Alternative potency tests for quality control of immunobiologicals: a critical review of the validation approach

Introduction: In addition to low reproducibility, in vivo potency tests used in the quality control of immunobiological products require too many animals, causing them significant pain and suffering. In the last decades, many studies have been conducted to validate alternative methods for quality control and batch release of products such as vaccines and other immunobiologicals, especially for potency tests. Objective: To discuss validation studies on alternative methods proposed for replacing the in vivo potency tests and the used statistical approach, as well as to propose harmonization of terminology and to design validation studies for alternative potency methods. Method: A review of scientific databases was carried out to compile the products, data on the validation procedures and to verify their inclusion in the pharmacopeias. Results: Four trials were incorporated into the pharmacopeias. Statistical approaches included mainly regression assessment, ANOVA and Chi-square test. Conclusions: It is a challenge to conduct appropriate validation studies that are widely accepted by regulatory authorities, especially where validation centers have not yet been established. A clear indicator of this difficulty was the low number of methods for biological products incorporated into the guidelines.TÍTULO PT: Testes de potência alternativos para controle de qualidade de imunobiológicos: revisão crítica da abordagem de validação Introdução: Os ensaios de potência in vivo utilizados no controle da qualidade de imunobiológicos requerem o uso de muitos animais, e além da baixa reprodutibilidade, causam dor e sofrimento significativos. Nas últimas décadas, muitos estudos foram desenvolvidos para validar métodos alternativos para o controle da qualidade e liberação de lotes de produtos como vacinas e outros imunobiológicos, especialmente para os testes de potência. Objetivo: Discutir os estudos de validação sobre métodos alternativos para substituir ensaios de potência in vivo, a abordagem estatística utilizada e propor a harmonização da terminologia e o desenho para os estudos de validação de métodos alternativos de potência. Método: Uma pesquisa de revisão foi realizada em bases de dados científicos para compilar os produtos e dados dos procedimentos de validação, verificando sua inclusão nas farmacopeias. Resultados: Quatro ensaios foram incorporados em farmacopeias. As abordagens estatísticas incluíram principalmente a avaliação da regressão, ANOVA e teste de Qui-quadrado. Conclusões: É um desafio realizar estudos de validação adequados que sejam amplamente aceitos pelas autoridades reguladoras, especialmente onde os centros de validação ainda não foram estabelecidos. Um indicador claro dessa dificuldade foi o baixo número de métodos para produtos biológicos incorporados nas diretrizes

USO DE BENZODIAZEPÍNICOS EM EMERGÊNCIAS PSIQUIÁTRICAS: UMA REVISÃO INTEGRATIVA DAS EVIDÊNCIAS

This article presents an integrative review on the use of benzodiazepines in psychiatric emergencies, aiming to compile and analyze the available evidence regarding their efficacy, safety, and clinical implications. Studies published between 2014 and 2024 were included, selected from PubMed, Scopus, and SciELO databases using keywords such as “benzodiazepines,” “psychiatric emergencies,” and “treatment.” Data analysis revealed that benzodiazepines are effective in the rapid stabilization of acute symptoms, such as psychomotor agitation and severe anxiety crises. However, prolonged use is associated with significant risks, including dependence, tolerance, and adverse effects, particularly in vulnerable populations like the elderly. Comparisons with other pharmacological interventions suggest that second-generation antipsychotics may be viable alternatives with a potentially more favorable adverse effect profile. The review also highlighted the importance of non-pharmacological interventions, such as nursing care, which can complement pharmacological treatment. It concludes that while benzodiazepines are a valuable tool in psychiatric emergencies, it is crucial to follow stringent clinical guidelines and personalize treatment to maximize benefits and minimize risks.Este artigo apresenta uma revisão integrativa sobre o uso de benzodiazepínicos em emergências psiquiátricas, com o objetivo de compilar e analisar as evidências disponíveis acerca de sua eficácia, segurança e implicações clínicas. Foram incluídos estudos publicados entre 2014 e 2024, selecionados nas bases de dados PubMed, Scopus e SciELO, utilizando palavras-chave como “benzodiazepínicos”, “emergências psiquiátricas” e “tratamento”. A análise dos dados revelou que os benzodiazepínicos são eficazes na estabilização rápida de sintomas agudos, como agitação psicomotora e crises de ansiedade severa. No entanto, o uso prolongado está associado a riscos significativos, incluindo dependência, tolerância e efeitos adversos, especialmente em populações vulneráveis como idosos. Comparações com outras intervenções farmacológicas sugerem que antipsicóticos de segunda geração podem ser alternativas viáveis, com um perfil de efeitos adversos potencialmente mais favorável. A revisão também destacou a importância das intervenções não farmacológicas, como a assistência de enfermagem, que podem complementar o tratamento farmacológico. Conclui-se que, embora os benzodiazepínicos sejam uma ferramenta valiosa em emergências psiquiátricas, é crucial seguir diretrizes clínicas rigorosas e personalizar o tratamento para maximizar os benefícios e minimizar os riscos. &nbsp

Eficácia dos Protocolos de Suporte Avançado de Vida no Atendimento Pré-Hospitalar de Parada Cardiorrespiratória: Uma Revisão Integrativa

This article presents an integrative review on the effectiveness of Advanced Life Support (ALS) protocols in the pre-hospital management of cardiac arrest. The research was conducted by analyzing nine studies selected from electronic databases, published between 2018 and 2023. The results indicate that the standardization of ALS practices, according to the American Heart Association (AHA) guidelines, significantly increases the rates of return of spontaneous circulation (ROSC) and survival to hospital discharge. Additionally, continuous education and regular training of healthcare professionals are crucial for the effectiveness of pre-hospital care. Adequate infrastructure and availability of resources are also determinants for the success of ALS interventions. The integration of educational technologies and technological advancements in the training of healthcare professionals proved to be a promising strategy to improve the application of protocols. This study contributes to the field of pre-hospital resuscitation by providing a comprehensive overview of the factors influencing the effectiveness of ALS protocols, highlighting the need for a multifaceted approach that combines standardization, continuous education, adequate resources, and technological innovations.Este artigo apresenta uma revisão integrativa sobre a eficácia dos protocolos de Suporte Avançado de Vida (SAV) no atendimento pré-hospitalar de parada cardiorrespiratória (PCR). A pesquisa foi conduzida através da análise de nove estudos selecionados em bases de dados eletrônicas, publicados entre 2018 e 2023. Os resultados indicam que a padronização das práticas de SAV, conforme as diretrizes da American Heart Association (AHA), aumenta significativamente as taxas de retorno da circulação espontânea (RCE) e a sobrevivência até a alta hospitalar. Além disso, a educação continuada e o treinamento regular dos profissionais de saúde são cruciais para a eficácia do atendimento pré-hospitalar. A infraestrutura adequada e a disponibilidade de recursos também são determinantes para o sucesso das intervenções de SAV. A integração de tecnologias educacionais e avanços tecnológicos na formação dos profissionais de saúde mostrou-se uma estratégia promissora para melhorar a aplicação dos protocolos. Este estudo contribui para o campo da ressuscitação pré-hospitalar ao fornecer uma visão abrangente sobre os fatores que influenciam a eficácia dos protocolos de SAV, destacando a necessidade de uma abordagem multifacetada que combine padronização, educação contínua recursos adequados e inovações tecnológicas

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt