Introduction: Les instillations nasales de solution saline isotonique (INSS) chez les enfants sont recommandées par les pédiatres et des oto-rhino-laryngologistes de notre institution dans le but de prévenir les otites moyennes aigues à répétition (OMAr). Cependant, aucune étude dans la littérature ne vient corroborer ou infirmer cette pratique. Objectifs: Déterminer l’efficacité des INSS dans la prévention des OMAr. Méthode: Projet pilote d’un essai clinique randomisé. Les enfants diagnostiqués avec des OMAr étaient éligibles. Les patients recrutés ont été randomisés en 2 groupes. Seul le groupe traitement procède aux INSS. L’issue primaire est l’incidence d’OMAr pendant une période de 3 mois. Résultats: Vingt-neuf patients satisfaisant les critères d’inclusion et d’exclusion ont consenti à participer. Le taux d’OMAr était inférieur dans le groupe traitement (p=0.03, chi-carré) Conclusion: Les INSS semblent efficaces dans la prévention des OMAr. Une étude multicentrique est indiquée pour vérifier la validité externe et confirmer la sécurité. / Introduction: Normal saline nasal cavity irrigations (NSNI) are commonly recommended by pediatricians and otolaryngologists to prevent recurrent acute otitis media (rAOM). However, no published scientific study corroborates or invalidates this practice. Goal: To determine the efficacy of NSNI to prevent rAOM. Method: Pilot randomized controlled clinical trial. All consecutive patients with a diagnosis of rAOM were eligible. Recruited patients were randomized in 2 groups. Only patients in the treatment group proceeded with NSNI. The primary outcome of the study was the incidence of rAOM observed during a 3 month period. Results: Twenty-nine patients met the inclusion and exclusion criteria and agreed to participate. There was a statistically significant lower incidence of rAOM in the treatment group (p=0.003, Fisher exact). Conclusion: Our results suggest that NSNI could effectively prevent rAOM. A larger scale randomized multicentre study is feasible, and it must be done in order to verify for external validity and to properly assess safety issues.

Introdução: A desobstrução rinofaríngea retrógrada (DRR) é uma técnica de fisioterapia respiratória aplicada em lactentes para desobstrução de vias aéreas superiores, podendo, inclusive, ser associada à irrigação nasal com salina isotônica para remoção de muco viscoso aderido às paredes das vias aéreas. Objetivo: Caracterizar o perfil de motociclistas profissionais expostos à poluição urbana no que se refere a transporte mucociliar nasal (TMCN), inflamação das vias aéreas superiores e sintomas nasais, e comparar o efeito da DRR isolada e associada à instilação de salina isotônica (DRR+S) nesta população. Métodos: Vinte e quatro voluntários divididos aleatoriamente em dois grupos (DRR e DRR+S) submeteram-se a 15 dias consecutivos de tratamento. A avaliação basal e a pós-intervenção constituíram-se da análise do teste de trânsito da sacarina, da celularidade total e diferencial do lavado nasal e dos sintomas de vias aéreas superiores por meio do questionário SNOT-20, bem como do estudo da exposição pessoal à poluição do ar, por meio da análise da concentração do NO2 de amostradores passivos. O TMCN foi avaliado pelo teste ANOVA não paramétrico com medidas repetidas e o SNOT-20 pelo teste Mann-Whitney. As correlações entre a concentração de NO2 e os desfechos das vias aéreas superiores foram testadas por meio do coeficiente de correlação de Spearman. Resultados: Os grupos apresentaram dados clínicos e demográficos semelhantes. O TMCN apresentou-se alterado em 25% dos voluntários e 100% deles apresentavam sintomas de vias aéreas superiores. Após os tratamentos, os sintomas de vias aéreas e o TMCN evidenciaram melhora significativa, apesar do aumento no número de macrófagos e células ciliadas do lavado nasal. Não houve correlação entre o NO2 e o TMCN, tampouco em relação aos sintomas de vias aéreas superiores. CONCLUSÃO: Técnicas não farmacológicas, simples e de baixo custo são efetivas para recuperar o TMCN alterado e melhorar os sintomas de vias aéreas superiores em adultos não tabagistas / Introduction: Rhinopharyngeal Retrograde Clearance (RRC) is a respiratory therapy technique applied to infants with upper airway obstruction that may also be associated with nasal irrigation with isotonic saline for removal of viscous mucus adhered to the walls of the airways. OBJECTIVE: Characterize the profile of professional motorcycles exposed to urban pollution in relation to the nasal mucociliary transport (NMCT), inflammation of the upper airways and nasal symptoms and compare the effect of DRR alone and associated with instillation of isotonic saline (RCC + S). Methods: Twenty-four volunteers were randomly divided into two groups (RCC and RCC + S) and were submitted to 15 consecutive days of treatment. The baseline and post-intervention consisted of analysis of the transit saccharin test, the total and differential cellularity nasal lavage, and symptoms of upper airway through the SNOT-20, as well as the study of personal exposure to air pollution, by analyzing the concentration of diffuse nitrogen dioxide monitoring system. The NMCT was evaluated with ANOVA for repeated measures and the SNOT-20 with the Mann-Whitney test. The correlations between the concentration of NO2 and the upper airway outcomes were tested using the Spearman correlation coefficient. Results: The groups showed similar demographic and clinical data. The NMCT was abnormal in 25% of the volunteers and 100% of the volunteers had symptoms of upper airways. After treatment the upper airway symptoms and the NMCT showed significant improvement despite the increase in the number of macrophages and ciliated cells on the nasal lavage. No correlation was observed between dioxide nitrogen and TMCN and with the symptoms of the upper airways. Conclusion: Nonpharmacological, simple and inexpensive techniques are effective to treat abnormal NMCT and improve symptoms of upper airway in nonsmoking adults

No description available.

Introduction: Les instillations nasales de solution saline isotonique (INSS) chez les enfants sont recommandées par les pédiatres et des oto-rhino-laryngologistes de notre institution dans le but de prévenir les otites moyennes aigues à répétition (OMAr). Cependant, aucune étude dans la littérature ne vient corroborer ou infirmer cette pratique. Objectifs: Déterminer l’efficacité des INSS dans la prévention des OMAr. Méthode: Projet pilote d’un essai clinique randomisé. Les enfants diagnostiqués avec des OMAr étaient éligibles. Les patients recrutés ont été randomisés en 2 groupes. Seul le groupe traitement procède aux INSS. L’issue primaire est l’incidence d’OMAr pendant une période de 3 mois. Résultats: Vingt-neuf patients satisfaisant les critères d’inclusion et d’exclusion ont consenti à participer. Le taux d’OMAr était inférieur dans le groupe traitement (p=0.03, chi-carré) Conclusion: Les INSS semblent efficaces dans la prévention des OMAr. Une étude multicentrique est indiquée pour vérifier la validité externe et confirmer la sécurité. / Introduction: Normal saline nasal cavity irrigations (NSNI) are commonly recommended by pediatricians and otolaryngologists to prevent recurrent acute otitis media (rAOM). However, no published scientific study corroborates or invalidates this practice. Goal: To determine the efficacy of NSNI to prevent rAOM. Method: Pilot randomized controlled clinical trial. All consecutive patients with a diagnosis of rAOM were eligible. Recruited patients were randomized in 2 groups. Only patients in the treatment group proceeded with NSNI. The primary outcome of the study was the incidence of rAOM observed during a 3 month period. Results: Twenty-nine patients met the inclusion and exclusion criteria and agreed to participate. There was a statistically significant lower incidence of rAOM in the treatment group (p=0.003, Fisher exact). Conclusion: Our results suggest that NSNI could effectively prevent rAOM. A larger scale randomized multicentre study is feasible, and it must be done in order to verify for external validity and to properly assess safety issues.

Introdução: A desobstrução rinofaríngea retrógrada (DRR) é uma técnica de fisioterapia respiratória aplicada em lactentes para desobstrução de vias aéreas superiores, podendo, inclusive, ser associada à irrigação nasal com salina isotônica para remoção de muco viscoso aderido às paredes das vias aéreas. Objetivo: Caracterizar o perfil de motociclistas profissionais expostos à poluição urbana no que se refere a transporte mucociliar nasal (TMCN), inflamação das vias aéreas superiores e sintomas nasais, e comparar o efeito da DRR isolada e associada à instilação de salina isotônica (DRR+S) nesta população. Métodos: Vinte e quatro voluntários divididos aleatoriamente em dois grupos (DRR e DRR+S) submeteram-se a 15 dias consecutivos de tratamento. A avaliação basal e a pós-intervenção constituíram-se da análise do teste de trânsito da sacarina, da celularidade total e diferencial do lavado nasal e dos sintomas de vias aéreas superiores por meio do questionário SNOT-20, bem como do estudo da exposição pessoal à poluição do ar, por meio da análise da concentração do NO2 de amostradores passivos. O TMCN foi avaliado pelo teste ANOVA não paramétrico com medidas repetidas e o SNOT-20 pelo teste Mann-Whitney. As correlações entre a concentração de NO2 e os desfechos das vias aéreas superiores foram testadas por meio do coeficiente de correlação de Spearman. Resultados: Os grupos apresentaram dados clínicos e demográficos semelhantes. O TMCN apresentou-se alterado em 25% dos voluntários e 100% deles apresentavam sintomas de vias aéreas superiores. Após os tratamentos, os sintomas de vias aéreas e o TMCN evidenciaram melhora significativa, apesar do aumento no número de macrófagos e células ciliadas do lavado nasal. Não houve correlação entre o NO2 e o TMCN, tampouco em relação aos sintomas de vias aéreas superiores. CONCLUSÃO: Técnicas não farmacológicas, simples e de baixo custo são efetivas para recuperar o TMCN alterado e melhorar os sintomas de vias aéreas superiores em adultos não tabagistas / Introduction: Rhinopharyngeal Retrograde Clearance (RRC) is a respiratory therapy technique applied to infants with upper airway obstruction that may also be associated with nasal irrigation with isotonic saline for removal of viscous mucus adhered to the walls of the airways. OBJECTIVE: Characterize the profile of professional motorcycles exposed to urban pollution in relation to the nasal mucociliary transport (NMCT), inflammation of the upper airways and nasal symptoms and compare the effect of DRR alone and associated with instillation of isotonic saline (RCC + S). Methods: Twenty-four volunteers were randomly divided into two groups (RCC and RCC + S) and were submitted to 15 consecutive days of treatment. The baseline and post-intervention consisted of analysis of the transit saccharin test, the total and differential cellularity nasal lavage, and symptoms of upper airway through the SNOT-20, as well as the study of personal exposure to air pollution, by analyzing the concentration of diffuse nitrogen dioxide monitoring system. The NMCT was evaluated with ANOVA for repeated measures and the SNOT-20 with the Mann-Whitney test. The correlations between the concentration of NO2 and the upper airway outcomes were tested using the Spearman correlation coefficient. Results: The groups showed similar demographic and clinical data. The NMCT was abnormal in 25% of the volunteers and 100% of the volunteers had symptoms of upper airways. After treatment the upper airway symptoms and the NMCT showed significant improvement despite the increase in the number of macrophages and ciliated cells on the nasal lavage. No correlation was observed between dioxide nitrogen and TMCN and with the symptoms of the upper airways. Conclusion: Nonpharmacological, simple and inexpensive techniques are effective to treat abnormal NMCT and improve symptoms of upper airway in nonsmoking adults

Target-based screening projects for bioactive (orphan) compounds have been shown in many cases to be insufficiently predictive for in vivo efficacy, leading to attrition in clinical trials. Phenotypic screening has hence undergone a renaissance in both academia and in the pharmaceutical industry, partly due to this reason. One key shortcoming of this paradigm shift is that the protein targets modulated need to be elucidated subsequently, which is often a costly and time-consuming procedure. In this work, we have explored both improved methods and real-world case studies of how computational methods can help in target elucidation of phenotypic screens. One limitation of previous methods has been the ability to assess the applicability domain of the models, that is, when the assumptions made by a model are fulfilled and which input chemicals are reliably appropriate for the models. Hence, a major focus of this work was to explore methods for calibration of machine learning algorithms using Platt Scaling, Isotonic Regression Scaling and Venn-Abers Predictors, since the probabilities from well calibrated classifiers can be interpreted at a confidence level and predictions specified at an acceptable error rate. Additionally, many current protocols only offer probabilities for affinity, thus another key area for development was to expand the target prediction models with functional prediction (activation or inhibition). This extra level of annotation is important since the activation or inhibition of a target may positively or negatively impact the phenotypic response in a biological system. Furthermore, many existing methods do not utilize the wealth of bioactivity information held for orthologue species. We therefore also focused on an in-depth analysis of orthologue bioactivity data and its relevance and applicability towards expanding compound and target bioactivity space for predictive studies. The realized protocol was trained with 13,918,879 compound-target pairs and comprises 1,651 targets, which has been made available for public use at GitHub. Consequently, the methodology was applied to aid with the target deconvolution of AstraZeneca phenotypic readouts, in particular for the rationalization of cytotoxicity and cytostaticity in the High-Throughput Screening (HTS) collection. Results from this work highlighted which targets are frequently linked to the cytotoxicity and cytostaticity of chemical structures, and provided insight into which compounds to select or remove from the collection for future screening projects. Overall, this project has furthered the field of in silico target deconvolution, by improving the performance and applicability of current protocols and by rationalizing cytotoxicity, which has been shown to influence attrition in clinical trials.