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

Extensive Sheep and Goat Production: The Role of Novel Technologies towards Sustainability and Animal Welfare

ReviewSheep and goat extensive production systems are very important in the context of global food security and the use of rangelands that have no alternative agricultural use. In such systems, there are enormous challenges to address. These include, for instance, classical production issues, such as nutrition or reproduction, as well as carbon-efficient systems within the climate-change context. An adequate response to these issues is determinant to economic and environmental sustainability. The answers to such problems need to combine efficiently not only the classical production aspects, but also the increasingly important health, welfare, and environmental aspects in an integrated fashion. The purpose of the study was to review the application of technological developments, in addition to remote-sensing in tandem with other state-of-the-art techniques that could be used within the framework of extensive production systems of sheep and goats and their impact on nutrition, production, and ultimately, the welfare of these species. In addition to precision livestock farming (PLF), these include other relevant technologies, namely omics and other areas of relevance in small-ruminant extensive production: heat stress, colostrum intake, passive immunity, newborn survival, biomarkers of metabolic disease diagnosis, and parasite resistance breeding. This work shows the substantial, dynamic nature of the scientific community to contribute to solutions that make extensive production systems of sheep and goats more sustainable, efficient, and aligned with current concerns with the environment and welfareinfo:eu-repo/semantics/publishedVersio

Extensive Sheep and Goat Production: The Role of Novel Technologies towards Sustainability and Animal Welfare

[EN] Sheep and goat extensive production systems are very important in the context of global food security and the use of rangelands that have no alternative agricultural use. In such systems, there are enormous challenges to address. These include, for instance, classical production issues, such as nutrition or reproduction, as well as carbon-efficient systems within the climate-change context. An adequate response to these issues is determinant to economic and environmental sustainability. The answers to such problems need to combine efficiently not only the classical production aspects, but also the increasingly important health, welfare, and environmental aspects in an integrated fashion. The purpose of the study was to review the application of technological developments, in addition to remote-sensing in tandem with other state-of-the-art techniques that could be used within the framework of extensive production systems of sheep and goats and their impact on nutrition, production, and ultimately, the welfare of these species. In addition to precision livestock farming (PLF), these include other relevant technologies, namely omics and other areas of relevance in small-ruminant extensive production: heat stress, colostrum intake, passive immunity, newborn survival, biomarkers of metabolic disease diagnosis, and parasite resistance breeding. This work shows the substantial, dynamic nature of the scientific community to contribute to solutions that make extensive production systems of sheep and goats more sustainable, efficient, and aligned with current concerns with the environment and welfareSIThe CECAV authors acknowledge financial support of the research unit, which was financed by the National Funds from FCT, the Portuguese Foundation for Science and Technology (FCT), project number UIDB/CVT/00772/2020. Financial support from FCT (Fundação para a Ciência e a Tecnologia, Lisboa, Portugal) in the form of infrastructural funding to LEAF (UID/AGR/04129) and PhD grants SFRH/BD/143992/2019 (DM Ribeiro) and 2021.07638.BD (L Sacarrão-Birrento). Author L.E.H.C. acknowledges funding from the Agencia Estatal de Investigación (Spain) (RYC2019- 027064-I/AEI/10.13039/501100011033

Brazilian Sepsis Epidemiological Study (BASES study)

INTRODUCTION: Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome METHODS: This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used. RESULTS: For the whole cohort, median age was 65.2 years (49–76), median length of stay was 2 days (1–6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract. CONCLUSION: Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate

Análise comparativa da percepção da perda auditiva com o resultado da audiometria em pacientes adultos e idosos do Hospital Bettina Ferro de Souza/PA / Comparative analysis of the perception of hearing loss with the result of audiometry in adult and elderly patients from the Bettina Ferro de Souza/PA Hospital

Introdução: A perda auditiva é um dos distúrbios da comunicação que mais afetam a sociabilidade e a qualidade de vida do ser humano. Estudos revelam que existe uma desproporção entre as queixas auditivas que o paciente leva ao consultório em relação à sua real condição auditiva. A audiometria é um exame realizado para avaliar a perda auditiva através de estímulos sonoros que variam em frequência (medida em Hertz – Hz) e intensidade, podendo assim verificar a perda auditiva, porém não refletem a dificuldade comunicativa do paciente. O Hearing Handicap Inventory for Adults – HHIA e o O Hearing Handicap Inventory for Elderly – HHIE são questionários que tem como objetivo verificar a percepção do indivíduo sobre seu problema auditivo relacionando-o com atividades do cotidiano, assim como estima-se a restrição da participação social. Objetivo: Identificar a correlação entre a percepção do paciente em relação à sua perda auditiva e o resultado da audiometria. Método: O trabalho foi um estudo comparativo-descritivo, transversal, individuado, não controlado, observacional, randomizado, realizado através da aplicação dos questionários em 27 pacientes atendidos pelo Serviço de Otorrinolaringologia do Hospital Bettina Ferro de Souza, de acordo com a faixa etária. Resultados: Observa-se que, tanto no escore total quanto nas subescalas, a única diferença significativa encontrada foi entre os escores de pacientes sem perda auditiva detectada pela audiometria e com grau de perda leve (leve + normal) e os com perda de grau profundo e severo (profundo + severo), sendo nesse último grupo sempre superiores. Além disso, não se observaram diferenças estatísticas significativas entre os sexos e a faixa etária quando comparados os escores das subescalas social e emocional do questionário handicap. Conclusão: Com este estudo, conclui-se que os pacientes apresentaram uma boa percepção auditiva sobre seu handicap quando comparados os resultados de sua respectiva audiometria, porém, é notória a falta de estudos que avaliam estas variáveis utilizando os questionários HHIA e HHIE, sugerindo a necessidade de pesquisa-lo no futuro

Evaluation in health: participatory methodology and involvement of municipal managers

ABSTRACT OBJECTIVE To analyze scopes and limits of the use of participatory methodology of evaluation with municipal health managers and administrators. METHODS Qualitative research with health policymakers and managers of the Comissão Intergestores Regional (CIR – Regional Interagency Commission) of a health region of the state of Sao Paulo in Brazil. Representatives from seven member cities participated in seven workshops facilitated by the researchers, with the aim of assessing a specific problem of the care line, which would be used as a tracer of the system integrality. The analysis of the collected empirical material was based on the hermeneutic-dialectic methodology and aimed at the evaluation of the applied participatory methodology, according to its capacity of promoting a process of assessment capable to be used as a support for municipal management. RESULTS With the participatory approach of evaluation, we were able to promote in-depth discussions with the group, especially related to the construction of integral care and to the inclusion of the user’s perspective in decision-making, linked to the search for solution to concrete problems of managers. By joint exploration, the possibility of using data from electronic information systems was opened, as well as information coming directly from the users of the services, to enhance discussions and negotiations between partners. The participants were disbelievers of the replication potential of this type of evaluation without the direct monitoring of the academy, given the difficulty of organizing the process in everyday life, already taken by emergency and political issues. CONCLUSIONS Evaluations of programs and services carried out within the Regional Interagency Commission, starting from the local interest and facilitating the involvement of its members by the use of participatory methodologies, can contribute to the construction of integral care. To the extent that the act of evaluating stay invested with greater significance to the local actors, its involvement with the evaluations at the federal level can also be stimulated

Epicoccum nigrum P16, a Sugarcane Endophyte, Produces Antifungal Compounds and Induces Root Growth

Background: Sugarcane is one of the most important crops in Brazil, mainly because of its use in biofuel production. Recent studies have sought to determine the role of sugarcane endophytic microbial diversity in microorganism-plant interactions, and their biotechnological potential. Epicoccum nigrum is an important sugarcane endophytic fungus that has been associated with the biological control of phytopathogens, and the production of secondary metabolites. In spite of several studies carried out to define the better conditions to use E. nigrum in different crops, little is known about the establishment of an endophytic interaction, and its potential effects on plant physiology. Methodology/Principal Findings: We report an approach based on inoculation followed by re-isolation, molecular monitoring, microscopic analysis, plant growth responses to fungal colonization, and antimicrobial activity tests to study the basic aspects of the E. nigrum endophytic interaction with sugarcane, and the effects of colonization on plant physiology. The results indicate that E. nigrum was capable of increasing the root system biomass and producing compounds that inhibit the in vitro growth of sugarcane pathogens Fusarium verticillioides, Colletotrichum falcatum, Ceratocystis paradoxa, and Xanthomomas albilineans. In addition, E. nigrum preferentially colonizes the sugarcane surface and, occasionally, the endophytic environment. Conclusions/Significance: Our work demonstrates that E. nigrum has great potential for sugarcane crop application because it is capable of increasing the root system biomass and controlling pathogens. The study of the basic aspects of the interaction of E. nigrum with sugarcane demonstrated the facultative endophytism of E. nigrum and its preference for the phylloplane environment, which should be considered in future studies of biocontrol using this species. In addition, this work contributes to the knowledge of the interaction of this ubiquitous endophyte with the host plant, and also to a better use of microbial endophytes in agriculture.State of Sao Paulo Research Foundation (FAPESP)FAPESP (State of Sao Paulo Research Foundation) [02/14143-3, 10/08286-2]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq