Les quatre principales activités de la gestion de risque thérapeutique comportent l’identification, l’évaluation, la minimisation, et la communication du risque. Ce mémoire aborde les problématiques liées à l’identification et à la minimisation du risque par la réalisation de deux études dont les objectifs sont de: 1) Développer et valider un outil de « data mining » pour la détection des signaux à partir des banques de données de soins de santé du Québec; 2) Effectuer une revue systématique afin de caractériser les interventions de minimisation de risque (IMR) ayant été implantées. L’outil de détection de signaux repose sur la méthode analytique du quotient séquentiel de probabilité (MaxSPRT) en utilisant des données de médicaments délivrés et de soins médicaux recueillis dans une cohorte rétrospective de 87 389 personnes âgées vivant à domicile et membres du régime d’assurance maladie du Québec entre les années 2000 et 2009. Quatre associations « médicament-événement indésirable (EI) » connues et deux contrôles « négatifs » ont été utilisés. La revue systématique a été faite à partir d’une revue de la littérature ainsi que des sites web de six principales agences réglementaires. La nature des RMIs ont été décrites et des lacunes de leur implémentation ont été soulevées. La méthode analytique a mené à la détection de signaux dans l'une des quatre combinaisons médicament-EI. Les principales contributions sont: a) Le premier outil de détection de signaux à partir des banques de données administratives canadiennes; b) Contributions méthodologiques par la prise en compte de l'effet de déplétion des sujets à risque et le contrôle pour l'état de santé du patient. La revue a identifié 119 IMRs dans la littérature et 1,112 IMRs dans les sites web des agences réglementaires. La revue a démontré qu’il existe une augmentation des IMRs depuis l’introduction des guides réglementaires en 2005 mais leur efficacité demeure peu démontrée. / The four main components of therapeutic risk management (RM) consist of risk detection (identification), evaluation, minimisation, and communication. This thesis aims at addressing RM methodologies within the two realms of risk detection and risk minimisation, through the conduct of two distinct studies: i) The development and evaluation of a data mining tool to support signal detection using health care claims databases, and ii) A systematic review to characterise risk minimisation interventions (RMIs) implemented so far. The data mining tool is based on a Maximised Sequential Probability Ratio Test (MaxSPRT), using drug dispensing and medical claims data found in the Quebec health claims databases (RAMQ). It was developed and validated in a cohort of 87,389 community-dwelling elderly aged 66+, randomly sampled from all elderly drug plan members between 2000 and 2009. Four known drug-AE associations and two "negative" controls were used. The systematic review on RMIs is based on a literature search as well as a review of the websites of six main regulatory agencies. Types of RMIs have been summarized and implementation gaps identified. The data mining tool detected signals in one of four of the known drug-AE associations. Major contributions are: a) The first signal detection data mining tool applied to a Canadian claims database; b) Methodological improvements over published methods by considering the depletion of susceptibles effect and adjusting for overall health status to control for prescription channelling. The review yielded 119 distinct RMIs from the literature and 1,112 from the websites. The review demonstrated that an increase in RMI numbers among websites occurred since the introduction of guidances in 2005, but their effectiveness remains insufficiently examined.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Les quatre principales activités de la gestion de risque thérapeutique comportent l’identification, l’évaluation, la minimisation, et la communication du risque. Ce mémoire aborde les problématiques liées à l’identification et à la minimisation du risque par la réalisation de deux études dont les objectifs sont de: 1) Développer et valider un outil de « data mining » pour la détection des signaux à partir des banques de données de soins de santé du Québec; 2) Effectuer une revue systématique afin de caractériser les interventions de minimisation de risque (IMR) ayant été implantées. L’outil de détection de signaux repose sur la méthode analytique du quotient séquentiel de probabilité (MaxSPRT) en utilisant des données de médicaments délivrés et de soins médicaux recueillis dans une cohorte rétrospective de 87 389 personnes âgées vivant à domicile et membres du régime d’assurance maladie du Québec entre les années 2000 et 2009. Quatre associations « médicament-événement indésirable (EI) » connues et deux contrôles « négatifs » ont été utilisés. La revue systématique a été faite à partir d’une revue de la littérature ainsi que des sites web de six principales agences réglementaires. La nature des RMIs ont été décrites et des lacunes de leur implémentation ont été soulevées. La méthode analytique a mené à la détection de signaux dans l'une des quatre combinaisons médicament-EI. Les principales contributions sont: a) Le premier outil de détection de signaux à partir des banques de données administratives canadiennes; b) Contributions méthodologiques par la prise en compte de l'effet de déplétion des sujets à risque et le contrôle pour l'état de santé du patient. La revue a identifié 119 IMRs dans la littérature et 1,112 IMRs dans les sites web des agences réglementaires. La revue a démontré qu’il existe une augmentation des IMRs depuis l’introduction des guides réglementaires en 2005 mais leur efficacité demeure peu démontrée. / The four main components of therapeutic risk management (RM) consist of risk detection (identification), evaluation, minimisation, and communication. This thesis aims at addressing RM methodologies within the two realms of risk detection and risk minimisation, through the conduct of two distinct studies: i) The development and evaluation of a data mining tool to support signal detection using health care claims databases, and ii) A systematic review to characterise risk minimisation interventions (RMIs) implemented so far. The data mining tool is based on a Maximised Sequential Probability Ratio Test (MaxSPRT), using drug dispensing and medical claims data found in the Quebec health claims databases (RAMQ). It was developed and validated in a cohort of 87,389 community-dwelling elderly aged 66+, randomly sampled from all elderly drug plan members between 2000 and 2009. Four known drug-AE associations and two "negative" controls were used. The systematic review on RMIs is based on a literature search as well as a review of the websites of six main regulatory agencies. Types of RMIs have been summarized and implementation gaps identified. The data mining tool detected signals in one of four of the known drug-AE associations. Major contributions are: a) The first signal detection data mining tool applied to a Canadian claims database; b) Methodological improvements over published methods by considering the depletion of susceptibles effect and adjusting for overall health status to control for prescription channelling. The review yielded 119 distinct RMIs from the literature and 1,112 from the websites. The review demonstrated that an increase in RMI numbers among websites occurred since the introduction of guidances in 2005, but their effectiveness remains insufficiently examined.

L’analyse de la causalité, qui consiste à déterminer si la prise d’un médicament est la cause de la survenue d’un événement, est la problématique centrale de la pharmacovigilance et de la pharmaco-épidémiologie.La première partie de ce travail aborde l’étude de la causalité au plan individuel, au travers des méthodes d’imputabilité. Nous avons d’abord comparé une méthode d’imputabilité récemment développée, la méthode logistique, et la méthode d’imputabilité officiellement utilisée en France à un jugement consensuel d’experts pris comme référence. Les résultats montrent que la méthode française d’imputabilité tend à sous-coter la responsabilité du médicament (faible sensibilité) alors que la méthode logistique tend à la surestimer (faible spécificité). Par la suite, une nouvelle version de la méthode française d’imputabilité visant à améliorer sa sensibilité et son pouvoir discriminant a été proposée. Le travail de validation portant sur cette méthode réactualisée montre une amélioration de sa sensibilité et des résultats se rapprochant plus du jugement consensuel d’experts. Pour la méthode logistique, les critères d’imputabilité et leurs poids ont été réévalués sur un échantillon plus important d’observations que celui ayant servi à la pondération initiale. La validité de cette nouvelle version et celle de l’un des algorithmes les plus couramment utilisés en pharmacovigilance, la méthode Naranjo, ont été comparées à un jugement consensuel d’experts. Les résultats concernant la validité interne et les qualités prédictives de la méthode Naranjo ne sont pas satisfaisants alors que la méthode logistique présente une spécificité améliorée ainsi qu’une bonne sensibilité et valeurs prédictives. Cette dernière méthode présente donc des caractéristiques qui devraient améliorer l’évaluation de la responsabilité des médicaments dans la survenue des événements indésirables. La mise en place de méthode d’imputabilité spécifique à une classe thérapeutique et/ou à un type d’événement indésirable pourrait aussi améliorer l’évaluation des événements indésirables. Nous proposons une grille d’imputabilité adaptée aux accidents hémorragiques sous antithrombotique. Dans la deuxième partie de cette thèse, l’analyse épidémiologique de la causalité est abordée en proposant deux méthodes : l’analyse populationnelle des cas individuels, en particulier leur délai de survenue après exposition médicamenteuse, et l’approche cas-population. Bien que beaucoup moins robustes que les méthodes classiques, elles sont testées sur des problématiques réelles de pharmacovigilance et les résultats montrent qu’elles peuvent être utiles pour une première exploration d’une association causale potentielle. En conclusion, ce travail méthodologique pourrait aider à mieux évaluer la responsabilité des médicaments dans la survenue d’événements indésirables après leurs autorisations de mise sur le marché. / The analysis of causality, which consists of determining if drug intake is the cause of the event occurrence, is the central issue of pharmacovigilance and pharmacoepidemiology. The first part of this work deals with the study of causality assessment methods at the level of individual cases. We first compared the recently developed logistic causality assessment method and the method officially used in France, to consensusual expert judgement taking as a reference. The results showed that the French causality assessment method tended to underestimate the responsibility of the drug (low sensitivity) whereas the logistic method tended to overestimate it (low specificity). Subsequently a new version of the French causality assessment method aiming to improve its sensitivity and discriminating power was proposed. The validation phase of this updated method showed improved sensitivity and a performance closer to consensual expert judgement. For the logistic method, the criteria of causality assessment and their weights were re-evaluated on a larger sample of drug-event pairs that had been used in the initial weighting. The validity of this method and that of one of the most commonly used algorithms in pharmacovigilance, the Naranjo method, were compared to consensual expert judgement. Results concerning the internal validity and the predictive qualities of the Naranjo method were not satisfactory while the logistic method presented an improved specificity and good sensitivity and predictive values. The logistic method now presents characteristics that should improve the assessment of drug responsibility in the occurrence of adverse events. The implementation of causality assessment method specific to a therapeutic class and / or to a type of adverse event could also improve the assessment of adverse events. We proposed a scale adapted to hemorrhages with antithrombotics and derived from the French causality assessment method. In the second part of this thesis, the epidemiological analysis of causality was tackled by proposing two methods: the populational analysis of individual cases, in particular their time to onset after drug exposure, and the case-population approach. Although less robust than the conventional methods, these were tested on real problems of pharmacovigilance and the results indicate that they may be useful for an initial exploration of a potential causal association. In conclusion, this methodological work could help to better assess drug causality in the occurrence of adverse event in post maketing surveillance.

Pharmacovigilance in healthcare is essential for safe drug treatment. Spontaneous reporting is the most common source of information in the context of implementing label changes and taking a drug off the market. However, underreporting is found to be very prevalent. One way to decrease underreporting is to include different categories of healthcare professionals in such reporting and to investigate attitudes towards and incentives for reporting adverse drug reaction (ADR)s. As nurses form the largest group of health professionals, a sample of nurses were allowed and encouraged to report ADR during a 12 month period after they had received training in pharmacovigilance. A questionnaire posted to physicians and nurses investigated their knowledge and attitudes towards reporting. Spontaneous reports of torsade de pointes (TdP) and erectile dysfunction (ED) were scrutinized with respect to the reported drugs, risk factors and if the reaction was listed in the summary of product characteristics (SPC). After training, the nurses produced relevant reports and three years after the introduction of nurses in the reporting scheme, more than half of the responding nurses were aware of their role as reporters. Both nurses and physicians stated that the most important factor for reporting a suspected ADR was the severity of the ADR and an ADR arising in response to a newly approved drug. A web-based reporting system was deemed to facilitate the reporting. In spontaneous reports of TdP, citalopram was reported as a suspected drug. However, neither QT prolongations, nor TdP, were labelled in the SPC. ED was reported for all antihypertensive drugs including angiotensin II type I blockers. A positive information component (IC), assessing the disproportionality between the observed and the expected number of reports, was found indicating that ED was reported more often in association with antihypertensive drug classes, except for angiotensinconverting enzyme inhibitors. This thesis demonstrates the importance of pharmacoviglilance in healthcare in terms of capturing new signals. By including nurses as reporters, the overall safety of drugs might improve. Information and education are needed to secure safe treatment when applying drugs.

Medication management constitutes a large part of registered nurses' (RNs) daily work in municipal elderly care. They are responsible for monitoring multimorbid older persons with extensive treatments, and they often work alone, without daily access to physicians. RNs’ drug monitoring is, in this thesis, based on the concept of pharmacovigilance. Pharmacovigilance is about the science and the activities that aim to improve patient care and safety in drug use, that is, to detect, assess, understand and prevent drug-related problems. The overall aim was to explore conditions for pharmacovigilance from a nursing perspective, focusing on implications of RNs’ competence and use of a computerized decision support system (CDSS). Both quantitative and qualitative research methods were used, including a questionnaire (I), focus group discussions (II), individual interviews (III) and an intervention study (IV). In total 216 RNs and 54 older persons participated from 13 special accommodations, located in three different regions. RNs who had completed further training in pharmacovigilance rated their medication competence higher than those who had not. However, there was no difference between groups in the number of pharmacovigilant activities they performed in clinical practice (I). The RNs appeared to act as “vigilant intermediaries” in drug treatment. They depended on the nursing staff's observations of drug-related problems. The RNs continuously controlled the work of staff and physicians, and attempted to compensate for shortcomings in competence, accessibility and continuity (II). RNs’ use of a CDSS was found to affect drug monitoring, including aspects of time, responsibility, standardization of the work, as well as access to knowledge and opportunities for evidence-based care (III). The CDSS detected significantly more drug-related problems when conducting medication reviews, than the RNs did. Nevertheless, this did not result in any significant improvement in the quality of drug use in the follow up, three and six months later (IV). This thesis contributes to the recognition of pharmacovigilance from a nursing perspective. Increased medication competence seems to be insufficient to generate pharmacovigilant activities. RNs depend on other health care professionals and organizational conditions in order to perform their work. A CDSS has the potential to support RNs, both in structured medication reviews and in daily clinical practice. Inter-professional collaboration is crucial, with or without a CDSS, and the entire team needs to be aware of and take responsibility. Other important conditions is the existence of well-functioning communication channels, competence across the team, and established procedures based on current guidelines.

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.

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: Reação Adversa a Medicamento (RAM) é qualquer resposta prejudicial ou indesejável e não intencional que ocorre com medicamentos em doses normalmente utilizadas no homem para profilaxia, diagnóstico, tratamento de doença ou para modificação de funções fisiológicas. Atualmente, representa uma das principais causas de morbidade e mortalidade na área da saúde. Objetivo: Analisar as reações adversas a medicamentos e fatores associados em pacientes ortopédicos tratados com antibióticos. Método: Coorte prospectiva conduzida com 273 pacientes ortopédicos internados no Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, Brasil. A coleta de dados ocorreu nos anos de 2012 e 2013, por meio de instrumento composto por variáveis demográficas-clínicas e terapia medicamentosa. Para identificação das RAMs realizou-se o monitoramento ativo, composto de: entrevista, análise de prontuários e exames laboratoriais. As RAMs consideradas graves foram analisadas por meio do formulário do Instituto Catalão de Farmacologia, Espanha. Na análise dos dados utilizaram-se os testes Mann-Whitney, Qui-Quadrado, exato de Fisher e regressão logística, com significância de p 0,05. Resultados: A incidência de RAM foi de 41%. O grupo com RAM apresentou maior média de idade (43,3; DP 10,9), tempo de internação (72,7; DP 40,9) e número de medicamentos concomitantes (13,2; DP 4,1). Os fatores associados foram número de medicamentos, uso de antimicobacteriano (OR 2,44; IC 1,3944,270) e carbapenêmicos (OR 2,38; IC 1,167 4,872). Identificaram-se 466 RAM, cuja maioria (67,1%) foi classificada como leve. No grupo de pacientes com RAMs graves identificaram-se leucopenia (46,6%), insuficiência renal aguda (40%) e hepatite medicamentosa (26,6%). Os antibióticos foram os principais medicamentos suspeitos de causar as RAMs graves (76,4%), sendo os mais frequentes (23,5%) formados pela tríade: amicacina + vancomicina + piperacilina com tazobactam. Conclusão: A incidência de RAM é maior quando se incorpora ao serviço de farmacovigilância a técnica de monitoramento contínuo dos pacientes hospitalizados e se utiliza a analise de exames laboratoriais como preditores para suspeitas de RAMs potencialmente graves / Introduction: Adverse Drug Reaction (ADR) is any noxious, undesired or unintended response which occurs in the use of normal dosages of drugs for prophylaxis, diagnosis, treatments or for modifying physiologic functions. Nowadays, ADR represents one of the main causes of morbidity and mortality in the health service area. Objective: To analyze the occurrence of adverse reaction to drugs and factors related to orthopedic patients treated with antibiotics. Method: The prospective cohort study was conducted in 273 orthopedic patients hospitalized at the Brazilian Institute of Traumatology and Orthopedics in Rio de Janeiro. The data collection was made during the years 2012 and 2013, using instruments composed by demographic-clinical variables and drug therapies. With the purpose of identifying occurrences of ADRs, during active monitoring, interviews were conducted, medical charts and exams were analyzed. In addition, the occurrence of ADRs considered harmful was analyzed by using a form provided by the Catalan Institute of Pharmacology, Spain. In the study of the data collected, was made use of Mann-Whitney tests, Chi-Squared test, Fishers exact test and logist regression, with p-value 0,05. Results: The occurrence of ADRs was of 41%. This group was composed by individuals with major age rage (43,3, SD 10,9), major time spent hospitalized (72,7; SD 40,9), and quantity of concurrent drugs used (13,2; SD 4,1). Also, the related factors were the number of drugs, the usage of Antimicobacterial agents (OR 2,44, CI 1,394-4,270) and Carbapenemases (OR 2,38; CI 1,167 4,872). During the study, there were identified 466 ADRs, and the majority (67,1%) was classified as low-grade. Additionally, in the group of patients with harm adverse reactions, it was possible to identify leukopenia (46,6%), acute kidney failure (40%) and drug-induced hepatitis (26,6%). The antibiotics were the main drugs suspected to be the cause of potentially harmful ADRs (76,4%), being the most frequent (23,5%) formed by the triad: amikacin + vancomycin + piperacillin-tazobactam. Conclusion: The occurrence of ADRs is higher when the practice of continuous monitoring of hospitalized patients is incorporated to the pharmacovigilance service, and the analyzes of lab exams are used as predictors for the suspicion of potentially harmful ADRs

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