Suchergebnisse

International audience ; IMPORTANCE: Histone deacetylase inhibitors have been repeatedly shown to elevate progranulin levels in preclinical models. This report describes the first randomized clinical trial of a histone deacetylase inhibitor in frontotemporal dementia (FTD) resulting from progranulin (GRN) gene variations. OBJECTIVE: To characterize the safety, tolerability, plasma pharmacokinetics, and pharmacodynamic effects of oral FRM-0334 on plasma progranulin and other exploratory biomarkers, including fluorodeoxyglucose (FDG)-positron emission tomography (PET), in individuals with GRN haploinsufficiency. DESIGN, SETTING, AND PARTICIPANTS: In this randomized, double-blind, placebo-controlled, dose-escalating, phase 2a safety, tolerability, and pharmacodynamic clinical study, 2 doses of a histone deacetylase inhibitor (FRM-0334) were administered to participants with prodromal to moderate FTD with granulin variations. Participants were recruited from January 13, 2015, to April 13, 2016. The study included 27 participants with prodromal (n = 8) or mild-to-moderate symptoms of FTD (n = 19) and heterozygous pathogenic variations in GRN and was conducted at multiple centers in North America, the UK, and the European Union. Data were analyzed from June 9, 2019, to May 13, 2021. INTERVENTIONS: Daily oral placebo (n = 5), 300 mg of FRM-0334 (n = 11), or 500 mg of FRM-0334 (n = 11) was administered for 28 days. MAIN OUTCOMES AND MEASURES: Primary outcomes were safety and tolerability of FRM-0334 and its peripheral pharmacodynamic effect on plasma progranulin. Secondary outcomes were the plasma pharmacokinetic profile of FRM-0334 and its pharmacodynamic effect on cerebrospinal fluid progranulin. Exploratory outcomes were FDG-PET, FTD clinical severity, and cerebrospinal fluid biomarkers (neurofilament light chain [NfL], amyloid β 1-42, phosphorylated tau 181, and total tau [t-tau]). RESULTS: A total of 27 participants (mean [SD] age, 56.6 [10.5] years; 16 women [59.3%]; 26 White participants [96.3%]) with GRN ...

In mid April 2020, with more than 2.5 billion people in the world following social distancing measures due to COVID-19, governments are considering relaxing lock-down. We combined individual clinical risk predictions with epidemic modelling to examine simulations of isolation and exit policies.Methods: We developed a method to include personalised risk predictions in epidemic models based on data science principles. We extended a standard susceptible-exposed-infected-removed (SEIR) model to account for predictions of severity, defined by the risk of an individual needing intensive care in case of infection. We studied example isolation policies using simulations with the risk-extended epidemic model, using COVID-19 data and estimates in France as of mid April 2020 (4 000 patients in ICU, around 7 250 total ICU beds occupied at the peak of the outbreak, 0.5 percent of patients requiring ICU upon infection). We considered scenarios varying in the discrimination performance of a risk prediction model, in the degree of social distancing, and in the severity rate upon infection. Confidence intervals were obtained using an Approximate Bayesian Computation approach. The framework may be used with other epidemic models, with other risk predictions, and for other epidemic outbreaks.

In mid April 2020, with more than 2.5 billion people in the world following social distancing measures due to COVID-19, governments are considering relaxing lock-down. We combined individual clinical risk predictions with epidemic modelling to examine simulations of isolation and exit policies.Methods: We developed a method to include personalised risk predictions in epidemic models based on data science principles. We extended a standard susceptible-exposed-infected-removed (SEIR) model to account for predictions of severity, defined by the risk of an individual needing intensive care in case of infection. We studied example isolation policies using simulations with the risk-extended epidemic model, using COVID-19 data and estimates in France as of mid April 2020 (4 000 patients in ICU, around 7 250 total ICU beds occupied at the peak of the outbreak, 0.5 percent of patients requiring ICU upon infection). We considered scenarios varying in the discrimination performance of a risk prediction model, in the degree of social distancing, and in the severity rate upon infection. Confidence intervals were obtained using an Approximate Bayesian Computation approach. The framework may be used with other epidemic models, with other risk predictions, and for other epidemic outbreaks.

The french government has presented its end of lockdown plan on Tuesday 28 April. Among the key measures, "test and isolate" all positive cases. For this purpose the french government is targeting 700,000 RT-PCR assays per week. This number has been sized up to test all new infected people each week as well as their contacts during the two days prior to symptoms. However, only clinical cases (and their contacts) are going to be teste but clinical cases represent less than 10% of all infected people. Most healthy carriers will remain invisible and-as they are also silent spreaders-require to be found. We propose here a testing strategy, combining virologic AND serologic tests, to identify most healthy carriers in a given territory. If generalized, this could make it possible to eradicate covid-19.

An effective and cost-efficient population-wide framework based on available and easy-to-use self-administered test is proposed with a potential to significantly improve the accuracy and timing of monitoring of Covid-19 epidemiological situation. Easy in development and introduction, such a framework can be an effective instrument in development of sustainable and effective epidemics control policies for Covid-19 as well as possible future epidemics. ; Une structure efficace et rentable à l'échelle de la population, basé sur des tests auto-administrés disponibles et faciles à utiliser, est proposé avec un potentiel pour améliorer considérablement la précision et la agilite de surveillance de la situation épidémiologique de Covid-19. Facile à développer et à introduire, une structure comme sa peut être un instrument efficace pour le développement de politiques durables et efficaces de lutte contre les épidémies de Covid-19 ainsi que d'éventuelles épidémies futures.

An effective and cost-efficient population-wide framework based on available and easy-to-use self-administered test is proposed with a potential to significantly improve the accuracy and timing of monitoring of Covid-19 epidemiological situation. Easy in development and introduction, such a framework can be an effective instrument in development of sustainable and effective epidemics control policies for Covid-19 as well as possible future epidemics. ; Une structure efficace et rentable à l'échelle de la population, basé sur des tests auto-administrés disponibles et faciles à utiliser, est proposé avec un potentiel pour améliorer considérablement la précision et la agilite de surveillance de la situation épidémiologique de Covid-19. Facile à développer et à introduire, une structure comme sa peut être un instrument efficace pour le développement de politiques durables et efficaces de lutte contre les épidémies de Covid-19 ainsi que d'éventuelles épidémies futures.

International audience ; IntroductionThe representation of the minor in advertisements is a topic that is scarcely studied and reflected in the bibliography, in social paediatrics as well as audio-visual communication. The aim of the present study is to describe how the minor is represented in the publicity that is conveyed through the internet, and whether or not that representation is adequate.Material and methodsAn analysis was made of all the advertisements in which minors appeared during a period of two months, on three days a week, on the most visited web pages in Spain. The evaluation on how the minor was represented was carried out with an evaluation tool, constructed by the authors, based on European and Spanish legislation, which showed a high concordance between evaluators. A descriptive analysis was performed on the categorical variables, and the inter-dependent relationship was established between them using the chi-squared test.ResultsA total of 173 advertisements were identified in which at least one minor appeared, which was generally represented solo (63.5%), in a natural environment (36.9%) and of school age (44.5%). The web pages of the "general press" are those that most frequently show advertisement in which minors are represented, through the use of banners (82%). In the majority of cases the inadequate use of the figure of the minor takes place using tactical representation, and not just strategic.ConclusionsThe image of the minor in the publicity that is conveyed via the most visited web pages in Spain is inadequate in 3 of every 3 advertisements. This misuse of the minor is usually seen in as unjustifiably strategic, and favouring non-positive values or that they favour situations of inequality ; IntroducciónLa representación del menor en los anuncios de publicidad es un tema poco investigado y reflejado en la bibliografía, tanto de la pediatría social como de la comunicación audiovisual. El objetivo del presente estudio es describir cómo se representa al menor en la publicidad que se ...

In mid April 2020, with more than 2.5 billion people in the world following social distancing measures due to COVID-19, governments are considering relaxing lock-down. We combined individual clinical risk predictions with epidemic modelling to examine simulations of isolation and exit policies.Methods: We developed a method to include personalised risk predictions in epidemic models based on data science principles. We extended a standard susceptible-exposed-infected-removed (SEIR) model to account for predictions of severity, defined by the risk of an individual needing intensive care in case of infection. We studied example isolation policies using simulations with the risk-extended epidemic model, using COVID-19 data and estimates in France as of mid April 2020 (4 000 patients in ICU, around 7 250 total ICU beds occupied at the peak of the outbreak, 0.5 percent of patients requiring ICU upon infection). We considered scenarios varying in the discrimination performance of a risk prediction model, in the degree of social distancing, and in the severity rate upon infection. Confidence intervals were obtained using an Approximate Bayesian Computation approach. The framework may be used with other epidemic models, with other risk predictions, and for other epidemic outbreaks.

The french government has presented its end of lockdown plan on Tuesday 28 April. Among the key measures, "test and isolate" all positive cases. For this purpose the french government is targeting 700,000 RT-PCR assays per week. This number has been sized up to test all new infected people each week as well as their contacts during the two days prior to symptoms. However, only clinical cases (and their contacts) are going to be teste but clinical cases represent less than 10% of all infected people. Most healthy carriers will remain invisible and-as they are also silent spreaders-require to be found. We propose here a testing strategy, combining virologic AND serologic tests, to identify most healthy carriers in a given territory. If generalized, this could make it possible to eradicate covid-19.

International audience ; IntroductionThe representation of the minor in advertisements is a topic that is scarcely studied and reflected in the bibliography, in social paediatrics as well as audio-visual communication. The aim of the present study is to describe how the minor is represented in the publicity that is conveyed through the internet, and whether or not that representation is adequate.Material and methodsAn analysis was made of all the advertisements in which minors appeared during a period of two months, on three days a week, on the most visited web pages in Spain. The evaluation on how the minor was represented was carried out with an evaluation tool, constructed by the authors, based on European and Spanish legislation, which showed a high concordance between evaluators. A descriptive analysis was performed on the categorical variables, and the inter-dependent relationship was established between them using the chi-squared test.ResultsA total of 173 advertisements were identified in which at least one minor appeared, which was generally represented solo (63.5%), in a natural environment (36.9%) and of school age (44.5%). The web pages of the "general press" are those that most frequently show advertisement in which minors are represented, through the use of banners (82%). In the majority of cases the inadequate use of the figure of the minor takes place using tactical representation, and not just strategic.ConclusionsThe image of the minor in the publicity that is conveyed via the most visited web pages in Spain is inadequate in 3 of every 3 advertisements. This misuse of the minor is usually seen in as unjustifiably strategic, and favouring non-positive values or that they favour situations of inequality ; IntroducciónLa representación del menor en los anuncios de publicidad es un tema poco investigado y reflejado en la bibliografía, tanto de la pediatría social como de la comunicación audiovisual. El objetivo del presente estudio es describir cómo se representa al menor en la publicidad que se ...

International audience ; INTRODUCTION: Acute malnutrition (AM) is a continuum condition, arbitrarily divided into moderate and severe AM (SAM) categories, funded and managed in separate programmes under different protocols. Optimising acute MAlnutrition (OptiMA) treatment aims to simplify and optimise AM management by treating children with mid-upper arm circumference (MUAC) <125 mm or oedema with one product-ready-to-use therapeutic food-at a gradually tapered dose. Our main objective was to compare the OptiMA strategy with the standard nutritional protocol in children 6-59 months presenting with MUAC <125 mm or oedema without additional complications, as well as in children classified as uncomplicated SAM (ie, MUAC <115 mm or weight-for-height Z-score (WHZ) <-3 or with oedema). METHODS AND ANALYSIS: This study was a non-inferiority, individually randomised controlled clinical trial conducted at community level in the Democratic Republic of Congo. Children 6-59 months presenting with MUAC <125 mm or WHZ <-3 or with bipedal oedema and without medical complication were included after signed informed consent in outpatient health facilities. All participants were followed for 6 months. Success in both arms was defined at 6 months post inclusion as being alive, not acutely malnourished per the definition applied at inclusion and without an additional episode of AM throughout the 6-month observation period. Recovery among children with uncomplicated SAM was the main secondary outcome. For the primary objective, 890 participants were needed, and 480 children with SAM were needed for the main secondary objective. We will perform non-inferiority analyses in per-protocol and intention-to-treat basis for both outcomes. ETHICS AND DISSEMINATION: Ethics approvals were obtained from the National Health Ethics Committee of the Democratic Republic of Congo and from the Ethics Evaluation Committee of Inserm, the French National Institute for Health and Medical Research (Paris, France). We will submit results ...

In mid April 2020, with more than 2.5 billion people in the world following social distancing measures due to COVID-19, governments are considering relaxing lock-down. We combined individual clinical risk predictions with epidemic modelling to examine simulations of isolation and exit policies.Methods: We developed a method to include personalised risk predictions in epidemic models based on data science principles. We extended a standard susceptible-exposed-infected-removed (SEIR) model to account for predictions of severity, defined by the risk of an individual needing intensive care in case of infection. We studied example isolation policies using simulations with the risk-extended epidemic model, using COVID-19 data and estimates in France as of mid April 2020 (4 000 patients in ICU, around 7 250 total ICU beds occupied at the peak of the outbreak, 0.5 percent of patients requiring ICU upon infection). We considered scenarios varying in the discrimination performance of a risk prediction model, in the degree of social distancing, and in the severity rate upon infection. Confidence intervals were obtained using an Approximate Bayesian Computation approach. The framework may be used with other epidemic models, with other risk predictions, and for other epidemic outbreaks.

In mid April 2020, with more than 2.5 billion people in the world following social distancing measures due to COVID-19, governments are considering relaxing lock-down. We combined individual clinical risk predictions with epidemic modelling to examine simulations of isolation and exit policies.Methods: We developed a method to include personalised risk predictions in epidemic models based on data science principles. We extended a standard susceptible-exposed-infected-removed (SEIR) model to account for predictions of severity, defined by the risk of an individual needing intensive care in case of infection. We studied example isolation policies using simulations with the risk-extended epidemic model, using COVID-19 data and estimates in France as of mid April 2020 (4 000 patients in ICU, around 7 250 total ICU beds occupied at the peak of the outbreak, 0.5 percent of patients requiring ICU upon infection). We considered scenarios varying in the discrimination performance of a risk prediction model, in the degree of social distancing, and in the severity rate upon infection. Confidence intervals were obtained using an Approximate Bayesian Computation approach. The framework may be used with other epidemic models, with other risk predictions, and for other epidemic outbreaks.

The french government has presented its end of lockdown plan on Tuesday 28 April. Among the key measures, "test and isolate" all positive cases. For this purpose the french government is targeting 700,000 RT-PCR assays per week. This number has been sized up to test all new infected people each week as well as their contacts during the two days prior to symptoms. However, only clinical cases (and their contacts) are going to be teste but clinical cases represent less than 10% of all infected people. Most healthy carriers will remain invisible and-as they are also silent spreaders-require to be found. We propose here a testing strategy, combining virologic AND serologic tests, to identify most healthy carriers in a given territory. If generalized, this could make it possible to eradicate covid-19.

International audience ; INTRODUCTION: Acute malnutrition (AM) is a continuum condition, arbitrarily divided into moderate and severe AM (SAM) categories, funded and managed in separate programmes under different protocols. Optimising acute MAlnutrition (OptiMA) treatment aims to simplify and optimise AM management by treating children with mid-upper arm circumference (MUAC) <125 mm or oedema with one product-ready-to-use therapeutic food-at a gradually tapered dose. Our main objective was to compare the OptiMA strategy with the standard nutritional protocol in children 6-59 months presenting with MUAC <125 mm or oedema without additional complications, as well as in children classified as uncomplicated SAM (ie, MUAC <115 mm or weight-for-height Z-score (WHZ) <-3 or with oedema). METHODS AND ANALYSIS: This study was a non-inferiority, individually randomised controlled clinical trial conducted at community level in the Democratic Republic of Congo. Children 6-59 months presenting with MUAC <125 mm or WHZ <-3 or with bipedal oedema and without medical complication were included after signed informed consent in outpatient health facilities. All participants were followed for 6 months. Success in both arms was defined at 6 months post inclusion as being alive, not acutely malnourished per the definition applied at inclusion and without an additional episode of AM throughout the 6-month observation period. Recovery among children with uncomplicated SAM was the main secondary outcome. For the primary objective, 890 participants were needed, and 480 children with SAM were needed for the main secondary objective. We will perform non-inferiority analyses in per-protocol and intention-to-treat basis for both outcomes. ETHICS AND DISSEMINATION: Ethics approvals were obtained from the National Health Ethics Committee of the Democratic Republic of Congo and from the Ethics Evaluation Committee of Inserm, the French National Institute for Health and Medical Research (Paris, France). We will submit results ...