Development and validation of a Medication Adherence Universal Questionnaire: the MAUQ.

BACKGROUND: Different questionnaires assess self-reported medication adherence and others quantify aspects of patients attitudes towards medication, but not together in a single instrument. Gathering these two aspects in a single instrument could reduce patients survey burden. AIM: The aim of this study was to develop the Medication Adherence Universal Questionnaire (MAUQ) using the Maastricht Utrecht Adherence in Hypertension short version (MUAH-16) factorial structure as the hypothesized model. METHOD: A multistep process started with the modification of the MUAH-16 to obtain the MAUQ. Patients using at least one antihypertensive medicine were recruited. The two questionnaires, the MUAH-16 and MAUQ, were applied. A confirmatory factor analysis (CFA) was performed using the initial MUAH-16 s-order 4-factor model. An additional bifactor model with four uncorrelated factors and an overall score was tested. The comparative fit index (CFI), root mean square error of approximation (RMSEA) with confidence intervals (CIs), and standardized root mean squared residual (SRMR) were used to assess both models. RESULTS: A sample of 300 hypertensive patients completed the instruments. The CFA with the second-order 4-factor solution resulted in similar results for the MUAH-16 and MAUQ: CFIs of 0.934 and 0.930, RMSEAs of 0.043 [CI 0.030-0.056] and 0.045 [CI 0.031-0.057] and SRMRs of 0.060 and 0.061, respectively. The CFA with the bifactor model showed slightly better results for both the MUAH-16 and MAUQ: CFIs of 0.974 and 0.976, RMSEAs of 0.030 [CI 0.005-0.046] and 0.028 [CI 0.001-0.044], and SRMRs of 0.043 and 0.044, respectively. CONCLUSION: CFA demonstrated that the MAUQ presented a better fit to both models than the MUAH-16, obtaining a robust universal free instrument to assess medicine-taking behaviour and four medicine beliefs components.

[Correction to the article "Medication Reconciliation During Admission to an Internal Medicine Department: A Pilot Study", Published as Ahead of Print on Acta Med Port 2022.] / Errata ao artigo "Reconciliação Terapêutica na Admissão de um Serviço de Medicina Interna: Estudo-Piloto", Publicado em Ahead of Print em Acta Med Port 2022.

Na página 9, Figura 2 onde se lê:73,53%Deverá ler-se:76,48%Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/16892.

Evaluation of a sample of Portuguese hypertensive patients' knowledge about hypertension and its influence on their beliefs and adherence to therapy.

INTRODUCTION AND OBJECTIVES: Patient knowledge about hypertension is an important patient-related determinant for poor blood pressure control and is a target for more effective interventions. We aimed to evaluate hypertensive patients' knowledge and awareness about hypertension and its influence on their beliefs about their medication and their adherence to antihypertensive therapy. METHODS: A cross-sectional study was conducted among adult patients attending one of the participating pharmacies and taking at least one antihypertensive drug. Data on personal and family history were collected, and Portuguese versions of the Hypertension Knowledge Test (HKT), Beliefs about Medicines Questionnaire (BMQ), and short version of the Maastricht Utrecht Adherence in Hypertension questionnaire (MUAH-16) were administered. RESULTS: A total of 240 patients were enrolled. The mean number of antihypertensive drugs used was 1.62±0.99, with 15.4% of patients treated with three or more drugs. More than 80% of patients knew the blood pressure therapeutic goals and identified overweight, sedentary lifestyle, and salt as risk factors for hypertension. Conversely, the majority of the patients were not aware of the asymptomatic characteristics of hypertension and believed that antihypertensive treatment had to be used for a limited time duration. Negative and significant correlations were found between the HKT and negative attitudes toward medication, but no association was found with positive attitudes. CONCLUSIONS: Hypertensive patients had good knowledge of hypertension risk factors but not of antihypertensive treatment. Increasing patient knowledge about hypertension may possibly reduce negative attitudes toward medication but will probably have no impact on positive attitudes.

[Medication Reconciliation During Admission to an Internal Medicine Department: A Pilot Study]. / Reconciliação Terapêutica na Admissão de um Serviço de Medicina Interna: Estudo-Piloto.

INTRODUCTION: The purpose of medication reconciliation is to promote patient safety by reducing medication errors and adverse events due to medication discrepancies in transition of care. The aim of this pilot study of medication reconciliation at the time of hospital admission was to identify the necessary resources for its implementation in clinical practice. MATERIAL AND METHODS: Pilot study with 100 patients admitted to an Internal Medicine department between October and December 2019, aged 18 and over, and chronically taking at least one medicine. The best possible medication history was obtained systematically, with subsequent identification, classification and resolution of the discrepancies. RESULTS: The study sample, in general characterized by polypharmacy and by having multiple long-term conditions, presented a mean age of 77.04 ± 13.74 years, being 67.0% male. Overall, 791 discrepancies were identified. Intentional discrepancies were 95.7% and 50.9% of them were documented. The difficulties encountered were mainly related with the access and quality of therapeutic information and communication problems between different healthcare professionals. The key priority resources that were identified were related with the process, tools, and personnel categories. CONCLUSION: The data revealed weaknesses in the clinical records available at the primary/hospital care interface. Optimization of data sources, standardization and informatization of the process, multidisciplinary approach and definition of priority groups were identified as opportunities for optimization.

Introdução: A reconciliação terapêutica visa promover a segurança do doente por meio da redução de erros de medicação e eventos adversos decorrentes de discrepâncias de medicação na transição de cuidados. Foi nosso objetivo realizar um estudo-piloto de reconciliação terapêutica no momento da admissão hospitalar para, a partir dele, identificarmos os recursos necessários para a sua implementação na prática clínica.Material e Métodos: Estudo-piloto com 100 doentes admitidos num serviço de Medicina Interna entre outubro e dezembro de 2019, com mais de 18 anos e a tomar cronicamente pelo menos um medicamento. A melhor história farmacoterapêutica possível foi obtida sistematicamente, com posterior identificação, classificação e resolução das discrepâncias.Resultados: A amostra em estudo, em geral polimedicada e com múltiplas morbilidades, apresentou uma média de idades de 77,04 ± 13,74 anos, sendo 67,0% do sexo masculino. Foram identificadas 791 discrepâncias e as intencionais (95,7%) estavam documentadas em 50,9% das situações. As dificuldades encontradas relacionaram-se principalmente com o acesso e a qualidade da informação terapêutica e com a dificuldade de comunicação entre os diversos profissionais de saúde. Os principais recursos prioritários identificados relacionaram-se com as categorias de processo, ferramentas e pessoal.Conclusão: Os dados revelaram fragilidades nos registos clínicos disponíveis na interface dos cuidados primários/hospitalares. A otimização das fontes de dados, normalização e informatização do processo, atuação multidisciplinar e definição de grupos prioritários foram identificadas como oportunidades de otimização.

Feasibility of cardiovascular risk screening in Portuguese community pharmacies.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of human mortality. As highly accessible and qualified health professionals, community pharmacists can be included in the early detection of patients at risk for CVD by implementing CVD screening programs. OBJECTIVE: To assess the feasibility of CVD risk screening services in Portuguese community pharmacies from the evaluation of customers acceptability. METHODS: A cross-sectional study was conducted in a community pharmacy in Portugal. The purpose of entering the pharmacy was recorded for all customers. Afterwards, the customers were invited to be interviewed by the pharmacist, who registered their willingness to participate and collected the participants' data and biochemical and physical parameters to assess their CV risk by applying the Systematic COronary Risk Evaluation (SCORE) model. For the participants who were not eligible for the SCORE-based risk assessment, the pharmacist considered the major modifiable CVD risk factors - hypertension, dyslipidemia, smoking habits, obesity, impaired fasting glucose and sedentary behavior - according to the ESC guidelines. RESULTS: Picking up medication was the most prevalent reason 69.8% (n=1,600) for entering the pharmacy, and among the contacted customers, 56.4% (n=621) agreed to have their CVD risk assessed. Of the 588 participants, 56.6% (n=333) were already on CV pharmacotherapy and were therefore not eligible for screening. Of the 43.4% (n=255) CV pharmacotherapy-naïve participants, 94.9% (n=242) were screened with at least one CVD risk factor; 52.9% (n=135) were not eligible for the SCORE assessment, of which 92.6% (n=125) presented CVD risk factors. Of the 120 SCORE eligible participants, 80.0% (n=96) were at least at moderate risk of CVD. CONCLUSIONS: We determined the feasibility of CVD risk screening in Portuguese community pharmacies, as we found high customer acceptability, noted the reasons for nonattendance, and found a high prevalence of CVD risk factors in at-risk patients. This is an opportunity for Portuguese community pharmacists to take a leading role in the early detection of CVD.

Feasibility of cardiovascular risk screening in Portuguese community pharmacies

Background: Cardiovascular disease (CVD) remains the leading cause of human mortality. As highly accessible and qualified health professionals, community pharmacists can be included in the early detection of patients at risk for CVD by implementing CVD screening programs. Objective: To assess the feasibility of CVD risk screening services in Portuguese community pharmacies from the evaluation of customers acceptability. Methods: A cross-sectional study was conducted in a community pharmacy in Portugal. The purpose of entering the pharmacy was recorded for all customers. Afterwards, the customers were invited to be interviewed by the pharmacist, who registered their willingness to participate and collected the participants’ data and biochemical and physical parameters to assess their CV risk by applying the Systematic COronary Risk Evaluation (SCORE) model. For the participants who were not eligible for the SCORE-based risk assessment, the pharmacist considered the major modifiable CVD risk factors - hypertension, dyslipidemia, smoking habits, obesity, impaired fasting glucose and sedentary behavior - according to the ESC guidelines Results: Picking up medication was the most prevalent reason 69.8% (n=1,600) for entering the pharmacy, and among the contacted customers, 56.4% (n=621) agreed to have their CVD risk assessed. Of the 588 participants, 56.6% (n=333) were already on CV pharmacotherapy and were therefore not eligible for screening. Of the 43.4% (n=255) CV pharmacotherapy-naïve participants, 94.9% (n=242) were screened with at least one CVD risk factor; 52.9% (n=135) were not eligible for the SCORE assessment, of which 92.6% (n=125) presented CVD risk factors. Of the 120 SCORE eligible participants, 80.0% (n=96) were at least at moderate risk of CVD (AU)

Implications of a defined daily dose fixed database for drug utilization research studies: The case of statins in Portugal.

AIMS: Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. METHODS: The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDDYEAR ) and by the DDD last-year approach (DDDLAST ). PDDs were calculated according to the year-by-year approach (PDDYEAR ). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDDYEAR and DDDYEAR units. RESULTS: The DDDYEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDDLAST and PDDYEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDDYEAR /1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009. CONCLUSIONS: A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies.

Contribution of Different Patient Information Sources to Create the Best Possible Medication History.

INTRODUCTION: Obtaining the best possible medication history is the crucial step in medication reconciliation. Our aim was to evaluate the potential contributions of the main data sources available - patient/caregiver, hospital medical records, and shared electronic health records - to obtain an accurate 'best possible medication history'. MATERIAL AND METHODS: An observational cross-sectional study was conducted. Adult patients taking at least one medicine were included. Patient interview was performed upon admission and this information was reconciled with hospital medical records and shared electronic health records, assessed retrospectively. Concordance between sources was assessed. In the shared electronic health records, information was collected for four time-periods: the preceding three, six, nine and 12-months. The proportion of omitted data between time-periods was analysed. RESULTS: A total of 148 patients were admitted, with a mean age of 54.6 ± 16.3 years. A total of 1639 medicines were retrieved. Only 29% were collected simultaneously in the three sources of information, 40% were only obtained in shared electronic health records and only 5% were obtained exclusively from patients. The total number of medicines gathered in shared electronic health records considering the different time frames were 778 (three-months), 1397 (six-months), 1748 (nine-months), and 1933 (12-months). DISCUSSION: The use of shared electronic health records provides data that were omitted in the other data sources available and retrieving the information at six months is the most efficient procedure to establish the basis of the best possible medication history. CONCLUSION: Shared electronic health records should be the preferred source of information to supplement the patient or caregiver interview in order to increase the accuracy of best possible medication history of the patient, particularly if collected within the prior six months.

Introdução: A obtenção da melhor história farmacoterapêutica possível é uma etapa crucial da reconciliação da medicação. O objetivo foi avaliar as potenciais contribuições das principais fontes de informação disponíveis ­ doente/cuidador, Processo Único, Plataforma de Dados da Saúde e ­ para obter uma mais exacta melhor história farmacoterapêutica possível. Material e Métodos: Foi realizado um estudo transversal observacional. Incluíram-se doentes adultos a tomar pelo menos um medicamento. A entrevista com o doente foi realizada na admissão e os dados do Processo Único e da Plataforma de Dados da Saúde recolhidos retrospetivamente. A concordância entre as fontes de informação foi avaliada. Na plataforma de dados da saúde, os dados foram recolhidos em quatro janelas temporais: os últimos três, seis, nove e 12- meses. Os dados omitidos entre os diferentes tempos foram analisados. Resultados: Participaram 148 doentes, com uma idade média de 54,6 ± 16,3 anos. Foram recolhidos 1639 medicamentos. Destes, 29% foram obtidos simultaneamente nas três fontes de informação, 40% foram obtidos apenas na Plataforma de Dados da Saúde e 5% foram obtidos exclusivamente a partir do doente. O número total de fármacos recolhidos na Plataforma de Dados da Saúde nos diferentes tempos foi 778 (três meses), 1397 (seis meses), 1748 (nove meses) e 1933 (12 meses). Discussão: A consulta da Plataforma de Dados da Saúde permite obter dados omitidos nas outras fontes de informação e a recolha dos seis meses precedentes é o procedimento mais eficiente para constituir a base da melhor história farmacoterapêutica possível. Conclusão: A Plataforma de Dados da Saúde deve ser a fonte de informação preferencial para complementar a entrevista do doente/cuidador de forma a aumentar a exatidão da melhor história farmacoterapêutica possível, particularmente se a informação for recolhida em relação aos seis meses precedentes.

Cross-cultural adaptation and validation of a European Portuguese version of the 8-item Morisky medication adherence scale.

INTRODUCTION AND OBJECTIVE: The 8-Item Morisky Medication Adherence Scale (MMAS-8) is one of the most widely used instruments to assess medication adherence, but a validated European Portuguese version of MMAS-8 does not exist. Our aim was to develop and validate a European Portuguese version of the MMAS-8. METHODS: A process of translation and back-translation of the original MMAS-8 was performed. The questionnaire was administered in nine community pharmacies and one public hospital between March 2014 and September 2015. Adult patients taking at least one antihypertensive drug were invited to participate. A confirmatory factor analysis was performed and internal consistency, convergent validity and concurrent validity were examined. RESULTS: A total of 472 patients were enrolled in the study. The mean MMAS-8 score obtained was 6.74±1.39. One hundred and thirty-two patients were classified as low adherers (28%), 181 (38.3%) as medium adherers and 159 (33.7%) as high adherers. For the factorial structure of the Portuguese version of the MMAS-8, the fit indices of the final model (chi-square [18] 48.465, p<0.001) are suggestive of very good fit, with comparative fit index 0.95, root mean square error of approximation 0.06 (90% confidence interval 0.04-0.08), and standardized root mean square residual 0.04, confirming that the construct tested was unidimensional. The Cronbach's alpha for all items was 0.60, and the translated version presents convergent validity and concurrent validity. CONCLUSION: A European Portuguese version of the MMAS-8 was created that maintained a similar structure to the original MMAS-8 and good psychometric properties.

A case study of polypharmacy management in nine European countries: Implications for change management and implementation.

BACKGROUND: Multimorbidity and its associated polypharmacy contribute to an increase in adverse drug events, hospitalizations, and healthcare spending. This study aimed to address: what exists regarding polypharmacy management in the European Union (EU); why programs were, or were not, developed; and, how identified initiatives were developed, implemented, and sustained. METHODS: Change management principles (Kotter) and normalization process theory (NPT) informed data collection and analysis. Nine case studies were conducted in eight EU countries: Germany (Lower Saxony), Greece, Italy (Campania), Poland, Portugal, Spain (Catalonia), Sweden (Uppsala), and the United Kingdom (Northern Ireland and Scotland). The workflow included a review of country/region specific polypharmacy policies, key informant interviews with stakeholders involved in policy development and implementation and, focus groups of clinicians and managers. Data were analyzed using thematic analysis of individual cases and framework analysis across cases. RESULTS: Polypharmacy initiatives were identified in five regions (Catalonia, Lower Saxony, Northern Ireland, Scotland, and Uppsala) and included all care settings. There was agreement, even in cases without initiatives, that polypharmacy is a significant issue to address. Common themes regarding the development and implementation of polypharmacy management initiatives were: locally adapted solutions, organizational culture supporting innovation and teamwork, adequate workforce training, multidisciplinary teams, changes in workflow, redefinition of roles and responsibilities of professionals, policies and legislation supporting the initiative, and data management and information and communication systems to assist development and implementation. Depending on the setting, these were considered either facilitators or barriers to implementation. CONCLUSION: Within the studied EU countries, polypharmacy management was not widely addressed. These results highlight the importance of change management and theory-based implementation strategies, and provide examples of polypharmacy management initiatives that can assist managers and policymakers in developing new programs or scaling up existing ones, particularly in places currently lacking such initiatives.

Developing an adherence in hypertension questionnaire short version: MUAH-16.

The Maastricht Utrecht Adherence in Hypertension (MUAH) questionnaire provides clinicians with information about the causes of a patient's poor adherence to antihypertensive drugs. In this study, the authors aimed to develop and validate a short version of the MUAH questionnaire. After an exploratory factor analysis, the number of MUAH items was reduced. The original MUAH questionnaire (model 1) was compared with the 16-item MUAH short version (model 2). Next, this short version of MUAH (MUAH-16) with all factors correlated (model 2a) was compared with the short version of MUAH with four subscales that contribute to a global factor of adherence (model 2b). Model 1 had a poor fit to the data (χ2 269 = 663.41, P < .001, comparative fit index = 0.695, root mean square error of approximation = 0.06), and model 2 had a very good fit to the data (χ2 100 = 171.07, P < .001, comparative fit index = 0.92, root mean square error of approximation = 0.04). When comparing model 2a with model 2b, the chi-square difference of the model (Δχ2 2 = 4.06; P = .067) revealed that the fits of both models were not significantly different. These findings suggest that MUAH-16 better represents a patient's adherence to antihypertensive medication than the original MUAH questionnaire.

Influence of the mode of administration on the results of medication adherence questionnaires.

INTRODUCTION AND OBJECTIVES: Adherence to medication regimen is commonly assessed through questionnaires, some of which are validated via self-administration. The inadequate health literacy of elderly people pushes researchers to the use of interviews as a method of administration. The aims of this study were to compare the results obtained with an interviewer-administered and a self-administered medication adherence questionnaire and to evaluate the consequences of the adherence status classification of individuals. METHODS: A cross-sectional study was performed in which the Medida de Adesão aos Tratamentos adherence questionnaire was administered to adult patients who were taking at least 1 antihypertensive drug. The data were collected in 7 community pharmacies in central Portugal between March 2014 and September 2015 in 2 different phases: in the first phase, the questionnaire was applied during a healthcare professional interview, and the second phase involved a self-report administration. A confirmatory factor analysis was conducted, and the measurement and structural invariances across the application methods were examined. RESULTS: A sample of 425 patients with a mean age of 68.21 ± 10.56 years participated in the study. The confirmatory factor analysis revealed that both the interview and self-report had a good fit with the original model, although the self-report results exhibited a better fit. In the interview administration, we obtained lower values for skewness and higher levels of kurtosis. The patients subjected to the interview administration presented with a 9.7% higher tendency to answer "never" when compared with the self-administered application, which overestimated adherence. CONCLUSIONS: The interview administration method induced bias that led to a higher percentage of "never" answers and a subsequent overestimation of adherence levels. Self-report administration should be preferred in the application of medication adherence questionnaires.

Cross-cultural adaptation of Hypertension Knowledge Test into European Portuguese

ABSTRACT We aim to validate a European-Portuguese version of the Hypertension Knowledge Test (HKT) questionnaire and examine its factorial structure with a confirmatory factor analysis (CFA). A process of translation and back-translation was performed. A cross-sectional study was developed in which all adult patients taking at least one antihypertensive drug were invited to participate. Data on personal and family history were collected, and the HKT, Strelec, and the Batalla questionnaires were administered. We enrolled 304 patients with a mean age of 68.12±10.83 years. The mean score of HKT was 15.33±2.79. CFA indicated that the construct being tested was unidimensional, and Cronbach's alpha (α=0.65) showed that the instrument had an acceptable internal consistency. When evaluating concurrent validity, HKT was significantly correlated with the Batalla and Strelec scores. Thus, the Portuguese version of HKT (HKT-pt-PT) can be used either in research or in clinical practice. With this version, a potential standard exists to evaluate knowledge about hypertension, which could avoid the practice of using non-validated questionnaires in Portugal and allow the cross-sectional and longitudinal comparability of studies.

Interação planta-medicamento: a especificidade da terapêutica cardiovascular / Plant-drug interaction: the specificity of cardiovascular therapy

O presente estudo teve como objetivos caracterizar a situação real do consumo de Plantas Medicinais (PM) numa amostra de pacientes com patologia cardiovascular e identificar potenciais interações entre as PM e a terapêutica farmacológica cardiovascular convencional.O estudo foi realizado numa Farmácia Comunitária em Portugal entre abril e junho de 2014. Dos 128 utentes abordados ao balcão que fazem uso da terapêutica cardiovascular, 65 (51%) faziam uso de PM, seja sob a forma de infusão, suplementos ou medicamentos à base de PM. Desses, 43 (66%) foram entrevistados, tendo 22 (34%) sido excluídos por não terem manifestado interesse em participar no estudo. Através da revisão da medicação efetuada para cada doente foram encontradas um total de 123 interações planta-medicamento, com uma média de 2,9 interações/doente, com potencial para diminuir o sucesso da terapêutica cardiovascular. O presente estudo demonstra como o serviço farmacêutico da revisão da medicação pode ser utilizado para otimizar a terapêutica dos doentes cardiovasculares quando estes tomam medicamentos e PM em simultâneo, o que evidencia a função do farmacêutico na sensibilização da população, no sentido de evitar situações prejudiciais para a saúde e bem estar do doente.

Assessing the impact of multi-compartment compliance aids on clinical outcomes in the elderly: a pilot study.

BACKGROUND: Medication non-adherence is a major problem for elderly people. Multicompartment compliance aids (MCAs) have been advocated as a solution for this problem. OBJECTIVE: To assess the impact of using MCAs in self-reported adherence and clinical biomarkers of elderly patients followed in a community pharmacy. SETTING: One community pharmacy at Sabugal (Portugal). METHODS: A four-month prospective, non-randomised, controlled study was performed. Autonomous patients aged 65 or more using 3 or more medicines and under follow-up in the pharmacy were invited to participate. All patients were offered to receive their medication in MCAs prepared in the pharmacy. Patients refusing the MCA were used as control. The intervention consisted of providing 4 weekly MCAs during the monthly visit. All patients received regular pharmacy counselling. Blood pressure (BP), lipid profile and glycaemia were assessed at baseline and monthly for all the patients. Morisky self-reported scale was applied at baseline and at the end of the study. Bivariate analysis and generalized estimation equations (GEE) were used. MAIN OUTCOME MEASURE: Self-reported medication adherence, clinical biomarkers: BP, lipid profile, glycaemia. RESULTS: 54 patients between 65 and 90 years were under follow-up. 44 patients accepted the MCA, constituting the intervention group. No difference in the baseline biomarkers between both groups was found. The bivariate pre-post analysis yielded significant improvements in the intervention groups, but not in the control, for glycaemia (p < 0.001), HDL-c (p = 0.018), and systolic (p < 0.001) and diastolic (p = 0.012) BP. However, when introducing the 'time in follow-up' in the GEE model, all the differences became non-significant, except systolic BP, but the time remained significant for all the biomarkers. CONCLUSION: MCAs apparently improve several clinical biomarkers in a cohort of patients under pharmacist's follow-up. When including the time in pharmacist's followup in a GEE, the effect of the MCA disappeared, remaining only the time as a significant variable. Not considering the time in follow-up may be overestimating the effect of MCAs.

Disposition of eslicarbazepine acetate in the mouse after oral administration.

Eslicarbazepine acetate is a promising antiepileptic drug structurally related to carbamazepine and oxcarbazepine, which is in the final phase of clinical development. The metabolism of eslicarbazepine acetate is clearly species dependent and, in this case, among small laboratory animals, the mouse seems to be the most relevant species to humans. Hence, the aim of this study was to investigate the plasma, brain and liver disposition of eslicarbazepine acetate in mice to better understand its disposition in humans. Adult male CD-1 mice were treated orally with a single dose of eslicarbazepine acetate 350 mg/kg. Blood samples, brain and liver tissues were taken at 0.25, 0.5, 0.75, 1, 2, 4, 6, 10, 16 and 24 h post-dose. Plasma and tissue levels of eslicarbazepine acetate and its metabolites (S-licarbazepine, R-licarbazepine and oxcarbazepine) were assessed by using high-performance liquid chromatography-ultraviolet detection. Both eslicarbazepine acetate and R-licarbazepine concentrations were below the limit of quantification of the assay in all matrices. Eslicarbazepine acetate was rapidly and extensively metabolized to S-licarbazepine (major metabolite), which was oxidized to oxcarbazepine to a small extent. The brain/plasma ratios suggest that the brain exposure to S-licarbazepine and oxcarbazepine was approximately 30% of their total systemic exposure. However, S-licarbazepine crossed the blood-brain barrier (BBB) less efficiently than oxcarbazepine. On the other hand, the liver/plasma ratios support the notion that S-licarbazepine undergoes hepatic accumulation, whereas oxcarbazepine appears to leave this compartment twice as fast as S-licarbazepine. Thus, the diffusion through the BBB is favourable to oxcarbazepine and the liver acts like a deposit of the pharmacologically active metabolite of eslicarbazepine acetate (S-licarbazepine).

Stereoselective disposition of S- and R-licarbazepine in mice.

The stereoselective disposition of S-licarbazepine (S-Lic) and R-licarbazepine (R-Lic) was investigated in plasma, brain, liver, and kidney tissues after their individual administration (350 mg/kg) to mice by oral gavage. Plasma, brain, liver, and kidney concentrations of licarbazepine enantiomers and their metabolites were determined over the time by a validated chiral HPLC-UV method. The mean concentration data, attained at each time point, were analyzed using a non-compartmental model. S-Lic and R-Lic were rapidly absorbed from gastrointestinal tract of mouse and immediately distributed to tissues supplied with high blood flow rates. Both licarbazepine enantiomers were metabolized to a small extent, each parent compound being mainly responsible for the systemic and tissue drug exposure. The stereoselectivity in the metabolism and distribution of S- and R-Lic was easily identified. An additional metabolite was detected following R-Lic administration and S-Lic showed a particular predisposition for hepatic and renal accumulation. Stereoselective processes were also identified at the blood-brain barrier, with the brain exposure to S-Lic almost twice that of R-Lic. Another finding, reported here for the first time, was the ability of the mouse to perform the chiral inversion of S- and R-Lic, albeit to a small extent.

Simultaneous and enantioselective liquid chromatographic determination of eslicarbazepine acetate, S-licarbazepine, R-licarbazepine and oxcarbazepine in mouse tissue samples using ultraviolet detection.

Herein is reported, for the first time, a simple and reliable chiral reversed-phase liquid chromatographic method coupled to ultraviolet (UV) detection for simultaneous determination of eslicarbazepine acetate (ESL) and its metabolites, S-licarbazepine (S-LC), R-licarbazepine (R-LC) and oxcarbazepine (OXC), in mouse plasma and brain, liver and kidney tissue homogenates. All analytes and the internal standard were extracted from plasma and tissue homogenates by a solid-phase extraction procedure using Waters Oasis hydrophilic-lipophilic balance cartridges. The chromatographic separation was performed by isocratic elution with water/methanol (88:12, v/v), pumped at a flow rate of 0.7 mL min(-1), on a LichroCART 250-4 ChiraDex (beta-cyclodextrin, 5 microm) column at 30 degrees C. The UV detector was set at 225 nm. Calibration curves were linear (r2 > or = 0.996) in the ranges 0.4-8 microg mL(-1), 0.1-1.5 microg mL(-1) and 0.1-2 microg mL(-1) for ESL and OXC and in the ranges 0.4-80 microg mL(-1), 0.1-15 microg mL(-1) and 0.1-20 microg mL(-1) for R-LC and S-LC in plasma, brain and liver/kidney homogenates, respectively. The overall precision not exceeded 11.6% (%CV) and the accuracy ranged from -3.79 to 3.84% (%bias), considering all analytes in all matrices. Hence, this method will be a useful tool to characterize the pharmacokinetic disposition of ESL in mice.

Enantioselective HPLC-UV method for determination of eslicarbazepine acetate (BIA 2-093) and its metabolites in human plasma.

Eslicarbazepine acetate (BIA 2-093) is a novel central nervous system drug undergoing clinical phase III trials for epilepsy and phase II trials for bipolar disorder. A simple and reliable chiral reversed-phase HPLC-UV method was developed and validated for the simultaneous determination of eslicarbazepine acetate, oxcarbazepine, S-licarbazepine and R-licarbazepine in human plasma. The analytes and internal standard were extracted from plasma by a solid-phase extraction using Waters Oasis HLB cartridges. Chromatographic separation was achieved by isocratic elution with water-methanol (88:12, v/v), at a flow rate of 0.7 mL/min, on a LichroCART 250-4 ChiraDex (beta-cyclodextrin, 5 microm) column at 30 degrees C. All compounds were detected at 225 nm. Calibration curves were linear over the range 0.4-8 microg/mL for eslicarbazepine acetate and oxcarbazepine, and 0.4-80 microg/mL for each licarbazepine enantiomer. The overall intra- and interday precision and accuracy did not exceed 15%. Mean relative recoveries varied from 94.00 to 102.23% and the limit of quantification of the assay was 0.4 microg/mL for all compounds. This method seems to be a useful tool for clinical research and therapeutic drug monitoring of eslicarbazepine acetate and its metabolites S-licarbazepine, R-licarbazepine and oxcarbazepine.