Statistical Considerations for the Design and Analysis of Pragmatic Trials in Aging Research.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

Kangaroo Baby Massage: An Intervention which Improves the Perceived Maternal Self-Efficacy / El masaje al bebé canguro, una intervención que mejora la autoeficacia materna percibida / Massagem no bebê canguru, uma intervenção que melhora a autoeficácia materna percebida

Abstract Introduction: The Kangaroo Baby Massage (KBM) is a technique designed for preterm and low birth weight newborns that eliminates the need for an incubator, providing a practical and beneficial option for mothers at home. Objective: To test the effect of the KBM on perceived maternal self-efficacy favoring the mother-infant interaction at home. Materials and methods: A pragmatic, double-blind, randomized clinical trial was conducted in three phases: 1) KBM integration with Kathryn Barnard's theory, 2) study design, and 3) implementation and outcome evaluation. Two groups were defined: The intervention group (KBM) and the control group (which used the kangaroo position without massage), each group consisted of 34 mother-infant pairs. Recruitment took place within an outpatient kangaroo program in Bogota, Colombia. Implementation and follow-up were conducted via teleconsultation, using the KBM video "Diary of My Kangaroo Baby" and simulators. The perceived maternal self-efficacy questionnaire was conducted at three points in time: prior to the study and on the 7th and 14th day after the study. The questionnaire was analyzed with a statistical design of longitudinal data in F1LDF1 factorial experiments. Results: Homogeneous groups were defined based on sociodemographic variables and maternal-perinatal history. Mothers who applied the KBM technique showed higher scores in perceived maternal self-efficacy at both 7 and 14 days compared to the control group mothers [RTE (lower limit; upper limit) - day 7: control = 0.502 (0.437; 0.567) vs. KBM = 0.503 (0.426; 0.581), and day 14: control = 0.564 (0.482; 0.640) vs. KBM = 0.719 (0.650; 0.776)]. Conclusion: The KBM is a nursing intervention that enhances perceived maternal self-efficacy, fostering greater family involvement and strengthening mother-child interaction.

Resumen Introducción: El masaje al bebé canguro (MBC) es una técnica para recién nacidos pretérmino y bajo peso al nacer que no requiere incubadora y favorece a las madres en el hogar. Objetivo: Probar el efecto del MBC sobre la autoeficacia materna percibida para favorecer la interacción madre-hijo en el hogar. Materiales y métodos: Ensayo clínico aleatorizado pragmático, doble ciego, desarrollado en tres fases: 1) integración MBC y teoría de Kathryn Barnard, 2) diseño del estudio y 3) ejecución y resultados. Se definieron dos grupos: intervención (MBC) y control (posición canguro sin masaje), con 34 diadas madre-hijo en cada grupo. Reclutamiento realizado en un programa canguro ambulatorio de Bogotá, Colombia. La ejecución y el seguimiento fue hecha a través de teleconsulta, el video MBC "Diario de mi bebé canguro" y simuladores. Se aplicó el cuestionario de autoeficacia materna percibida en tres momentos: antes de iniciar el estudio y a los días 7 y 14 después del estudio. Se analizó con un diseño estadístico de datos longitudinales en experimentos factoriales F1LDF1. Resultados: Fueron definidos grupos homogéneos en las variables sociodemográficas y de antecedentes materno-perinatales. Las madres que aplicaron el MBC registraron puntajes más altos de autoeficacia materna percibida a los 7 y 14 días, en comparación con las madres del control [RTE (límite inferior; límite superior) - día 7: control = 0.502 (0.437; 0.567) vs. MBC = 0.503 (0.426; 0.581), y día 14: control = 0.564 (0.482; 0.640) vs. MBC = 0.719 (0.650; 0.776)]. Conclusión: El MBC es una intervención de enfermería que mejoró la autoeficacia materna percibida, favoreciendo la participación de la familia y la interacción madre-hijo.

Resumo Introdução: A massagem no bebê canguru (MBC) é uma técnica para bebês prematuros e de baixo peso que não necessita de incubadora e que dá apoio às mães no domicílio. Objetivo: Testar o efeito da MBC na autoeficácia materna percebida para apoiar a interação mãe-bebê em casa. Materiais e método: Ensaio clínico randomizado, pragmático, duplo-cego, desenvolvido em três fases: i) integração da MBC e da teoria de Kathryn Barnard, ii) desenho do estudo e iii) execução e resultados. Foram definidos dois grupos: intervenção (MBC) e controle (posição canguru sem massagem), com 34 díades mãe-bebê em cada grupo. O recrutamento foi realizado em um programa canguru ambulatorial em Bogotá, Colômbia. A implementação e o acompanhamento foram feitos por meio de teleconsultas, do vídeo MBC "Diário do meu bebê canguru" e de simuladores. O questionário de autoeficácia materna percebida foi aplicado em três momentos: antes do início do estudo e nos dias 7 e 14 após o estudo. Ele foi analisado com um projeto estatístico de dados longitudinais em experimentos fatoriais F1LDF1. Resultados: Foram definidos grupos homogêneos para variáveis sociodemográficas e histórico ma-terno-perinatal. As mães que aplicaram o MBC registraram pontuações mais altas de autoeficácia materna percebida aos 7 e 14 dias, em comparação com as mães do controle [RTE (limite inferior; limite superior) - dia 7: controle = 0,502 (0,437; 0,567) vs. MBC = 0,503 (0,426; 0,581), e dia 14: controle = 0,564 (0,482; 0,640) vs. MBC = 0,719 (0,650; 0,776)]. Conclusões: a MBC é uma intervenção de enfermagem que melhorou a autoeficácia materna percebida, favorecendo o envolvimento familiar e a interação entre mãe e filho.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study.

Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study / Estudo retrospectivo de vida-real, em centro único, para avaliação do comportamento da fosfatase alcalina total após terapia com rádio-223 no câncer de próstata resistente a castração

Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

Recruitment, retention, and adherence of family caregivers: Lessons from a multisite trial / Reclutamiento, retención y adherencia de los cuidadores familiares: Lecciones de un ensayo clínico multi-sitio / Recrutamento, retenção e adesão de cuidadores familiares: lições de um estudo clínico multi-site

Objective. To describe the recruitment, retention of family caregivers, and adherence to a telephone based intervention evaluated in a multi-site trial and provide recommendations for the design of future studies. Methods.A descriptive study based on a secondary analysis of a multi-site clinical development in Colombia and Brazil. Recruitment was measured by the number of participants eligible and consented. Retention was assessed by the percentage of participants with outcomes data at two follow-ups. The intervention adherence was measured by the percentage of the caregiver who received the intervention. Results. Of the family caregivers assessed, 63% were eligible, and 32.9% declined to be in the study for time restriction or no interest. In Colombia, the total retention rate of caregivers was 63.4% at the first follow-up and 48% at the second follow-up, while in Brazil was Invest Educ Enferm. 2023; 41(2): e04Recruitment, retention, and adherence of family caregivers:Lessons from a multisite trialde 52.8% and 46.2%, respectively. At the end of the study, the sample comprised 28 and 70 caregivers in the intervention and control groups, respectively, for a retention rate of 47%. Of 104 family caregivers allocated to the intervention group, 42 (40.3%) received five sessions. Most reported not completing the Caregiver's Activity Diary. Conclusion.The recruitment of family caregivers, participant retention, and adherence to the telephone intervention was unsuccessful. Future studies should apply an assessment tool during the recruitment of family caregivers and replace the term "caregiver" with "care provider" in the material involved in the research; define a retention protocol before starting the study and involve family caregivers in the design of the interventions

Objetivo. Describir el reclutamiento, la retención y la adherencia de los cuidadores familiares en una intervención educativa telefónica evaluada en un ensayo multi-sitio y ofrecer recomendaciones para el diseño de futuros estudios. Métodos. Estudio descriptivo basado en un análisis secundario de un desarrollo clínico multicéntrico en Colombia y Brasil. El reclutamiento se midió por el número de participantes elegibles y que dieron su consentimiento. La retención se evaluó por el porcentaje de participantes con datos de resultados en dos seguimientos. La adherencia a la intervención se determinó por el porcentaje de cuidadores que recibieron la intervención. Resultados. De los cuidadores familiares evaluados, 63% fueron elegibles, y 32.9% declinaron participar en el estudio por restricción de tiempo o falta de interés. En Colombia, la tasa de retención total de cuidadores fue de 63.4% en el primer seguimiento y de 48% en el segundo, mientras que en Brasil fue de 52.8% y 46.2%, respectivamente. Al final del estudio, la muestra comprendía 28 y 70 cuidadores en los grupos de intervención y control, respectivamente, para una tasa de retención del 47%. De los 104 cuidadores familiares asignados al grupo de intervención, 42 (40,3%) recibieron cinco sesiones. La mayoría no completó el diario de actividades del cuidador.Conclusión. El reclutamiento de cuidadores familiares, la retención de participantes y la adherencia a la intervención telefónica no tuvieron éxito. Los estudios futuros deberían aplicar una herramienta de evaluación durante Invest Educ Enferm. 2023; 41(2): e04Leidy Johanna Rueda Díaz • Erika de Souza GuedesDiná de Almeida Lopes Monteiro da Cruzel reclutamiento de los cuidadores familiares y sustituir el término "cuidador" por "proveedor de cuidados" en el material empleado en la investigación; definir un protocolo de retención antes de iniciar el estudio e involucrar a los cuidadores familiares en el diseño de las intervenciones

Objetivo. Descrever o recrutamento, retenção e adesão de cuidadores familiares em uma intervenção telefônica avaliada num estudo clínico multi-site e oferecer recomendações para o desenho de estudos futuros. Métodos. Estudo descritivo baseado em análise secundária de um desenvolvimento clínico multicêntrico na Colômbia e no Brasil. O recrutamento foi medido pelo número de participantes elegíveis e que deram consentimento. A retenção foi avaliada pela porcentagem de participantes com dados de resultado em dois acompanhamentos. A adesão à intervenção foi determinada pela porcentagem de cuidadores que receberam a intervenção. Resultados. Dos cuidadores familiares avaliados, 63% eram elegíveis, e 32.9% se recusaram a participar do estudo por limitação de tempo ou falta de interesse. Na Colômbia, a taxa de retenção total dos cuidadores foi de 63.4% no primeiro acompanhamento e 48% no segundo, enquanto no Brasil foi de 52.8% e 46.2%, respectivamente. Ao final do estudo, a amostra foi composta por 28 e 70 cuidadores nos grupos intervenção e controle, respectivamente, para uma taxa de retenção de 47%. Dos 104 cuidadores familiares designados para o grupo de intervenção, 42 (40.3%) receberam cinco sessões. A maioria não preencheu o diário de atividades do cuidador. Conclusão. Recrutamento de cuidadores familiares, retenção de participantes e adesão à intervenção telefônica não tiveram sucesso. Estudos futuros devem aplicar uma ferramenta de avaliação durante o recrutamento de cuidadores familiares e substituir o termo 'cuidador' por 'fornecedor de cuidados' em material de pesquisa; definir um protocolo de retenção antes de iniciar o estudo e envolver os cuidadores familiares no desenho das intervenções.Descritores: caregivers; enfermagem; doença crónica; telefone; cooperação e adesão ao tratamento.

Explanatory and pragmatic clinical trials Methodological differences / Ensayos clínicos explicativos y pragmáticos Diferencias metodológicas

Abstract Introduction: Clinical trials are experimental studies whose results can lead to the best level of evidence expected for healthcare practice; however, their designs have multiple methodological variants needed to ensure their objectives are met. Objective: To describe the methodological aspects to be considered in designing explanatory and pragmatic clinical trials. Materials and methods: A review of the literature including articles published from 2016-2020: original or review articles describing the methodological aspects of clinical trials. The search and selection were performed on Google Scholar, Scopus and PubMed, obtaining a total of 47 articles for the analysis. Results: Six relevant methodological aspects show differences in clinical trial design with regard to: the purpose and objective; participant recruitment; participant assignment; masking and/ or blinding; data analysis; and internal and external validity. Conclusion: Both types of clinical trials currently have benefits and barriers to overcome for their performance in the clinical setting; health researchers must have a detailed understanding of their methodological requirements to enable them to carry out these types of studies more accurately. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2614).

Resumen Introducción: Los ensayos clínicos son estudios experimentales cuyo resultado puede conducir al mejor nivel de evidencia esperado para la práctica en salud; sin embargo, sus diseños presentan numerosas variantes metodológicas necesarias para garantizar el cumplimiento de sus objetivos. Objetivo: Describir los aspectos metodológicos a tener en cuenta en el diseño de los ensayos clínicos explicativos y pragmáticos. Material y métodos: Revisión de literatura que incluyó manuscritos publicados entre los años 2016-2020, artículos originales o de revisión que describieran aspectos metodológicos de los ensayos clínicos. La búsqueda y selección se realizó en Google Scholar, Scopus y Pubmed, obteniendo un total de 47 manuscritos para el análisis. Resultados: Seis aspectos metodológicos relevantes muestran diferencias en el diseño de los ensayos clínicos en cuanto a: el propósito y objetivo, reclutamiento de los participantes, asignación de participantes, enmascaramiento y/o cegamiento, análisis de los datos obtenidos, validez interna y externa. Conclusión: ambas formas de ensayos clínicos muestran actualmente beneficios y barreras por sortear para su desarrollo en el ámbito clínico; es indispensable que los investigadores en salud, conozcan en detalle sus requerimientos metodológicos, con el objetivo de poder realizar de una manera más acertada este tipo de estudios. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2614).

Recruitment, retention, and adherence of family caregivers: Lessons from a multisite trial.

Objective: To describe the recruitment, retention of family caregivers, and adherence to a telephone based intervention evaluated in a multi-site trial and provide recommendations for the design of future studies. Methods: A descriptive study based on a secondary analysis of a multi-site clinical development in Colombia and Brazil. Recruitment was measured by the number of participants eligible and consented. Retention was assessed by the percentage of participants with outcomes data at two follow-ups. The intervention adherence was measured by the percentage of the caregiver who received the intervention. Results: Of the family caregivers assessed, 63% were eligible, and 32.9% declined to be in the study for time restriction or no interest. In Colombia, the total retention rate of caregivers was 63.4% at the first follow-up and 48% at the second follow-up, while in Brazil was de 52.8% and 46.2%, respectively. At the end of the study, the sample comprised 28 and 70 caregivers in the intervention and control groups, respectively, for a retention rate of 47%. Of 104 family caregivers allocated to the intervention group, 42 (40.3%) received five sessions. Most reported not completing the Caregiver's Activity Diary. Conclusion: The recruitment of family caregivers, participant retention, and adherence to the telephone intervention was unsuccessful. Future studies should apply an assessment tool during the recruitment of family caregivers and replace the term "caregiver" with "care provider" in the material involved in the research; define a retention protocol before starting the study and involve family caregivers in the design of the interventions.

¿El entrenamiento en lectura de creencias puede influir sobre la competencia pragmática?: un estudio sobre las relaciones de estas capacidades cognitivas en la infancia / Can belief- reading training influence pragmatic competence? A study on the relationships of these cognitive abilities in childhood

Resumen Con el objetivo de indagar respecto a la influencia de la lectura de creencias sobre la competencia pragmática, en el presente estudio 56 niños de entre 48 y 54 meses pertenecientes al programa Buen Comienzo de la ciudad de Medellín participaron en un diseño experimental pre-post con grupo control. Para la evaluación de la lectura de creencias se adaptaron al español cuatro pruebas de la escala de Wellman y Liu (2004), mientras que para evaluar la competencia pragmática se adaptaron cuatro situaciones comunicativas propuestas por Sacco et al. (2008). Para la manipulación de la variable se llevaron a cabo 10 sesiones de entrenamiento en lectura de creencias. De acuerdo con los resultados intragrupo, el programa de entrenamiento fue efectivo para mejorar la variable entrenada, pues el grupo experimental mejoró su desempeño en la lectura de creencias (p = .007; d = -.663) y en la competencia pragmática (p = .007; d = .648); no obstante, aunque se encontraron diferencias significativas entre el grupo experimental y el grupo control para la lectura de creencias (p = .001; d = .472), no fue así para el desempeño en la competencia pragmática (p = .340; d = .143). A la luz de estos resultados, no es posible asegurar una relación de influencia de la lectura de creencias sobre la competencia pragmática; sin embargo, se encontró un modelo de regresión lineal satisfactorio cuando se incluyeron en los análisis variables sociodemográficas. Al final del artículo se discute respecto a la necesidad de integrar variables de contexto cuando se indaga por una posible relación de influencia de una variable psicológica sobre otra.

Abstract In order to investigate the influence of belief-reading on pragmatic competence, 56 children between 48 and 54 months old, belonging to the program Buen Comienzo [Good Start] in the city of Medellin, participated in a pre-post experimental design with a control group. For the evaluation of belief-reading, four tests of the Wellman and Liu (2004) Scale were adapted to Spanish; while for the evaluation of pragmatic competence, four communicative situations proposed by Sacco et., al. (2008) were adapted. For the manipulation of the variable, 10 training sessions in belief-reading were carried out. According to the intragroup results, the training program was effective in improving the trained variable, as the experimental group improved its performance in belief reading (p=,007; d= -,663) and pragmatic competence (p=,007; d=,648). However, although significant differences were found between the experimental group and the control group for belief reading (p=,001; d=,472), this was not the case for performance in pragmatic competence (p=,340; d=,143). In light of these results, it is not possible to ensure a relationship of influence of belief reading on pragmatic competence. Nevertheless, a satisfactory linear regression model was found when sociodemographic variables were included in the analyzes. The need to integrate context variables when inquiring about a possible relationship of influence of one psychological variable on another is discussed.

The Neural Substrate of Speech Act Recognition.

Pragmatic competence demands linguistic, but also communicative, social and cognitive competence. Successful use of language in social interaction requires mutual understanding of the speaker's intentions; without it, a conversation cannot proceed. The term speech act refers to what a speaker intends to accomplish when saying something. The purpose of this study was to contribute to the identification of the neural substrate of speech act recognition and to the characterization of the cognitive processes that may be involved. The recognition of speech acts resulted in greater activation of frontal regions, precuneus and posterior cingulate gyrus. From all cognitive and behavioral measures obtained, only the scores in mental flexibility predicted the change in blood oxygen level dependent (BOLD) signal in the precuneus. These results, support the idea that speech act recognition requires the inference of intention, executive functions, including memory and entails the activation of areas of social cognition that participate in several brain networks i.e., the Intention Processing, the Default Mode and Theory of Mind networks, and areas involved in planning and guiding behavior.

Midiendo el espectro de los trastornos del lenguaje a los trastornos del espectro autista: Consenso Latinoamericano Delphi Modificado / Measuring the spectrum from language disorders to autism spectrum disorders: modified Delphi Latin American Consensus

INTRODUCCIÓN: Existen diferentes posturas en cuanto a la delimitación entre los trastornos del lenguaje y de la comunicación; sobre todo al acuñar las definiciones, sus limitantes y particularmente poder medir los pronósticos y diferentes procesos a lo largo del neurodesarrollo. El presente consenso busca unir las diferentes visiones de la región latinoamericana sobre los Trastornos del Desarrollo del Lenguaje (TDL) y Trastornos del Espectro Autista (TEA), homologar taxonomías y evolución a lo largo de los primeros años de vida. MÉTODO: Se realizó un estudio Delphi Modificado para llegar a un consenso sobre la definición más adecuada y diagnóstico temprano de los TDL y TEA. RESULTADOS: Un total de 34 profesionales de 11 países de la región aceptaron la invitación para participar en el consenso e incluyó a distintos especialistas a cargo del cuidado de estos pacientes. Se realizaron dos rondas de evaluación llegando a un acuerdo y consenso en todos los ítems. CONCLUSIONES: El término "Riesgo para Trastornos de la Comunicación y del Lenguaje" es creado para referirse a los niños que no caen en ninguna categoría diagnóstica en etapas tempranas del desarrollo. Consideramos que tanto el uso de este término como el del resto de los mismos, alcanzados por consenso, permitirá coincidir en distintos puntos para la caracterización del TDL y TEA, todo ello contribuirá a evaluar de forma más específica cuáles son las intervenciones adecuadas que mejoren el pronóstico y modifiquen las trayectorias del desarrollo de esta población en nuestra región.

INTRODUCTION: There are different points of view regarding the delimitation between language and communication disorders; especially when establishing the definitions, their limitations and above all being able to measure prognoses and different processes throughout neurodevelopment. The present consensus seeks to unify the different points of view of the Latin American region on Language Development Disorders (LDD) and Autism Spectrum Disorders (ASD), standardize the taxonomies and evolution throughout the first years of life. METHOD: A Modified Delphi study was carried out to reach a consensus on the most adequate definition and early diagnosis of TDL and ASD. RESULTS: A total of 34 professionals from 11 countries in the region accepted the invitation to participate in the consensus and included different specialists in charge of the care of these patients. Two rounds of evaluation were carried out, reaching an agreement and consensus on all items. CONCLUSIONS: The term "Risk for Communication and Language Disorders" is created to refer to children who do not fall into any diagnostic category in early stages of development. We consider that using this term as well as the rest of the terms reached by consensus in the present work will allow to match in different points for the characterization of TDL and ASD, this will contribute to a more specific evaluation regarding the appropriate interventions to improve prognosis and modify development trajectories of this population in our region.

Early use of corticosteroids in non-critical patients with COVID-19 pneumonia (PREDCOVID): a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To evaluate the efficacy of early treatment with prednisone to decrease the progression of COVID-19 pneumonia. TRIAL DESIGN: This is a pragmatic, non-blinded, randomized, two arms, parallel trial. PARTICIPANTS: Patients between 18 and 90 years, with COVID-19 pneumonia, confirmed by RT PCR. The setting for the trial is the Hospital Santiago Oriente which is a secondary level hospital with an emergency room, intensive care, and all basic specialties of medicine. INCLUSION CRITERIA: 18 years or more COVID-19 confirmed by RT-PCR Oxygen requirements up to 35% by venturi mask or 5 liters per minute by nasal cannula (approximately FiO2 40%) Consent form signed Exclusion Criteria: Previous steroid use for more than 48 hours. Pregnancy Chronic respiratory failure Requirements of mechanical ventilation (invasive or no invasive) Chronic liver damage Child Pugh B or C Chronic kidney disease stage IV or V. Immunosuppressed Participation in another trial. INTERVENTION AND COMPARATOR: Experimental arm Prednisone 40 mg days 1 to 4. Then Prednisone 20 mg days 5 to 8. Usual care defined by the attending physician. Control arm No intervention. Usual care defined by the attending physician. MAIN OUTCOMES: Primary outcome Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation or All-cause Death by Day 28 Secondary outcomes (followed until day 28). Time to respiratory deterioration Incidence of patients requiring mechanical ventilation: Number of days on mechanical ventilation Special emphasis will be placed on observing the following serious adverse events Deterioration of the glycemic profile that requires the use of insulin Delirium Incidence of hospital infections (pneumonia, urinary tract infection, device associated infections) Cumulative incidence of grade 3 and 4 adverse events (AE). Interruption or temporary suspension of treatment for any reason RANDOMISATION: Randomisation in permuted block. Computer generated random numbers in an allocation rate of 1:1. Stata 14.0 was used. Allocated by the principal investigator (direct communication). BLINDING (MASKING): Patients not blinded. Caregivers not blinded. Participants not blinded. Statistician will not know the allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 92 patients in each arm. 184 total number of patients. TRIAL STATUS: Protocol version 2.0., approved October 2, 2020. Trial ongoing. Recruitment start: June 23, 2020. Anticipate finish recruiting: November 30, 2020. The protocol has been submitted before the last patient and last visit. The delay in sending to publication is responsibility of the authors. TRIAL REGISTRATION: Early Use of Corticosteroids in Non-critical Patients With COVID-19 Pneumonia (PREDCOVID). Registration number NCT04451174 . Date of trial registration: June 26, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

De moralidad y eticidad. Dos dimensiones para la bioética / Morality and ethics. Two dimensions for bioethics

La Bioética tiene como reto argumentar en un contexto de multiplicidad de voces éticas. El mundo de hoy está constituido por "amigos" y "extraños" morales, al decir de T. Engelhardt, lo que torna difícil la búsqueda de autoridad moral con base en un mismo contenido. La Bioética debe proponer interpretaciones y noemas para la acción en diversos escenarios: justicia sanitaria, investigación clínica, biodiversidad, genética, entre otros. Siendo éste el reto de la Bioética, resulta útil distinguir, según ha expuesto J. Habermas, lo pragmático, lo ético y lo moral como diferentes usos de la Razón Práctica. Se trata de un lenguaje que pertenece a la tradición kantiana, de la cual hoy todos formamos parte cuando se hace filosofía sobre lo moral. A pesar de que T. Engelhardt no cree en la Teoría de la Acción Comunicativa de Habermas como solución al problema moral contemporáneo, el lenguaje de este último puede ser clave para el ámbito de la Bioética

Bioethics, in providing a stage for interdisciplinary discussion has as its challenge to argue in a context in which there is a multiplicity of ethical voices. The world today, consists of moral "relatives" and moral "strangers", as said by T Engelhardt; the difficulty lies in the return to the search for a moral authority with a communal base content. Bioethics must put forth interpretations and appoint norms for the working in diverse scenarios as justice in health, clinical research, biodiversity and genetics amongst others. This challenge for bioethics results in a useful distinction, following that, which has been expressed by J. Habermas: the pragmatic, the ethical and moral used as different applications of Practical Reason. Furthermore to speak of a language which belongs to the Kantian tradition, of which today we are all part whenever philosophy concerns that which is moral. Despite the fact that T Engelhardt does not believe Habermas´s Theory of Communicative Action to be a solution to the contemporary moral problem, the language of this work may be vital for the field of Bioethics

A Bioética tem como desafio argumentar num contexto de multiplicidade de vozes éticas. O mundo hoje está constituído por "amigos" e "estranhos" morais, no dizer de T. Engelhardt, o que torna difícil a busca de autoridade moral tendo como base um único conteúdo. A Bioética deve propor interpretações e normas para ação em diversos cenários: justiça sanitária, investigação clínica, biodiversidade, genética, entre outros. Sendo este o desafio da Bioética, parece útil distinguir, como já exposto por J. Habermas, o pragmático, o ético e o moral como diferentes aportes da Razão Prática. Trata-se de linguagem que tem origem na tradição kantiana, da qual todos fazemos parte quando se refere a filosofia sobre moral.Mesmo considerando que T. Engelhardt não acredita na teoria da Ação Comunicativa de Habermas como instrumento para a solução do problema moral contemporâneo, a linguagem desse último pensador pode ser decisiva para a Bioética

Comunicação Alternativa para Alunos com Autismo na Escola: uma Revisão da Literatura / Alternative Communication for Students with Autism at School: a Literature Review

RESUMO: Estudos meta-analíticos e descritivos conduzidos nas últimas décadas têm demonstrado a efetividade da Comunicação Alternativa e Ampliada (CAA) para pessoas com Transtorno do Espectro Autista (TEA). A maior parte dessas investigações tem focado, contudo, na efetividade clínica da CAA sem atentar para os aspectos pragmáticos da comunicação assistida em contextos não estruturados, como a escola. O objetivo desta investigação foi ampliar, por meio de uma revisão integrativa da literatura, o acervo de pesquisas tratadas em revisões anteriores e, assim, analisar os contextos em que a CAA foi utilizada com educandos com TEA na escola regular. Para isso, foi realizada uma busca no portal de periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e no catálogo eletrônico de teses e dissertações dessa mesma agência com termos previamente definidos. As oito pesquisas encontradas, publicadas entre 2015 e 2018, incluíram participantes entre 3 e 12 anos de idade que utilizavam sistemas assistidos de comunicação, sendo predominantes as pranchas/álbuns de CAA ou pictogramas avulsos. Todos os estudos foram conduzidos na sala de aula regular e/ou nas Salas de Recursos Multifuncionais, mas dois deles incluíram o ambiente domiciliar. A despeito do uso da CAA em contextos naturais envolver interlocutores conhecidos, foram identificadas lacunas em aspectos pragmáticos da comunicação dos educandos. Observou-se a predominância da comunicação imperativa, a qual focava primordialmente nos comportamentos pragmáticos de solicitação. Embora limitações tenham sido identificadas, os estudos revelaram resultados positivos sobre o uso da CAA para alunos com TEA.

ABSTRACT: Meta-analytical and descriptive studies conducted in recent decades have demonstrated the effectiveness of Augmentative and Alternative Communication (AAC) for people with Autism Spectrum Disorders (ASD). Most of these investigations have focused, however, on the clinical effectiveness of AAC without considering pragmatic aspects of assisted communication in unstructured contexts, such as schools. Te aim of this investigation was to expand, through an integrative literature review, the current body of research, analyzing the contexts where AAC was used with students with ASD in regular schools. In this sense, a search was carried out on the Coordination for the Improvement of Higher Education Personnel (CAPES) journals portal and on the electronic catalog of theses and dissertations of this same agency with previously defined terms Te eight studies found, published between 2015 and 2018, included participants between 3 and 12 years of age who used assisted communication systems, primarily AAC boards and picture cards. All studies were conducted in the regular classroom and / or Multifunctional Resource Rooms, but two included the home environment. Despite the use of AAC in natural contexts, involving known interlocutors, gaps were identified in pragmatic aspects of student communication. Tere was a predominance of imperative communication, focusing primarily on pragmatic solicitation behaviors. Despite the limitations identified, the studies revealed positive results on the use of AAC for students with ASD.

Prefrontal gray matter volume in adults bipolar I outpatients is associated with history of suicide attempts?

ABSTRACT Background: Patients with Bipolar Disorder (BD) have the highest lifetime risk for suicidal behavior (SB) compared to other psychiatric disorders. Neuroimaging research provides evidence of some structural and functional abnormalities in the brain of BD suicide attempters (SA), but interpretation of these findings may represent a number of features. Objective: The purpose of this study was to evaluate the volume of the prefrontal cortex in euthymic BD type I outpatients, with and without history of SA. Methods: 36 euthymic BD I outpatients (18 with and 18 without suicide attempt history) were underwent structural MRI and total and regional gray matter volumes were assessed and compared with 22 healthy controls (HC). Results: We did not found any differences in all areas between suicidal and non-suicidal BD I patients and BD patients as a group compared to HC as well. Discussion: our findings suggest that can be a different subgroups of patients in relation to prefrontal cortex volumes according to some clinical and socio-demographic caractheristics, such as number of previous episodes and continuous use of medical psychotropic drugs that may induce neuroplasticity phenomena, which restore cerebral volume and possibly can lead to long-term euthymia state.

Pragmatic Language and Schizophrenia: Interpretation of Metaphors

ABSTRACT Background: Schizophrenia is a severe and chronic psychiatric disorder with significant cognitive deficits, which are considered structural markers for the disease. Language disturbances have an important role in patients' social functioning and interpersonal relationships. Objectives: Evaluate the capacity to understand pragmatic language in schizophrenic patients, through the comprehension of non-literal meaning in metaphors and the ability to use contextual clues to better understand their meanings. Methods: Thirty patients were evaluated using Abbreviated Intelligence Scale (WASI), Interpretation of Metaphors subtest of the Montreal Communication Evaluation Battery (MAC). Results: The linear regression model showed that schizophrenic patients presented below average performance in the interpretation of metaphors task, with tendency to concrete interpretations. Variables such as IQ, WASI Vocabulary subtest and years since onset influenced the patients' pragmatic language skills. This relation was not found for family history. Existence of the metaphor in native colloquial language (Portuguese) and being given alternatives to choose from, enhanced patients' performance. Discussion: Results corroborate findings regarding this population's difficulties in the language cognitive domain. Development of interventions aiming comprehension of pragmatic language could help ease patients' social difficulties, especially if started early at onset. Also, better understanding of this deficit can help create rehabilitation strategies.

The impact of two root canal treatment protocols on the oral health-related quality of life: a randomized controlled pragmatic clinical trial.

AIM: To assess the impact of two root canal treatment protocols on the oral health-related quality of life (OHRQoL) of patients in need of root canal treatment on their anterior teeth. METHODOLOGY: The sample consisted of 120 participants (mean age: 34 years) enrolled in a pragmatic randomized clinical trial evaluating two root canal treatment protocols. Anterior teeth with nonvital pulps were allocated for root canal preparation with either hand files and filled with lateral compaction of gutta-percha (manual protocol) or canal preparation with a single file in a reciprocating movement and filled with a single cone technique (Reciproc protocol). OHRQoL data were assessed using the Oral Health Impact Profile instrument (OHIP-14), which was administered before the root canal intervention (baseline), and 6 and 12 months after treatment. Demographic and clinical characteristics of participants were collected at baseline. Data were analysed using bivariate analyses, Poisson univariate and multiple regression (α = 0.05). RESULTS: The drop-out rate from baseline was 27% and 28% at 6 and 12 months after treatment, respectively. Both root canal protocols significantly enhanced patients' OHRQoL, regardless of the follow-up time (P < 0.001). After 6 months, patients treated with the Reciproc protocol had significantly lower OHIP-14 overall scores (P = 0.030), as well as significantly lower scores for psychological discomfort (P = 0.031) and social disability (P = 0.013). After 12 months, no significant difference was observed between the two root canal protocols for OHIP-14 overall scores (P = 0.174). Either large or moderate effect sizes were observed for all domains and overall scores at both evaluation times, irrespective of the protocol. Low-income persons (RR = 2.03) and the Reciproc protocol (RR = 1.52) had a higher likelihood of a positive impact on OHRQoL 12 months after root canal treatment. CONCLUSIONS: The two root canal protocols improved the OHRQoL and differences in scores were observed only after 6 months with poorer OHRQoL for the manual protocol. After 12 months, patients with low-income status and treated with Reciproc were associated with a greater improvement in OHRQoL scores.

The Effect of a Priest-Led Intervention on the Choice and Preference of Soda Beverages: A Cluster-Randomized Controlled Trial in Catholic Parishes.

BACKGROUND: Latin America ranks among the regions with the highest level of intake of sugary beverages in the world. Innovative strategies to reduce the consumption of sugary drinks are necessary. PURPOSE: Evaluate the effect of a one-off priest-led intervention on the choice and preference of soda beverages. METHODS: We conducted a pragmatic cluster-randomized trial in Catholic parishes, paired by number of attendees, in Chimbote, Peru between March and June of 2017. The priest-led intervention, a short message about the importance of protecting one's health, was delivered during the mass. The primary outcome was the proportion of individuals that choose a bottle of soda instead of a bottle of water immediately after the service. Cluster-level estimates were used to compare primary and secondary outcomes between intervention and control groups utilizing nonparametric tests. RESULTS: Six parishes were allocated to control and six to the intervention group. The proportion of soda selection at baseline was ~60% in the intervention and control groups, and ranged from 56.3% to 63.8% in Week 1, and from 62.7% to 68.2% in Week 3. The proportion of mass attendees choosing water over soda was better in the priest-led intervention group: 8.2% higher at Week 1 (95% confidence interval 1.7%-14.6%, p = .03), and 6.2% higher at 3 weeks after baseline (p = .15). CONCLUSIONS: This study supports the proof-of-concept that a brief priest-led intervention can decrease sugary drink choice. CLINICAL TRIAL INFORMATION: ISRCTN, ISRCTN24676734. Registered 25 April 2017, https://www.isrctn.com/ISRCTN24676734.

Practice based research in dentistry: an alternative to deal with clinical questions

Abstract Clinical interventions in dental practice should be determined based on the best scientific evidence available. Well-designed randomized clinical trials (RCTs) provide important evidence supporting the efficacy of interventions and are usually considered as the best primary evidence. However, the strict criteria adopted by most RCTs reduce their external validity since some findings from these studies might not work under usual conditions. On the other hand, practice-based research (PBR) studies have been designed to better define the effectiveness of clinical interventions under settings closer to "real-world" conditions. Therefore, this review aimed to describe different PBR designs discussing some advantages and limitations of such studies. The stimulus to organization PBR networks is discussed since the studies performed by these networks involve large number of clinicians and important conclusions can be drawn. Designs of observational studies including surveys and cohort studies based on practice are presented. Survey methods are important to know the behavior of practitioners regarding diagnostic and decision of treatment. Cohorts allow assessing different cofounders contributing to some outcome since large sample sizes and long follow-up periods can be observed in some of these studies. Pragmatic trials designed to take place in real-world clinical practice settings are also discussed as a useful design to assess the effectiveness of clinical interventions. In conclusion, this review sought to present PBR studies as alternative designs to answer clinical questions, but not replacing randomized clinical trials.

Pragmatic randomized controlled trial of a web-based intervention for alcohol use among Brazilian college students: Motivation as a moderating effect.

BACKGROUND: Web-based personalized normative feedback (PNF) interventions are less effective than their laboratory versions. Participant motivation may account for this reduced effect, but there is only a limited amount of research into the influence of motivation on PNF effectiveness. We evaluated the effectiveness of a web-based PNF in reducing alcohol use and consequences among college students with different motivation levels. METHODS: Pragmatic randomized controlled trial among Brazilian college drinkers aged 18-30 years (N = 4460). Participants were randomized to a Control or PNF group and followed-up after one (T1), three (T2) and six (T3) months. Outcomes were: AUDIT score (primary outcome), the number of consequences, and the typical number of drinks. Motivation for receiving the intervention was assessed with a visual analog scale (range: 0-10). Generalized mixed models assessed intervention effects via two paradigms: observed cases and attrition models. RESULTS: PNF reduced the number of typical drinks at T1 (OR = 0.71, p = 0.002), T2 (OR = 0.60, p < 0.001) and T3 (OR = 0.68, p = 0.016), compared to the control. Motivated students (score ≥3) receiving PNF also reduced the number of typical drinks at T1 (OR = 0.60, p < 0.001), T2 (OR = 0.55, p < 0.001) and T3 (OR = 0.56, p = 0.001), compared to the control. However, the attrition models were more robust at T1 and T2. In contrast, low-motivated students receiving the PNF increased AUDIT score at T3 (b = 1.49, p < 0.001). CONCLUSIONS: The intervention reduced alcohol use, and motivation for receiving the intervention moderated the intervention effects. Motivated students reduced their typical alcohol use, whereas low-motivated students increased their AUDIT score.