Extração de recomendações farmacológicas para subsidiar o processo de adaptação de guias de prática clínica utilizados no tratamento da fibrilação atrial não valvar - uma revisão sistemática de guias de prática clínica / Extraction of pharmacological recommendations to support the process of adaptation of clinical practice guides used in the treatment of non-valvular atrial fibrillation a systematic review of clinical practice guidelines

A fibrilação atrial (FA) não valvar é a arritmia cardíaca mais comum em adultos, principalmente na população idosa. Para o tratamento da FA, recomenda-se a utilização de guias de prática clínica (GPCs), que são documentos que apresentam as melhores e mais atualizadas evidências para o tratamento dos pacientes acometidos por essa arritmia. Todavia, o processo de desenvolvimento dos GPCs requer recursos humanos, financeiros e tempo. Assim, a adaptação dos referidos documentos é uma opção para reduzir a duplicação de esforços e possibilitar sua adequação para uso local. O objetivo deste trabalho foi elaborar uma matriz de recomendações farmacológicas para subsidiar o processo de adaptação de GPCs utilizados no tratamento da fibrilação atrial não valvar. Para tanto, aplicou-se o método ADAPTE: revisão sistematizada de GPCs, avaliação e seleção dos GPCs de qualidade e elaboração da matriz. Foram considerados elegíveis 26 GPCs com recomendações farmacológicas para assistência primária da fibrilação atrial não valvar em adultos, publicados em inglês, espanhol ou português no período de abril de 2014 a abril de 2019 e indexados às bases de referência: MEDLINE, Embase, Cochrane Library e em 12 bases de dados específicas. A qualidade dos GPCs, foi avaliada pela aplicação do instrumento Appraisal of Guidelines for Research & Evaluarion II (AGREE II), sendo considerados de alta qualidade aqueles que apresentaram nota igual ou superior a 60 % no domínio Rigor de desenvolvimento. Todas as etapas foram realizadas por, pelo menos, 2 avaliadores e em caso de discrepância, um terceiro avaliador participou do processo. Dos 26 GPCs avaliados apenas 7 (26,9%) foram considerados de alta qualidade. A maioria dos GPCs utiliza o escore CHA2DS2-VASc, que indica a profilaxia tromboembólica em pacientes com FA não valvar a partir da pontuação 1 (fator de risco não sexual) e sugere a anticoagulação com anticoagulantes de ação direta. Houve pouca ênfase à complexidade da profilaxia de eventos tromboembólicos em idosos. Esta matriz visa contribuir para que sejam realizadas discussões e adaptações de GPCs destinado ao tratamento da FA não valvar com ênfase nas demandas e necessidades locais

Non-valvular atrial fibrillation (AF) is the most common cardiac arrhythmia in adults, especially in the elderly population. For the treatment of AF, the use of clinical practice guidelines (CPGs) is recommended, which are documents that present the best and most up-to-date evidence for the treatment of patients who are affected by this arrhythmia. However, the CPGs development process requires human, financial and time resources. However, the adaptation of documents is an option to reduce the duplication of efforts and make it possible to adapt them for any local use. The objective of this work was to elaborate a matrix of pharmacological treatment to support the process of adaptation of CPGs used in the treatment of non-valvular atrial fibrillation. Therefore, the ADAPTE method was applied: systematic review of CPGs, evaluation and selection of quality CPGs and matrix definition. Twenty-six CPGs were considered eligible with pharmacological recommendations for primary care of non-valvular atrial fibrillation valid in adults, published in English, Spanish or Portuguese from April 2014 to April 2019 and indexed to the following reference databases: MEDLINE, Embase, Cochrane Library and in 12 specific databases. The quality of the CPGs was assessed by applying the Assessment of Guidelines for Research and Assessment II (AGREE II) instrument, being considered of high those who had a grade equal to or greater than 60% in the domain Rigour of development. All steps were performed by a least 2 evaluators and in case of discrepancy, a third evaluator participated in the process. Of the 26 CPGs evaluated, only 7 (26.9%) were considered to be of high quality. Most CPGs use the CHA2DS2-VASc score, which indicates thromboembolic prophylaxis in patients with non-valvular AF from score 1 (non-sexual risk factor), and suggest anticoagulation with direct-acting anticoagulants. There was little emphasis on the complexity of prophylaxis for thromboembolic events in the elderly. This matrix aims to contribute to discussion and adaptations of CPGs for the treatment of non-valvar AF with the emphasis on local demands and needs

Strategies towards expansion of chemical space of natural product-based compounds to enable drug discovery

Natural products (NPs) are an excellent source of biologically active molecules that provide many biologically biased features that enable innovative designing of synthetic compounds. NPs are characterized by high content of sp3-hybridized carbon atoms; oxygen; spiro, bridged, and linked systems; and stereogenic centers, with high structural diversity. To date, several approaches have been implemented for mapping and navigating into the chemical space of NPs to explore the different aspects of chemical space. The approaches providing novel opportunities to synthesize NP-inspired compound libraries involve NP-based fragments and ring distortion strategies. These methodologies allow access to areas of chemical space that are less explored, and consequently help to overcome the limitations in the use of NPs in drug discovery, such as lack of accessibility and synthetic intractability. In this review, we describe how NPs have recently been used as a platform for the development of diverse compounds with high structural and stereochemical complexity. In addition, we show developed strategies aiming to reengineer NPs toward the expansion of NP-based chemical space by fragment-based approaches and chemical degradation to yield novel compounds to enable drug discovery