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Cannabis sativa is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for Cannabis sativa potential effects, especially tetrahydrocannabinol and cannabidiol. Scientific development has shown interest in the potential of cannabidiol in various health conditions, as it has demonstrated lower adverse events and great pharmacological potential, especially when administered topically. The present study aims to carry out a scoping review, focusing on the use of cannabidiol, in vivo models, for topical administration. Thus, the methodological approach used by the Joanna Briggs Institute was applied, and the studies were selected based on previously established inclusion criteria. Even though more information regarding the dose to achieve pharmacological potential is still needed, cannabidiol demonstrated potential in treating and preventing different conditions, such as glaucoma, atopic dermatitis, epidermolysis bullosa, and pyoderma gangrenosum.

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OBJECTIVE: The objective of this study was to assess the quality of clinical practice guidelines (CPGs) for the pharmacological treatment of depression along with their recommendations and factors associated with higher quality. DESIGN: We conducted a systematic review that included CPGs for the pharmacological treatment of depression in adults. DATA SOURCES: We searched for publications from 1 January 2011 to 31 December 2021, in MEDLINE, Cochrane Library, Embase, PsycINFO, BVS and 12 other databases and guideline repositories. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included CPGs containing recommendations for the pharmacological treatment of depression in adults at outpatient care setting, regardless of whether it met the U.S. National Academy of Medicine criteria, or not. If a CPG included recommendations for both children and adults, they were considered. No language restriction was applied. DATA EXTRACTION AND SYNTHESIS: Data extraction was also conducted independently and in duplicate, a process that was validated in a previous project. The quality of the CPGs and their recommendations were assessed by three independent reviewers using Appraisal of Guidelines for Research and Evaluation (AGREE II) and Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX). A CPG was considered to be of high quality if AGREE II Domain 3 was ≥60%; while their recommendations were considered high if AGREE-REX Domain 1 was ≥60%. RESULTS: Seventeen out of 63 (27%) CPGs were classified as high quality, while 7 (11.1%) had high-quality recommendations. The factors associated with higher-scoring CPGs and recommendations in the multiple linear regression analyses were 'Handling of conflicts of interest', 'Multiprofessional team' and 'Type of institution'. 'Inclusion of patient representative in the team' was also associated with higher-quality recommendations. CONCLUSIONS: The involvement of professionals from diverse backgrounds, the handling of conflicts of interest, and the inclusion of patients' perspectives should be prioritised by developers aiming for high-quality CPGs for the treatment of depression.

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INTRODUCTION: The production of clinical practice guidelines (CPGs) has grown in the past years. Notwithstanding, the quality of these documents and their recommendations for the treatment of schizophrenia in children and adolescents is still unknown. OBJECTIVE: To assess the quality of the guidelines and recommendations for the treatment of schizophrenia in this population. METHODS: CPGs from 2004 to December 2020 were identified through a systematic search on EMBASE, MEDLINE, PsycINFO, PubMed, Epistemonikos, VHL, Global Index Medicus and specific CPG databases. The CPGs' quality was independently assessed by three reviewers using AGREE II and they were considered of high quality if they scored ≥60% in domains 3 and 6. The evidence classification systems were described, the quality of recommendations was assessed in pairs using AGREE-REX and the recommendations were compared. RESULTS: The database search retrieved 3182 results; 2030 were screened and 29 were selected for full-text reading. Four guidelines were selected for extraction. Two CPGs were considered of high quality in the AGREE II assessment. We described the commonly agreed recommendations for each treatment phase. The pharmacological recommendations were described in all treatment phases. Scores of AGREE-REX were lower for psychosocial recommendations. CONCLUSION: There are still few clinical studies and CPGs regarding schizophrenia in children and adolescents. The quality of the documents was overall low, and the quality of the recommendations report has much to improve. There is also a lack of transparency about the quality of the evidence and the strength of the recommendations. PROTOCOL REGISTRATION NUMBER: CRD42020164899.

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Abstract Hepatic injury has been documented in patients with coronavirus disease 2019 (COVID-19). However, pharmacotherapy can frequently impact liver alterations, given the known hepatotoxic potential of drugs not effective to treat COVID-19. The objective of the present study was to evaluate reports of suspected liver reactions to drugs used for treating COVID-19, compare their use for other indications among patients with COVID-19, and assess possible interactions between them. We obtained reports on drugs used to treat COVID-19 (tocilizumab, remdesivir, hydroxychloroquine, and/or lopinavir/ritonavir), registered on June 30, 2020, from the Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard. We then analyzed the risk of developing liver events with these drugs by calculating the reported odds ratios (ROR). We identified 662, 744, and 1381 reports related to tocilizumab, lopinavir/ ritonavir, and hydroxychloroquine use, respectively. The RORs (95% confidence intervals) were 6.32 (5.28-7.56), 6.12 (5.22-7.17), and 9.07 (8.00-10.29), respectively, demonstrating an increased risk of liver events among patients with COVID-19 when compared with uninfected patients. The elevated risk of reporting adverse liver events in patients with COVID-19 who receive these drugs, alone or in combination, highlights the need for careful drug selection and efforts to reduce drug combinations without notable benefits. Similar to any other condition, the use of drugs without established efficacy should be avoided.

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Pharmacogenetics is the relationship between an individual's genetic variations and their response to pharmacological treatment. We conducted an overview of reviews on the use of post-treatment pharmacogenetic testing for oncology, based on clinically relevant gene-drug pairs. We conducted a search on Medline, Embase and Cochrane Library, from their inception to 18 June 2020. We selected six eligible systematic reviews. The most studied drug categories were estrogen agonists/antagonists and fluoropyrimidines associated with cytochrome P450 and dihydropyrimidine dehydrogenase genes (CYP2D6 and DPYD), but many studies were classified as being of critically low or low quality. There is a need for more high-quality primary studies and systematic reviews that assess the risk of bias, with consistent definitions of clinical outcomes to consider the benefits of pharmacogenetic testing for oncology.

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INTRODUCTION: Depression is a serious and widespread mental health disorder. Although effective treatment does exist, a significant proportion of patients with depression fail to respond to antidepressant treatment trials, a condition named treatment-resistant depression. Efficient approach should be given this condition in order to revert the burden caused by depression. Clinical practice guidelines (CPGs) are evidence-based health promotion instruments to improve diagnosis and treatment. CPGs recommendations for treatment-resistant depression must be trustworthy. The objective of the proposed study is to systematically identify, appraise the quality of CPGs for the treatment of depression and elaborate a synthesis of recommendations for treatment-resistant depression of CPGs considered to be of high quality and with high quality recommendations. METHODS AND ANALYSIS: We will search the databases of organizations, such as PubMed, Embase, Cochrane Library, PsycInfo, and the Virtual Health Library, and organizations that develop CPGs. Three independent researchers will assess the quality of the CPGs and their recommendations using the AGREE II and AGREE-REX instruments, respectively. Given the identification of divergences and convergences as well as weak and strong points among high quality CPGs, our work may help developers, clinicians and eventually patients. ETHICS AND DISSEMINATION: No ethical approval is required for a systematic review, as no patient data will be used. The research results will be disseminated in conferences and submitted to a peer reviewed journal.

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OBJECTIVE: To assess similarities and differences in the recommended sequence of strategies among the most relevant clinical practice guidelines (CPGs) for the treatment of depression in adults with inadequate response to first-line treatment. DATA SOURCES: We performed a systematic review of the literature spanning January 2011 to August 2020 in Medline, Embase, Cochrane Library and 12 databases recognised as CPGs repositories. CPGs quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). STUDY SELECTION: The eligibility criteria were CPGs that described pharmacological recommendations for treating depression for individuals aged 18 years or older in outpatient care setting. We included CPGs considered of high-quality (≥80% in domain 3 of AGREE II) or recognised as clinically relevant. DATA EXTRACTION: Two independent researchers extracted recommendations for patients who did not respond to first-line pharmacological treatment from the selected CPGs. RESULTS: We included 46 CPGs and selected 8, of which 5 were considered high quality (≥80% in domain 3 of AGREE II) and 3 were recognised as clinically relevant. Three CPGs did not define inadequate response to treatment and 3 did not establish a clear sequence of strategies. The duration of treatment needed to determine that a patient had not responded was not explicit in 3 CPGs and was discordant in 5 CPGs. Most CPGs agree in reassessing the diagnosis, assessing the presence of comorbidities, adherence to treatment, and increase dosage as first steps. All CPGs recommend psychotherapy, switching antidepressants, and considering augmentation/combining antidepressants. CONCLUSION: Relevant CPGs present shortcomings in recommendations for non-responders to first-line antidepressant treatment including absence and divergencies in definition of inadequate response and sequence of recommended strategies. Overall, most relevant CPGs recommend reassessing the diagnosis, evaluate comorbidities, adherence to treatment, increase dosage of antidepressants, and psychotherapy as first steps. PROSPERO REGISTRATION NUMBER: CRD42016043364.

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Pharmacogenetics (PGx) is the relationship between an individual's genetic variations and the response to pharmacological treatment. We chose to perform an overview of reviews on PGx testing-guided treatment for cardiovascular diseases, based on clinically relevant gene-drug pairs. We conducted a search on Medline, Embase and Cochrane Library, from their inception to 18 June 2020. The most studied gene-drug pairs were clopidogrel and warfarin associated with cytochrome p450 and vitamin K epoxide reductase complex subunit 1 genes (CYP2C19, CYP2C9 and VKORC1), classified as critically low quality. There is a need for more quality primary studies and systematic reviews that assess the risk of bias, with consistent definitions of clinical outcomes to consider the benefits of PGx testing for cardiovascular diseases.

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Clinical practice guidelines are statements that include recommendations intended to optimize patient care, are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options, and ensure that the best available clinical knowledge is used to provide effective and quality care. They can reduce inappropriate care and variability in clinical practice and can support the translation of new research knowledge into clinical practice. Recommendations from clinical practice guidelines can support health professionals by facilitating the decision-making process, empowering them to make more informed health care choices, clarifying which interventions should be priorities based on a favorable tradeoff, and discouraging the use of those that have proven ineffective, dangerous, or wasteful. This review aims to summarize the key components of high-quality and trustworthy guidelines. Articles were retrieved from various libraries, databases, and search engines using free-text term searches adapted for different databases, and selected according to author discretion. Clinical practice guidelines in geriatrics can have a major impact on prevention, diagnosis, treatment, rehabilitation, health care, and the management of diseases and conditions, but they should only be implemented when they have high-quality, rigorous, and unbiased methodologies that consider older adult priorities and provide valid recommendations.

As diretrizes de prática clínica são declarações que incluem recomendações destinadas a otimizar o atendimento ao paciente, informadas por uma revisão sistemática de evidências e uma avaliação dos benefícios e malefícios de opções alternativas de atendimento, garantindo que o melhor conhecimento clínico disponível seja usado para fornecer atendimento eficaz e de qualidade. Elas contribuem reduzindo os cuidados inadequados e a variabilidade na prática clínica e podem apoiar a tradução de novos conhecimentos de pesquisa. As recomendações dessas diretrizes podem apoiar os profissionais de saúde, facilitando o processo de tomada de decisão, capacitando-os a fazer escolhas de cuidados de saúde mais informadas, esclarecendo quais intervenções devem ser prioritárias com base em um trade-off favorável e desencorajando o uso daquelas comprovadamente ineficazes, perigosas ou que consistam em desperdício. Esta revisão visa resumir os principais componentes de diretrizes confiáveis e de alta qualidade. Os artigos foram recuperados de várias bibliotecas, bancos de dados e mecanismos de busca por meio de buscas de termos de texto livre adaptados para diferentes bancos de dados e selecionados de acordo com o critério do autor. As diretrizes de prática clínica em geriatria podem ter grande impacto na prevenção, diagnóstico, tratamento, reabilitação, assistência à saúde e manejo de doenças e condições, mas só devem ser implementadas quando tiverem metodologias de alta qualidade, rigorosas e imparciais, que considerem as prioridades da pessoa idosa e forneçam recomendações válidas.

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The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

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Pharmacogenetic testing is available to healthcare professionals to guide drug selection and prevent adverse events. However, its implementation in the clinical practice of psychiatry/neurology still has barriers, mainly due to a lack of evidence. We conducted a literature search on Cochrane Library, Embase and Pubmed, from their inception to 18 June 2020. We included 16 published systematic reviews. The most studied drug categories were anticonvulsants and selective serotonin reuptake inhibitors associated with human leukocyte antigen and cytochrome P450 genes (HLA-A, HLA-B, CYP2C9, CYP2D6, CYP2C19), classified as critically low quality/low quality. There is a need for more robust studies with adequate design to assess the potential benefits of adopting pharmacogenetics in health systems and services.

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OBJECTIVE: To describe the methodological characteristics and good research practices of COVID-19 interventional studies developed in Brazil in the first months of the pandemic. METHODS: We reviewed the bulletin of the National Research Ethics Committee - Coronavirus Special Edition (Comissão Nacional de Ética em Pesquisa - CONEP-COVID) (May 28, 2020) and the databases of the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC) to identify interventional studies registered in Brazil that assessed drug type, biological therapy, or vaccines. We described their methodological characteristics and calculated their power for different effect magnitudes. RESULTS: A total of 62 studies were included, 55 retrieved from the CONEP website, and 7 from registry databases. The most tested pharmacological interventions in these studies were: chloroquine/hydroxychloroquine, azithromycin, convalescent plasma, tocilizumab, sarilumab, eculizumab, vaccine, corticosteroids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, and lopinavir/ritonavir. Out of 22 protocols published on registry databases until May 2020, 18 (82%) were randomized clinical trials, and 13 (59%) had an appropriate control group. However, 9 (41%) of them were masked, and only 5 (24%) included patients diagnosed with a specific laboratory test (for example, reverse transcription polymerase chain reaction - RT-PCR). Most of these studies had power > 80% only to identify large effect sizes. In the prospective follow-up, 60% of the studies available at CONEP until May 2020 had not been published on any registry platform (ICTRP/ReBEC/ClinicalTrials) by July 21, 2020. CONCLUSION: The interventions evaluated during the Brazilian research response reflect those of international initiatives, but with a different distribution and a large number of studies assessing hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.

OBJETIVO: Descrever as características metodológicas e de boas práticas em pesquisa dos estudos de intervenção para COVID-19 desenvolvidos no Brasil nos primeiros meses da pandemia. MÉTODOS: Revisamos o boletim da Comissão Nacional de Ética em Pesquisa - edição especial Coronavírus (CONEP-COVID) (28 de maio de 2020) e as bases International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov e Registro Brasileiro de Ensaios Clínicos (ReBEC) para identificar estudos registrados no Brasil que avaliassem intervenções de tipo de medicamento, terapia biológica ou vacinas. Descrevemos as características metodológicas e calculamos o poder para diferentes magnitudes de efeito. RESULTADOS: Foram incluídos 62 estudos, 55 identificados no site da CONEP e mais sete nas bases de registro. As intervenções medicamentosas mais frequentemente testadas nesses estudos foram: cloroquina/hidroxicloroquina, azitromicina, plasma convalescente, tocilizumabe, sarilumabe, eculizumabe, vacina, corticoides, anticoagulantes, n-acetilcisteína, nitazoxanida, ivermectina e lopinavir/ritonavir. De 22 protocolos publicados até maio de 2020 nas bases de registro, 18 (82%) eram ensaios clínicos randomizados e 13 (59%) tinham grupo controle adequado. Entretanto, nove (41%) eram mascarados e somente cinco (24%) incluíam pacientes diagnosticados com teste de laboratório específico (por exemplo, transcrição reversa seguida de reação em cadeia da polimerase - RT-PCR). A maioria desses trabalhos teria poder > 80% apenas para identificar grandes tamanhos de efeito. Em seguimento prospectivo, observamos que 60% dos estudos disponíveis na CONEP até maio de 2020 não estavam em nenhuma das plataformas de registro (ICTRP/ReBEC/ClinicalTrials) até o dia 21 de julho de 2020. CONCLUSÃO: As intervenções avaliadas durante a resposta brasileira em pesquisa refletem iniciativas internacionais, porém com distribuição diferente, tendo número elevado de estudos que avaliam hidroxicloroquina/cloroquina. Limitações no delineamento metodológico e planejamento amostral representam desafios que podem afetar o alcance dos trabalhos.

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Abstract: The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

Resumo: De acordo com a Agência de Controle de Alimentos e Medicamentos dos Estados Unidos (FDA), a prescrição do remdesivir deve ser feita com cautela em pacientes com taxa de filtração glomerular estimada (TFGe) < 30, sendo que diversos estudos relatam risco de eventos adversos renais. São limitados os dados disponíveis sobre o perfil de segurança renal do remdesivir. Assim, analisamos as reações adversas renais e urinárias atribuídas ao remdesivir e notificadas em um grande base de dados abertos de farmacovigilância. Obtivemos notificações sobre remdesivir e outros medicamentos usados para tratar a COVID-19 (tocilizumabe, hidroxicloroquina, lopinavir/ritonavir) registradas até 30 de setembro de 2020 do Sistema de Notificação de Eventos Adversos da FDA (FAERS). Analisamos as razões de chances de notificação (RORs) para notificações de eventos adversos renais e urinários referentes ao remdesivir e outros medicamentos. Encontramos 2.922 notificações sobre remdesivir registradas no FAERS para COVID-19. Entre esses casos, foram notificados 493 efeitos adversos renais e urinários (16,9%). Os eventos mais frequentes foram lesão renal aguda (338; 11,6%), comprometimento renal (86; 2,9%) e insuficiência renal (53; 1,8%). Comparado com a hidroxicloroquina, lopinavir/ritonavir ou tocilizumabe, o uso do remdesivir esteve associado com um aumento das chances de notificação de transtornos renais e urinários, independentemente do sexo e idade dos pacientes (2,53; IC95%: 2,10-3,06). A ROR permaneceu significativo quando limitamos a análise à hidroxicloroquina (4,31; IC95%: 3,25-5,71) ou ao tocilizumabe (3,92; IC95%: 2,51-6,12). Nossos resultados corroboram outros estudos e destacam a utilidade para profissionais da saúde que usam esse novo antiviral para tratar a COVID-19, sobretudo em função de sua baixa eficácia.

Resumen: La Agencia Americana de Control de Alimentos y Medicamentos (FDA) ha destacado que la prescripción de remdesivir debe ser prudente con pacientes con tasa de filtración glomerular estimada (TGFe) < 30; además, algunos estudios informaron del riesgo de reacciones adversas renales. La información disponible sobre el perfil de seguridad renal, en el caso del remdesivir, es limitada. Por ello, analizamos las reacciones adversas renales y urinarias atribuidas al remdesivir e notificadas en una extensa base de datos abierta de farmacovigilancia. Obtuvimos las notificaciones de remdesivir y otros medicamentos usados para tratar la COVID-19 (tocilizumab, hidroxicloroquina, lopinavir/ritonavir) registrados el 30 de septiembre de 2020 por el Sistema de Notificación de Eventos Adversos de la FDA (FAERS). Analizamos las odds ratios informadas (RORs) en el caso de informes de eventos adversos renales y urinarios adversos relacionados con el remdesivir y otros medicamentos. En el FAERS, encontramos 2.922 notificaciones de remdesivir registradas como medicament sospechoso usado en COVID-19. De estos, habían 493 con efectos renales y urinarios adversos (16,9%). Los efectos adversos más frecuentes fueron lesiones renales agudas (338; 11,6%), insuficiencia renal (86; 2,9%), y fallo renal (53; 1,8%). Frente a hidroxicloroquina, lopinavir/ritonavir, o tocilizumab, el uso de remdesivir se asoció con un riesgo mayor de notificar alteraciones renales y urinarios, independientemente del género y edad de los pacientes (2,53; IC95%: 2,10-3,06). La ROR permaneció significativo al restringir el análisis a la hidroxicloroquina (4,31; IC95%: 3,25-5,71) o tocilizumab (3,92; IC95%: 2,51-6,12). Nuestros resultados corroboran datos previos, algo que podría ser extremadamente útil para los profesionales de la salud que decidan usar este nuevo antiviral para tratar la COVID-19, sobre todo conociendo su baja eficacia.

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INTRODUCTION: The number of clinical practice guidelines (CPGs) have increased substantially mainly in the paediatric area of mental health. However, little is known about the quality or how recommendations for the treatment of disorders such as schizophrenia in children and adolescents have changed over time. The aim of this study will be to assess the quality of the development of CPGs for the treatment and management of schizophrenia in children and adolescents over time using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and to compare the recommendations and interventions described in these documents. METHODS AND ANALYSIS: CPGs will be identified using a prospective protocol through a systematic search of multiple databases (Medline, Embase, Health Systems Evidence, Epistemonikos, Lilacs, etc) and guideline websites from 2004 to December 2020. The quality of the guidelines will be assessed by three reviewers, independently using the AGREE II. CPGs will be considered of high-quality if they scored ≥60% in four or more domains of the AGREE II instrument. Non-parametric tests will be used to test for the change of quality over time. We will summarise the different evidence grading systems and compare the recommendations. ETHICS AND DISSEMINATION: Ethical approval is not required since it is a literature-based study. Future results of the research can be submitted for publication in scientific journals of high impact, peer reviewed and also published in national and international conferences. The results derived from this study will contribute to the improvement of health institutions and policies, informing about existing recommendation guidelines and about deficiencies and qualities found in those. This study may also identify key areas for future research. This study may guide the search and choice for high quality CPGs by health policy makers and health professionals and subsidise future adaptations. PROTOCOL REGISTRATION NUMBER: CRD42020164899.

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Depression affects over 300 million individuals worldwide and is responsible for most of the 800,000 annual suicides. Clinical practice guidelines (CPGs) for treatment of depression, founded on scientific evidence, are essential to improve patient care. However, economic and sociocultural factors may influence CPG elaboration, potentially leading to divergences in their recommendations. Consequently, we analyzed pharmacological recommendations for the treatment of depression from the most relevant CPGs. We included four CPGs with scores ≥ 80% for Domain 3 (rigor of development) on the Appraisal of Guidelines for Research and Evaluation and two other commonly used CPGs. The recommendations, their strengths, and the level of evidence were extracted from each CPG by two independent researchers and grouped as follows: (1) general recommendations for the pharmacological treatment for depression (suicide risk, acute treatment, continuation and maintenance phases, and treatment discontinuation); (2) treatment of non-responsive or partially responsive patients; and (3) treatment for subtypes of depression (chronic, psychotic, catatonic, melancholic, seasonal, somatic, mixed, and atypical). Only 50% of CPGs included recommendations for the risk of suicide associated with pharmacotherapy. All CPGs included serotonin selective reuptake inhibitors (SSRIs) as first-line treatment; however, one CPG also included agomelatine, milnacipran, and mianserin as first-line alternatives. Recommendations for depression subtypes (catatonic, atypical, melancholic) were included in three CPGs. The strength of recommendation and level of evidence clearly differed among CPGs, especially regarding treatment augmentation strategies. We conclude that, although CPGs converged in some recommendations (e.g., SSRIs as first-line treatment), they diverged in cardinal topics including the absence of recommendations regarding the risk of suicide associated with pharmacotherapy. Consequently, the recommendations listed in a specific CPG should be followed with caution.

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WHAT IS KNOWN AND OBJECTIVES: Schizophrenia is a serious mental disorder and is associated with substantial economic and social burden. Cost-effectiveness analysis is important to assess the costs of different therapeutic options. However, there is a lack of information on the reporting quality of economic evaluations, cost drivers, as well as updated data focused on aripiprazole, an antipsychotic drug commonly prescribed in schizophrenia. This study evaluates and summarizes the evidence of economic evaluations of the use of aripiprazole in schizophrenia. In addition, we aimed to identify cost drivers and critically assess the reporting qualities of these studies. METHODS: A comprehensive literature research was conducted using PubMed, NHS Economic Evaluation Database, CEA Registry and LILACS databases dated until March 2018. Full economic analyses of aripiprazole in schizophrenia that were based on decision analytical models and published in English, Portuguese or Spanish languages were included. Two independent authors identified the studies and performed data extraction and quality assessment using 24 items from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. RESULTS AND DISCUSSION: A total of 79 potential studies were identified, of which 17 studies performing model-based economic evaluations fully met the eligibility criteria. Of these, 15 were industry-funded studies. A trend favouring olanzapine, lurasidone and paliperidone could be observed, whereas aripiprazole was extensively described as a dominated alternative. However, notably, 93% of the industry-funded studies presented results favouring their sponsors, only two of them being the manufacturer of aripiprazole. Cost drivers were usually related to the relapse rates/probabilities regardless of the funding source. The overall quality of reporting of the economic analyses was poor, with most studies scoring around 12-13 points. The most frequent problems were the lack of description of relevance of the outcome measures, characteristics of the base case population and report of precision measures for all the parameters of the model. WHAT IS NEW AND CONCLUSION: No consistent conclusion on the cost-effectiveness of aripiprazole could be drawn due to the context-specific costs, conflicting parameters of effectiveness and safety, and bias related to industry sponsorship. Cost drivers, though, were usually related to the relapse rates/probabilities. In addition, poor reporting quality of the studies performing full economic analysis requires further improvement to ensure greater transparency of the findings.

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Background: Implementation is a key step in ensuring that high-quality clinical practice guideline (CPG) recommendations are followed and have a positive impact. This step must be planned during CPG development. This study aims to inform professionals tasked with developing and implementing CPGs regarding implementation strategies and tools reported in high-quality CPGs for chronic non-communicable diseases (NCDs). Methods: NCD guidelines were selected based on Appraisal of Guideline Research and Evaluation (AGREE) II assessment. CPGs with a score of ≥60% in AGREE II domains 3 (rigor of development), 5 (applicability), and 6 (editorial independence), were considered high quality. The content related to implementation was extracted from CPG full texts and complementary materials. Implementation strategies and tools were assessed and classified using Mazza taxonomy. Results: Twenty high-quality CPGs were selected, most of which were developed by government institutions (16; 80%) with public funding (16; 80%); almost half (9; 45%) addressed the treatment of cardiovascular diseases. The countries with the most high-quality CPGs were the UK (6; 30%) and Colombia (5; 25%). These countries also had the highest average number of strategies, Colombia with 28 (SD = 1) distributed in all levels, and the UK with 15 (SD = 7), concentrating on professional and organizational levels. Although the content of the Colombian CPGs was similar regardless the disease, the CPGs from the UK were specific and contained data-based feedback reports and information on CPG compliance. Implementation strategies most frequently identified were at the professional level, such as distributing reference material (18; 80%) and educating groups of healthcare professionals (18; 80%). At the organizational level, the most frequent strategies involve changes in structure (15; 75%) and service delivery method (13; 65%). Conclusion: Countries with established CPG programs, such as the UK and Colombia, where identified as having the highest number of high-quality CPGs, although CPG implementation content had significant differences. Among high-quality CPGs, the most common implementation strategies were at the professional and organizational levels. There is still room for improvement regarding the implementation strategies report, even among high-quality CPGs, especially concerning monitoring of implementation outcomes and selection of strategies based on relevant implementation barriers.

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Resumo Objetivo Identificar preditores do conhecimento inadequado sobre medicamentos prescritos a pacientes ambulatoriais muito idosos e seus cuidadores. Método O conhecimento sobre os medicamentos prescritos para 80 pacientes com 80 anos ou mais de idade foi avaliado por meio de um questionário validado, em uma entrevista realizada com os pacientes ou seus cuidadores (quando os pacientes apresentavam dificuldades de comunicação, demência ou qualquer necessidade de assistência para ajudá-los a usar medicamentos). Dois modelos de regressão logística hierárquica avaliaram a associação entre conhecimento inadequado sobre medicamentos e variáveis ​​sociodemográficas e medicamentosas. Resultados Trinta e nove (48,8%) entrevistados eram cuidadores. Conhecimento inadequado foi encontrado em 81,5% (404/496) dos medicamentos prescritos. Forma de administração, Dose, Frequência e Duração do Tratamento foram os aspectos de maior conhecimento, enquanto Reações Adversas, Precauções, Interações e Contraindicações, os de menor. No primeiro modelo, o conhecimento inadequado foi associado à escolaridade do ensino fundamental completo ao médio incompleto (Razão de Chances (RC):0,12; p=0,018), do médio ao superior incompleto (RC:0,12; p<0,001), superior completo (RC:0,13; p<0,001), agentes que atuam no sistema renina-angiotensina (SRA) (RC:0,30; p=0,001), diuréticos (RC:0,31; p=0,013) e antitrombóticos (RC:12,59; p=0,027). No segundo modelo, os preditores foram cuidadores (RC:0,17; p<0,001), agentes que atuam no SRA (RC:0,33; p=0,002), diuréticos (RC:0,35; p=0,024) e antitrombóticos (RC:12,57; p=0,026). Conclusão A maioria dos medicamentos prescritos para pessoas muito idosas é pouco conhecida. Além disso, o aconselhamento acerca de informações sobre medicamentos deve ser mais intensivo para os pacientes do que para seus cuidadores, com foco em informações de segurança e ser direcionado a antitrombóticos.

Abstract Objective Identify predictors of inadequate knowledge about the medication prescribed to very old outpatients and their caregivers. Method The knowledge on the medication prescribed for 80 patients aged 80 years and over was assessed using a validated questionnaire to interview patients or their caregivers (when patients had communication difficulties, dementia, or any need for care to help them take the medication). Two hierarchical logistic regression models assessed the association between inadequate knowledge of the medication and sociodemographic and drug variables. Results Thirty-nine (48.8%) respondents were caregivers. Inadequate knowledge was found in 81.5% (404/496) of medication prescribed. Route of Administration, Dose, Frequency, and Duration of Treatment were the aspects of greatest knowledge, whereas Adverse Effects, Precautions, Interactions, and Contraindications were the least known ones. In the first model, inadequate knowledge was associated to the level of education from complete elementary school to incomplete high school (Odds Ratio (OR): 0.12; p=0.018), from high school to incomplete higher education (OR: 0.12; p<0.001), complete higher education (OR: 0.13; p<0.001), agents acting on the renin-angiotensin system (RAS) (OR: 0.30; p=0.001), diuretics (OR: 0.31; p=0.013) and antithrombotic (OR: 12.59; p=0.027). In the second model, the predictors were caregivers (OR: 0.17; p<0.001), agents working in the RAS (OR: 0.33; p=0.002), diuretics (OR: 0.35; p=0.024) and antithrombotic (OR: 12.57; p=0.026). Conclusion Most of the medication prescribed for very old people is not very well known. Also, advice on drug information should be more intensive to patients than to their caregivers, with a focus on safety information and targeted at antithrombotics.