Cost-effectiveness analysis of anti–IL-5 therapies of severe eosinophilic asthma in Spain

Asma eosinofílica greu; Comparació indirecta del tractament; MepolizumabSevere eosinophilic asthma; Indirect treatment comparison; MepolizumabAsma eosinofílica severa; Comparación de tratamiento indirecto; MepolizumabAim To analyse the cost-effectiveness of MEP with standard of care (SoC) versus other anti-IL-5 therapies approved for the treatment of severe eosinophilic asthma (SEA) patients, within the Spanish National Health System (NHS) perspective. Methods A Markov model with a 4-week cycle length was used to compare MEP with BEN and RES as therapies added to SoC in the management of SEA, in terms of cost per QALY gained and incremental cost-effectiveness ratio (ICER). Costs (€2019) were obtained from public sources, while utilities and transition probabilities were retrieved from literature, e.g. network meta-analysis. Continuation criteria for biological treatment and reduction of oral corticosteroids (OCS) was set at 50% minimum reduction of exacerbation rate. Adverse events related to chronic OCS use included diabetes, osteoporosis, cataracts, acute myocardial infarct, and peptic ulcer. The analysis was performed over a 5-year time horizon from the National Healthcare System (NHCS) perspective, with a yearly discount rate of 3% applied to both costs and QALYs. Probabilistic sensitivity analysis and univariate deterministic sensitivity analysis were performed to address uncertainty around the cost-effectiveness results. Results On top of SoC, the model indicates that MEP is dominant (lower cost, higher benefit) compared to BEN and RES: For BEN and RES, respectively, treatment with MEP had a point estimate of 0.076 and 0.075 additional QALYs, and savings of €3,173.47 and €7,772.95 per patient. The findings were robust to variation as estimated using sensitivity analysis. Conclusions MEP is a cost-effective treatment in comparison with BEN and RES added to SoC for patients with SEA in the Spanish setting.This study was funded by GlaxoSmithKline [Study code: HO-19-19968]

Influence of the environment on the characteristics of asthma

Environmental sciences; Health careCiències ambientals; Atenció sanitàriaCiencias Ambientales; Atención sanitariaFew studies have compared the prevalence of asthma in urban and rural settings or explored the issue of whether these two manifestations of the disease may represent different phenotypes. The aim of this study was: (a) to establish whether the prevalence of asthma differs between rural and urban settings, and b) to identify differences in the clinical presentation of asthma in these two environments. Descriptive epidemiological study involving individuals aged 18 or over from a rural (n = 516) and an urban population (n = 522). In the first phase, individuals were contacted by letter in order to organize the administration of a first validated questionnaire (Q1) designed to establish the possible prevalence of bronchial asthma. In the second phase, patients who had presented association patterns in the set of variables related to asthma in Q1 completed a second validated questionnaire (Q2), designed to identify the characteristics of asthma. According to Q1, the prevalence of asthma was 15% (n = 78) and 11% (n = 59) in rural and urban populations respectively. Sixty-five individuals with asthma from the rural population and all 59 individuals from the urban population were contacted and administered the Q2. Thirty-seven per cent of the individuals surveyed had previously been diagnosed with bronchial asthma (35% in the rural population and 40% in the urban setting). In the urban asthmatic population there was a predominance of women, a greater personal history of allergic rhinitis and a family history of allergic rhinitis and/or eczema. Asthma was diagnosed in adulthood in 74.8% of the patients, with no significant differences between the two populations. Regarding symptoms, cough (morning, daytime and night) and expectoration were more frequent in the urban population. The prevalence of asthma does not differ between urban and rural settings. The differences in exposure that characterize each environment may lead to different manifestations of the disease and may also affect its severity.MJC is supported by the Miguel Servet program of the Instituto de Salud Carlos III (MSII17/00025). This project received funding from the Fundació Catalana de Pneumologia (FUCAP), FIS PI18/00344, Fondo Europeo de Desarrollo Regional (FEDER) and Menarini. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Trends in prevalence and the effects on hospital outcomes of dementia in patients hospitalized with acute COPD exacerbation

Aims: To assess changes in prevalence and the effects on hospital outcomes of dementia among patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD); and to evaluate sexdifferences, as well as the impact of COVID-19 pandemic in this relationship. Methods: We used a nationwide discharge database to select patients admitted with AE-COPD in Spain from 2011 to 2020. We identified those with any type of dementia, vascular dementia (VaD) or Alzheimer’s disease (AD). Results: We identified 658,429 hospitalizations with AE-COPD (4.45% had any type of dementia, 0.79% VaD and 1.57% AD). The presence of any type of dementia remained stable from 2011 to 2015, and increased significantly between 2016 and 2020. For VaD, the time trend showed no change until 2020, when a significant increment was found. The probability of AD decreased significantly overtime. The in-hospital mortality (IHM) among patients with any type of dementia remained stable overtime until 2020, when it increased significantly. Older age, higher comorbidity, COVID-19, and use of mechanical ventilation were variables associated to IHM. Women had lower risk of dying in the hospital than men in all subgroups. Conclusions: After a previous period of stability, the prevalence of any type of dementia increased over the last 5 years of the study, although we identified different trends depending on the specific cause of dementia. The IHM remained stable overtime until 2020, when it increased, probably related to the COVID-19 pandemic. It is remarkable the protective effect of female sex for IHM.Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEResearch Aid 2022Sociedad Madrileña de Neumología y Cirugía de Tórax (NEUMOMADRID)Comunidad de MadridUniversidad Complutense de Madrid. Grupo de Investigación en Epidemiología de las Enfermedades Crónicas de Alta Prevalencia en EspañaSociedad Española de Neumología y Cirugía de Tórax (SEPAR)pu

Time Trends in Clinical Characteristics and Hospital Outcomes of Hospitalizations for Lung Transplantation in COPD Patients in Spain from 2016 to 2020—Impact of the COVID-19 Pandemic

This study is part of the research funded by: Sociedad Española de Neumología y Cirugía de Tórax (SEPAR), Research Aid 2022, Project number 1309; and Sociedad Madrileña de Neumología y Cirugía de Tórax (NEUMOMADRID), XXII Awards Edition, 2022, and by: Convenio V-PRICIT de la Comunidad de Madrid y la Universidad Complutense de Madrid (“Programa de Excelencia para el Profesorado Universitario” INV.AY.20.2021.1E126), and by: Universidad Complutense de Madrid. Grupo de Investigación en Epidemiología de las Enfermedades Crónicas de Alta Prevalencia en España (970970).(1) Background: To examine the clinical characteristics and hospital outcomes of hospitalization for lung transplantation in COPD patients in Spain from 2016 to 2020; and to assess if the COVID-19 pandemic has affected the number or the outcomes of lung transplantations in these patients. (2) Methods: We used the Spanish National Hospital Discharge Database to select subjects who had a code for COPD (ICD-10: J44) and had undergone a lung transplantation (ICD-10 codes OBYxxxx). (3) Results: During the study period, 704 lung transplants were performed among COPD patients (single 31.68%, bilateral 68.32%). The absolute number of transplants increased with raising rates of 8%, 14% and 19% annually from 2016 to 2019. However, a marked decrease of −18% was observed from 2019 to year 2020. Overall, 47.44% of the patients suffered at least one complication, being the most frequent lung transplant rejection (24.15%), followed by lung transplant infection (13.35%). The median length of hospital stay (LOHS) was 33 days and the in-hospital-mortality (IHM) was 9.94%. Variables associated with increased risk of mortality were a Comorbidity Charlson Index ≥ 1 (OR 1.82; 95%CI 1.08–3.05) and suffering any complication of the lung transplantation (OR 2.14; 95%CI 1.27–3.6). COPD patients in 2020 had a CCI ≥ 1 in a lower proportion than 2019 patients (29.37 vs. 38.51%; p = 0.015) and less frequently suffered any complications after the lung transplantation (41.26 vs. 54.6%; p = 0.013), no changes in the LOHS or the IHM were detected from 2019 to 2020. (4) Conclusions: Our study showed a constant increase in the number of lung transplantations from 2016 to 2019 in COPD patients, with a drop from 2019 to 2020, probably related to the COVID-19 pandemic. However, no changes in LOHS or IHM were detected over time.Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUESociedad Española de Neumología y Cirugía de Tórax (SEPAR)Sociedad Madrileña de Neumología y Cirugía de Tórax (NEUMOMADRID)Convenio V-PRICITUniversidad Complutense de MadridUniversidad Complutense de Madrid. Grupo de Investigación en Epidemiología de las Enfermedades Crónicas de Alta Prevalencia en España (970970)pu

Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

The polyhedric reality of the interaction between COVID-19, asthma and inhaled corticosteroids

The impact of ICS on the prognosis for #COVID19 in #asthma patients requires a thorough evaluation of a range of factors that interact in this process, in order to draw solid conclusions, since at the present time the debate continues https://bit.ly/3xLNBr