Impact of a pharmaceutical care programme for patients with chronic disease initiated at the emergency department on drug-related negative outcomes: a randomised controlled trial.

BACKGROUND: The resolution of potential drug-related problems is a priority of pharmaceutical care programmes. OBJECTIVES: To assess the clinical impact on drug-related negative outcomes of a pharmaceutical care programme focusing on the resolution of potential drug-related problems, initiated in the emergency department for patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD). METHODS: Controlled trials, in which older adults (≥65 years) receiving four or more medications admitted to the emergency department for ≥12 hours for worsening of HF and/or COPD were randomised (1:1) to either a pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department (intervention group (IG)) or standard care (control group). Comparisons between the groups were made for the proportion of patients with drug-related negative outcomes, number of drug-related negative outcomes per patient, mean stay, patients readmitted within 180 days and 180-day mortality. RESULTS: 118 patients were included, 59 in each group. Fewer patients in the IG had drug-related negative outcomes (37 (62.7%) vs 47 (79.7%) in the control group (p=0.042)). Fewer drug-related negative outcomes per patient occurred in the IG (56 (0.95 per patient) vs 85 (1.44 per patient) in the control group (p=0.01)). The mean stay was similar between groups (194.7 hours in the IG vs 242.5 hours in the control group (p=0.186)). No difference in revisits within 180 days was found (32 (54.24%) in the IG vs 22 (37.3%) in the control group (p=0.065)). 180-Day mortality was detected in 11 (18.6%) patients in the IG compared with 13 (22%) in the control group (p=0.647). CONCLUSION: A pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department has a favourable clinical impact, as it reduces the number and prevalence of drug-related negative outcomes. No difference was found in other outcome variables.Trial registration number NCT02368548.

Effectiveness of the Dader Method for Pharmaceutical Care on Patients with Bipolar I Disorder: Results from the EMDADER-TAB Study.

BACKGROUND: Bipolar I disorder (BD-I) is a chronic illness characterized by relapses alternating with periods of remission. Pharmacists can contribute to improved health outcomes in these patients through pharmaceutical care in association with a multidisciplinary health team; however, more evidence derived from randomized controlled trials (RCTs) is needed to demonstrate the effect of pharmaceutical care on patients with BD-I. OBJECTIVE: To assess the effectiveness of a pharmaceutical intervention using the Dader Method on patients with BD-I, measured by the decrease in the number of hospitalizations, emergency service consultations, and unscheduled outpatient visits from baseline through 1 year of follow-up. METHODS: This study is based on the EMDADER-TAB trial, which was an RCT designed to compare pharmaceutical care with the usual care given to outpatients with BD-I in a psychiatric clinic. The main outcome was the use of health care services, using Kaplan-Meier methods and Cox regression. The trial protocol was registered in ClinicalTrials.gov (Identifier NCT01750255). RESULTS: 92 patients were included in the EMDADER-TAB study: 43 pharmaceutical care patients (intervention group) and 49 usual care patients (control group). At baseline, no significant differences in demographic and clinical characteristics were found across the 2 groups. After 1 year of follow-up, the risk of hospitalizations and emergencies was higher for the control group than for the intervention group (HR = 9.03, P = 0.042; HR = 3.38, P = 0.034, respectively); however, the risk of unscheduled outpatient visits was higher for the intervention group (HR = 4.18, P = 0.028). There was no "placebo" treatment, and patients in the control group might have produced positive outcomes and reduced the magnitude of differences compared with the intervention group. CONCLUSIONS: Compared with usual care, pharmaceutical care significantly reduced hospitalizations and emergency service consultations by outpatients with BD-I. DISCLOSURES: This study received funding from the Universidad de Antioquia, Committee for Development Research and Sustainability Program, CODI, (2013-2014 and 2014-2015). Humax Pharmaceutical provided support for the initial development of the EMDADER-TAB trial without commercial interest in the outcomes derived from the trial. Salazar-Ospina reports grants from Credito Beca Francisco José de Caldas Scholarship for Doctoral Programs (528), which also contributed to the support of this study. González-Avendaño is an employee of Humax Pharmaceutical. The other authors have nothing to disclose. Study concept and design were contributed by Benjumea, Faus, and Rodriguez, along with Salazar-Ospina and Amariles. Salazar-Ospina took the lead in data collection, assisted by González-Avendaño, and data interpretation was performed by Salazar-Ospina, Hincapié-García, and González-Avendaño. The manuscript was written primarily by Salazar-Ospina, with assistance from Amariles and González-Avendaño, and revised by all the authors.

Relevancia clínica de las interacciones medicamentosas en pacientes infectados con el virus de la inmunodeficiencia humana: actualización 2009-2014 / The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2009-2014

Objective: To update information about drug interactions in patients with HIV/AIDS. Methods: Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. Results: Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. Conclusions: The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

Objetivo: Actualizar información sobre interacciones medicamentosas en pacientes con VIH/SIDA. Métodos: Revisión estructurada en MEDLINE/PubMed utilizando los términos Mesh: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions, entre mayo de 2009 y diciembre de 2014. Publicaciones sobre interacciones medicamentosas, en humanos, en inglés o español y con acceso a texto completo fueron seleccionadas. Además, se incluyeron referencias de artículos considerados relevantes. La inclusión de los artículos fue evaluada por tres investigadores independientes y, en caso de requerirlo, por consenso entre ellos. La relevancia clínica se estableció en cuatro niveles, acorde con la gravedad y probabilidad de ocurrencia de la interacción. Resultados: Se identificaron 546 artículos, de los cuales se seleccionaron 273; además, se incluyeron 11 referencias relevantes. Se identificaron 935 parejas de interacciones medicamentosas, 95,7% farmacocinéticas. De este grupo, 823 mediadas por inducción o inhibición enzimática y 67 por cambios en la biodisponibilidad. De las 935 parejas de interacciones, 402 (43%) fueron relevantes clínicamente (niveles 1 o 2). Conclusiones: Las interacciones medicamentosas con anti-retrovirales de mayor relevancia clínica se deben a mecanismos farmacocinéticos, principalmente inducción o inhibición enzimática. Acorde con revisiones previas, los inhibidores de proteasa continúan siendo los anti-retrovirales con mayor número de interacciones relevantes.

[Reliability and external validity of a questionnaire to assess the knowledge about risk and cardiovascular disease and in patients attending Spanish community pharmacies]. / Fiabilidad y validez externa de un cuestionario de conocimiento sobre riesgo y enfermedad cardiovascular en pacientes que acuden a farmacias comunitarias de España.

OBJECTIVES: To determine the test-retest reliability of a questionnaire, with a validation preliminary, to assess knowledge of cardiovascular risk (CVR) and cardiovascular disease in patients attending community pharmacies in Spain. To complement the external validity, establishing the relationship between an educational activity and the increase in knowledge about CVR and cardiovascular disease. DESIGN: Sub-analysis of a controlled clinical study, EMDADER-CV, in which a questionnaire about knowledge concerning CVR was applied at 4 different times. LOCATION: Spanish Community Pharmacies. PARTICIPANTS: There were 323 patients in the control group, from the 640 who completed the study. MAIN MEASUREMENTS: Intraclass correlation coefficient to assess the reliability in 3 comparisons (post-educational activity with week 16, post-educational activity with week 32, and week 16 with week 32); and the non-parametric Friedman test to establish the relationship between an oral and written educational activity with increasing knowledge. RESULTS: For the 323 patients in the 3 comparisons, the intraclass correlation coefficient values were 0.624; 0.608 and 0.801, respectively (fair-good to excellent reliability). So, the Friedman test showed a statistically significant relationship between educational activity and increased knowledge (p < .0001). CONCLUSIONS: According to the intraclass correlation coefficient, the questionnaire aimed at assessing the knowledge on CVR and cardiovascular disease has a reliability between acceptable and excellent, which added to the previous validation, shows that the instrument meets the criteria of validity and reliability. Furthermore, the questionnaire showed the ability to relate an increase in knowledge with an educational intervention, feature that complements its external validity.

[The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2009-2014]. / Relevancia clínica de las interacciones medicamentosas en pacientes infectados con el virus de la inmunodeficiencia humana: actualización 2009-2014.

OBJECTIVE: To update information about drug interactions in patients with HIV/AIDS. METHODS: Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. RESULTS: Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. CONCLUSIONS: The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.

BACKGROUND: Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. OBJECTIVE: The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. METHODS: We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. MAIN OUTCOME MEASURES: Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. RESULTS: A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. CONCLUSION: Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.

Effect of a pharmacist intervention on asthma control. A cluster randomised trial.

INTRODUCTION: Achievement and maintenance of good asthma control is a major objective in asthma management. However, asthma control in many patients is suboptimal, due to improper use of asthma medications and non-adherence. The aim of this study was to evaluate the effect of a pharmacist intervention on asthma control in adult patients. METHODS: A 6-month cluster randomized controlled trial was undertaken with allocation of community pharmacies to intervention or control group. Adult asthma patients in the intervention group received a protocol-based intervention addressing individual needs related to asthma control, inhaler technique and medication adherence. Patients in the control group received usual care. Main variables were measured at baseline, 3 and 6 months. RESULTS: 336 patients completed the study, 150 in the control group and 186 in the intervention group. The intervention resulted in enhanced asthma control: Patients receiving the intervention had an Odds ratio of 3.06 (95% CI:1.63-5.73; p < 0.001) of having controlled asthma six months later. In the intervention group mean ACQ scores significantly improved [0.66 points (SD: 0.78); p < 0.001] and the number of controlled asthma patients increased by 30.1% (p < 0.001) after 6 months. The intervention also resulted in improved medication adherence (by 40.3%, p < 0.001) and inhaler technique (by 56.2%, p < 0.001). No significant changes for any of these variables were observed in the control group. CONCLUSION: The AFasma study focused on the important outcomes of asthma management, and showed that through the designed intervention, community pharmacists can increase controlled asthma patients compared to usual care. Trial registration NCT01085474.

Impact of a community pharmacists' hypertension-care service on medication adherence. The AFenPA study.

BACKGROUND: One of the main factors associated with the inadequacy of blood pressure control is patients' non-adherence to antihypertensive drug therapy. OBJECTIVES: To determine the effect of an intervention program on antihypertensive medication adherence in the community pharmacy setting. METHODS: Treated hypertensive patients were enrolled in a 6-month controlled study involving thirteen Spanish community pharmacies. A pharmacist intervention program which consisted of specific education on issues related to medication adherence and hypertension was provided. Additionally, patients were provided with a home blood pressure monitoring device and instructed to measure their blood pressure. The control group received usual pharmacy care. Antihypertensive medication adherence was evaluated by pill counts at baseline and at the end of the study. RESULTS: Data from 176 patients were included in and analyzed in the study: 89 in the control group and 87 in the intervention group. The percentage of adherence for intervention group patients increased between baseline and the end of the study (86.0% vs. 96.5%), while it didn't change in the control group (86.5% vs. 85.4%). The proportion of patient adherence at the end of the study was higher in the intervention group compared to the control group (96.5% vs. 85.4%; P = .011). The odds of adherence to antihypertensive drug therapy in the intervention group was 4.07 (95% CI: 1.04-15.95; P = .044) times higher than the control group. CONCLUSIONS: In this sample of treated hypertensive patients, the pharmacist intervention was associated with significant improvement in antihypertensive medications adherence, compared to usual care.

The antioxidant effect of ß-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation.

Plant-based whole foods provide thousands of bioactive metabolites to the human diet that reduce the risk of developing chronic diseases. ß-Caryophyllene (CAR) is a common constituent of the essential oil of numerous plants, vegetables, fruits and medicinal herbs, and has been used as a flavouring agent since the 1930 s. Here, we report the antioxidant activity of CAR, its protective effect on liver fibrosis and its inhibitory capacity on hepatic stellate cell (HSC) activation. CAR was tested for the inhibition of lipid peroxidation and as a free radical scavenger. CAR had higher inhibitory capacity on lipid peroxidation than probucol, α-humulene and α-tocopherol. Also, CAR showed high scavenging activities against hydroxyl radical and superoxide anion. The activity of 5-lipoxygenase, an enzyme that actively participates in fibrogenesis, was significantly inhibited by CAR. Carbon tetrachloride-treated rats received CAR at 2, 20 and 200 mg/kg. CAR significantly improved liver structure, and reduced fibrosis and the expression of Col1a1, Tgfb1 and Timp1 genes. Oxidative stress was used to establish a model of HSC activation with overproduction of extracellular matrix proteins. CAR (1 and 10 µm) increased cell viability and significantly reduced the expression of fibrotic marker genes. CAR, a sesquiterpene present in numerous plants and foods, is as a natural antioxidant that reduces carbon tetrachloride-mediated liver fibrosis and inhibits hepatic cell activation.

Effect of a pharmacist intervention in Spanish community pharmacies on blood pressure control in hypertensive patients.

PURPOSE: The effect of a protocol-based pharmacist intervention on blood pressure (BP) control among treated hypertensive patients who use community pharmacies was studied. METHODS: A quasi-experimental study with a control group was conducted at 13 community pharmacies in Jaén and Granada in Spain. Hypertensive patients over age 18 years who were receiving antihypertensive treatment were eligible for participation. The protocol-based intervention consisted of three components: (1) patient education about hypertension, (2) home blood pressure monitoring (HBPM), and (3) referral to a physician through personalized reports when necessary. The control group received the standard of care. BP control was assessed at the beginning and end of the study. Results Data were collected from 176 patients. In the intervention group (n = 87), significant baseline-to-endpoint reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed: 6.8 mm Hg (p < 0.001) and 2.1 mm Hg (p = 0.032), respectively. The changes in SBP and DBP in the intervention group at the end of the study were significantly greater than those in the control group (difference between adjusted mean change, 5.7 mm Hg for SBP [p = 0.001] and 2.6 mm Hg for DBP [p = 0.013]). The odds of achieving BP control in the intervention group was 2.46 times higher than in the control group (95% confidence interval, 1.15-5.24; p = 0.020). CONCLUSION: A protocol-based community pharmacist intervention in combination with HBPM significantly reduced SBP and DBP and increased the percentage of patients with controlled BP compared with patients receiving the standard of care.

Terms used in patient safety related to medication: a literature review.

PURPOSE: There is a lack of homogeneity in the terminology used in the context of patient safety related to medication. The aim of this review was to identify the terms and definitions used in patient safety related to medication within the scientific literature. METHODS: Original and review articles that were indexed between 1998 and 2008 in MEDLINE and EMBASE and contained terms used in patient safety related to medication were included. Terms and definitions were extracted and categorised according to whether its definition referred to the process of medication use, or to the clinical outcome of medication use, or both. RESULTS: Of 2564 articles, 147 were included. Sixty terms used in patient safety related to medication with 189 different definitions were identified. Among terms that referred only to the process of medication use (n = 23), medication error provided the greatest number of definitions (n = 29). Among terms that referred only to the clinical outcome of medication use (n = 31), adverse drug event provided the greatest number of definitions (n = 15). Finally, among terms that referred both to the process of use and to the clinical outcome of medication use (n = 13), drug-related problem provided the greatest number of definitions (n = 7). CONCLUSIONS: A multitude of terms and definitions are used in patient safety related to medication. This heterogeneity makes it difficult to compare the results among studies and to appreciate the true magnitude of the problem. Classifying and unifying the terminology is necessary to advance in patient safety strategies.

Effectiveness of Dader Method for pharmaceutical care on control of blood pressure and total cholesterol in outpatients with cardiovascular disease or cardiovascular risk: EMDADER-CV randomized controlled trial.

BACKGROUND: Although some studies have demonstrated that pharmacist intervention can improve drug therapy among patients with cardiovascular disease (CVD), more evidence derived from randomized controlled trials (RCTs) is needed, including assessment of the effect of community pharmacist interventions in patients with CVD. OBJECTIVE: To assess the effectiveness of the Dader Method for pharmaceutical care on achieving therapeutic goals for blood pressure (BP), total cholesterol (TC), and both BP and TC (BP/TC) in patients with CVD and/or high or intermediate cardiovascular (CV) risk attending community pharmacies in Spain. METHODS: Patients aged 25 to 74 years attending community pharmacies with a prescription for at least 1 drug indicated for CVD or CV risk factors were randomized to 2 groups: an intervention group that received pharmaceutical care, which was provided by specially trained pharmacists working in collaboration with physicians, and a control group that received usual care (routine dispensing counseling) and verbal and written counseling regarding CVD prevention. Patients were recruited from December 2005 to September 2006, and both groups were followed for 8 months. Study outcomes were assessed at baseline and at 16 and 32 weeks after randomization. The primary outcome measures were the proportions of patients achieving BP, TC, and BP/TC therapeutic goals (BP lower than 140/90 mm Hg for patients with uncomplicated hypertension and lower than 130/80 mm Hg for patients with diabetes, chronic kidney disease, or history of myocardial infarction or stroke; TC lower than 200 mg per dL for patients without CVD and lower than 175 mg per dL for patients with CVD). Secondary outcomes were mean BP and TC values. BP was assessed manually by the pharmacist after a 10-minute rest in the supine position. This measurement was performed twice for every participant, and the average of the 2 measurements was calculated. TC was measured by the pharmacist during the study visit using the enzymatic dry method. Statistical analyses were performed using 2-tailed McNemar tests, Pearson chi-square tests, and Student's t-tests; P < 0.05 was considered statistically significant. RESULTS: 714 patients were included in the study (356 intervention, 358 control), and the mean [SD] age was 62.8 [8.1] years. The 2 groups were similar at baseline in clinical and demographic characteristics, including the proportion of patients at therapeutic goals for BP, TC, and BP/TC. After 8 months of follow-up, there were statistically significant differences in favor of pharmaceutical care in the proportions of patients who achieved therapeutic goals for BP (52.5% vs. 43.0%, P=0.017), TC (56.5% vs. 44.1%, P=0.001), and BP/TC (37.1% vs. 21.8%, P < 0.001). CONCLUSION: Compared with usual care plus written education, pharmaceutical care focused on patient evaluation and follow-up in collaboration with physicians improved the achievement of BP, TC, and BP/TC treatment goals in patients with CVD and/or high or intermediate CV risk attending community pharmacies in Spain.

[Usefulness of ambulatory blood pressure monitoring for clinical decisions making]. / Utilidad de la monitorización ambulatoria de la presión arterial en la toma de decisiones clínicas.

Ambulatory blood pressure monitoring (ABPM) is a useful diagnostic and therapeutic tool in hypertensive patients. ABMP is a technique in which multiple blood pressure (BP) measurements are taken over a 24-48-hour period, providing a continuous BP record during the patient's normal daily activities. By more reliably measuring BP, ABPM has been shown to be a better predictor of end-organ damage and cardiovascular outcome than BP measured in the clinic setting. The use of ABPM enables a more accurate assessment and an improved management of hypertensive patients. Moreover, ABPM is more closely related to treatment-induced changes in BP, so that treatment can be optimized more efficiently and more patients can achieve BP targets with appropriate therapy. Therefore, information provided by ABMP may be very useful for clinical decision making. The present article offers an updated and comprehensive view of the prognostic value of ABMP and the potential interest of this technique for treatment decision making.