Population variability in animal health: Influence on dose-exposure-response relationships: Part II: Modelling and simulation

During the 2017 Biennial meeting, the American Academy of Veterinary Pharmacology and Therapeutics hosted a 1‐day session on the influence of population variability on dose‐exposure‐response relationships. In Part I, we highlighted some of the sources of population variability. Part II provides a summary of discussions on modelling and simulation tools that utilize existing pharmacokinetic data, can integrate drug physicochemical characteristics with species physiological characteristics and dosing information or that combine observed with predicted and in vitro information to explore and describe sources of variability that may influence the safe and effective use of veterinary pharmaceuticals

Dimensions of oral cancer in Europe: an epidemiological study

Objectivo: O objetivo deste estudo é fornecer uma revisão atualizada da incidência, prevalência e mortalidade do cancro oral na Europa e analisar o papel do médico dentista no âmbito desta doença. Método: bases de dados científicas (especialmente GCO IARC) foram usadas para recuperar dados sobre cancro oral em vários países europeus. As taxas de incidência, prevalência e mortalidade entre homens e mulheres em cada país foram comparadas e analisadas para fornecer uma visão geral da situação na Europa. Esta análise foi completada por um foco no papel do médico dentista durante todo o percurso do doente, desde a prevenção ao diagnóstico e acompanhamento do tratamento e vigilância. Resultados: o cancro oral é um importante problema de saúde e a redução da sua incidência e mortalidade depende da prevenção primária ainda não padronizada a nível europeu. À luz dos dados recuperados, observamos diferenças signifcativas entre os países europeus e entre homens e mulheres em cada país. Isso pode ser explicado por um contexto político, económico e cultural diferente, além de fatores individuais (baixa escolaridade e baixos rendimentos) que podem ser um obstáculo ao acesso aos cuidados básicos de saúde. Conclusão: Só podemos esperar que os países continuem e reforcem seus esforços na prevenção primária e secundária, promovam treino dedicado ao cancro oral para dentistas e sensibilizem os pacientes, e que a união europeia estabeleça diretrizes para todos os países.Objectives: The aim of this study is to provide an up-to-date review of the incidence, prevalence, and mortality of oral cancer in Europe and analyze the role of dental practitioner within the scope of this disease. Methods: Scientific databases (especially GCO IARC) were used to retrieve data regarding oral cancer in several European countries. Incidence, prevalence and mortality rates between man and woman in each country were compared and analyzed to provide an overview of the situation in Europe. This analysis was completed by a focus on the role of dental practitioner during the whole patient path, from prevention to diagnosis and follow-up treatment and surveillance. Results: Oral cancer is a major health issue and the reduction of its incidence and mortality depends on primary prevention which is not yet standardized at the European level. In the light of the data retrieved, we observed significant differences between European countries so as between men and women in each country. It can be explained by a different political, economic, and cultural context, in addition to individual factors (low education and low income), which can be an obstacle to access to care. Conclusion: We can only hope that countries will continue and reinforce their efforts in primary and secondary prevention, promote training dedicated to oral cancer for dental practitioners and educate patients, and that the European Union will set guidelines for all countries

A Review of Relevant Therapeutic Targets for the Management of Congestive Heart Failure in Dogs: Present and Future Directions

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature

Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed-Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats

The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed‐effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first‐order absorption best described robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip‐flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population

“What happened to battles are ugly affairs?”: Fighting Girls in the Films \u3ci\u3eThe Chronicles of Narnia\u3c/i\u3e, Chapters 1, 2 and 3

Although C.S. Lewis’s Chronicles of Narnia (1950-1956) are still hugely popular today, some critics have accused the books of representing masculinity and femininity in an outmoded way. The three Walden Media films, The Lion, the Witch and the Wardrobe (2005), Prince Caspian (2008) and The Voyage of the Dawn Treader (2010), appear to adopt a more contemporary perspective, especially as far as the representation of fighting girls is concerned. While Lewis seemed slightly reluctant to show women playing an active role on the battlefield, Andrew Adamson, who directed the first two films, lets Susan, the female protagonist, fight alongside the boys and even gives her a leading role in the battle scenes of the 2008 film. However, the presence of fighting girls remains largely symbolic, because they are artificially put forward in The Lion, the Witch and the Wardrobe, and because their actions are presented in a stereotypical fashion in Prince Caspian. As for the director of the third film Michael Apted, he treats Lucy, the female protagonist who replaces her older sister Susan, in a much more egalitarian way

Intestinal Stem Cells to Advance Drug Development, Precision, and Regenerative Medicine: A Paradigm Shift in Translational Research

Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at lower costs compared with live animal studies. Importantly, because they are derived from individuals with different genotypes, environmental risk factors and drug sensitivity profiles, organoids are a highly relevant screening system for personalized therapy in both human and veterinary medicine. Lastly, and in the context of patient-specific congenital diseases, orthotopic transplantation of engineered organoids could repair and/or replace damaged epithelial tissues reported in various GI diseases, such as inflammatory bowel disease, cystic fibrosis, and tuft enteropathy. Ongoing translational research on organoids derived from dogs with naturally occurring digestive disorders has the potential to improve the predictability of preclinical models used for optimizing the therapeutic management of severe chronic enteropathies in human patients