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

The laboratory-assessed performance predictors of elite cross-country marathon mountain bikers

The study aimed to investigate the relationship between laboratory-assessed variables and cross-country marathon mountain biking (XCM-MTB) performance to suggest a more practical approach to monitor performance during the competitive phase. Nine elite athletes performed a battery of tests during the competitive phase of the season, one week before the race. Correlations between the physiological and neuromuscular laboratory-assessed variables and mean race completion time were verified and a multiple regression model was calculated. Cycling economy (r=0.86), power output at the first (POVT1; r=-0.73) and second ventilatory threshold (POVT2; r=-0.94), VO2peak (r=-0.71), peak power output (r=-0.91); peak power (r=-0.80), and mean power (r=-0.85) were very strongly related to race performance. TMG-derivate factors as rectus femoris (r=-0.61) and biceps femoris (r=-0.59) contraction velocity, 30-cm drop jump performance (r=-0.59), mean propulsive power in jump squat at 40% (JS40%; r=-0.65) and 60% (JS60%; r=-0.62) of athlete’s body weight and lower limbs maximal isometric voluntary strength (r=-0.59) were strongly related to race completion time. In an isolated way, the POVT2 explained 87% of race performance. Although both physiological and neuromuscular variables are related to XCM performance, the POVT2 seems to be the main variable during the competitive phase and an easy-to-apply approach should be used to monitor athletes’ performance

Biomecânica aplicada à prevenção de traumas em dançarinos de pole dance: revisão sistemática

Introdução: Tendo o seu primeiro registro em meados do século XII na Índia, o Pole Dance ou MallaKhamb, era um exercício apenas para homens que usavam postes de madeira para obtenção de força e resistência. PD é a arte de realizar sequências de figuras plásticas estáticas e dinâmicas, usando a força dos pulsos, e o atrito das pernas e do abdômen para pendurar em um poste vertical. Tendo como principal objetivo alcançar e manter harmoniosamente tais figuras. Por possuir um nível extenso de treinamento, o PD pode e deve ser considerado sim um esporte acrobático com sério potencial de lesão. Metodologia: A pesquisa caracteriza-se como uma revisão sistemática de estudos e contempla os procedimentos metodológicos PRISMA (MOHER). Descritores utilizados: "pole dance", "Injures", "biomechanical" e, operadores booleanos “and” e “or”. Resultados: Dittrich e et al (2020), constataram uma prevalência maior de lesões na cabeça, coluna e ombro, decorrentes de quedas durante a execução de figuras suspensas devido à alta energia cinética do acidente, achados semelhantes aos de Ruscello et al que afirmam que em algumas figuras as taxas de aceleração vertical positiva e negativa podem alcançar até 2G e rotação de 400° por segundo. Já Szopa e et al (2022) descreveu achados antagônicos aos de Drittrich com uma incidência maior em extremidades inferiores (59%) à extremidades superiores (39%), sendo o menor percentual de lesões na coluna e tronco. Músculos e tendões foram os mais lesionados (25%), seguidos por articulações e ligamentos (23%). O tipo de lesão mais comum foi contusão (60%). Sendo que 86% da amostra relatou sofrer algum tipo de lesão e 56% algum tipo de relesão. Conclusão: Conclui-se que a biomecânica aplicada ao esporte é de extrema importância na prevenção e no plano terapêutico para reabilitação de lesões e acometimentos maléficos aos atletas

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised