Methodological Quality of Pulmonary Arterial Hypertension Treatment Evidence-Based Guidelines: A Systematic Review Using the AGREE II and AGREE REX Tools.

PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis, and its management should be grounded in well-developed clinical practice guidelines (CPG). Thus, we critically assess the methodological quality of the available CPG for pharmacological treatments for PAH. METHODS: A systematic review (CRD42023387168) was performed in PubMed, Cochrane, Embase, and Tripdatabase (Jan-2023). Eligible records were appraised by four reviewers using the Appraisal of Guidelines, Research, and Evaluation Collaboration tool (AGREE II) and the complementary tool for assessing recommendations' quality and certainty, AGREE REX. Descriptive statistics were used to summarize the data. RESULTS: Overall, 31 guidelines, mainly authored by professional societies (90%), targeting only physicians as primary users (84%), were identified. Guidelines presented a moderate overall quality (scores of 63% and 51% in AGREE II and AGREE REX, respectively), with a few domains showing slight improvements over the years. AGREE II "Scope and Purpose" (94%) and "Presentation Clarity" (99%) domains obtained the highest scores. The items related to "Stakeholder involvement," "Editorial independence," and "Clinical applicability" (AGREE REX) were fairly reported. Conversely, CPG lacks rigor in development (32% score, AGREE II), scarcely discusses the role of stakeholders, and provides deficient data on the implementation of recommendations (scores of 35% and 46% in AGREE II and AGREE REX, respectively). No differences in the quality of guidelines published by different developers or countries were observed (p > 0.05). CONCLUSION: Methodological weaknesses are common among guidelines addressing PAH treatment, especially regarding scientific rigor, stakeholders' values and preferences, and facilitators and barriers to implementability. Particular attention should be given to developing future guidelines.

Análise de impacto orçamentário de dispositivos contraceptivos na saúde suplementar brasileira / Budget impact analysis of contraceptive devices on Brazilian supplementary health

Objetivo: Analisar o impacto orçamentário da adoção de dispositivos contraceptivos reversíveis de longa duração em uma operadora de plano de saúde localizada no Sul do Brasil. Especificamente, analisamos a incorporação do implante subdérmico de etonogestrel (Implanon®) como alternativa ao sistema intrauterino de levonorgestrel (DIU Mirena® ou DIU Kyleena®), ao longo de um período de 15 anos. Métodos: Realizamos uma análise do impacto orçamentário incremental, considerando a inclusão gradual do implante subdérmico de etonogestrel. Foram considerados dados de uma operadora de planos de saúde com mais de 600.000 beneficiários. O horizonte temporal de 15 anos permitiu uma avaliação abrangente dos efeitos financeiros. Resultados: Identificamos 5.345 pacientes elegíveis para a utilização de contraceptivos reversíveis de longa duração. No cenário em que somente o sistema intrauterino de levonorgestrel era adotado, projetou-se um impacto orçamentário total de R$ 746.379.857,80 ao longo de 15 anos. No cenário alternativo, com a incorporação gradual do implante subdérmico, o impacto orçamentário total foi calculado em R$ 689.800.196,83. Isso resultou em um impacto orçamentário incremental negativo de -R$ 56.579.660,97 ao longo do período. Conclusão: A análise de impacto orçamentário realizada indica um potencial benefício financeiro ao adotar o implante subdérmico de etonogestrel como alternativa ao sistema intrauterino de levonorgestrel para contracepção. Esse achado sugere possíveis reduções de custos na área de saúde suplementar no Brasil, reforçando a importância de avaliar opções economicamente viáveis.

Objective: To analyze the budgetary impact of the adoption of long-acting reversible contraceptive devices in a health plan operator located in southern Brazil. Specifically, we analyzed the incorporation of the etonogestrel subdermal implant (Implanon®) as an alternative to the levonorgestrel intrauterine system (Mirena® IUD or Kyleena® IUD), over a period of 15 years. Methods: We performed an analysis of the incremental budgetary impact, considering the gradual inclusion of the etonogestrel subdermal implant. Data from a health plan operator with more than 600,000 beneficiaries were considered. The 15-year time horizon allowed for a comprehensive assessment of the financial effects. Results: We identified 5,345 patients eligible for the use of long-acting reversible contraceptives. In the scenario where only the levonorgestrel intrauterine system was adopted, a total budget impact of BRL 746,379,857.80 was projected over 15 years. In the alternative scenario, with the gradual incorporation of the subdermal implant, the total budgetary impact was calculated at BRL 689,800,196.83. This resulted in a negative incremental budgetary impact of -R$56,579,660.97 over the period. Conclusion: The budget impact analysis carried out indicates a potential financial benefit in adopting the etonogestrel subdermal implant as an alternative to the levonorgestrel intrauterine system for contraception. This finding suggests possible cost reductions in the supplementary healthcare area in Brazil, reinforcing the importance of evaluating economically viable options.

Mapping the characteristics, methodological quality and standards of reporting of network meta-analyses on antithrombotic therapies: An overview.

BACKGROUND: Although a large number of network meta-analyses (NMAs) in the field of cardiology are available, little is known about their methodological quality. We aimed to map the characteristics and critically appraised the standards of conduct and evidence reporting of NMAs assessing antithrombotic therapies for the treatment or prophylaxis of heart diseases and cardiac surgical procedures. METHODS: We systematically searched PubMed and Scopus to identify NMAs comparing the clinical effects of antithrombotic therapies. Overall characteristics of the NMAs were extracted and their reporting quality and methodological quality were evaluated using the PRISMA-NMA checklist and AMSTAR-2, respectively. RESULTS: We found 86 NMAs published between 2007 and 2022. Comparisons among direct-acting oral anticoagulants were available in 61 (71%) NMAs. Although around 75% of NMAs stated that they followed international guidelines for conduct and reporting, only one third provided a protocol/register. Complete search strategies and publication bias assessment were lacking in around 53% and 59% of studies, respectively. Most NMAs (n = 77, 90%) provided supplemental material; however, only 5 (6%) made the complete raw data available. Network diagrams were depicted in most studies (n = 67, 78%), yet network geometry was described in only 11 (12.8%) of them. Mean adherence to the PRISMA-NMA checklist was 65.1 ± 16.5%. AMSTAR-2 assessment showed 88% of the NMAs had critically low methodological quality. CONCLUSION: Although there is a wide diffusion of NMA-type studies on antithrombotics for heart diseases, their methodological and reporting quality remains suboptimal. This may reflect fragile clinical practices due to misleading conclusions from critically low-quality NMAs.

Efficacy and safety of immunotherapies for the treatment of high-grade gliomas: a systematic review and meta-analysis

Background/Aim: High-grade gliomas are aggressive brain neoplasms usually refractory to treatment. Recently new treatment approaches have emerged, including immunotherapies. Hence, the aim of the present study was to evaluate the efficacy and safety of immunotherapies in adult patients with high-grade gliomas. Methods: Searches were performed in three databases for relevant studies published until December 2020. Title and abstract screening, full-text review, data extraction, and risk of bias assessment were performed independently by two reviewers. Risk of bias assessment was performed according to the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Meta-analyses were performed with Review Manager software (version 5.4.1), using risk ratio and 95% confidence intervals as measure of effect, the Mantel-Haenszel method, and random effects models. The quality of evidence assessment was conducted according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nineteen studies were included in the systematic review, of which 15 reported comparable data for meta-analyses. The outcomes assessed in the meta-analyses were overall survival (OS) and progression-free survival (PFS), with subgroups at 6, 12, and more than 12 months. No statistical differences were observed between immunotherapy and conventional treatment, except for the OS subgroup over 12 months. The certainty on the evidence was moderate. Conclusion: There was no evidence of an additional benefit of immunotherapy compared to standard treatment in the synthesis of results from clinical trials. Further high-quality clinical trials are needed to improve the quality of evidence concerning immunotherapies for the treatment of high-grade gliomas.