Effectiveness and cost-effectiveness of a collaborative deprescribing intervention of proton-pump-inhibitors on community-dwelling older adults: Protocol for the C-SENIoR, a pragmatic non-randomized controlled trial.

INTRODUCTION: Worldwide, demographic ageing is a major social, economic and health challenge. Despite the increase in life expectancy, elderly often live with multiple chronic conditions, exposing them to multiple medications. Concerns have been raised about the growing issue of inappropriate long-term usage of proton-pump inhibitors (PPI), which have been associated with adverse outcomes and increased healthcare costs. Deprescribing is a recommended intervention to reduce or withdraw medicines that might be causing harm or might no longer be of benefit. This protocol details a trial to assess the effectiveness and cost-effectiveness of a collaborative deprescribing intervention of PPI among community-dwelling elderly, involving community pharmacists and general practitioners. METHODS AND ANALYSIS: A pragmatic, multicentre, two-arm, non-randomised controlled trial of a structured PPI collaborative deprescribing intervention in the primary care setting with a 6-month follow-up will be conducted. Patients must be 65 years old or older, live in the community and have been using PPI for more than 8 weeks. We hypothesize that the intervention will reduce the PPI usage in the intervention group compared to the control group. The primary outcome is the successful discontinuation or dose decrease of any PPI, defined as a statistically significant absolute 20% reduction in medication use between the intervention and control groups at 3- and 6-month follow-ups. An economic evaluation will be conducted alongside the trial. This study was approved by the Ethics Research Committee of Nova Medical School, NOVA University of Lisbon and by the Ethics Committee from the Local Health Unit Alto Minho, Portugal. DISCUSSION: This pragmatic trial will provide evidence on the effectiveness and cost-effectiveness of a patient-centred collaborative deprescribing intervention in the community setting in Portugal. It will also inform improvements for the development of future multi-faceted interventions that aim to optimise medication for the community-dwelling elderly. CLINICAL TRIAL REGISTRATION: ISRCTN 49637686.

Estimating Type 2 Diabetes Prevalence: A Model of Drug Consumption Data.

Observational, cross-sectional prevalence studies are costly and time-consuming. The development of indirect methods estimating prevalence used to obtain faster, less-expensive, and more robust results would be an advantage for several healthcare applications. This study aimed to use the drug dispensing data from community pharmacies to estimate the prevalence of Type 2 Diabetes mellitus (T2DM) in the Portuguese population. A cross-sectional study was conducted using a database of dispensed medicines with an indication for Diabetes mellitus in 2018 and 2021, stratified by geographic region. The methodology was based on a sequential method of acquiring prevalence estimates obtained through exposure to medicines using the daily doses defined per thousand inhabitants per day and adjusted to the rate of adherence to therapy, prescription patterns, and concomitance of antidiabetic drugs. The estimated overall T2DM prevalence in 2018 was 13.9%, and it was 14.2% for 2021. The results show the increased consumption of antidiabetic drugs, with fixed-dose combination antidiabetics and new antidiabetics being particularly important in 2021. This work allowed for the development of a model to obtain the estimated prevalence of T2DM based on drug consumption, using a simple, fast, and robust method that is in line with the available evidence. However, with the recent expanding indications for new antidiabetics, the inclusion of further data in the model needs to be studied.

Real-World Effectiveness in Hypertension and Hyperlipidemia Collaborative Management between Pharmacies and Primary Care in Portugal: A Multicenter Pragmatic Controlled Trial (USFarmácia®).

There is evidence of the efficacy of collaborative health interventions with pharmacies and primary care providers but little of its real-world effectiveness. We aimed to assess the effectiveness and discuss the design and challenges of hypertension and hyperlipidemia management between pharmacies and primary care providers using real-world data exchange between providers and experimental bundled payment. This was a pragmatic, quasi-experimental controlled trial. We collected patient-level data from primary care prescription claims and Electronic Medical Record databases, a pharmacy claims database, and patient telephone surveys at several time points. The primary outcomes were changes in blood pressure and total cholesterol. We used matched controls with difference-in-differences estimators in a Generalized Linear Model (GLM) and controlled interrupted time series (CITS). We collected additional data for economic and qualitative studies. A total of 6 Primary Care Units, 20 pharmacies, and 203 patients entered the study. We were not able to observe significant differences in the effect of intervention vs. control. We experienced challenges that required creative strategies. This real-world trial was not able to show effectiveness, likely due to limitations in the primary care technology which affected the sample size. It offers, however, valuable lessons on methods, strategies, and data sources, paving the way for more real-world effectiveness trials to advance value-based healthcare.

COVID-19 pandemic and the quality of antibiotic use in primary care: an interrupted time-series study.

The coronavirus disease-19 pandemic and the related public health mitigation measures have impacted the transmission of infectious diseases; however, their impact on the use of antibacterials has not yet been extensively evaluated. This study evaluated the impact of the pandemic on the consumption patterns of antibacterials for systemic use in primary care in Portugal. An interrupted time-series analysis was performed using the autoregressive integrated moving average model of the antibacterials dispensed in the community pharmacies in Portugal from 1 January 2016 to 30 June 2022. Monthly rates of absolute consumption (all antibacterials for systemic use, and specifically penicillins; cephalosporins; macrolides, lincosamides, and streptogramins; and quinolones) and the relative consumption of antibacterials (penicillins sensitive to ß-lactamase, penicillin combinations including ß-lactamase inhibitors, third- and fourth-generation cephalosporins, fluoroquinolones, and the ratio of broad- to narrow-spectrum antibacterials) were estimated. Antibiotic consumption was expressed in defined daily doses per 1000 inhabitants per day (DID). In Portugal, the consumption of antibacterials (J01) declined sharply immediately after the beginning of the pandemic, having a significant reduction of >5 DID (P < .0001). A similar, short-term impact was found for penicillins (-2.920 DID; P < .0001); cephalosporins (-0.428 DID; P < .0001); macrolides, lincosamides, and streptogramins (-0.681 DID; P = .0021); and quinolones (-0.320 DID; P < .0001). A long-term increase was found for cephalosporins (+0.019 DID per month; P < .0001). Relative consumption changes were only found for third- and fourth-generation cephalosporins (0.0734%). Our study suggests that the coronavirus disease-19 pandemic may have resulted in a decrease in antibiotic use, with no significant changes in the relative dispense. Uncertainties regarding the long-term effects of the pandemic and its impact on the rates of resistance remain.

A cross-country utilization patterns comparison of high expenditure therapeutic groups between Portugal and six European countries: the two sides of the Portuguese coin.

BACKGROUND: Understanding variability in prescribing patterns through comparative drug utilization studies can contribute to improve an efficient, effective and safe use of medicines. OBJECTIVES: To perform a cross-country comparison of consumption patterns of ambulatory high expenditure therapeutic groups between Portugal and six European countries and simulate potential cost-saving scenarios through the adoption of the different prescribing patterns of studied countries. METHODS: Cross-country comparison of 2019 drug consumption patterns between Portugal, Denmark, England, Finland, the Netherlands, Norway, and Spain. Analysis comprised antihypertensive drugs, glucose lowering drugs (GLD), insulins, lipid lowering drugs (LLD) and oral anticoagulants. Cost-saving analysis were performed using the Portugal average annual cost/daily defined dose and the potential reduction in expenditure simulating other European countries consumption pattern scenarios. RESULTS: Portugal had the lowest consumption uptake of metformin and the highest consumption of GLD (30.1%) and LLD (8.5% vs <3%) fixed-dose combinations. Annual cost-savings scenarios showed that Portugal would have saved between 53 M€ and 305 M€ if it had the same prescribing patterns than Norway or the Netherlands, respectively. CONCLUSIONS: Different utilization patterns across countries were found. Although Portugal has the lowest gross domestic product per capita among the countries studied, it had the highest uptake of newly and costly drugs.

Characteristics of Oral Corticosteroid Users Among Persons with Asthma on GINA Step 3 Therapy and Above: A Cross-Sectional Study in Portuguese Community Pharmacies.

Purpose: Oral corticosteroids (OCS) are frequently used in asthma management but have an important risk-profile. The aim of the study is to characterize and compare the sociodemographic and clinical characteristics, treatment regimen and asthma control between OCS users and non-users among the population of asthma patients (≥18 years) at GINA step 3 and above treated with a fixed combination of an inhaled corticosteroid and a long-acting beta-agonist (ICS/LABA). Methods: Cross-sectional study in Portuguese community pharmacies. Data was collected via paper-based interview delivered at the pharmacy (sociodemographic characteristics and asthma treatment regimen, namely ICS/LABA and OCS utilization), followed by a telephonic interview collecting smoking history, comorbidities, body mass index (BMI), history of exacerbations and asthma-related healthcare resource utilization (HCRU) in the previous 12 months, as well as asthma control using the Control of Allergic Rhinitis and Asthma Test (CARAT®). Results: A total of 347 patients recruited in 98 pharmacies were included in the analysis. Of those, 328 had completed both questionnaires. A quarter of the individuals reported OCS use in the previous 12 months (OCS users), either as add-on therapy (6%) or exacerbation treatment (19%). Patients were mostly females (72%), with an average age of 59.5 years (SD=15.4). OCS users were significantly older and reported more frequently having conjunctivitis (25.9% vs 15.0%), osteoporosis (25.9% vs 13.4%), arthritis (14.6% vs 6.9%), and gastrointestinal disease (16.1% vs 8.1%). OCS users also reported greater urgent HCRU: unscheduled consultations (33.3% vs 9.3%) and emergency department (ED) visits (32.1% vs 12.1%). Both groups presented poor disease control (85.2% of OCS users vs 72.9% of non-OCS users). Conclusion: These results highlight the burden of OCS therapy to asthma patients and the need to improve asthma management, by adopting OCS sparing strategies in this subgroup of patients.

Real-World Impact of Transferring the Dispensing of Hospital-Only Medicines to Community Pharmacies During the COVID-19 Pandemic.

OBJECTIVES: In Portugal, the dispensing of most outpatient specialty medicines is performed exclusively through hospital pharmacies and totally financed by the National Health Service. During the COVID-19 first wave, the government allowed the transfer of the dispensing of hospital-only medicines (HOMs) to community pharmacies (CPs). This study aimed to measure the value generated by the intervention of CP in the dispensing of HOM. METHODS: A single-arm, before-and-after study with 3-month follow-up was conducted enrolling a randomly selected sample of patients or caregivers with at least 1 dispensation of HOM through CP. Data were collected by telephone interview. Main outcomes were patients' self-reported adherence (Measure Treatment Adherence), health-related quality of life (EQ-5D 3-Level), satisfaction with the service, and costs related to HOM access. RESULTS: Overall 603 subjects were recruited to participate in the study (males 50.6%) with mean 55 years old (SD = 16). The already high mean adherence score to therapy improved significantly (P < .0001), and no statistically significant change (P > .5757) was found in the mean EQ-5D score between baseline (0.7 ± 0.3) and 3-month follow-up (0.8 ± 0.3). Annual savings account for €262.1/person, arising from travel expenses and absenteeism reduction. Participants reported a significant increase in satisfaction levels in all evaluated domains-pharmacist's availability, opening hours, waiting time, privacy conditions, and overall experience. CONCLUSIONS: Changing the dispense setting to CP may promote better access and satisfaction. Moreover, it ensures the persistence of treatments, promotes savings for citizens, and reduces the burden of healthcare services, representing a crucial public health measure.

Drug shortages in community pharmacies: Impact on patients and on the health system.

BACKGROUND: Worldwide, drug shortages are a critical public health concern. Consequences range from inconvenience and distress to more serious concerns related to negative clinical, humanistic and economic outcomes. OBJECTIVE: This study aimed to investigate the impact of drug shortages at the community pharmacies on patients and on the health system in Portugal. METHODS: A national, cross-sectional, multicenter study was conducted in Portuguese community pharmacies during April 2019. The proportion of patients reporting drug shortages, types of drugs affected and consequent economic burden to patients and the health system were estimated. Regional and urban setting stratification was performed. RESULTS: A total of 71.1% of pharmacies participated in the study and 22,830 patient surveys were retrieved. About 52.2% of patients experienced a drug shortage in the past 12 months; 21.5% had to see a physician to change the prescription and 5.7% declared treatment discontinuation because of this shortage. The estimated economic impact of shortages related to additional physician appointments varied between €2.1-€4.4 million for patients and €35.3-€43.8 million for the National Health Service. Drug shortages were mostly felt in rural and inner regions and least felt in the islands. CONCLUSION: This national study showed that community pharmacy drug shortages are a national problem with negative consequences on patients and the health system, which need to be tackled and mitigated.

Characteristics of Reliever Inhaler Users and Asthma Control: A Cross-Sectional Multicenter Study in Portuguese Community Pharmacies.

PURPOSE: SABA overuse might indicate poorly managed or uncontrolled asthma and be responsible for poor health outcomes. The aim of this study integrated in new fourth multi-design SABINA+ pillar was to characterize the population using short-acting ß2-agonists for asthma and examine the patterns of its use among community pharmacy customers in Portugal, as well as identify characteristics associated with disease control and explore potential differences between GINA treatment steps. PATIENTS AND METHODS: This cross-sectional multicenter study was conducted in Portuguese community pharmacies between 29 May 2018 and 15 August 2018. Participants were adults (age ≥18 years) self-reporting asthma diagnosis recruited in the context of a short-acting ß2-agonist dispense. A two-part questionnaire (pharmacist interview and self-administered) was used to collect information about sociodemographic characteristics, comorbidities, reliever inhaler use, healthcare resource consumption and self-reported disease control (assessed by the Control of Allergic Rhinitis and Asthma Test - CARAT®). Descriptive statistics was done to characterize the study sample. After categorizing patients according to GINA steps, based on their therapeutic regimen, we performed an exploratory subgroup analysis to evaluate if there were any differences between such groups in terms of the variables collected. A logistic regression was used to identify the potential determinants of overall disease control. RESULTS: Around 50.8% of patients were male, and the average age was 52 years old. Half of the patients never smoked, and 51.9% were employed. More than half of the patients report inhaler overreliance - purchasing more than 1 pack in 3 months (65.0%) or using the inhaler on more than 8 days over the previous 4 weeks (50.2%). Of the total number of patients in the study, 79.1% had poorly controlled asthma symptoms, and 78.7% had overall poorly controlled respiratory symptoms. We found statistically significant differences between GINA treatment steps in all sociodemographic characteristics (sex, mean age, education level, employment status); maximum number of SABA uses in 24h, CARAT score (total an asthma sub-score); history of exacerbations requiring ED visits or treatment with OCS for at least 3 days in the previous 12 months. Logistic regression revealed that patients reporting SABA use in more than 8 days in the previous 4 weeks and patients with at least 1 exacerbation requiring treatment with OCS for at least 3 days in the previous 12 months have greater odds of poor disease control [adjusted OR (95% CI): 2.6 (1.3-5.2) and 3.0 (1.3-6.6)]. CONCLUSION: Based on the results of this study, it can be inferred that the asthma population using SABA is largely uncontrolled and uses reliever inhalers excessively.

Effectiveness of an intervention to improve antibiotic-prescribing behaviour in primary care: a controlled, interrupted time-series study.

BACKGROUND: High rates of antibiotic misprescribing in primary care, with alarming clinical and economic consequences, highlight the urgent need for interventions to improve antibiotic prescribing in this setting. OBJECTIVES: To assess the effectiveness on antibiotic prescribing quality indicators of a multifaceted intervention targeting health professionals' and patients' behaviour regarding antibiotic use. METHODS: We conducted a pragmatic cluster-randomized controlled trial in the catchment area covered by Portugal's Central Regional Health Administration. The intervention consisted of a multidisciplinary, multifaceted programme involving physicians, pharmacists and patients, and comprising outreach visits for physicians and pharmacists, and educational materials for health professionals and patients. The following were assessed: relative ratios of prescription of penicillins sensitive to ß-lactamase, penicillin combinations including ß-lactamase inhibitors, third- and fourth-generation cephalosporins and fluoroquinolones; and the ratio of broad- to narrow-spectrum antibiotics. An interrupted time-series analysis for multiple-group comparisons was performed. The study protocol was registered on Clinical.trials.gov (NCT02173509). RESULTS: The participation rate in the educational intervention was 64% (197/309 GPs) in a total of 25 counties. Statistically significant improvements were obtained, not only in the relative prescription of penicillins sensitive to ß-lactamase (overall relative change of +896%) and penicillin combinations including ß-lactamase inhibitors (-161%), but also in the ratio of broad- to narrow-spectrum antibiotics (-200%). Statistically significant results were also obtained for third- and fourth-generation cephalosporins, though only in the immediate term. CONCLUSIONS: This study showed that quality indicators of antibiotic prescribing can be improved by tackling influences on behaviour including knowledge and attitudes surrounding physicians' clinical practice. Accordingly, these determinants must be considered when implementing interventions aimed at improving antibiotic prescribing.

Computerized Clinical Decision Support Systems and Antibiotic Prescribing: A Systematic Review and Meta-analysis.

PURPOSE: The aim of this study was to perform a systematic review and meta-analysis of studies performed in primary care centers and hospital facilities that evaluated the effectiveness of computerized clinical decision support systems (CDSSs) in decision making on the prescription of any given antibiotic. METHODS: We conducted a search of the MEDLINE and EMBASE databases. A meta-analysis was then conducted of all variables with results reported in >2 studies. FINDINGS: A total of 42 of the 46 studies included in the review identified a statistically significant advantage for CDSSs in ≥1 study variables. The effect of CDSSs on the percentage accuracy of the antibiotic spectrum prescribed empirically with respect to the microbial agent's susceptibility, which is one of the most frequently studied outcome variables, was examined in 7 studies, all undertaken in hospital settings. In all these studies but one, CDSSs resulted in a statistically significant increase in percentage accuracy. The other study variables present in >2 studies had more inconsistent results. Although the results of the meta-analysis of the variables percentage accuracy, antibiotic prescription rate in hospital, percentage adherence to antibiotic prescription guidelines in primary care or hospital, and percentage of inappropriate prescriptions for antibiotics in primary care were statistically significantly favorable to CDSSs; in the case of hospital length of stay and mortality, they were favorable although not statistically significantly. IMPLICATIONS: CDSSs appear to be useful for variables such as the percentage of appropriate empirical treatment in the hospital setting or to induce changes in antibiotics prescription rate. Even so, more better quality studies are required to draw clearer conclusions in respect of morbidity and mortality outcome variables and other settings.

Medicinal Product Regulation: Portugal׳s Framework.

PURPOSE: The pharmaceutical industry is one of the most tightly regulated sectors, and it is essential to know each country׳s legal framework to understand the regulation, approval, and marketing of medicinal products for human use. This article describes the main statutes and procedures governing medicinal products for human use in Portugal and the role of the country׳s National Medicines and Health Products Authority (Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.; INFARMED). METHODS: From the most recently available data, an update of requests and approvals concerning marketing authorizations, variations, pricing, and reimbursements is provided. Data were sourced from the INFARMED website, Infomed (database of medicinal products for human use), and periodic reports issued by national authorities. Organic laws, acts, and law decrees published in the government gazette (Diário da República) are cited and reproduced as required. FINDINGS: In 2015 Portugal ranked fifth in the European System of Medicines Evaluation in terms of the number of completed procedures as a reference member state. Approximately 80% of all approved drug applications in Portugal in 2015 were for generic drugs, mostly pertaining to the nervous system. In Portugal, INFARMED monitors drug quality, safety profile, and efficacy in all stages of the drug life cycle, ensuring patients' safety. IMPLICATIONS: The Portuguese market for medicinal products for human use has been appreciably changed by the advent of generic drugs. There is an increased trend for new request applications for biological and biotechnological substances.

Decreasing antibiotic use through a joint intervention targeting physicians and pharmacists.

AIM: To decrease population antibiotic use through an educational intervention targeting primary care physicians' and community pharmacists' attitudes and knowledge. METHODS: We designed a pragmatic cluster-randomized trial covering all National Health System primary care physicians and all community pharmacists' in a region in the north of Portugal. The study protocol was registered on ClinicalTrials.gov (identifier: NCT02173509). RESULTS: After adjustment for baseline values and comparison with the control group, the intervention was associated with a significant reduction in overall antibiotic use in the year following the intervention. The effect was most marked for tetracyclines, macrolides and cephalosporins. No statistically significant differences were observed for fluoroquinolone consumption. CONCLUSION: Multifaceted interventions involving physicians, pharmacists and general public proved effective in reducing antibiotic consumption in the population.

Determinants of physician antibiotic prescribing behavior: a 3 year cohort study in Portugal.

Objectives Antibiotic misprescription is a major driver of resistance, which is a worldwide public health problem. Therefore, our aim is to assess the influence of the determinants of physician prescribing on the quality of antibiotic use. Methods A 3 year cohort study including all primary-care physicians working in Portugal's Central Regional Health Administration (n = 1094) was conducted. We assessed the determinants of prescribing using a pre-validated, personally addressed, reply-paid, self-administered questionnaire (sent four times to non-responders, between September 2011 and February 2012) designed to collect information on physicians' attitudes to and knowledge of antibiotic prescribing as well as their socio-demographic and professional data. To evaluate antibiotic prescribing, we've calculated ESAC 12 quality indicators per physician per year, allowing us to stratify them as good or poor prescribers according to their performance on those indicators. Associations between determinants and outcomes were fitted with generalized linear mixed models. Results The overall response rate was 46.1%. Emergency activity (OR [95% CI] = 0.29 [0.16-0.54]; p < 0.05) and workload (number of patients seen per day: OR [95% CI] = 0.97 [0.94-1.00]; p < 0.05; number of patients seen per week in emergencies: OR [95% CI] = 0.98 [0.97-0.99]; p < 0.05) were both related to poor quality of antibiotic prescribing. Statistically significant odds ratios were also obtained for ignorance (IqOR [95% CI] = 2.14 [1.31-3.52]), complacency (1/IqOR [95% CI] = 1.19 [1.01-1.41]) and responsibility of others (1/IqOR [95% CI] = 1.78 [1.10-3.06]). Conclusions The above results serve to emphasize workload, working at emergency departments and physicians' attitudes identified as critical factors affecting antibiotic prescribing. This provides new insights for clinicians, researchers and policy makers when it comes to developing and improving the clinical and economic outcomes of antibiotic use. Key limitations of the study included the difficulty of results extrapolation and the limitations of the stratification method based on the antibiotic prescribing quality indicators.

Physicians' attitudes and knowledge concerning antibiotic prescription and resistance: questionnaire development and reliability.

BACKGROUND: Understanding physicians' antibiotic-prescribing behaviour is fundamental when it comes to improving antibiotic use and tackling the growing rates of antimicrobial resistance. The aim of the study was to develop and validate--in terms of face validity, content validity and reliability--an instrument designed to assess the attitudes and knowledge underlying physician antibiotic prescribing. METHODS: The questionnaire development and validation process comprised two different steps, namely: (1) content and face validation, which included a literature review and validation both by physicians and by Portuguese language and clinical psychology experts; and (2) reliability analysis, using the test-retest method, to assess the questionnaire's internal consistency (Cronbach's alpha) and reproducibility (intraclass correlation coefficient--ICC). The questionnaire includes 17 items assessing attitudes and knowledge about antibiotic prescribing and resistances and 9 items evaluating the importance of different sources of knowledge. The study was conducted in the catchment area covered by Portugal's Northern Regional Health Administration and used a convenience sample of 61 primary-care and 50 hospital-care physicians. RESULTS: Response rate was 64% (49% to retest) for primary-care physicians and 66% (60% to retest) for hospital-care physicians. Content validity resulted in 9 changes to professional concepts. Face validity assessment resulted in 19 changes to linguistic and interpretative terms. In the case of the reliability analysis, the ICC values indicated a minimum of fair to good reproducibility (ICC > 0.4), and the Cronbach alpha values were satisfactory (α > 0.70). CONCLUSIONS: The questionnaire developed is valid--in terms of face validity, content validity and reliability--for assessing physicians' attitudes to and knowledge of antibiotic prescribing and resistance, in both hospital and primary-care settings, and could be a very useful tool for characterising physicians' antibiotic-prescribing behaviour.

Safety Alerts: An Observational Study in Portugal.

PURPOSE: The information that is available when marketing authorizations are approved is limited. Pharmacovigilance has an important role during the postauthorization period, and alerts published by national authorities allow health care professionals to be informed about new data on safety profiles. This study therefore sought to analyze all safety alerts published by the Portuguese National Authority of Medicines and Health Products I.P. (INFARMED). METHODS: We conducted an observational study of all alerts published on the INFARMED website from January 2002 through December 2014. From the data included in the alerts, the following information was abstracted: active substance name (and trade name), event that led to the alert, and the resulting safety measures. Active substances were classified according to the Anatomical Therapeutic Chemical (ATC) code. FINDINGS: A total of 562 alerts were published, and 304 were eligible for inclusion. The musculoskeletal system was the ATC code with more alerts (n = 53), followed by the nervous system (n = 42). Communication of the information and recommendations to the health care professionals and the public in general was the most frequent safety measure (n = 128), followed by changes in the Summary of the Product Characteristics and package information leaflet (n = 66). During the study period, 26 marketing authorizations were temporarily suspended and 10 were revoked. IMPLICATIONS: The knowledge of the alerts published during the postmarketing period is very useful to the health care professionals for improving prescription and use of medicines and to the scientific community for the development of new researches.

Educational interventions to improve prescription and dispensing of antibiotics: a systematic review.

BACKGROUND: Excessive and inappropriate antibiotic use contributes to growing antibiotic resistance, an important public-health problem. Strategies must be developed to improve antibiotic-prescribing. Our purpose is to review of educational programs aimed at improving antibiotic-prescribing by physicians and/or antibiotic-dispensing by pharmacists, in both primary-care and hospital settings. METHODS: We conducted a critical systematic search and review of the relevant literature on educational programs aimed at improving antibiotic prescribing and dispensing practice in primary-care and hospital settings, published in January 2001 through December 2011. RESULTS: We identified 78 studies for analysis, 47 in primary-care and 31 in hospital settings. The studies differed widely in design but mostly reported positive results. Outcomes measured in the reviewed studies were adherence to guidelines, total of antibiotics prescribed, or both, attitudes and behavior related to antibiotic prescribing and quality of pharmacy practice related to antibiotics. Twenty-nine studies (62%) in primary care and twenty-four (78%) in hospital setting reported positive results for all measured outcomes; fourteen studies (30%) in primary care and six (20%) in hospital setting reported positive results for some outcomes and results that were not statistically influenced by the intervention for others; only four studies in primary care and one study in hospital setting failed to report significant post-intervention improvements for all outcomes. Improvement in adherence to guidelines and decrease of total of antibiotics prescribed, after educational interventions, were observed, respectively, in 46% and 41% of all the reviewed studies. Changes in behaviour related to antibiotic-prescribing and improvement in quality of pharmacy practice was observed, respectively, in four studies and one study respectively. CONCLUSION: The results show that antibiotic use could be improved by educational interventions, being mostly used multifaceted interventions.

PERSYVE - Design and validation of a questionnaire about adverse effects of antihypertensive drugs.

OBJECTIVE: The aim of this study was to design and validate a questionnaire to measure perceived symptoms associated with antihypertensive drugs (PERSYVE). METHODS: THE PERSYVE DEVELOPMENT AND VALIDATION INCLUDED FOUR STAGES: 1) item development (bibliographic review and questionnaire elaboration); 2) face and content validation; 3) field testing (pre-test); and 4) test-retest validation, assessment of internal consistency (Cronbach's alpha) and reproducibility over time (intraclass correlation coefficient and Cohen's kappa coefficient). RESULTS: PERSYVE IS DIVIDED INTO SIX SECTIONS ACCORDING TO RESULTS OBTAINED FROM THE LITERATURE REVIEW: (1) drug adherence, (2) perceived symptoms and how they affect quality of life (five-point Likert scale), (3) communication with health professionals, (4) perception of symptoms as adverse reactions, (5) influence on therapy compliance, and (6) adoption of non-pharmacological methods for blood pressure control. Content and face validation of the questionnaire led to some vocabulary changes and the introduction of section 2.1. Field-testing (n=26) revealed high comprehensibility of the questions. The Cronbach's alpha, calculated for section 2 (five-point Likert scale) was 0.850. PERSYVE was reproducible (n=167): kappa values presented fair to substantial reproducibility and, in section 2, ICC values resulted in good to excellent reproducibility. CONCLUSION: Results showed that PERSYVE is a well-structured, objective, patient-friendly, valid and reliable questionnaire. PERSYVE can be a very useful instrument in hypertensive patients' monitoring and in the screening of adverse effects.

PERSYVE - Design and validation of a questionnaire about adverse effects of antihypertensive drugs / PERSYVE - Diseño y validación de un cuestionario sobre efectos adversos de antihipertensivos

Objective: The aim of this study was to design and validate a questionnaire to measure perceived symptoms associated with antihypertensive drugs (PERSYVE). Methods: The PERSYVE development and validation included four stages: 1) item development (bibliographic review and questionnaire elaboration); 2) face and content validation; 3) field testing (pre-test); and 4) test-retest validation, assessment of internal consistency (Cronbach’s alpha) and reproducibility over time (intraclass correlation coefficient and Cohen’s kappa coefficient). Results: PERSYVE is divided into six sections according to results obtained from the literature review: (1) drug adherence, (2) perceived symptoms and how they affect quality of life (five-point Likert scale), (3) communication with health professionals, (4) perception of symptoms as adverse reactions, (5) influence on therapy compliance, and (6) adoption of non-pharmacological methods for blood pressure control. Content and face validation of the questionnaire led to some vocabulary changes and the introduction of section 2.1. Field-testing (n=26) revealedhigh comprehensibility of the questions. The Cronbach's alpha, calculated for section 2 (five-point Likert scale) was 0.850. PERSYVE was reproducible (n=167): kappa values presented fair to substantial reproducibility and, in section 2, ICC values resulted in good to excellent reproducibility. Conclusion: Results showed that PERSYVE is a wellstructured, objective, patient-friendly, valid and reliable questionnaire. PERSYVE can be a very useful instrument in hypertensive patients’ monitoring and in the screening of adverse effects (AU)

Objetivo: El objetivo de este estudio fue diseñar y validar un cuestionario para medir los síntomas percibidos asicados a medicamentos antihipertensivos (PERSYVE). Métodos: El desarrollo y validación de PERSYVE incluyó cuatro etapas: 1) desarrollo de ítems (revisión bibliográfica y elaboración del cuestionario); 2) validación de rostro y de contenido; 3) prueba de campo (pre-test); y 4) validación test-retest, evaluación de la consistencia interna (alfa de Chronbach) y reproductibilidad en el tiempo (coeficiente de correlación intra-clases y coeficiente kappa de Cohen). Resultados: De acuerdo con los resultados obtenidos de la revisión de la literatura, PERSYVE se divide en seis secciones: (1) adherencia a medicamentos, (2) síntomas percibidos y como afectan a la calidad de vida (escala Likert de cinco puntos), (3) comunicación con los profesionales de la salud, (4) percepción de síntomas como reacciones adversas, (5) influencia en el cumplimiento del tratamiento, y (6) adopción de métodos no farmacológicos para el control de la presión arterial. La validación de rostro y de contenido del cuestionario llevaron a algunos cambios de vocabulario y a la introducción de la sección 2.1. El ensayo de campo (n=26) reveló una alta comprensibilidad de las preguntas. El alfa de Cronbach calculado para la sección 2 (escala de Likert de 5 puntos) fue de 0,850. PERSYVE fue reproducible (n=167): valores de kappa presentaron una reproductibilidad sustancial y, en la sección 2, los valores de ICC resultaron de buenos a excelentes. Conclusión: Los resultados demostraron que PERSYVE es un cuestionario bien estructurado, objetivo, fácil de usar para el paciente, válido y confiable. PERSYVE puede ser un instrumento muy útil en la monitorización de pacientes hipertensos y en el rastreo de efectos adversos (AU)

Understanding physician antibiotic prescribing behaviour: a systematic review of qualitative studies.

Inappropriate prescription has been associated with mounting rates of antibiotic resistance worldwide, demanding more detailed studies into physicians' decision-making process. Accordingly, this study sought to explore physicians' perceptions of factors influencing antibiotic prescribing. A systematic search was performed for qualitative studies focused on understanding physicians' perceptions of the factors, attitudes and knowledge influencing antibiotic prescription. Of the total of 35 papers selected for review purposes, 18 solely included physicians and the remaining 17 also included patients and/or other healthcare providers. Data collection was based mainly on interviews, followed by questionnaires and focus groups, and the methodologies mainly used for data analysis were grounded theory and thematic analysis. Factors cited by physicians as having an impact on antibiotic prescribing were grouped into those that were intrinsic (group 1) and those that were extrinsic (group 2) to the healthcare professional. Among the former, physicians' attitudes, such as complacency or fear, were rated as being most influential on antibiotic prescribing, whilst patient-related factors (e.g. signs and symptoms) or healthcare system-related factors (e.g. time pressure and policies/guidelines implemented) were the most commonly reported extrinsic factors. These findings revealed that: (i) antibiotic prescribing is a complex process influenced by factors affecting all the actors involved, including physicians, other healthcare providers, healthcare system, patients and the general public; and (ii) such factors are mutually dependent. Hence, by shedding new light on the process, these findings will hopefully contribute to generating new and more effective strategies for improving antibiotic prescribing and allaying global concern about antibiotic resistance.