In 1995, the Global Initiative for Asthma (GINA) published an evidence-based workshop report as a guide to clinicians managing asthma patients, and has updated it annually to ensure that ...recommendations remain current. Although the report has been widely disseminated and influenced clinical practice and research, its major objective, of forming the basis for local and national initiatives to improve services for asthma patients, remains to be achieved. Over recent years, the science of guideline implementation has progressed, and encouraging examples of successful asthma programmes have been published. This report is intended to draw on this experience and assist with the translation of asthma guideline recommendations into quality programmes for patients with asthma using current knowledge translation principles. It also provides examples of successful initiatives in various socioeconomic settings.
The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local ...circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes.
GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting β2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS–formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA.
Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS–formoterol as the reliever at all steps: as needed only in Steps 1–2 (mild asthma), and with daily maintenance ICS–formoterol (maintenance-and-reliever therapy, “MART”) in Steps 3–5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS–long-acting β2-agonist (Steps 3–5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6–11 years, new treatment options are added at Steps 3–4.
Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.
El Informe sobre la Estrategia Global para el Manejo y la Prevención del Asma (GINA) proporciona a los clínicos una estrategia basada en la evidencia que se actualiza anualmente para el manejo y la prevención del asma, la cual puede adaptarse a las circunstancias locales (por ejemplo, en cuanto a acceso a medicamentos). Este artículo resume las recomendaciones clave de la GINA 2021 y la evidencia que apoya los cambios recientes.
La GINA recomienda que el asma en adultos y adolescentes no se trate con agonistas β2 de acción corta (SABA) en monoterapia, debido a los riesgos que acompañan a la monoterapia con SABA y a su uso excesivo, y a la evidencia que demuestra los beneficios del uso de corticosteroides inhalados (ICS). Diversos ensayos clínicos de gran tamaño muestran que la combinación de ICS-formoterol a demanda reduce el número de exacerbaciones graves en el asma leve en ≥ 60% en comparación con los SABA en monoterapia, presentando también resultados similares en las exacerbaciones, síntomas, función pulmonar y efectos antiinflamatorios que el uso diario de ICS más SABA a demanda.
Los cambios clave en la GINA 2021 incluyen la división del algoritmo de tratamiento para adultos y adolescentes en dos vías. La vía 1 (la preferencial) cuenta con ICS–formoterol a dosis bajas como tratamiento de rescate en todos los escalones: a demanda solo en los escalones 1–2 (asma leve), y como tratamiento de mantenimiento diario (control y rescate, MART) en los pasos 3–5. La vía 2 (la alternativa) cuenta con SABA a demanda en todos los escalones, más tratamiento regular con ICS (paso 2) o ICS-Agonista β2 de acción prolongada en los escalones 3–5. Para los adultos con asma moderada a grave, la GINA realiza recomendaciones adicionales en el escalón 5, con el agregado de agonistas muscarínicos de larga duración y azitromicina y de tratamientos biológicos en el asma grave. Para los niños entre seis y 11 años, se han añadido opciones nuevas de tratamiento en los escalones 3 y 4.
En todos los grupos de edad y gravedad, sigue siendo esencial una valoración personalizada regular, el tratamiento de los factores de riesgo modificables, la educación para el autocontrol de síntomas, técnicas y habilidades del paciente, el ajuste apropiado de la medicación y las revisiones para optimizar la evolución del asma.
Abstract
Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled ...at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor. Using liver fibrosis as a model for in-depth investigations, we first show that
BNC2
expression is induced in both mouse and human fibrotic livers from different etiologies and decreases upon human liver fibrosis regression. Importantly, we found that
BNC2
transcriptional induction is a specific feature of myofibroblastic activation in fibrotic tissues. Mechanistically, BNC2 expression and activities allow to integrate pro-fibrotic stimuli, including TGFβ and Hippo/YAP1 signaling, towards induction of matrisome genes such as those encoding type I collagen. As a consequence,
Bnc2
deficiency blunts collagen deposition in livers of mice fed a fibrogenic diet. Additionally, our work establishes BNC2 as potentially druggable since we identified the thalidomide derivative CC-885 as a BNC2 inhibitor. Altogether, we propose that BNC2 is a transcription factor involved in canonical pathways driving myofibroblastic activation in fibrosis.
ObjectiveThe objective of this article is to explore the characteristics of older adults visiting the ED for suicidal thoughts and/or voluntary intoxication.MethodsAll older adults (65 years or ...older) who visited one of the five University Hospital Center (CHU) of Quebec EDs in 2016 and who reported suicidal thoughts or intoxication in triage or received a relevant discharge diagnosis were included.ResultsA total of 478 ED visits were identified, of which 332 ED visits (n=279 patients) were included. The mean age was 72.6 (standard deviation 6.8) years old and 41.6% were female. Mood disorders (41.2%) and alcoholism (40.5%) were common. Nearly 30% of all ED visits (n=109) resulted in a referral for a mental health assessment. In the subsequent year (2017), 38.4% returned to the ED for suicidal ideations. There were 7.9% who attended the ED five times or more.ConclusionsED visits for suicidal thoughts and intoxication in older adults are common among men with known mood disorders or alcoholism. ED dispositions are variable, and access to a mental health assessment is not consistent.
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•Reference methods validation for proteins, carbohydrates, lipids and COD analyses.•Proteins, carbohydrates, lipids and COD prediction using NIR spectroscopy.•NIR spectroscopy is a ...new accurate and fast method of solid waste characterization.•NIR spectroscopy characterization is very relevant for large-scale applications.
The development of anaerobic digestion involves both co-digestion of solid wastes and optimization of the feeding recipe. Within this context, substrate characterisation is an essential issue. Although it is widely used, the biochemical methane potential is not sufficient to optimize the operation of anaerobic digestion plants. Indeed the biochemical composition in carbohydrates, lipids, proteins and the chemical oxygen demand of the inputs are key parameters for the optimisation of process performances.
Here we used near infrared spectroscopy as a robust and less-time consuming tool to predict the solid waste content in carbohydrates, lipids and nitrogen, and the chemical oxygen demand. We built a Partial Least Square regression model with 295 samples and validated it with an independent set of 46 samples across a wide range of solid wastes found in anaerobic digestion units. The standard errors of cross-validation were 90mgO2⋅gTS−1 carbohydrates, 2.5∗10−2g⋅gTS−1 lipids, 7.2∗10−3g⋅gTS−1 nitrogen and 99mgO2⋅gTS−1 chemical oxygen demand. The standard errors of prediction were 53mgO2⋅gTS−1 carbohydrates, 3.2∗10−2g⋅gTS−1 lipids, 8.6∗10−3g⋅gTS−1 nitrogen and 83mgO2⋅gTS−1 chemical oxygen demand. These results show that near infrared spectroscopy is a new fast and cost-efficient way to characterize solid wastes content and improve their anaerobic digestion monitoring.
We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with ...trastuzumab emtansine (T-DM1).
The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor-negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing.
The median follow-up was 57.1 months (interquartile range, 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio HR, 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities 12.5%). Similar rates of grade ≥ 3 (55.4%
51.8%) and serious adverse events (23.3%
21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80).
The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.
This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure ...involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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