Rachel Riera

Introduction: Givinostat, a histone deacetylase inhibitor, has been investigated for the treatment of Duchenne Muscular Dystrophy (DMD) and slow muscle degradation. DMD is a genetic neuromuscular degenerative disease that begins in early childhood. It is an X-linked recessive disorder characterized by mutations in the dystrophin gene and progressive and severe muscle weakness and atrophy are the main characteristics of this disease. DMD predominantly affects boys, while most females are asymptomatic carriers, with a global prevalence estimated at 19.8 cases per 100,000 live male births. Objective: To evaluate the efficacy and safety of Givinostat for individuals with DMD based on evidence from randomized controlled trials (RCTs). Methodology: We conducted a systematic review following PRISMA guidance, focusing on RCTs assessing Givinostat versus placebo, standard care, no treatment, or any active pharmacological intervention in DMD. CENTRAL, MEDLINE, Embase, PEDro and LILACS were searched (August 2025) without restrictions. Two reviewers independently selected studies, extracted data, and appraised risk of bias using the original Cochrane tool. Certainty of evidence was assessed using GRADE. The protocol was prospectively registered in the PROSPERO database (CRD420251107551). Results: Two RCTs were included, although one is still ongoing. EPIDYS (n=179) compared Givinostat (13 mg to 47 mg twice daily) with placebo for 72 weeks. There is uncertainty regarding the effects of Givinostat on global symptom assessment (mean difference [MD] 1.91; 95% CI 0.30 to 3.53; n=120; very low certainty), serious adverse events (risk ratio [RR] 2.07; 95% CI 0.45 to 9.44; n=179; very low certainty), functional capacity assessed by two different instruments (n=120; very low certainty), and quality of life (MD 3.70; 95% CI −2.30 to 9.70; n=120; very low certainty). Givinostat may have little or no effect on the risk of any adverse events (RR 1.02; 95% CI 0.94 to 1.10; n=179; low certainty). Conclusions: Current evidence on the efficacy of Givinostat remains uncertain, while it may have little or no effect on the risk of any adverse events. Further well-designed RCTs with larger sample sizes and varying disease stages are needed to reduce these uncertainties.

Os Núcleos de Apoio Técnico do Poder Judiciário (NATJus) elaboram notas técnicas que subsidiam decisões judiciais sobre acesso a tecnologias em saúde, e o julgamento dos Temas 6 e 1234 pelo Supremo Tribunal Federal ampliou o impacto desses documentos técnico-científicos na prática judicial. A constatação de que notas técnicas sobre uma mesma tecnologia e um mesmo diagnóstico podem chegar a conclusões diferentes é, por vezes, lida como sinal de fragilidade técnica. Este artigo examina seis fontes de divergência entre notas técnicas, a saber, a evolução das evidências científicas ao longo do tempo; a atualização dos relatórios de recomendação e dos Protocolos Clínicos e Diretrizes Terapêuticas (PCDT) da Comissão Nacional de Incorporação de Tecnologias no SUS (Conitec); as particularidades clínicas de pacientes que compartilham o mesmo código da Classificação Internacional de Doenças (CID) e solicitam a mesma tecnologia; a incompletude dos documentos apresentados no processo; o grau de incerteza das evidências disponíveis; e as diferenças entre as políticas de saúde estaduais e municipais. Argumenta-se que uma medida de inconsistência, dissociada da análise de cada caso concreto, não permite distinguir variação legítima de erro, e que parte da divergência decorre da própria contextualização que se espera de uma nota técnica. Os Temas 6 e 1234 representam avanço na coerência das decisões, mas se organizam em torno das avaliações da Conitec. Para os casos sem avaliação da Conitec, faz-se necessária a construção de consensos sobre a análise de evidências incertas e sobre o papel das avaliações econômicas, além da padronização de campos nas notas técnicas que tornem explícitas as razões de cada conclusão. Reduzir o papel dos NATJus não resolveria a divergência e tenderia a ampliá-la, pois as decisões voltariam a depender de documentos produzidos pelas partes, sem método comum nem tentativa de controle de conflitos de interesse, além de interromper o aperfeiçoamento continuado das notas técnicas e comprometer a confiança nos documentos que oferecem ao magistrado uma análise independente das evidências.

To assess the characteristics and methodological quality of systematic reviews on medical education. This meta‐research considered systematic reviews on medical education published in MEDLINE (PubMed). The following outcomes were assessed: (i) general characteristics of systematic reviews, (ii) frequency and type of methodological tool and/or guidance used for conducting the systematic review, (iii) adequacy to the AMSTAR‐2 items, (iv) association between the methodological tool/guide used and the adequacy of the AMSTAR‐2 and (v) frequency of systematic reviews that referred to the use of the PRISMA statement for their reporting. Forty‐eight systematic reviews published between 2004 and 2023 were included; 77.1% addressed intervention questions, and the outcomes assessed were predominantly knowledge, attitude, skills and behaviour. According to the AMSTAR‐2 assessment, 93.8% of the systematic reviews were classified as critically low quality, including 91.9% of intervention reviews and 100% of reviews addressing frequency or unclear review questions. Overall, 43.8% inappropriately reported using the PRISMA statement as methodological guidance, whereas 18.8% reported using the PRISMA statement as a reporting guideline. Eight reviews (16.7%) followed the methodological recommendations of the Cochrane Handbook or BEME, and three of them were classified as low or moderate quality. Reviews that reported using an appropriate methodological guide showed higher AMSTAR‐2 adequacy (63% [47–74] versus 35% [27–42], p = 0.0016). Considering the substantial methodological limitations identified across the included systematic reviews, there is an evident need for guidance and training on the methodological process of systematic reviews in medical education, including the planning, conduct and reporting stages, to improve the quality of the evidence supporting teaching and learning strategies. Context and implications: Rationale for this study: Systematic reviews in medical education have increased substantially, yet their methodological rigour and adherence to established standards remain uncertain. Why the new findings matter: This meta‐research found that most systematic reviews in medical education are of critically low methodological quality and frequently misuse reporting guidelines, such as PRISMA, as methodological frameworks. Implications for researchers, educators and journal editors: Researchers would benefit from targeted training on the appropriate planning and conduct of systematic reviews, using established methodological and reporting frameworks (e.g. Cochrane, BEME, PRISMA). Educators and editors should encourage methodological literacy, promote adherence to standards and strengthen peer‐review processes to improve the reliability and usefulness of evidence supporting teaching and learning in medical education.

Background: The classification of primary studies is a critical methodological step in the conduct of systematic reviews. The current Cochrane approach categorizes studies as ‘included’, ‘excluded’, ‘ongoing’ or ‘awaiting classification’, primarily based on study eligibility and completion status. However, the concept of an ‘ongoing’ clinical trial is itself poorly defined across registries and methodological guidelines, introducing a layer of subjectivity that undermines reproducibility. Methods: We propose a revised classification framework that replaces study status with outcome data availability as the primary classification criterion. Results: The proposed framework introduces three changes: (1) splitting the ‘included studies’ category into ‘included studies with analysable outcome data‘ and ‘included studies without analysable outcome data’; (2) eliminating the ‘ongoing studies’ category, whose function is absorbed by the two proposed categories; and (3) restricting ‘awaiting classification’ exclusively to studies where eligibility could not be determined. Conclusion: This framework makes more explicit how many eligible studies could not contribute to outcome analysis due to reporting‐related problems, thereby increasing transparency and reducing ambiguity in the categorization process. Future empirical studies measuring inter‐rater reliability and the operational precision of the proposed categories are needed to validate this proposal.

Introduction: Givinostat, a histone deacetylase inhibitor, has been investigated for the treatment of Duchenne Muscular Dystrophy (DMD) and slow muscle degradation. DMD is a genetic neuromuscular degenerative disease that begins in early childhood. It is an X-linked recessive disorder characterized by mutations in the dystrophin gene and progressive and severe muscle weakness and atrophy are the main characteristics of this disease. DMD predominantly affects boys, while most females are asymptomatic carriers, with a global prevalence estimated at 19.8 cases per 100,000 live male births. Objective: To evaluate the efficacy and safety of Givinostat for individuals with DMD based on evidence from randomized controlled trials (RCTs). Methodology: We conducted a systematic review following PRISMA guidance, focusing on RCTs assessing Givinostat versus placebo, standard care, no treatment, or any active pharmacological intervention in DMD. CENTRAL, MEDLINE, Embase, PEDro and LILACS were searched (August 2025) without restrictions. Two reviewers independently selected studies, extracted data, and appraised risk of bias using the original Cochrane tool. Certainty of evidence was assessed using GRADE. The protocol was prospectively registered in the PROSPERO database (CRD420251107551). Results: Two RCTs were included, although one is still ongoing. EPIDYS (n=179) compared Givinostat (13 mg to 47 mg twice daily) with placebo for 72 weeks. There is uncertainty regarding the effects of Givinostat on global symptom assessment (mean difference [MD] 1.91; 95% CI 0.30 to 3.53; n=120; very low certainty), serious adverse events (risk ratio [RR] 2.07; 95% CI 0.45 to 9.44; n=179; very low certainty), functional capacity assessed by two different instruments (n=120; very low certainty), and quality of life (MD 3.70; 95% CI −2.30 to 9.70; n=120; very low certainty). Givinostat may have little or no effect on the risk of any adverse events (RR 1.02; 95% CI 0.94 to 1.10; n=179; low certainty). Conclusions: Current evidence on the efficacy of Givinostat remains uncertain, while it may have little or no effect on the risk of any adverse events. Further well-designed RCTs with larger sample sizes and varying disease stages are needed to reduce these uncertainties.