La iatrogénie médicamenteuse à l’hôpital est un problème majeur de santé publique dont les causes sont multiples. Les bilans de médications et le rôle des cohortes de patients pourraient permettre de diminuer ce phénomène. L’objectif de cette thèse d’apporter des éléments utiles à la décision publique sur l’évolution des pratiques pharmaceutiques et l’effet iatrogène des médicaments et d’autre part de fournir des outils directement utiles au pharmacien afin de cibler les patients les plus à risques d’évènements iatrogènes médicamenteux. Ce travail se décline en trois séquences : (i) définition et contexte, (ii) évaluation de l’impact clinique et économique du pharmacien clinicien dans une démarche pro-active de soins pharmaceutiques dans les unités de soins, (iii) facteurs de risque d’événements indésirables médicamenteux à court terme et à long terme. Au vu de ces résultats et des données de la littérature, il apparaît que les bilans de médication est un moyen d’optimisation de la qualité et de l’efficience des soins. / Medication errors in hospital is a major public health problem with multiple reasons. Medication reviews and the role of cohorts of patients could help reduce this phenomenon. The objective of this thesis is to provide useful elements for public decision on the evolution of pharmaceutical practices and the adverse drugs reactions and secondly to provide tools directly useful to the pharmacist to target patients most at risk of adverse drugs events. This work is divided into three parts: (i) definition and context, (ii) evaluation of the clinical and economic impact of the clinical pharmacist in a pro-active approach of pharmaceutical care in the care units, (iii) risk factors adverse drug events in the short and long term. In view of these results and data from the literature, it appears that medication reports are a means of optimizing the quality and efficiency of care.

Yes / Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (1) investigate the prevalence of anticholinergic prescribing for older patients, and (2) examine anticholinergic burden according to frailty status. Methods: Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage (SAIL) databank including patients aged ≥65 at their first GP consultation between 1st January and 31st December 2018. Frailty was identified using the electronic Frailty Index (eFI) and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to 1) describe the type and frequency of anticholinergics prescribed; 2) to estimate the association between frailty and cumulative ACB score (ACB-Sum). Results: In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared to patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061–1.064), moderate frailty, adj OR 1.134 (95%CI 1.131–1.136), severe frailty, adj OR 1.208 (95%CI 1.203–1.213)). Conclusions: Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications given the risks of functional and cognitive decline that frailty presents. / NIHR / Research Development Fund Publication Prize Award winner, May 2023.

The overall aim of this thesis was to evaluate clinical pharmacist interventions with the focus on methods aiming to improve the quality of drug therapy and increase patient safety. Adverse drug events caused by medication errors, suboptimal dosages and inappropriate prescribing are common causes of drug-related morbidity and mortality. Clinical pharmacists integrated in multi-professional health-care teams are increasingly addressing these issues. A randomised controlled trial (RCT) was conducted to investigate the effectiveness of clinical pharmacists’ interventions in reducing morbidity and use of hospital care for patients 80 years or older. The results showed that the intervention group had fewer visits to hospital and that the intervention was cost-effective. In a subsequent study based on the population in the RCT, the appropriateness of prescribing was assessed using three validated tools. The results indicated improved appropriateness of prescribing for the intervention group as a result of the intervention. The tools and the number of drugs at discharge were then tested for validity in terms of causal links between the scores at discharge and hospitalisation. No clear correlations between high scores for the tools or a high number of drugs and increased risk of hospitalisation could be detected. During the inclusion period of the RCT a survey based study was conducted where the perceived value of ward-based clinical pharmacists, from the perspective of hospital-based physicians and nurses as well as from general practitioners (GPs) was evaluated. The respondents were positive to the new collaboration to a high degree and stated increased patient safety and improvements in patients’ drug therapy as the main advantages. In the last study the frequency and severity of prescription and transcription errors, when patients enrolled in the multidose-dispensed medications (MDD) system are discharged from hospital, was investigated. The results showed that errors frequently occur when MDD patients are hospitalised.

Older people admitted to hospital are at high risk of rehospitalization and medication errors. We have demonstrated, in a randomized controlled trial, that a clinical pharmacist intervention reduces the incidence of revisits to hospital for patients aged 80 years or older admitted to an acute internal medicine ward. The aims of this thesis were to further study the effects of the intervention and to investigate possibilities of targeting the intervention by identifying predictors of treatment response or adverse health outcomes. The effect of the pharmacist intervention on the appropriateness of prescribing was assessed, by using three validated tools. This study showed that the quality of prescribing was improved for the patients in the intervention group but not for those in the control group. However, no association between the appropriateness of prescribing at discharge and revisits to hospital was observed. Subgroup analyses explored whether the clinical pharmacist intervention was equally effective in preventing emergency department visits in patients with few or many prescribed drugs and in those with different levels of inappropriate prescribing on admission. The intervention appeared to be most effective in patients taking fewer drugs, but the treatment effect was not altered by appropriateness of prescribing. The most relevant risk factors for rehospitalization and mortality were identified for the same study population, and a score for risk-estimation was constructed and internally validated (the 80+ score). Seven variables were selected. Impaired renal function, pulmonary disease, malignant disease, living in a nursing home, being prescribed an opioid and being prescribed a drug for peptic ulcer or gastroesophageal reflux disease were associated with an increased risk, while being prescribed an antidepressant drug (tricyclic antidepressants not included) was linked with a lower risk. These variables made up the components of the 80+ score. Pending external validation, this score has potential to aid identification of high-risk patients. The last study investigated the occurrence of prescription errors when patients with multi-dose dispensed (MDD) drugs were discharged from hospital. Twenty-five percent of the MDD orders contained at least one medication prescription error. Almost half of the errors were of moderate or major severity, with potential to cause increased health-care utilization.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Introduction. Drug-related problems are frequent in clinical practice and are related to increased morbidity and mortality as well as health care costs. In this context, Medication Review (MR) services may be key elements in improving the use of medicines. However, there are few studies on implementation, monitoring, evaluation and improvement of the quality of such services. Therefore, there is a need for further research with focus on the subject with the aim of defining scientific models for these services. Aim. To develop quality indicators for Medication Review services. Methods. Initially, an overview of systematic reviews was performed in the databases Embase, LILACS, PubMed, Scopus, The Cochrane Library and Web of Science using the key words "medication review", "pharmacist" and "systematic review". Subsequently, a methodological development study was realized in two subsequent steps. In the first step, variables used to describe MR practices with potential to constitute indicators were identified through the reviews included in the overview. In the second step, a panel of experts categorized the variables in structure, processes and outcomes; choosen variables that could give support to the development; and, developed quality indicators for MR services. The quality indicators were reviewed and ranked by a senior-evaluator as the approach, source and pre-specification. Results. In the overview, 11 systematic reviews met the inclusion criteria. It was observed that MR is approached as both clinical service and pharmaceutical intervention adopting ten different terminologies. Regardless of terminologies, the main objective of MR practice is to identify and solve drug-retated problems. Most of the reviews presented methodological quality below ideal. In addition, none of the reviews focused on quality assessment of the MR practice. In the methodological development study, 272 variables were extracted from the reviews; 253 variables were chosen for the development of indicators; and, 71 quality indicators for MR services were developed. Of these, four were of structure, 45 of processes and 22 of outcomes. In addition, most indicators were classified as explicit (n = 55), empirical (n = 7) and quantitative (n = 61). Conclusion. Heterogeneity of terminologies, definitions and approach of MR as well as the low methodological rigor of the studies limit the comparison of this practice. Thus, it is necessary an international agreement on the MR process and to stablish minimum quality standards for the MR practice, which can be done through quality indicators. In this scenario, the combination of scientific evidence and a panel of experts may assist in the development of indicators for MR services. Given the above, the results obtained in conjunction with indicators developed from other sources could support the construction of scientific models to implement, assess, optimize and compare quality of MR practices. / Introdução. Problemas farmacoterapêuticos são frequentes na prática clínica e estão relacionados ao aumento da morbimortalidade e os custos com serviços de saúde. Nesse contexto, serviços de Revisão da Farmacoterapia (RF) podem ser elementos-chave na melhora do processo de uso dos medicamentos. Entretanto, são escassos estudos sobre implantação, monitorização, avaliação e aprimoramento da qualidade destes serviços. Logo, são necessárias mais pesquisas sobre o tema a fim de definir modelos científicos para estes serviços. Objetivo. Desenvolver indicadores de qualidade para serviços de Revisão da Farmacoterapia. Metodologia. Inicialmente, foi realizada uma overview de revisões sistemáticas nas bases de dados Embase, LILACS, PubMed, Scopus, The Cochrane Library e Web of Science utilizando os descritores “medication review” “pharmacist” e “systematic review”. Posteriormente, foi realizado um estudo de desenvolvimento metodológico em duas etapas subsequentes. Na primeira etapa, variáveis utilizadas para descrever a prática da RF com potencial de constituir indicadores foram identificadas a partir das revisões incluídas na overview. Posteriormente, um painel de especialistas categorizou as variáveis em estrutura, processos e resultados; elegeu as variáveis que poderiam dar subsídio ao desenvolvimento; e, desenvolveu indicadores de qualidade para serviços de RF. Os indicadores foram revisados e classificados por uma avaliadora-sênior quanto à abordagem, fonte e pré-especificação. Resultados. Na overview, 11 revisões sistemáticas preencheram os critérios de inclusão. Observou-se que, a RF é abordada tanto como serviço clínico quanto intervenção farmacêutica adotando dez diferentes terminologias. Independente das terminologias, o principal objetivo da prática da RF é identificar e resolver problemas farmacoterapêuticos. A maioria das revisões apresentaram qualidade metodológica abaixo do ideal. Ademais, nenhuma das revisões tinha foco em avaliação da qualidade da prática da RF. No estudo de desenvolvimento metodológico, 272 variáveis foram extraídas a partir das revisões; 253 variávies foram eleitas para o desenvolvimento dos indicadores; e, 71 indicadores de qualidade para serviços de RF foram desenvolvidos. Destes, quatro foram de estrutura, 45 de processos e 22 de resultados. Além disso, a maioria dos indicadores foi classificada como explícito (n=55), empírico (n=7) e quantitativo (n=61). Conclusões. A heterogeneidade das terminologias, definições e abordagem da RF bem como o baixo rigor metodológico dos estudos limitam a comparação desta prática. Assim, é necessário consensuar internacionalmente o processo da RF e padrões mínimos de qualidade para a prática, o que pode ser feito por meio de indicadores de qualidade. Neste cenário, a combinação entre evidência científica e consenso de especialistas pode auxiliar no desenvolvimento de indicadores para RF. Frente ao exposto, os resultados obtidos em conjunto com indicadores desenvolvidos a partir de outras fontes poderão embasar a construção de modelos científicos para implantar, avaliar, otimizar e comparar a qualidade da RF. / São Cristóvão, SE

Background: The purpose of drug treatment is to reduce morbidity and mortality, and to improve health-related quality of life. However, there are frequent problems associated with drug treatment, especially among the elderly. The aim of this thesis was to investigate the impact of clinical pharmacy services within a multiprofessional healthcare team on quality and safety of patients’ drug therapy, and to study the frequency and nature of medication history errors on admission to hospital. Methods: A model for clinical pharmacy services within a multiprofessional healthcare team (the Lund Integrated Medicines Management model, LIMM) was introduced in three hospital wards. On admission of patients to hospital, clinical pharmacists conducted medication reconciliation (i.e. identified the most accurate list of a patient’s current medications) to identify any errors in the hospital medication list. To identify, solve and prevent any other drug-related problems, the clinical pharmacists interviewed patients and performed medication reviews and monitoring of drug therapy. Drug-related problems were discussed within the multiprofessional team and the physicians adjusted the drug therapy as appropriate. Results: On admission to hospital, drug-related problems, such as low adherence to drug therapy and concerns about treatment, were identified. Different statistical approaches to present results from ordinal data on adherence and beliefs about medicines were suggested. Approximately half of the patients were affected by errors in the medication history at admission to hospital; patients who had many prescription drugs had a higher risk for errors. Medication reconciliation and review reduced the number of inappropriate medications and reduced drug-related hospital revisits. No impact on all-cause hospital revisits was demonstrated. Conclusion: Patients admitted to hospital are at high risk for being affected by medication history errors and there is a high potential to improve their drug therapy. By reducing medication history errors and improving medication appropriateness, clinical pharmacy services within a multiprofessional healthcare team improve the quality and safety of patients’ drug therapy. The impact of routine implementation of medication reconciliation and review on healthcare visits will need further evaluation; the results from this thesis suggest that drug-related hospital revisits could be reduced. / Läkemedelsgenomgångar och läkemedelsavstämning - LIMM-modellen