Applications of telemedicine in the integral management of chronic obstructive pulmonary disease: systematic review

Resumen: Introducción. La enfermedad pulmonar obstructiva crónica es una enfermedad común, prevenible y tratable. Constitu- ye en la actualidad la 4a causa de mortalidad a nivel mundial con tendencia ascendente. Es una entidad muy infradiag- nosticada, que supone un elevado gasto a la Sanidad Pública y una importante pérdida de calidad de vida de las perso- nas que la padecen. En la actualidad no existe un programa de cribado eficaz y el seguimiento de los pacientes es una tarea difícil. Material y métodos. Se ha realizado una búsqueda sistemática de artículos relacionados con el manejo de la EPOC basado en el uso de las tecnologías. Las bases de datos utilizadas han sido: MEDLINE, Web of Science y Cochrane Library, además de las páginas web de organismos como WHO, SEPAR y GOLD. Se han incluido un total de 12 ar- tículos. Resultados. Del total de 12 artículos, 7 encontraron beneficios estadísticamente significativos de la aplicación de estas intervenciones en comparación con la asistencia sanitaria habitual. Entre los beneficios observados se encuentran un aumento de la adherencia a los tratamientos, un aumento de la calidad de vida, un mejor control sintomático y una re- ducción del número de exacerbaciones agudas. Conclusiones. La telemedicina es una herramienta potente que ofrece un amplio abanico de posibilidades para el mane- jo de la EPOC: telemonitorización, coaching electrónico, prevención temprana de las exacerbaciones, screening, tele- rehabilitación... Sin embargo, las evidencias existentes son insuficientes por lo que se requieren estudios potentes para poder extraer conclusiones firmes. Palabras clave: telemedicina; EPOC; telemonitorización; telerehabilitación. Abstract: Introduction. Chronic Obstructive Pulmonary Disease is a common, preventable and treatable disease. It is currently the 4th cause of mortality worldwide with an upward trend. It is a underdiagnosed entity, which implies a high cost to Public Health, and a huge loss of quality of life for the people who suffer it. Currently, there is no effective screening program, and follow-up is a difficult task. Material and methods. A systematic review was made of articles related to the management of COPD based on the use of the technologies. The databases used were: MEDLINE, Web of Science and Cochrane Library in addition to the websites of organizations such as WHO, SEPAR and GOLD. A total of 12 articles have been included. Results. Of the total of 12 articles, 7 found statistically significant benefits of the application of these interventions in comparison with the usual healthcare. Among the benefits there is an increase in treatment adherence, an increase in quality of life, better control of their symptoms and a reduction in the number of accute exacerbations. Conclusions. Telemedicine is a powerful tool that offers a wide range of possibilities for the management of COPD: telemonitoring, electronic coaching, early prevention of exacerbations, screening, telerehabilitation... However, the existing evidence is weak so it is required the development of powerful studies in order to establish firm conclusions. Keywords: telemedicine; COPD; telemonitoring; telerehabilitation

The effects of an appropriate behavior program on elementary school children social skills development in physical education

The purpose of this study was to see the effects of an appropriate behavior development program in relation to the improvement of fair play and social skills behaviors of elementary school children during the physical education class. The participants of this study were 204 students from 5th and 6th grade from seven different public schools in Castilla-La Mancha, Spain. Data was collected through a questionnaire to measure students' pre and post appropriate behaviors when winning, appropriate behaviors when loosing, appropriate behaviors during the game, fair play skills and social skills, during the physical education class. Results from this study revealed that participants improved their behaviors with the implementation of the intervention (appropriate behavior program), generating positive changes in students? attitudes and social skills during physical education class. In relation to children gender, girls had better scores than boys in relation to appropriate behaviors when losing. Further, when comparing students' age, those from 10 to 11 years old scored higher in fair play behaviors and social skills. In conclusion, the intervention program was effective to improve the behaviors of the school children, generating positive changes in their attitudes and social skills during physical education.Fil: Gil Madrona, Pedro. Universidad de Castilla-La Mancha; EspañaFil: Gutiérrez Marín, Eva Cristina. Universidad de Castilla-La Mancha; EspañaFil: Cupani, Marcos. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Samalot Rivera, Amaury. State University of New York; Estados UnidosFil: Díaz Suárez, Arturo. Universidad de Murcia; EspañaFil: López Sánchez, Guillermo F.. Universidad de Murcia; Españ

Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19

Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline. Conclusions and Relevance Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs. Trial Registration ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT0437258

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.

BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.)

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele