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Background: Surveillance of healthcare-associated infections (HAIs) is an essential component of hospital infection prevention and control systems. We aimed to assess the quality of the data compiled by the Brazilian HAI Surveillance System from pediatric (PICUs) and neonatal intensive care units (NICUs), between 2012 and 2021. Methods: Data Quality Review, including adherence, completeness, internal consistency, consistency over time, and consistency of population trend, were computed at both national and state levels based on quality metrics from World Health Organization Toolkit. Incidence rates (or incidence density) of ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI) were obtained from the Brazilian National Nosocomial Infections Surveillance (NNIS) system. Data on sepsis-related mortality, spanning the period from 2012 to 2021, were extracted from the Brazilian National Health Service database (DATASUS). Additionally, correlations between sepsis-related mortality and incidence rates of VAP or CLABSI were calculated. Results: Throughout the majority of the study period, adherence to VAP reporting remained below 75%, exhibiting a positive trend post-2016. Widespread outliers, as well as inconsistencies over time and in population trends, were evident across all 27 states. Only four states maintained consistent adherence levels above 75% for more than 8 years regarding HAI incidence rates. Notably, CLABSI in NICUs boasted the highest reporting adherence among all HAIs, with 148 periods out of 270 (54.8%) exhibiting reporting adherence surpassing 75%. Three states achieved commendable metrics for CLABSI in PICUs, while five states demonstrated favorable results for CLABSI in NICUs. Conclusions: While adherence to HAI report is improving among Brazilian states, an important room for improvement in the Brazilian NNIS exists. Additional efforts should be made by the Brazilian government to improve the reliability of HAI data, which could serve as valuable guidance for hospital infection prevention and control policies.

Abstract Background This study aimed to synthetize the evidence on the effectiveness of harm minimization interventions on reducing blood-borne infection transmission and injecting behaviors among people who inject drugs (PWID) through a comprehensive overview of systematic reviews and evidence gap mapping. Methods A systematic review was conducted with searches in PubMed and Scopus to identify systematic reviews assessing the impact of interventions aimed at reducing the harms associated with injectable drug use. The overall characteristics of the studies were extracted and their methodological quality was assessed using AMSTAR-2. An evidence gap map was constructed, highlighting the most frequently reported outcomes by intervention (CRD42023387713). Results Thirty-three systematic reviews were included. Of these, 14 (42.2%) assessed the impact of needle/syringe exchange programs (NSEP) and 11 (33.3%) examined opioid agonist therapy (OAT). These interventions are likely to be associated with reductions of HIV/HCV incidence (10–40% risk reduction for NSEP; 50–60% for OAT) and sharing injecting paraphernalia (50% for NSEP, 25–85% for OAT), particularly when combined (moderate evidence). Behavioral/educational interventions were assessed in 12 reviews (36.4%) with most authors in favor/partially in favor of the use of these approaches (moderate evidence). Take-home naloxone programs and supervised-injection facilities were each assessed in two studies (6.1%), which reported inconclusive results (limited/inconsistent evidence). Most authors reported high levels of heterogeneity and risk of bias. Other interventions and outcomes were inadequately reported. Most systematic reviews presented low or critically low quality. Conclusion The evidence is sufficient to support the effectiveness of OAT, NSEP and their combination in reducing blood-borne infection transmission and certain injecting behaviors among PWID. However, evidence of other harm minimizations interventions in different settings and for some outcomes remain insufficient.

La farmacia y las ciencias farmacéuticas abarcan una serie de disciplinas diferentes. La Farmacia Asistencial se ha definido como “la disciplina científica que estudia los diferentes aspectos de la práctica de la farmacia y su impacto en los sistemas de atención de la salud, el uso de medicamentos y la atención al paciente”. Por lo tanto, los estudios de Farmacia Asistencial abarcan tantos elementos de farmacia clínica como de farmacia social. Como cualquier otra disciplina científica, la práctica de la farmacia clínica y social difunde los resultados de la investigación utilizando revistas científicas. Los editores de revistas de farmacia clínica y farmacia social tienen un papel en la promoción de la disciplina al mejorar la calidad de los artículos publicados. Como ha ocurrido en otras áreas del cuidado de la salud (es decir, medicina y enfermería), un grupo de editores de revistas de práctica farmacéutica clínica y social se reunió en Granada, España, para discutir cómo las revistas pueden contribuir a fortalecer la práctica farmacéutica como disciplina. El resultado de esa reunión se compiló en estas Declaraciones de Granada, que comprenden 18 recomendaciones reunidas en seis temas: el uso apropiado de la terminología, los resúmenes con impacto, la necesidad de la revisión por pares, la dispersión de revistas, el uso más eficaz e inteligente de los indicadores bibliométricos y la selección por parte de los autores de la revista de práctica farmacéutica más adecuada para presentar su trabajo.

Abstract Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as “the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care”. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors' selection of the most appropriate pharmacy practice journal to submit their work.

SARS-CoV-2 infection and its clinical manifestations (COVID-19) quickly evolved to a pandemic and a global public health emergency. The limited effectivity of available treatments aimed at reducing virus replication and the lessons learned from other coronavirus infections (SARS-CoV-1 or NL63) that share the internalization process of SARS-CoV-2, led us to revisit the COVID-19 pathogenesis and potential treatments.Virus protein S binds to the angiotensin-converting enzyme 2 (ACE2) initiating the internalization process. Endosome formation removes ACE2 from the cellular membrane preventing its counter-regulative effect mediated by the metabolism of angiotensin II to angiotensin (1–7). Internalized virus-ACE2 complexes have been identified for these coronaviruses. SARS-CoV-2 presents the highest affinity for ACE2 and produces the most severe symptoms. Assuming ACE2 internalization is the trigger for COVID-19 pathogenesis, accumulation of angiotensin II can be viewed as the potential cause of symptoms. Angiotensin II is a strong vasoconstrictor, but has also important roles in hypertrophy, inflammation, remodeling, and apoptosis. Higher levels of ACE2 in the lungs explain the acute respiratory distress syndrome as primary symptoms. Most of the described findings and clinical manifestations of COVID-19, including increased interleukin levels, endothelial inflammation, hypercoagulability, myocarditis, dysgeusia, inflammatory neuropathies, epileptic seizures and memory disorders can be explained by excessive angiotensin II levels.Several meta-analyses have demonstrated that previous use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were associated with better prognosis for COVID-19. Therefore, pragmatic trials to assess the potential therapeutic benefits of renin-angiotensin-aldosterone system inhibitors should be urgently promoted by health authorities to widen the therapeutic options for COVID-19. Resumo: A infeção por SARS-CoV-2 e as suas manifestações clínicas (COVID-19) evoluíram rapidamente para uma pandemia e um problema de saúde pública global. A efetividade limitada dos tratamentos existentes orientados apenas para a redução da replicação do vírus e as lições aprendidas com outros coronavírus que utilizam o mesmo recetor de internalização levaram-nos a revisitar a patogénese da Covid-19 e potenciais tratamentos.A proteína S do vírus liga-se à enzima conversora de angiotensina de tipo 2 (ECA2) iniciando o processo de internalização. A afinidade do SARS-CoV-2 para a ECA2 é superior à dos outros coronavirus, o que se correlaciona com a gravidade dos sintomas. A ECA2 acompanha o vírus no endossoma, tendo sido identificados complexos vírus-ECA2 internalizados dos três coronavírus referidos. A ausência da ECA2 na membrana celular compromete o metabolismo da angiotensina II em angiotensina (1-7), pelo que a acumulação de angiotensina II pode ser vista como a causa potencial dos sintomas. A angiotensina II é um potente vasoconstritor mas também desempenha papéis importantes em processos fisiopatológicos como a inflamação, fibrose, hipertrofia e apoptose. Níveis mais elevados de angiotensina II nos pulmões explicariam a síndrome de insuficiência respiratória aguda como síndrome primária. A maioria das alterações de parâmetros e outras manifestações clínicas, tais como o aumento dos níveis de interleucinas, a inflamação endotelial, a hipercoagulabilidade, a miocardite, a disgeusia, as neuropatias inflamatórias, as convulsões epiléticas e os distúrbios da memória, pode ser explicada por níveis excessivos de angiotensina II.Várias meta-análises demonstraram que o uso prévio de inibidores da enzima conversora da angiotensina (IECAs) ou antagonistas dos recetores da angiotensina (ARAs) está associado a um melhor prognóstico para a Covid-19. Deste modo, ensaios pragmáticos para avaliar os potenciais benefícios terapêuticos dos inibidores do sistema renina-angiotensina-aldosterona (SRAA) deveriam ser promovidos urgentemente pelas autoridades de saúde para se diversificar as opções terapêuticas para a Covid-19.

Abstract Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as “the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care”. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors’ selection of the most appropriate pharmacy practice journal to submit their work.

Objective: To assess the predictive value of prior carbapenem-resistant Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA) colonization established in surveillance cultures for subsequent infection by these pathogens in ICU patients. Methods: A cohort study was performed with patients admitted to the intensive care unit for at least 48 h. Negative and positive predictive values, sensitivity, and specificity of surveillance cultures in CRAB and CRPA were measured. Results: 693 infected patients were included. Patients previously colonized by CRAB and CRPA were more likely to be infected by these pathogens: adjusted OR: 10.34 (6.58 - 16.45; p < 0.001) and 2.30 (3.88 - 10.26; p < 0.001), respectively. We found high negative predictive values of surveillance cultures for CRAB (87.18%) and CRPA (88.30%) and high specificity 91.96% and 90.13%, respectively. Conclusions: Patients not colonized by CRAB and CRPA were less prone to infection by these pathogens. These findings may contribute to the choice of empirical antimicrobial therapy and discourage the prescription of antibiotics against these pathogens in patients without previous colonization.

La farmacia y las ciencias farmacéuticas abarcan una serie de disciplinas diferentes. La farmacia práctica se ha definido como "la disciplina científica que estudia los diferentes aspectos de la práctica de la farmacia y su impacto en los sistemas sanitarios, el uso de los medicamentos y la atención al paciente". Así pues, los estudios sobre la farmacia práctica abarcan tanto elementos de farmacia clínica como de farmacia social. Como cualquier otra disciplina científica, la farmacia práctica clínica y social difunde los resultados de la investigación mediante revistas científicas. Los editores de revistas de farmacia clínica y farmacia social tienen un papel en la promoción de la disciplina mediante la mejora de la calidad de los artículos publicados. Al igual que ha ocurrido en otras áreas sanitarias (medicina y enfermería), un grupo de editores de revistas de farmacia práctica clínica y social se reunió en Granada, España, para debatir cómo las revistas podrían contribuir a fortalecer la farmacia práctica como disciplina. El resultado de esa reunión se recogió en esta Declaración de Granada, que comprende 18 recomendaciones agrupadas en seis temas: el uso adecuado de la terminología, los resúmenes con impacto, las revisiones por pares requeridas, la dispersión de revistas, un uso más eficaz y prudente de los indicadores bibliométricos de revistas y artículos, y la selección por parte de los autores de la revista de farmacia práctica más adecuada para presentar sus trabajos.

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. Resumo: Introdução e objetivos: O conhecimento dos doentes sobre hipertensão é um importante fator associado ao mau controlo da pressão arterial e é uma das variáveis consideradas para desenhar intervenções mais efetivas. O nosso objetivo foi avaliar o conhecimento dos doentes hipertensos sobre hipertensão e determinar a sua influência nas crenças sobre medicação e na adesão à terapêutica destes doentes. Métodos: Estudo transversal. Doentes adultos que se dirigiram a uma das farmácias participantes e a tomar pelo menos um medicamento anti-hipertensor foram convidados. Foram recolhidos dados sobre a história familiar e pessoal e administradas as versões portuguesas dos questionários Hypertension Knowledge Test (HKT), Beliefs about Medicines Questionnaire (BMQ) e versão curta do Maastricht Utrecht Adherence in Hypertension questionnaire (MUAH-16). Resultados: Foram incluídos 240 doentes no estudo. O número médio de anti-hipertensores utilizados foi 1,62±0,99, usando 15,4% dos doentes três ou mais fármacos. Mais de 80% dos doentes sabia os valores de pressão arterial ideais e reconheceram obesidade, sedentarismo e sal como fatores de risco para a hipertensão. No entanto, a maioria dos doentes não estava ciente das características assintomáticas da hipertensão e acreditava que os anti-hipertensores deviam ser utilizados por tempo limitado. Correlações negativas e significativas foram encontradas entre o score obtido no HKT e as atitudes negativas em relação à medicação, mas não foi encontrada nenhuma associação com as atitudes positivas. Conclusões: Os doentes hipertensos têm um bom conhecimento sobre os fatores de risco da hipertensão, mas não sobre o seu tratamento. Aumentar os conhecimentos dos doentes sobre hipertensão pode reduzir as atitudes negativas associadas à medicação, mas provavelmente não terá nenhum impacto nas atitudes positivas.

Introduction Sickle cell disease (SCD), an inherited haemoglobinopathy, has important impact on morbidity and mortality, especially in paediatrics. Previous systematic reviews are limited to adult patients or focused only on few therapies. We aim to synthesise the evidence on efficacy and safety of pharmacological interventions for managing SCD in children and adolescents.Methods and analysis This systematic review protocol is available at Open Science Framework (doi:10.17605/OSF.IO/CWAE9). We will follow international recommendations on conduction and report of systematic reviews and meta-analyses. Searches will be conducted in PubMed, Scopus and Web of Science (no language nor time restrictions) (first pilot searches performed in May 2022). We will include randomised controlled trials comparing the effects of disease-modifying agents in patients with SCD under 18 years old. Outcomes of interest will include: vaso-occlusive crisis, haemoglobin levels, chest syndrome, stroke, overall survival and adverse events. We will provide a narrative synthesis of the findings, and whenever possible, results will be pooled by means of pairwise or Bayesian network meta-analyses with surface under the cumulative ranking curve analyses. Different statistical methods and models will be tested. Dichotomous outcomes will be reported as OR, risk ratio or HR, while continuous data will be reported as standard mean differences, both with 95% CI/credibility interval. The methodological quality of the trials will be evaluated using the Risk of Bias 2.0 tool, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and dissemination This study refers to a systematic review, so no ethics approval is necessary. We intent to publish our findings in international, peer-reviewed journal. Data will also be presented to peers in scientific events. Additionally, the results obtained in this study may contribute towards the update of therapeutic guidelines and for the development of health policies for SCD.PROSPERO registration number CRD42022328471.

Abstract The delivery of clinical pharmacy services has been growing in Brazilian community pharmacies, and it is necessary to have a comprehensive understanding of the topic. This scoping review aimed to provide an overview of Brazilian studies about clinical pharmacy services in community pharmacies. Original research articles, with no restriction of time, study design, or patient’s health condition, were included. Searches were conducted in PubMed, Scopus, Web of Science, Scielo, and Lilacs. Two reviewers conducted the screening, full-text reading, and data extraction independently. ROB and ROBINS-I were used for the assessment of quality. Charts and tables were built to summarise the data. Seventy-two articles were included. A diversity of study designs, number of participants, terms used, and outcomes was found. São Paulo and Sergipe States had the highest number of studies (n=10). Pharmacists’ interventions were not fully reported in 65% of studies, and most studies presented an unclear risk of bias. Studies were very diverse, impairing the comparisons between the results and hindering their reproducibility. This review suggests using guidelines and checklists for better structuration of pharmacists’ interventions as well as reporting results and measuring fidelity in future research.

Abstract Pharmacists acting in pharmacies and drugstores stores are some of the most accessible healthcare providers and the last to intervene before the patient takes their medicine. This puts the pharmacist in a position of authority that should be harnessed for the benefit of health. Thus, this professional is strategic for performing pharmacovigilance. Our objective of this study was to interrogate the practice of pharmacists in relation to pharmacovigilance activities, and to identify difficulties and possible stimuli for the improvement these activities in pharmacies and drugstores. The information was collected through an online questionnaire via Survey Monkey®. The data were analyzed statistically using SPSS software. Responses were received from 5174 pharmacists: mostly young women within five years of graduation and experience in pharmaceutical retail. 81% of them reported having identified suspected substandard medicines, but only 16% used the Brazilian notification system Notivisa. More than 85% of pharmacists agreed with the importance of pharmacovigilance and the recognition of reporting services as part of pharmacist duties and pharmaceutical care. The main barriers to making notifications were the lack of access and knowledge about Notivisa. Pharmacists agreed that simplifying the system would be a stimulus for notifications, and requested more feedback from notifications, as well as material and courses to understand the notification process. Pharmacists have important data to feed into pharmacovigilance systems, recognize their responsibilities and are willing to contribute, but still demonstrate low compliance. Simplification of the system and training on it are likely to increase notifications.

ABSTRACT BACKGROUND: Despite the several options available for supplements containing vitamins C and E, evidence regarding the prevalence of deficiency or insufficiency of these vitamins is weak. OBJECTIVES: To estimate the prevalence of deficiency or insufficiency of vitamins C and E and associated factors among women of childbearing age, in Brazil. DESIGN AND SETTING: Systematic review and meta-analysis conducted at a Brazilian public university. METHODS: A search from index inception until May 2020 was conducted. Meta-analyses were performed using inverse variance for fixed models, with summary proportions calculation using Freeman-Tukey double arcsine (base case). Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. RESULTS: Our review identified 12 studies, comprising 1,316 participants, especially breastfeeding women. There was at least one quality weakness in all studies, mainly regarding sampling method (i.e. convenience sampling) and small sample size. The prevalence of vitamin C deficiency ranged from 0% to 40%. Only vitamin E deficiency was synthetized in meta-analyses, with mean prevalences of 6% regardless of the alpha-tocopherol cutoff in plasma, and 5% and 16% for cutoffs of < 1.6-12.0 mmol/l and < 16.2 mmol/l, respectively. The cumulative meta-analysis suggested that a trend to lower prevalence of vitamin E deficiency occurred in recent studies. CONCLUSIONS: Although the studies identified in this systematic review had poor methodological and reporting quality, mild-moderate vitamin C and E deficiencies were identified, especially in breastfeeding women. Thus, designing and implementing policies does not seem to be a priority, because the need has not been properly dimensioned among women of childbearing age in Brazil. REGISTRATION NUMBER IN PROSPERO: CRD42020221605.

Background: Medical Subject Headings (MeSH) thesaurus contribute towards efficient searching of biomedical information. However, insufficient coverage of specific fields and inaccuracies in the indexing of articles can lead to bias during literature retrieval. Objectives: This meta-research study aimed to assess the use of ‘Pharmaceutical Services’ MeSH terms in studies evaluating the effect of pharmacists' interventions. Methods: An updated systematic search (Jan-2022) to gather meta-analyses comparing pharmacists' interventions vs. other forms of care was performed. All MeSH terms allocated to the MEDLINE record of each primary study included in the selected meta-analyses were systematically extracted. Terms from the ‘Pharmaceutical Services’ branch, including its descendants, as well as other 26 pharmacy-specific MeSH terms were identified. The assignment of these terms as a ‘Major MeSH’ was also evaluated. Descriptive statistics and social network analyses to evaluate the co-occurrence of the MeSH terms in the articles were conducted. Sensitivity analyses including only meta-analyses with declared objectives mentioning the words ‘pharmacist’ or ‘pharmacy’ were performed (SPSS v.24.0). Results: Overall, 138 meta-analyses including 2012 primary articles were evaluated. A median of 15 [IQR 12–18] MeSH terms were assigned per article with a slight positive time-trend (Spearman rho = 0.193; p < 0.001). Only 36.6% (n = 736/2012) and 58.1% (n = 338/1099) of studies were indexed with one MeSH term from the ‘Pharmaceutical Services’ branch in the overall and sensitivity analyses, respectively. In

Limonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cells lines (especially hepatocellular carcinoma—HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds.

Anticholinergic burden tools have relevant pharmacological gaps that may explain their limited predictive ability for clinical outcomes. The aim of this study was to provide a universal pharmacological-based list of drugs with their documented affinity for muscarinic receptors. A comprehensive literature review was performed to identify the anticholinergic burden tools. Drugs included in these instruments were searched in four pharmacological databases, and the investigation was supplemented with PubMed. The evidence regarding the potential antagonism of the five muscarinic receptors of each drug was assessed. The proportion of drugs included in the tools with an affinity for muscarinic receptors was evaluated. A universal list of drugs with anticholinergic activity was developed based on their documented affinity for the different subtypes of muscarinic receptors and their ability to cross the blood-brain barrier. A total of 23 tools were identified, including 304 different drugs. Only 48.68%, 47.70%, 48.03%, 43.75%, and 42.76% of the drugs had an affinity to the M1, M2, M3, M4, and M5 receptor, respectively, reported in any pharmacological database. The proportion of drugs with confirmed antagonism varied among the tools (36.8% to 100%). A universal pharmacological-based list of 133 drugs is presented. It should be further validated in different clinical settings.

Regulatory agencies are responsible for collecting and evaluating spontaneous reports of suspected problems related to medications, including those from substandard medicines (SM). Objectives: The aim was to evaluate the profile of SM reports submitted to the Brazilian Health Surveillance Notification System (Notivisa) and classify these reports objectively by means of lexicographic analysis. Methods: Was extracted all SM reports available in Notivisa during the period 1 January 2007 to 31 December 2017. Descriptive statistics were performed and the reasons for SM reporting were standardized (using OpenRefine and Microsoft Excel). The following analyses were performed using IRAMuTeQ 0.7 alpha2: lexicographic analysis to obtain the frequency of active words; descending hierarchical classification (DHC) to categorize the active words into lexical classes; factorial correspondence analysis (FCA) to obtain graphs of the classes. Approved by the Ethics Committee of the Hospital do Trabalhador/SES/PR CAAE 81873417.3.0000.5225 (protocol number: 2.506.594). Results: A total of 61,775 reports were analyzed, most of them reported by hospitals (46%). The DHC of the reasons for SM produced four classes visualized in the FCA: (i) packaging problems (16%) mainly leakages/opening issues; (ii) inadequate drug identification (22%), such as illegible label information; (iii) stability and contamination issues (11%) such as presence of particles; (iv) damaged tablets/blisters (23%) mainly broken tablets. Most SM (52%) were solutions for parenteral use; sodium chloride (9%), glucose and dipyrone (3%) were the products with most complaints. Conclusions: The reasons for SM reporting can be objectively classified into classes that represent the main problems submitted to Notivisa. This classification could guide the standardization of SM reporting and contribute to improving surveillance reporting systems worldwide.

Objective We assessed the extent of lag times in the publication and indexing of network meta-analyses (NMAs).Study design This was a survey of published NMAs on drug interventions.Setting NMAs indexed in PubMed (searches updated in May 2020).Primary and secondary outcome measures Lag times were measured as the time between the last systematic search and the article submission, acceptance, online publication, indexing and Medical Subject Headings (MeSH) allocation dates. Time-to-event analyses were performed considering independent variables (geographical origin, Journal Impact Factor, Scopus CiteScore, open access status) (SPSS V.24, R/RStudio).Results We included 1245 NMAs. The median time from last search to article submission was 6.8 months (204 days (IQR 95–381)), and to publication was 11.6 months. Only 5% of authors updated their search after first submission. There is a very slightly decreasing historical trend of acceptance (rho=−0.087; p=0.010), online publication (rho=−0.080; p=0.008) and indexing (rho=−0.080; p=0.007) lag times. Journal Impact Factor influenced the MeSH allocation process, but not the other lag times. The comparison between open access versus subscription journals confirmed meaningless differences in acceptance, online publication and indexing lag times.Conclusion Efforts by authors to update their search before submission are needed to reduce evidence production time. Peer reviewers and editors should ensure authors’ compliance with NMA standards. The accuracy of these findings depends on the accuracy of the metadata used; as we evaluated only NMA on drug interventions, results may not be generalisable to all types of studies.

A implementação de serviços farmacêuticos clínicos, seja em âmbito público ou privado, não tem alcançado os níveis desejados. Uma das explicações para esse fato pode residir no desenho desses serviços que por vezes são serviços amplos, complexos e com objetivos demasiado ambiciosos. A partir de processos de reengineering, uma carteira de serviços farmacêuticos clínicos no âmbito do Componente Especializado da Assistência Farmacêutica (CEAF) da Secretaria de Estado da Saúde do Paraná (SES/PR), está sendo desenhada com intuito de melhorar os desfechos clínicos resultantes do uso de medicamentos desse componente. A proposta é implementar vários serviços com objetivos específicos utilizando a seleção de pacientes guiada por dados (data driven). Implementar esses serviços e torná-los sustentáveis é o desafio que se apresenta à Assistência Farmacêutica da SES/PR para os próximos anos com o objetivo de contribuir para melhoria da saúde dos pacientes e para a racionalização de recursos do sistema de saúde.

We aimed to determine how Portuguese physicians handle major bleeding. We also aim to establish global diagnostic and therapeutic recommendations to be followed in clinical practice by using a step-wise approach of evidence generation. This study followed a three-step process: a steering committee desk review, a Delphi technique, an expert panel meeting. A modified 3-round Delphi including 31 statements was performed. Questions were answered in a five-point Likert-type scale. Consensus threshold was established as a percentage of agreement among participants ≥90% in the first round, and ≥85% in the second and third rounds. The level of consensus achieved by panelists was discussed with the scientific committee (January-2020). Fifty-one physicians participated in the study (compliance rate >90%). Analyzing the three rounds, consensus was reached on 20 items (64.5%) in the first, 4/11 items (36.4%) in the second and 6/7 items (85.7%) in the third. One statement about administration of clotting factor concentrates for bleeding control did not reach consensus. A high level of consensus was reached toward the need for implementing Patient Blood Management strategies in Portuguese hospitals, reduce exposure to allogeneic blood components, to use goal directed therapies for acquired bleeding management, and the need for evaluating blood transfusion indirect costs. A final version with 12 recommendations was built, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Our results provide critically appraised and updated evidence on bleeding coagulopathies management in Portugal. Additional studies, mainly about indirect costs of blood transfusion, are needed.

BackgroundScholarly publishing system relies on external peer review. However, the duration of publication process is a major concern for authors and funding bodies.ObjectiveTo evaluate the duration of the publication process in pharmacy practice journals compared with other biomedical journals indexed in PubMed.MethodsAll the articles published from 2009 to 2018 by the 33 pharmacy practice journals identified in Mendes et al. study and indexed in PubMed were gathered as study group. A comparison group was created through a random selection of 3000 PubMed PMIDs for each year of study period. Articles with publication dates outside the study period were excluded. Metadata of both groups of articles were imported from PubMed. The duration of editorial process was calculated with three periods: acceptance lag (days between 'submission date' and 'acceptance date'), lead lag (days between 'acceptance date' and 'online publication date'), and indexing lag (days between 'online publication date' and 'Entry date'). Null hypothesis significance tests and effect size measures were used to compare these periods between both groups.ResultsThe 33 pharmacy practice journals published 26,256 articles between 2009 and 2018. Comparison group random selection process resulted in a pool of 23,803 articles published in 5,622 different journals. Acceptance lag was 105 days (IQR 57-173) for pharmacy practice journals and 97 days (IQR 56-155) for the comparison group with a null effect difference (Cohen's d 0.081). Lead lag was 13 (IQR 6-35) and 23 days (IQR 9-45) for pharmacy practice and comparison journals, respectively, which resulted in a small effect. Indexing lag was 5 days (IQR 2-46) and 4 days (IQR 2-12) for pharmacy practice and control journals, which also resulted in a small effect. Slight positive time trend was found in pharmacy practice acceptance lag, while slight negative trends were found for lead and indexing lags for both groups.ConclusionsPublication process duration of pharmacy practice journals is similar to a general random sample of articles from all disciplines.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant inherited disorder that results in decreased circulating levels of alpha-1 antitrypsin (also known as alpha-1 proteinase inhibitor) and predisposes affected individuals to early onset lung and liver disease. There is currently no cure for alpha-1 antitrypsin deficiency. However, appropriate treatment and a high standard of clinical care can prevent patients from being seriously affected and having to undergo major medical interventions, such as organ transplantation. Beyond managing the symptoms associated with alpha-1 antitrypsin deficiency, alpha-1 proteinase inhibitor therapy is the only treatment for the condition’s underlying cause. Early diagnosis is important to ensure efficient therapeutic strategies and to minimize further deterioration of lung function. alpha-1 antitrypsin deficiency is under diagnosed globally, partly because the disease has no unique presenting symptoms. This document was prepared by a Portuguese multidisciplinary group and it aims to set out comprehensive principles of care for Alpha-1 antitrypsin deficiency. These include the importance of registries, the need for clinical research, the need for consistent recommendations (regarding diagnosis, treatment and monitoring), the role of reference centres, the requirement for sustained access to treatment, diagnostic and support services, and the role of patient organizations.

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.

ObjectivesCurrent evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease.MethodsSystematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted.ResultsSixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure.ConclusionsThe comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.

Background and objectives: Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. Methods: Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10 g.dL−1 and the other blood products by routine coagulation and ROTEM® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. Results and conclusions: Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units. Resumo: Justificativa e objetivos: A cirurgia no grande queimado causa hemorragia de grande porte e disfunção da coagulação. Os algoritmos de tratamento guiados por ROTEM® e fator VIIa reduzem as necessidades de hemoderivados, mas falta evidência em relação ao fator XIII. A deficiência do fator XIII altera a estabilidade do coágulo e diminui a cicatrização. Este estudo avalia a eficácia e a segurança da correção do fator XIII e sua repercussão nas necessidades transfusionais na cirurgia do queimado. Métodos: Estudo retrospectivo randomizado de 40 doentes submetidos à cirurgia na Unidade de Queimados alocados em grupo A com estudo do fator XIII (n = 20) e grupo B sem estudo (n = 20). A transfusão eritrocitária foi guiada por gatilho de hemoglobina de 10 g.dL−1 e os outros hemoderivados por testes de coagulação de rotina e ROTEM®. A análise do consumo de hemoderivados incluiu unidades de eritrócitos, plasma fresco congelado, plaquetas e fibrinogênio. A análise dos biomarcadores da coagulação comparou os valores pré e pós-operatórios. Resultados e conclusões: O grupo A (com estudo de fator XIII) e o grupo B apresentaram área de superfície corporal total queimada idêntica. Todos os doentes do grupo A revelaram déficit pré-operatório de fator XIII, cuja correção reduziu significativamente a transfusão de unidades de concentrado eritrocitário (1,95 vs. 4,05, p = 0,001). Os biomarcadores de coagulação pré e pós-operatórios foram semelhantes entre os grupos, revelaram que os testes de coagulação de rotina não identificam o déficit de fator XIII. Sem eventos tromboembólicos registrados. A correção do fator XIII na cirurgia do queimado revelou-se segura e eficaz na redução da transfusão perioperatória de unidades de eritrócitos. Keywords: Intensive care, Burned, Surgery, Coagulation and hemostasis, Factor XIII, Palavras-chave: Cuidados intensivos, Queimados, Cirurgia, Coagulação e hemostase, Fator XIII

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

Abstract Background Vitamins are essential micronutrients with antioxidant potential that may provide a complementary treatment for patients with chronic diseases. Our aim was to assess the effect of vitamin supplementation on the antioxidant status and glycemic index of type 2 diabetes mellitus patients. Methods We performed a systematic review with meta-analyses. Electronic searches were conducted in PubMed, Scopus, and Web of Science (December 2017). Randomized controlled trials evaluating the effect of any vitamin or vitamin complex supplementation on antioxidant status as primary outcome were included. The outcomes considered were: reduction of malondialdehyde (MDA); augmentation of glutathione peroxidase (GPx); changes in total antioxidant capacity (TAC), enhance in superoxide dismutase enzyme—SOD, and thiobarbituric acid reactive substances (TBARS). Outcomes of glycemic control were also evaluated. Pairwise meta-analyses were performed using software Review Manager 5.3. Results Thirty trials fulfilled the inclusion criteria, but only 12 could be included in the meta-analyses of antioxidant outcomes. The most commonly studied vitamins were B, C, D and E. Vitamin E was related to significant reduction of blood glucose as well as glycated hemoglobin compared to placebo, while both vitamins C and E were mainly associated with reducing MDA and TBARS and elevating GPx, SOD and TAC, compared to placebo. However, outcome reports in this field are still inconsistent (e.g. because of a lack of standard measures). Conclusions Supplementation of vitamin E may be a valuable strategy for controlling diabetes complications and enhancing antioxidant capacity. The effects of other micronutrients should be further investigated in larger and well-designed trials to properly place these complementary therapies in clinical practice.

Background Pharmacists‐led medication reviews (MRs) are claimed to be effective for the control of cardiovascular diseases; however, the evidence in the literature is conflicting. The main objective of this meta‐analysis was to analyze the impact of pharmacist‐led MRs on cardiovascular disease risk factors overall and in different ambulatory settings while exploring the effects of different components of MRs. Methods and Results Searches were conducted in PubMed, Web of Science, Embase, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library Central Register of Controlled Trials database. Randomized and cluster randomized controlled trials of pharmacist‐led MRs compared with usual care were included. Settings were community pharmacies and ambulatory clinics. The classification used for MRs was the Pharmaceutical Care Network Europe as basic (type 1), intermediate (type 2), and advanced (type 3). Meta‐analyses in therapeutic goals used odds ratios to standardize the effect of each study, and for continuous data (eg, systolic blood pressure) raw differences were calculated using baseline and final values, with 95% CIs. Prediction intervals were calculated to account for heterogeneity. Sensitivity analyses were conducted to test the robustness of results. Meta‐analyses included 69 studies with a total of 11 644 patients. Sample demographic characteristics were similar between studies. MRs increased control of hypertension (odds ratio, 2.73; 95% prediction interval, 1.05–7.08), type 2 diabetes mellitus (odds ratio, 3.11; 95% prediction interval, 1.17–5.88), and high cholesterol (odds ratio, 1.91; 95% prediction interval, 1.05–3.46). In ambulatory clinics, MRs produced significant effects in control of diabetes mellitus and cholesterol. For community pharmacies, systolic blood pressure and low‐density lipoprotein values decreased significantly. Advanced MRs had larger effects than intermediate MRs in diabetes mellitus and dyslipidemia outcomes. Most intervention components had no significant effect on clinical outcomes and were often poorly described. CIs were significant in all analyses but prediction intervals were not in continuous clinical outcomes, with high heterogeneity present. Conclusions Intermediate and advanced MRs provided by pharmacists may improve control of blood pressure, cholesterol, and type 2 diabetes mellitus, as statistically significant prediction intervals were found. However, most continuous clinical outcomes failed to achieve statistical significance, with high heterogeneity present, although positive trends and effect sizes were found. Studies should use a standardized method for MRs to diminish sources of these heterogeneities.

Background: Medication non-adherence remains a significant problem for the health care system with clinical, humanistic and economic impact. Dispensing data is a valuable and commonly utilized measure due accessibility in electronic health data. The purpose of this study was to analyze the changes on adherence implementation rates before and after a community pharmacist intervention integrated in usual real life practice, incorporating big data analysis techniques to evaluate Proportion of Days Covered (PDC) from pharmacy dispensing data.Methods: Retrospective observational study. A de-identified database of dispensing data from 20,335 patients (n = 11,257 on rosuvastatin, n = 6,797 on irbesartan, and n = 2,281 on desvenlafaxine) was analyzed. Included patients received a pharmacist-led medication adherence intervention and had dispensing records before and after the intervention. As a measure of adherence implementation, PDC was utilized. Analysis of the database was performed using SQL and Python.Results: Three months after the pharmacist intervention there was an increase on average PDC from 50.2% (SD: 30.1) to 66.9% (SD: 29.9) for rosuvastatin, from 50.8% (SD: 30.3) to 68% (SD: 29.3) for irbesartan and from 47.3% (SD: 28.4) to 66.3% (SD: 27.3) for desvenlafaxine. These rates declined over 12 months to 62.1% (SD: 32.0) for rosuvastatin, to 62.4% (SD: 32.5) for irbesartan and to 58.1% (SD: 31.1) for desvenlafaxine. In terms of the proportion of adherent patients (PDC >= 80.0%) the trend was similar, increasing after the pharmacist intervention from overall 17.4 to 41.2% and decreasing after one year of analysis to 35.3%.Conclusion: Big database analysis techniques provided results on adherence implementation over 2 years of analysis. An increase in adherence rates was observed after the pharmacist intervention, followed by a gradual decrease over time. Enhancing the current intervention using an evidence-based approach and integrating big database analysis techniques to a real-time measurement of adherence could help community pharmacies improve and sustain medication adherence.

IntroductionAdherence-enhancing interventions have been assessed in the literature, however heterogeneity and conflicting findings have prohibited a consensus on the most effective approach to maintain adherence over time. With the ageing population and growth of chronic conditions, evaluation of sustainable strategies to improve and maintain medication adherence long term is paramount. We aimed to determine the comparative effectiveness of interventions for improving medication adherence over time among adults with any clinical condition.Materials and methodsMeta-analyses evaluating interventions to improve medication adherence were searched in PubMed in January 2019 and reviewed for primary studies. Experimental studies with a comparison group assessing an intervention to enhance medication adherence in adult patients with reported adherence outcomes were included. Two authors extracted data for study characteristics, interventions and adherence outcomes. Interventions were categorized into four groups or combinations: educational, attitudinal, technical and rewards. Four network meta-analyses were performed to compare interventions based on patient follow-up time. Medication adherence effect sizes were reported as odds ratios (OR) with a 95% credibility interval (CrI) and surface under the cumulative ranking curve (SUCRA) to allow ranking probabilities. Risk of bias was assessed as per Cochrane guidelines.ResultsData was obtained from 69 meta-analyses with 468 primary studies being included in qualitative synthesis. The four networks compromised of 249 studies in total (0-3 month follow-up: 99 studies, 4-6 months: 104, 7-9 months: 18, ≥10 months: 94). Interventions showing success in follow-ups of less than 10 months varied across time. Significant effects compared to standard of care (SOC) were found in technical (4-6 months: OR 0.34, 95% CrI 0.25-0.45) and attitudinal interventions (7-9 months: 0.37, 0.17-0.84). Multicomponent interventions demonstrated effectiveness compared to standard of care with an additive effect displayed, particularly in longer follow-ups (educational + attitudinal + technical interventions ≥10 months: OR 0.49, 95% CrI 0.27-0.88).DiscussionAll interventions reviewed improved medication adherence compared to standard of care. Multicomponent interventions displayed the most promising results in maintenance of long-term medication adherence. Technical and reward components enhanced adherence on a short-term basis, while educational and attitudinal interventions evolved over time to be more effective in follow-ups greater than 7 months. Sustainability of adherence to medications over time is dependent upon multicomponent interventions including educational, attitudinal and technical aspects to modify and enhance patient medication-taking behavior. Future research should focus on the most cost-effective approaches able to be integrated into routine practice.

BackgroundThe conduction and report of network meta-analysis (NMA), including the presentation of the network-plot, should be transparent. We aimed to propose metrics adapted from graph theory and social network-analysis literature to numerically describe NMA geometry.MethodsA previous systematic review of NMAs of pharmacological interventions was performed. Data on the graph's presentation were collected. Network-plots were reproduced using Gephi 0.9.1. Eleven geometric metrics were tested. The Spearman test for non-parametric correlation analyses and the Bland-Altman and Lin's Concordance tests were performed (IBM SPSS Statistics 24.0).ResultsFrom the 477 identified NMAs only 167 graphs could be reproduced because they provided enough information on the plot characteristics. The median nodes and edges were 8 (IQR 6-11) and 10 (IQR 6-16), respectively, with 22 included studies (IQR 13-35). Metrics such as density (median 0.39, ranged 0.07-1.00), median thickness (2.0, IQR 1.0-3.0), percentages of common comparators (median 68%), and strong edges (median 53%) were found to contribute to the description of NMA geometry. Mean thickness, average weighted degree and average path length produced similar results than other metrics, but they can lead to misleading conclusions.ConclusionsWe suggest the incorporation of seven simple metrics to report NMA geometry. Editors and peer-reviews should ensure that guidelines for NMA report are strictly followed before publication.

Scholarly publishing is in a crisis, with the many stakeholders complaining about different aspects of the system. Authors want fast publication times, high visibility and publications in high-impact journals. Readers want freely accessible, high-quality articles. Peer reviewers want recognition for the work they perform to ensure the quality of the published articles. However, authors, peer reviewers, and readers are three different roles played by the same group of individuals, the users of the scholarly publishing system—and this system could work based on a collaborative publishing principle where “nobody pays, and nobody gets paid”.

In the past years, several factors such as evidence-based healthcare culture, quality-linked incentives, and patient-centered actions, associated with an important increase of financial constraints and pressures on healthcare budgets, resulted in a growing interest by policy-makers in enlarging pharmacists’ roles in care. Numerous studies have demonstrated positive therapeutic outcomes associated with pharmaceutical services in a wide array of diseases. Yet, the evidence of the economic impact of the pharmacist in decreasing total health expenditures, unnecessary care, and societal costs relies on well-performed, reliable, and transparent economic evaluations, which are scarce. Pharmacoeconomics is a branch of health economics that usually focuses on balancing the costs and benefits of an intervention towards the use of limited resources, aiming at maximizing value to patients, healthcare payers and society through data driven decision making. These decisions can be guide by a health technology assessment (HTA) process that inform governmental players about medical, social, and economic implications of development, diffusion, and use of health technologies – including clinical pharmacy interventions. This paper aims to provide an overview of the important concepts in costing in healthcare, including studies classification according to the type of analysis method (e.g. budget-impact analysis, cost-minimization analysis, cost-effectiveness analysis, cost-utility analysis), types of costs (e.g. direct, indirect and intangible costs) and outcomes (e.g. events prevented, quality adjusted life year - QALY, disability adjusted life year - DALY). Other key components of an economic evaluation such as the models’ perspective, time horizon, modelling approaches (e.g. decision trees or simulation models as the Markov model) and sensitivity analysis are also briefly covered. Finally, we discuss the methodological issues for the identification, measurement and valuation of costs and benefits of pharmacy services, and suggest some recommendations for future studies, including the use of Value of Assessment Frameworks.

This is the first question one should consider before submitting a paper to an international journal. The answer is simple: If researchers or practitioners from another country can learn something from your paper that can influence a practice or a research they are involved in, then your paper is relevant for an international audience. There are many elements that can influence in this cross-border transferability. One could think that having a big “n”, or performing complex statistical calculations, or using complicated study designs makes the paper more attractive to colleagues from other countries. These elements can help, but they are not sufficient. On the other hand, one could think that a study performed in a small hospital in a given country will never be of interest for these foreign colleagues. That is not necessarily correct. Let’s burst some myths.

Peer review provides the foundation for the scholarly publishing system. The conventional peer review system consists of using authors of articles as reviewers for other colleagues’ manuscripts in a collaborative-basis system. However, authors complain about a theoretical overwhelming number of invitations to peer review. It seems that authors feel that they are invited to review many more manuscripts than they should when taking into account their participation in the scholarly publishing system. The high number of scientific journals and the existence of predatory journals were reported as potential causes of this excessive number of reviews required. In this editorial, we demonstrate that the number of reviewers required to publish a given number of articles depends exclusively on the journals’ rejection rate and the number of reviewers intended per manuscript. Several initiatives to overcome the peer review crises are suggested.

The interrelationship between governmental policies and objectives in primary health care and community pharmacy/pharmacists’ strategic plans are of the outmost importance, having significant professional, economic and practical consequences for the future of the pharmacy profession, research, education and health care. Sharing information of the potential and real impact on current and future practice of community pharmacy/pharmacists, be it in product or service, in primary care would benefit many stakeholders. In order to create and focus professional and scientific debate the journal has commissioned key experts to contribute a series of country case studies. The aim of the series is to promulgate and disseminate country-based information on primary health care and community pharmacy/pharmacist.

Background: Medication non-adherence has a dynamic, temporal and multifactorial nature with a significant impact on economic and clinical outcomes. Interventions to improve adherence are complex and require adaptation to patients' needs, which may include patient's medical conditions. The aim of this study was to assess the comparative effectiveness of medication adherence interventions per type of clinical condition on adult patients.Methods: A systematic review with network meta-analysis was performed (PROSPERO registration number of CRD42018054598). An initial Pubmed search was conducted to select meta-analyses reporting results of interventions aiming to improve medication adherence. Primary studies were selected and those reporting results with a long-term follow up (≥10 months) on adult patients were included for data extraction. Study characteristics, description of interventions and adherence outcomes were extracted. Adherence interventions were classified in four groups: educational, attitudinal, technical, and rewards. Clinical conditions were classified in four groups: circulatory system and metabolic diseases, infectious diseases, musculoskeletal diseases, and mental, behavioral or neurodevelopmental disorders. Network meta-analyses with effect sizes expressed as odds ratio (OR) with a 95% credibility interval (CrI) were built. Ranking probabilities for each measure of adherence were calculated by using surface under the cumulative ranking analysis (SUCRA).Results: A total of 61 meta-analysis and 149 primary studies were included in the qualitative synthesis and 80 primary studies in the quantitative analysis. The most effective interventions were: educational + technical 79.6% [OR: 0.44 (CrI: 0.26, 0.73)] and 73.3% [OR: 0.56 (0.36, 0.84)] in circulatory system and metabolic diseases and infectious diseases respectively. Attitudinal intervention had the greatest probability for musculoskeletal diseases of 92.3% in SUCRA [OR: 0.30 (0.10, 0.86)]. Finally, educational + attitudinal interventions had the greatest effect (SUCRA 73.8%) for mental, behavioral or neurodevelopmental disorders, although this was not significant according to consistency analysis.Conclusion: Effectiveness of interventions seems to be related to the clinical condition. Educational and technical interventions resulted in a major effect on long-term management of medication adherence in patients with infectious diseases (HIV) and circulatory system and metabolic diseases whereas attitudinal components presented a higher effect on musculoskeletal and mental, behavioral or neurodevelopmental disorders.

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.

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.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.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.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.

Network meta-analysis (NMA) is a new tool developed to overcome some limitations of pairwise meta-analyses. NMAs provide evidence on more than two comparators simultaneously. This study aimed to map the characteristics of the published NMAs on drug therapy comparisons.A systematic review of NMAs comparing pharmacological interventions was performed. Searches in Medline (PubMed) and Scopus along with manual searches were conducted. The main characteristics of NMAs were systematically collected: publication metadata, criteria for drug inclusion, statistical methods used, and elements reported. A methodological quality score with 25 key elements was created and applied to the included NMAs. To identify potential trends, the median of the publication year distribution was used as a cut-off.The study identified 365 NMAs published from 2003 to 2016 in more than 30 countries. Randomised controlled trials were the primary source of data, with only 5% including observational studies, and 230 NMAs used a placebo as a comparator. Less than 15% of NMAs were registered in PROSPERO or a similar system. One third of studies followed PRISMA and less than 9% Cochrane recommendations. Around 30% presented full-search strategies of the systematic review, and 146 NMAs stated the selection criteria for drug inclusion. Over 75% of NMAs presented network plots, but only half described their geometry. Statistical parameters (model fit, inconsistency, convergence) were properly reported by one third of NMAs. Although 216 studies exhibited supplemental material, no data set of primary studies was available. The methodological quality score (mean 13·9; SD 3·8) presented a slightly positive trend over the years.The map of the published NMAs emphasises the potential of this tool to gather evidence in healthcare, but it also identified some weaknesses, especially in the report, which limits its transparency and reproducibility.

Inappropriate use of multiple medicines (inappropriate polypharmacy) is a major challenge in older people with consequences of increased prevalence and severity of adverse drug reactions and interactions, and reduced medicines adherence. The aim of this study was to determine the levels of consensus amongst key stakeholders in the European Union (EU) in relation to aspects of the management of polypharmacy in older people.Forty-six statements were developed on aspects of healthcare structures, processes and desired outcomes, with consensus defined at ≥ 80% agreement. Panel members were strategists (e.g. directors, leading clinicians and commissioners) from each of the 28 EU member states, with a target recruitment of five per member state. Three Delphi rounds were conducted via email, with panel members being provided with summative results and collated, anonymised comments at the commencement of Rounds 2 and 3.Ninety panel members were recruited (64.3% of target), with high participation levels throughout the three Delphi rounds (91.1%, 83.3%, 72.2%). During Round 1, consensus was obtained for 27/46 statements (58.7%), with an additional two statements in Round 2 and none in Round 3. Consensus was obtained for statements relating to: potential gain arising from polypharmacy management (3/4 statements); strategic development (7/7); change management (5/7) indicator measures (4/6); legislation (0/3); awareness raising (5/5); polypharmacy reviews (5/7); and EU vision (0/7). Analysis of free text comments indicated that the vision statements were too ambitious and not achievable by the specified timeframe of 2025.Consensus was obtained amongst key EU strategists around many aspects of polypharmacy management in older people. Notably, no consensus was achieved in relation to statements relating to the need to alter legislation in areas of healthcare delivery, remuneration and practitioner scope of practice. While the vision for the EU by 2025 was considered rather ambitious, there is great potential and clear opportunity to advance polypharmacy management throughout the EU and beyond.

Este estudo avaliou a morbimortalidade relacionada a medicamentos no Brasil, sua prevalência, grupos farmacológicos e fatores de risco, Foi realizada uma revisão sistemática de estudos observacionais publicados até agosto de 2012, sem restrição de data de início, nas bases de dados Medline, Lilacs, Scielo, Embase, IPA, Science Direct, Scopus e Web of Science, Foram selecionados estudos nacionais avaliando a ocorrência de qualquer tipo de dano ocasionado por medicamento, Foram incluídos 45 estudos, A maior prevalência de evento adverso a medicamento foi observada em hospitais, em adultos e idosos, variando de 15,6% a 34,1%, Nas creches, 19,9% das crianças sofreram alguma reação adversa, Em serviços de emergência, 25% dos adultos ou idosos sofreram dano relacionado à falha terapêutica, Medicamentos atuantes no sistema nervoso central foi o principal grupo farmacológico envolvido, Os principais fatores de risco foram idade, presença de comorbidades e uso de > 5 medicamentos, Os resultados encontrados são alarmantes e demonstram a necessidade da avaliação e estratificação de risco populacional, ações preventivas e de intervenção precoce que possam reduzir o impacto da morbimortalidade relacionada a medicamentos no Brasil.

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CONTEXT AND OBJECTIVES The Beliefs about Medicines Questionnaire (BMQ-Specific) has proven useful for measuring patients' beliefs and associating them with non-adherence to treatment in several illness groups. The aim was to cross-culturally adapt the BMQ-Specific into Portuguese for the general population of medicine users. DESIGN AND SETTING Cross-sectional study conducted among users of public hospitals and outpatient clinics in Guarda and Covilhã, Portugal. METHODS The BMQ-Specific was translated using international recommendations for performing cross-cultural adaptation and was administered to 300 patients. An initial principal component analysis (PCA) was conducted with the extraction criterion of eigenvalue > 1.0, followed by a second PCA with restriction to two components. Reliability was assessed by calculating Cronbach's alpha coefficient. RESULTS The mean scores obtained for the Necessity and Concerns subscales of the Portuguese BMQ-Specific were 19.9 (standard deviation, SD = 2.8) (range 10 to 25) and 17.7 (SD = 3.9) (range 6 to 30), respectively. The first PCA produced an unstable three-component structure for the Portuguese BMQ-Specific. The final PCA solution yielded a two-component structure identical to the original English version (a five-item Necessity and a six-item Concerns subscale), and explained 44% of the variance. Cronbach's alpha for the complete Portuguese BMQ-Specific was 0.70, and 0.76 and 0.67 for the Necessity and Concerns subscales, respectively. CONCLUSION A cross-culturally adapted Portuguese version of the BMQ-Specific questionnaire for use among the general population of medicine users was obtained, presenting good internal consistency and component structure identical to the original English version. CONTEXTO E OBJETIVO O Beliefs about Medicines Questionnaire (BMQ-Específico) tem se mostrado útil na mensuração sobre as crenças dos pacientes e associando-os à não adesão ao tratamento em vários grupos de doença. O objetivo foi realizar a adaptação transcultural do BMQ-Específico em Português para a população geral de usuários de medicamentos. TIPO DE ESTUDO E LOCAL Estudo transversal conduzido com usuários de hospitais públicos e clínicas ambulatoriais em Guarda e Covilhã, Portugal. MÉTODOS O BMQ-Específico foi traduzido utilizando-se recomendações internacionais para realizar a adaptação transcultural e foi administrado a 300 pacientes. Uma primeira análise de componentes principais (ACP) com critério de extração eigenvalue > 1.0 foi realizada, seguida de uma segunda ACP com restrição para dois componentes. A confiabilidade foi avaliada calculando-se o coeficiente alfa de Cronbach. RESULTADOS Os escores médios obtidos para as subescalas de Necessidade e Preocupação do BMQ-específico em Português foram de 19,9 (desvio padrão, DP = 2,8; intervalo 10 a 25) e 17,7 (DP = 3,9; intervalo 6 a 30), respectivamente. A primeira ACP produziu estrutura instável de três componentes para o BMQ-específico em português. A solução final de ACP produziu estrutura de dois componentes idênticos à versão original em inglês (subescala de Necessidade de 5 itens e subescala de Preocupação de 6 itens), explicando 44% da variância. Alfa de Cronbach para o BMQ-Específico em Português completo foi de 0,70, sendo 0,76 e 0,67 para as subescalas de Necessidade e Preocupação, respectivamente. CONCLUSÃO A versão adaptada do questionário BMQ-Específico em português para ser utilizada na população em geral dos usuários de medicamentos foi obtida, apresentando boa consistência interna e estrutura do componente idêntica à versão original em inglês.

Introducción: Los organismos internacionales farmacéuticos reclaman una educación farmacéutica más centrada en el paciente, que de apoyo a las funciones de la atención farmacéutica. Para ello, se han desarrollado marcos de competencias, que no siempre se han asociado a los correspondientes contenidos docentes. Objetivo: Identificación sistemática de los contenidos programáticos del área de farmacia práctica, mediante la creación de un árbol de codificación de contenidos. Método: Análisis cualitativo de los contenidos docentes de asignaturas del área de farmacia práctica de los planes de estudios de las facultades de farmacia de Australia, Canadá, Estados Unidos, y Nueva Zelanda. Los syllabus fueron obtenidos de las páginas web de las facultades de farmacia, excluyendo las que no tenían el plan de estudios completo disponible en inglés. Se solicitó a los responsables de las asignaturas información adicional por correo electrónico. Se creó un árbol de contenidos inicial a partir de directrices del Accreditation Council for Pharmacy Education. Se realizó un proceso iterativo de codificación dirigida, para obtener el árbol final de códigos que permitiese clasificar los contenidos docentes del área de farmacia práctica. Resultados: Se incluyeron 110 facultades (Australia=15; Canadá=5; Estados Unidos=89; y Nueva Zelanda=1), con 8733 asignaturas, de las que 1703 (19.5%) pertenecían al área de farmacia práctica y presentaban syllabus con información detallada. Se obtuvo respuesta con información adicional de 119 asignaturas. El análisis de contenido convirtió el árbol inicial de 39 categorías, en un árbol final de codificación con 3 niveles jerárquicos y 69 categorías. Conclusión: En los países del análisis, aproximadamente el 20% de las asignaturas pertenecen al área de farmacia práctica. Se ha conseguido un árbol de codificación y clasificación de los contenidos docentes de farmacia práctica. Futuros estudios deberían mapear las asignaturas actuales para determinar si los contenidos identificados están siendo enseñados.