das autoridades sanitárias no mundo todo. Em hospitais, a farmácia é elo importante no complexo processo de utilização de medicamentos interligando várias ações desenvolvidas em diferentes setores. Sua estrutura física, recursos humanos e tecnológicos e sua organização são fundamentais na prevenção dos erros com medicamentos. Objetivo - Avaliar erros de dispensação de medicamentos em hospital e os fatores envolvidos. Métodos A pesquisa foi realizada em um hospital universitário no Paraná, utilizando-se de três estratégias. 1ª Foram conferidos, de acordo com a prescrição, os medicamentos dispensados pela farmácia para as clínicas médica e cirúrgica no período de 4 a 19 de janeiro de 2010. Os medicamentos analisados eram separados utilizando-se a cópia carbonada da prescrição e dispensados de forma individualizada por paciente ou coletiva, em embalagem plástica (caixas ou sacos), separados por horário de administração, para 24 horas de atendimento. 2 a - Foram entrevistados 19 funcionários da farmácia envolvidos no processo de dispensação sobre erros nesse processo. 3ª Foram avaliados dezenove relatos voluntários de erros de dispensação de medicamentos ocorridos no hospital, entre outubro de 2006 a janeiro de 2010. Resultados Foram analisadas 259 dispensações, 1.963 medicamentos e 4.099 doses. Durante a observação, houve 61 erros de dispensação em 48 prescrições. Os erros ocorreram em 3,2 por cento dos medicamentos e em 1,71 por cento das doses dispensadas. Os erros de dispensação mais freqüentes foram: omissão de medicamento prescrito (23 por cento ); dispensação de medicamento não prescrito (14,8 por cento ); medicamento dispensado na ausência de informação ou contendo informação duvidosa ou ilegível (14,8 por cento ); concentração incorreta (9,8 por cento ); horário incorreto (9,8 por cento ) e medicamento incorreto (6,6 por cento ). Os erros estiveram associados ao número de medicamentos por prescrição e 33 por cento dos erros envolveram medicamentos potencialmente perigosos. Nas entrevistas, foram relatados, como fatores contribuintes para a ocorrência de erros de dispensação, problemas relacionados à comunicação, como: legibilidade da grafia dos prescritores; prescrições ambíguas, incompletas ou confusas e similaridade dos nomes de medicamentos. Em relação às condições de trabalho destacaram-se: pouco tempo para dispensação, sobrecarga de trabalho, nível de ruído, interrupções e distrações. Quanto às questões pessoais, 50 por cento relataram falta de conhecimento sobre medicamentos, estresse e cansaço. Os tipos de erros e os fatores envolvidos foram similares aos de pesquisas semelhantes. Conclusões Os dados sugerem baixa frequencia de erros quando comparados a outros estudos nacionais, o que pode ter ocorrido pela organização do processo de dispensação, dividido em etapas (triagem da prescrição, fracionamento e reembalagem, separação e fechamento das embalagens). A conferência dos medicamentos pela enfermagem e a notificação voluntária mostraram-se importantes na identificação de erros de dispensação. A investigação das circunstâncias de ocorrência dos erros pode oferecer informações importantes para desenvolver estratégias de prevenção / Introduction - Drugs make a significant contribution to improving people\'s quality of life, but are not without risks. Errors involving medications have attracted attention of health professionals, institutions and authorities worldwide. In hospitals, the pharmacy is an important link in the complex drug use process, as it interconnects various actions carried out in different areas. Its physical structure, human and technological resources, and its organization are critical in drug error prevention. Objective - Evaluate drug dispensing errors in hospitals and the factors involved. Methods - The survey was conducted at a university hospital in the state of Paraná, using three strategies. 1 st - The drugs the pharmacies dispensed to the medical clinics and to surgery were compared to the prescriptions in the period ranging from January 4 to 19, 2010. The drugs under analysis were segregated using the carbon copy of the prescription and dispensed individually, per patient, or collectively, in plastic packaging (boxes or bags), separated by time of administration for 24 hours of care. 2 nd - Nineteen employees involved in the pharmacy dispensing process were interviewed concerning errors in this process. 3 rd - Nineteen voluntary reports of medication dispensing errors occurring in the hospital between October 2006 and January 2010 were evaluated. Results - 259 dispensations, 1,963 drugs and 4,099 doses were analyzed. During the observation period, there were 61 dispensing errors in 48 prescriptions. The errors occurred in 3.2 per cent of the drugs and in 1.71 per cent of doses dispensed. The most common dispensing errors were: omission of a prescribed drug (23 per cent ); dispensing of a drug that had not been prescribed (14.8 per cent ); drug dispensed in the absence of information or containing questionable or unreadable information (14.8 per cent ); improper concentration (9.8 per cent ); wrong time (9.8 per cent ); and wrong drug (6.6 per cent ). The errors were associated with the number of drugs per prescription, and 33 per cent of the errors involved potentially dangerous drugs. During the interviews, issues related to communications were reported as contributing factors to dispensing errors and included readability of the prescriber\'s spelling, ambiguous, incomplete, and confusing prescriptions, in addition to drug name similarity. Insofar as working conditions were concerned, the following matters stand out: little time for dispensing, work overload, noise levels, interruptions and distractions. As for personal issues, 50 per cent reported a lack of knowledge about drugs, stress and fatigue. The types of errors and the factors involved were similar to those of similar surveys. Conclusions - The data suggest a low frequency of errors when compared to other national studies, which may have occurred on account of the organization of the dispensing process, divided into steps (screening prescription, fractioning and repackaging, sorting and closing of packages). Drug checking by the nurses and voluntary reporting were important in identifying dispensing errors. The investigation of the circumstances under which errors occurred can provide important information to develop prevention strategies

Introdução - Os recém-nascidos são considerados vulneráveis a eventos adversos a medicamentos pela imaturidade fisiológica, pela necessidade de se considerar as proporções corporais ao determinar dosagens de fármacos, pelas limitações práticas durante a administração medicamentosa e pela alta proporção de medicamentos utilizados para o seu tratamento quando em cuidados hospitalares. Além disso, a população de recém-nascidos geralmente não é incluída nos estudos clínicos de utilização de medicamentos. Neste contexto, a terapêutica farmacológica em recémnascidos termina na extrapolação das informações que levam à aprovação do registro de medicamentos para uso em adultos ou em crianças mais velhas. Apesar da relevância do tema, a identificação dos eventos adversos relacionados a medicamentos em hospitais ainda é realizada por meio da notificação voluntária. Estima-se que este método detecte apenas de 5 a 10 por cento dos eventos adversos por medicamentos ocorridos em uma instituição de cuidado à saúde. Uma ferramenta conhecida como trigger foi demonstrada como uma técnica mais efetiva em relação ao convencional sistema de notificação voluntária em pacientes hospitalizados. Um trigger é definido como um rastreador encontrado a partir da revisão de prontuários de pacientes, permitindo selecionar os registros nos prontuários os quais existe maior probabilidade de ter ocorrido um evento adverso a medicamento. Objetivo - Utilizar rastreadores para a identificação de eventos adversos a medicamentos (EAM) em recém-nascidos hospitalizados. Métodos Trata-se de um estudo de coorte prospectivo observacional. A pesquisa foi realizada no Hospital Universitário da Universidade de São Paulo, nas unidades de cuidados intermediários neonatal convencional e terapia intensiva neonatal, durante o período de março a setembro de 2015. Foram incluídos os recém-nascidos hospitalizados que utilizaram medicamentos durante a internação. Uma lista de rastreadores foi desenvolvida para ser utilizada na identificação de EAM nesta população. Os prontuários dos recémnascidos eram avaliados, a fim de detectar primeiramente a existência de um rastreador. Se o rastreador fosse encontrado, era registrado e seguia-se com uma revisão mais detalhada à procura de possíveis EAM relacionados. Os recém-nascidos foram acompanhados até a sua alta ou até completarem 29 dias de vida. O desempenho de cada um dos rastreadores para identificar EAM foi calculado. As frequências dos EAM foram determinadas. As características dos eventos adversos e dos medicamentos relacionados foram descritas. Resultados O estudo incluiu 125 recém-nascidos. Foram encontrados 925 rastreadores, que foram positivos 208 vezes para identificar suspeitas de eventos adversos a medicamentos e que corresponderam ao número final de 115 EAM. A taxa de rendimento geral dos rastreadores foi 22,5 por cento. A incidência geral de EAM foi 46,4 por cento (IC 37,6; 55,1). A taxa geral de EAM por 1000 pacientes-dia foi 81,6 (IC 67,4; 98,0). Os EAM mais frequentes foram: diarreia (29,6 por cento), vômito (23,5 por cento), hipersedação (7,0 por cento) e hiperglicemia (5,2 por cento). Os medicamentos mais frequentes associados aos EAM foram: antibióticos (39,4 por cento), analgésicos (13 por cento), vitaminas (12,5 por cento), cafeína (11,1 por cento) e psicolépticos (8,7 por cento). Entre os rastreadores de alto desempenho destacam-se: hipersedação, prescrição de metadona/lorazepam e prescrição de flumazenil. Estes rastreadores identificaram EAM relacionados aos analgésicos e psicolépticos, duas das classes terapêuticas mais implicadas em EAM neste estudo. Conclusões - Os EAM mais frequentes identificados pelos rastreadores foram: diarreia, vômito, hipersedação e hiperglicemia. Os medicamentos mais frequentes associados a EAM foram: antibióticos, analgésicos, vitaminas, cafeína e psicolépticos. A incidência geral de EAM de 46,4 por cento e a taxa de incidência foi 81,6 EAM por 1000 pacientes-dia. A busca ativa de EAM por rastreadores permite uma análise focada de elementos específicos nos prontuários de pacientes. Este tipo de pesquisa permite a identificação de um maior número de EAM que podem passar despercebidos em simples revisão de prontuários. / Introduction - Newborns are considered vulnerable to adverse drug events because of their physiological immaturity, to consider the body proportions to determine dosages of drugs, the practical limitations during drug administration and the high proportion of drugs used for their treatment while in hospital care. Furthermore, the population of newborns is usually not included in clinical trials for the approval of new drugs. In this context, drug therapy in children is based on extrapolation of information that lead to the approval of the drug for use in adults or in older children. Despite the relevance of the subject, the identification of adverse drug events in hospitals is still carried out through voluntary reporting. It is estimated that this method detects only 5 to 10 per cent of the adverse events occurred by medications in a health care institution. A tool known as \"trigger\" is shown as a superior method compared to the conventional voluntary reporting system in hospitalized patients. A \"trigger\" is defined as a \"flag\" found from the patient chart review, allowing to select the records in the charts that are most likely to have experienced an adverse drug event. Aim - Use triggers to identify adverse drug events (ADE) in hospitalized newborns. Methodology - This is an observational prospective cohort study. The study was conducted at the University Hospital of the University of São Paulo, in the neonatal conventional intermediate care unit and in the neonatal intensive care unit, from March to September 2015. Hospitalized newborns were included using medications during hospitalization. A trigger list was made to identify ADE in this population. The triggers on this list were actively sought in medical charts of newborns. If a trigger was found, it was registered and followed up with a more detailed search for potential ADEs that occurred. Newborns were followed until their discharge or until completing 29 days of life. The performance of each trigger to identify ADE was calculated. The frequencies of ADE were determined. The characteristics of adverse events and related drugs have been described. Results - The study included 125 newborns. 925 triggers were found, which were positive 208 times to identify suspected ADE. That corresponded to the final number of 115 ADE. The overall triggers rate was 22.5 per cent . The overall incidence of ADE was 46.4 per cent (CI 37.6; 55.1). The overall frequency of ADEs per 1,000 patient-days was 81.6 (CI 67.4; 98.0). The most common ADE were diarrhea (29.6 per cent), vomiting (23.5 per cent), oversedation (7.0 per cent) and hyperglycemia (5.2 per cent). The most common medications associated with ADEs were antibiotics (39.4 per cent), analgesics (13 per cent), vitamins (12.5 per cent), caffeine (11.1 per cent) and psycholeptics (8.7 per cent). Among the highperformance trigger, it stand out: \"oversedation,\" \"prescription of methadone / lorazepam\" and \"prescription of flumazenil.\" These triggers identified ADE related to analgesics and psycholeptics, two of the therapeutic classes more involved in ADE in this study. Conclusions Frequent EAM identified by triggers were diarrhea , vomiting, hyperglycemia and oversedation . The most common medications associated with ADE were antibiotics, analgesics, vitamins, caffeine and psycholeptics. The overall incidence of EAM 46.4 per cent and the incidence rate was 81.6 EAM per 1000 patient-days. The active search for ADE by triggers allows a focused review of specific elements in the patient records. This kind of search allows the identification of a greater number of ADE that could go unnoticed in simple review of medical records.

Signal detection from Adverse Event Reports (AERs) is important for identifying and analysing drug safety concern after a drug has been released into the market. A safety signal is defined as a possible causal relation between an adverse event and a drug. There are a number of safety signal detection algorithms available for detecting drug safety concern. They compare the ratio of observed count to expected count to find instances of disproportionate reportings of an event for a drug or combination of events for a drug. In this thesis, we present an algorithm to mine the AERs to identify drugs which show sudden and large changes in patterns of reporting of adverse events. Unlike other algorithms, the proposed algorithm creates time series for each drug and use it to identify start of a potential safety problem. A novel vectorized timeseries utilizing multiple attributes has been proposed here. First a time series with a small time period was created; then to remove local variations of the number of reports in a time period, a time-window based averaging was done. This method helped to keep a relatively long time-series, but eliminated local variations. The steps in the algorithm include partitioning the counts on attribute values, creating a vector out of the partitioned counts for each time period, use of a sliding time window, normalizing the vectors and computing vector differences to find the changes in reporting over time. Weights have been assigned to attributes to highlight changes in the more significant attributes. The algorithm was tested with Adverse Event Reporting System (AERS) datasets from Food and Drug Administation (FDA). From AERS datasets the proposed algorithm identified five drugs that may have safety concern. After searching literature and the Internet it was found that the five drugs the algorithm identified, two were recalled, one was suspended, one had to undergo label change and the other one has a lawsuit pending against it.

Magistro baigiamajame darbe nagrinėjamas farmakologinio budrumo teisinis reguliavimas. Pirmajame skyriuje analizuojama farmakologinio budrumo sąvoka, rūšys, pateikiama trumpa farmakologinio budrumo istorija. Antrame skyriuje analizuojami šiuo metu galiojantys Europos Sąjungos teisės aktai, reglamentuojantys farmakologinį budrumą, palyginant juos su 2012 m. liepą įsigaliosiančiais teisės aktais, pabrėžiant esminius pakeitimus ir jų reikšmę Europos Sąjungos farmakologinio budrumo sistemai. Trečiajame skyriuje yra atliekama Lietuvos Respublikos teisės aktų, reglamentuojančių farmakologinį budrumą, analizė bei įvertinamas nacionalinės farmakologinio budrumo sistemos efektyvumas. / The legal regulation of pharmacovigilance is overviewed in this master thesis. In the first part the concept, sorts and history of pharmacovigilance are analysed. In the second part the current European Union legislation on pharmacovigilance is analysed, comparing it to legislation that will come into force in july, 2012, pointing to the main changes and its meaning to the European Union system of pharmacovigilance. In the third part Lithuanian legislation on pharmacovigilance is analysed and the efficiency of national system of pharmacovigilance is assessed.

Tikslas: Išanalizuoti Lietuvos visuomenės vaistinėse dirbančių farmacijos specialistų požiūrį į pacientams suteikiamą informaciją apie galimus vaistų nepageidaujamus poveikius. Darbo metodika: Tyrimui atlikti buvo taikomas analizės metodas – anketavimas. Apklausta 230 farmacijos specialistų dirbančių visuomenės vaistinėse. Tyrimo duomenys apdoroti naudojant SPSS 17.0 versiją. Darbe pateikiami grafikai ir lentelės sudaryti MS Excel 2007 programa. Rezultatai: Daugumos farmacijos specialistų (98,2%) nuomone, teikti informaciją apie NRV yra būtina. Pagrindiniai veiksmai, pacientui pasireiškus NRV, yra paciento nukreipimas pas gydytoją (93,8%) arba konsultavimas (73,0%). Tik 4 proc. respondentų nesusiduria su problemomis teikiant informaciją susijusią su NRV. Pagrindiniai barjerai iš farmacijos specialisto pusės yra laiko (83,7%) bei žinių (57,2%) trūkumas, o iš paciento pusės – nenoras išklausyti suteikiamos informacijos (63,9%), nedrąsa klausti (44,6%), konfidencialumo (42,1%) bei išsilavinimo (41,6%) trūkumas. Nustatyta, kad ne visos vaistų grupės yra vienodai svarbios suteikiant informaciją apie NRV (p<0,05). Pagrindinės vaistų grupės yra antidepresantai (82,4%), krešumo sistemą veikiantys vaistai (82,4%), antibiotikai (79,4%), antipsichoziniai vaistai (73,5%) bei NVNU (67,6%). Išvados: 1. Farmacijos specialistų nuomone, informacijos apie NRV teikimas pacientams yra būtinas, tačiau ne visi sutinka, kad jis yra pagrindinis asmuo, galintis suteikti šią informaciją. Daugiau nei... [toliau žr. visą tekstą] / Objective: To analyze the attitude of pharmaceutical professionals working in Lithuanian community pharmacies towards providing information about adverse drug reactions. Methods: A questionnaire method was aplied during this research. 230 of 264 pharmacists working in community pharmacies participated in the survey (response rate 87,1%). Results: The majority of pharmaceutical professionals (98,2%) believed that the provision of information about adverse drug reactions (ADRs) is necessary. 97,8% of respondents said that they spoke to patients about reported adverse effects to drugs.The main pharmacists actions after receiving information that patients experienced ADRs were consulting (93,8%) or reffering the patient to a doctor (73,0%). Almost all (96%) respondents told that they have problems when providing information about ADRs. 3 out of 4 specialists point out that the main problem is the lack of time. Approximately half of them think that they lack of knowledge to provide such information. Problems encountered from the patient‘s side is their unwillingness to listen to the information provided (63,9%), timidity to ask for such information (44,6%), lack of privacy (42,1%) and education (41,6%).It was found that not all drug groups are equally important in providing information about ADRs (p<0,05). The main groups of medicines are antidepressants (82.4%), coagulation system drugs (82.4%), antibiotics (79.4%), antipsychotics (73.5%) and NSAIDs (67.6%). Conclusion: According... [to full text]

Background: Drug interactions resulting in adverse drug reactions (ADRs) represent a major health problem both for individuals and society in general. Post-marketing pharmacovigilance reporting databases with compiled individual case safety reports (ICSRs) have been shown to be particularly useful in the detection of novel drug - ADR combinations, though these reports have not been fully used to detect adverse drug interactions. Aim: To explore the potential to identify drug interactions using ICSRs and to develop a method to facilitate the detection of adverse drug interaction signals in the WHO Global ICSR Database, VigiBase. Methods: All six studies included in this thesis are based on ICSRs available in VigiBase. Two studies aimed to characterise drug interactions reported in VigiBase. In the first study we examined if contraindicated drug combinations (given in a reference source of drug interactions) were reported on the individual reports in the database, and in the second study we examined the scientific literature for interaction mechanisms for drug combinations most frequently co-reported as interacting in VigiBase. Two studies were case series analyses where the individual reports were manually reviewed. The two remaining studies aimed to develop a method to facilitate detection of novel adverse drug interactions in VigiBase. One examined what information (referred to as indicators) was reported on ICSRs in VigiBase before the interactions became listed in the literature. In the second methodological study, logistic regression was used to set the relative weights of the indicators to form triage algorithms. Three algorithms (one completely data driven, one semi-automated and one based on clinical knowledge) based on pharmacological and reported clinical information and the relative reporting rate of an ADR with a drug combination were developed. The algorithms were then evaluated against a set of 100 randomly selected case series with potential adverse drug interactions. The algorithm’s performances were then evaluated among DDAs with high coefficients. Results: Drug interactions classified as contraindicated are reported on the individual reports in VigiBase, although they are not necessarily recognised as interactions when reported. The majority (113/123) of drug combinations suspected for being responsible for an ADR were established drug interactions in the literature. Of the 113 drug interactions 46 (41%) were identified as purely pharmacodynamic; 28 (25%) as pharmacokinetic; 18 (16%) were a mix of both types and for 21 (19%) the mechanism have not yet been identified. Suspicions of a drug interaction explicitly noted by the reporter are much more common for known adverse drug interactions than for drugs not known to interact. The clinical evaluation of the triage algorithms showed that 20 were already known in the literature, 30 were classified as signals and 50 as not signals. The performance of the semi-automated and the clinical algorithm were comparable. In the end the clinical algorithm was chosen. At a relevant level, 38% were of the adverse drug interactions were already known in the literature and of the remaining 80% were classified as signals for this algorithm. Conclusions: This thesis demonstrated that drug interactions can be identified in large post-marketing pharmacovigilance reporting databases. As both pharmacokinetic and pharmacodynamic interactions were reported on ICSRs the surveillance system should aim to detect both. The proposed triage algorithm had a high performance in comparison to the disproportionality measure alone.

abstract: Social media is becoming increasingly popular as a platform for sharing personal health-related information. This information can be utilized for public health monitoring tasks such as pharmacovigilance via the use of Natural Language Processing (NLP) techniques. One of the critical steps in information extraction pipelines is Named Entity Recognition (NER), where the mentions of entities such as diseases are located in text and their entity type are identified. However, the language in social media is highly informal, and user-expressed health-related concepts are often non-technical, descriptive, and challenging to extract. There has been limited progress in addressing these challenges, and advanced machine learning-based NLP techniques have been underutilized. This work explores the effectiveness of different machine learning techniques, and particularly deep learning, to address the challenges associated with extraction of health-related concepts from social media. Deep learning has recently attracted a lot of attention in machine learning research and has shown remarkable success in several applications particularly imaging and speech recognition. However, thus far, deep learning techniques are relatively unexplored for biomedical text mining and, in particular, this is the first attempt in applying deep learning for health information extraction from social media. This work presents ADRMine that uses a Conditional Random Field (CRF) sequence tagger for extraction of complex health-related concepts. It utilizes a large volume of unlabeled user posts for automatic learning of embedding cluster features, a novel application of deep learning in modeling the similarity between the tokens. ADRMine significantly improved the medical NER performance compared to the baseline systems. This work also presents DeepHealthMiner, a deep learning pipeline for health-related concept extraction. Most of the machine learning methods require sophisticated task-specific manual feature design which is a challenging step in processing the informal and noisy content of social media. DeepHealthMiner automatically learns classification features using neural networks and utilizing a large volume of unlabeled user posts. Using a relatively small labeled training set, DeepHealthMiner could accurately identify most of the concepts, including the consumer expressions that were not observed in the training data or in the standard medical lexicons outperforming the state-of-the-art baseline techniques. / Dissertation/Thesis / Doctoral Dissertation Biomedical Informatics 2016

A despeito de suas limitações, os dados do SIHSUS são os mais sistemáticos e abrangentes sobre as Reações Adversas e Intoxicações a medicamentos que provocam hospitalização. Eles demonstram a importância das ações de educação e investigação de casos do Programa Nacional de Farmacovigilância para possibilitar o diagnóstico mais acurado e superação do quadro atual de ocorrência desses agravos, além da possibilidade de o SIH/SUS ser utilizado sistematicamente como fonte de dados na detecção e análise dos problemas relacionados a medicamentos. No período de 1999 a 2007, foram emitidas 6.670.609 AIH (tipo 1), entre as quais 3.611 foram classificadas como internações devidas a RAM e 4.675 como Intoxicações, correspondendo, respectivamente, às taxas médias de 5,41 casos por 104 AIH e 7,2 casos por 104 AIH. Ocorreram 137 óbitos (3,79% das AIH) por RAM e 207 (4,43% das AIH) por Intoxicações na população internada. Tanto as RAM como as Intoxicações tiveram menor chance de levar ao óbito quando comparados às outras causas. Uma característica da distribuição dos RAM foi concentrar 62% das AIH nas faixas etárias de 20 a 59 anos de idade (grupo adulto). Nas Intoxicações merece destaque a elevada proporção de AIH na faixa etária de 0-4 anos (14,29%). As AIH registradas com causas básicas relacionados a RAM foram principalmente de pacientes do sexo masculino, já as Intoxicações foram principalmente de pacientes do sexo feminino. Em ambos tipos de agravos estes pacientes foram internados em hospitais que não faziam parte da Rede de Hospitais Sentinelas do Programa Nacional de Farmacovigilância. No entanto, a probabilidade destes hospitais registrarem as AIH com códigos CID-10 referentes às RAM é maior, o que ocorre provavelmente por estarem mais capacitados em diagnosticar este tipo de agravo. Porém este fato não foi observado para as Intoxicações. Os fármacos que causaram os agravos estudados são psicoativos. Este estudo apresentou algumas evidências sobre a distribuição da morbi-mortalidade provocada por medicamentos entre pacientes internados em hospitais conveniados ao SUS no período de 1999-2007, baseadas nas informações das AIH, que podem ser úteis ao Programa de Farmacovigilância no Estado do Rio de Janeiro. / Despite its limitations, the data SIHSUS are the most systematic and comprehensive on Adverse Reactions and Drug Poisonings causing hospitalization. They demonstrate the importance of these actions and investigation of cases of National Pharmacovigilance Programme to enable the most accurate and overcoming the current frame of event occurrences diagnosis, beyond the possibility of SIH / SUS be systematically used as a data source in the detection and analysis of drug-related problems. In the period 1999-2007, were issued 6,670,609 AIH (type 1), among which 3,611 were classified as hospitalizations due to poisoning as RAM and 4675, corresponding, respectively, at average rates of 5.41 cases per 104 AIH and 7.2 cases per 104 AIH. There were 137 deaths (3.79% of AIH) by RAM and 207 (4.43% of AIH) by poisoning in hospitalized population. Both the RAM as poisoning were less likely to cause death when compared to other causes. A characteristic distribution of RAM was concentrating 62% of AIH in the age groups 20-59 years of age (adult group). In Poisoning deserves the high proportion of AIH aged 0-4 years (14.29%). The AIH registered root causes related ADRs were mostly male patients, since the poisoning were mainly female patients. In both types of injuries these patients were admitted to hospitals that were not part of the Network of Sentinel Hospitals of the National Pharmacovigilance Programme. However, the likelihood of these hospitals register the AIH with ICD-10 codes related to RAM is higher, which is probably because they are better able to diagnose this type of offense. However this was not observed for the poisoning. The drugs that caused the diseases studied are psychoactive. This study presented some evidence on the distribution of morbidity and mortality caused by drugs among patients admitted to the SUS hospitals during the period 1999-2007, based on the information of AIH, which may be useful to Pharmacovigilance Programme in the State of Rio de Janeiro .