| 11. |
- Sena, AG, et al.
(author)
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FIRST LINE TREATMENT WITH CONVENTIONAL SYNTHETIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: A MULTINATIONAL POPULATION-BASED COHORT FROM 14 REAL WORLD HEALTHCARE DATABASES AND 9 COUNTRIES - REALITY VERSUS GUIDELINES
- 2020
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 327-327
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Conference paper (other academic/artistic)abstract
- Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared
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| 12. |
- Duong, Janna K., et al.
(author)
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The variability in beta-cell function in placebo-treated subjects with type 2 diabetes : application of the weight-HbA1c-insulin-glucose (WHIG) model
- 2017
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In: British Journal of Clinical Pharmacology. - : WILEY-BLACKWELL. - 0306-5251 .- 1365-2125. ; 83:3, s. 487-497
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Journal article (peer-reviewed)abstract
- AIM The weight-glycosylated haemoglobin (HbA1C)-insulin-glucose (WHIG) model describes the effects of changes in weight on insulin sensitivity (IS) in newly diagnosed, obese subjects receiving placebo treatment. Thismodel was applied to a wider population of placebo-treated subjects, to investigate factors influencing the variability in IS and beta-cell function. METHODS The WHIG model was applied to the WHIG dataset (Study 1) and two other placebo datasets (Studies 2 and 3). Studies 2 and 3 consisted of nonobese subjects and subjects with advanced type 2 diabetes mellitus (T2DM). Body weight, fasting serum insulin (FSI), fasting plasma glucose (FPG) and HbA1c were used for nonlinear mixed-effects modelling (using NONMEM v7.2 software). Sources of interstudy variability (ISV) and potential covariates (age, gender, diabetes duration, ethnicity, compliance) were investigated. RESULTS An ISV for baseline parameters (body weight and beta-cell function) was required. The baseline beta-cell function was significantly lower in subjects with advanced T2DM (median difference: Study 2: 15.6%, P < 0.001; Study 3: 22.7%, P < 0.001) than in subjects with newly diagnosed T2DM (Study 1). A reduction in the estimated insulin secretory response in subjects with advanced T2DM was observed but diabetes duration was not a significant covariate. CONCLUSION The WHIG model can be used to describe the changes in weight, IS and beta-cell function in the diabetic population. IS remained relatively stable between subjects but a large ISV in beta-cell function was observed. There was a trend towards decreasing beta-cell responsiveness with diabetes duration, and further studies, incorporating subjects with a longer history of diabetes, are required.
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| 14. |
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| 15. |
- Gazagnes, Simon, et al.
(author)
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Interpreting the Si ii and C ii Line Spectra from the COS Legacy Archive Spectroscopic SurveY Using a Virtual Galaxy from a High-resolution Radiation-hydrodynamic Simulation
- 2023
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Journal article (peer-reviewed)abstract
- Observations of low-ionization state metal lines provide crucial insights into the interstellar medium (ISM) of galaxies, yet, disentangling the physical processes responsible for the emerging line profiles is difficult. This work investigates how mock spectra generated using a single galaxy in a radiation-hydrodynamical simulation can help us interpret observations of a real galaxy. We create 22,500 C ii and Si ii spectra from the virtual galaxy at different times and through multiple lines of sight and compare them with the 45 observations of low-redshift star-forming galaxies from the COS Legacy Spectroscopic SurveY (classy). We find that the mock profiles provide accurate replicates of the observations of 38 galaxies with a broad range of stellar masses (106–109M⊙) and metallicities (0.02–0.55 Z⊙). Additionally, we highlight that aperture losses explain the weakness of the fluorescent emission in several classy spectra and must be accounted for when comparing simulations to observations. Overall, we show that the evolution of a single simulated galaxy can produce a large diversity of spectra whose properties are representative of galaxies of comparable or smaller masses. Building upon these results, we explore the origin of the continuum, residual flux, and fluorescent emission in the simulation. We find that these different spectral features all emerge from distinct regions in the galaxy's ISM, and their characteristics can vary as a function of the viewing angle. While these outcomes challenge simplified interpretations of down-the-barrel spectra, our results indicate that high-resolution simulations provide an optimal framework to interpret these observations.
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| 16. |
- Hernandez-Pacheco, N, et al.
(author)
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Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use
- 2021
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 57:5
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Journal article (peer-reviewed)abstract
- Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.MethodsA genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.Results10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at theCACNA2D3-WNT5Alocus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found.ConclusionsThe intergenic region ofCACNA2D3andWNT5Awas revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.
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| 17. |
- Hernandez-Pacheco, N, et al.
(author)
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Identification of ROBO2 as a Potential Locus Associated with Inhaled Corticosteroid Response in Childhood Asthma
- 2021
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In: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:8
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Journal article (peer-reviewed)abstract
- Inhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma. A genome-wide association study (GWAS) of the change in lung function after 6 weeks of ICS treatment was performed in 166 asthma patients from the SLOVENIA study. Patients with an improvement in lung function ≥8% were considered as ICS responders. Suggestively associated variants (p-value ≤ 5 × 10−6) were evaluated in an independent study (n = 175). Validation of the association with asthma exacerbations despite ICS use was attempted in European (n = 2681) and admixed (n = 1347) populations. Variants previously associated with ICS response were also assessed for replication. As a result, the SNP rs1166980 from the ROBO2 gene was suggestively associated with the change in lung function (OR for G allele: 7.01, 95% CI: 3.29–14.93, p = 4.61 × 10−7), although this was not validated in CAMP. ROBO2 showed gene-level evidence of replication with asthma exacerbations despite ICS use in Europeans (minimum p-value = 1.44 × 10−5), but not in admixed individuals. The association of PDE10A-T with ICS response described by a previous study was validated. This study suggests that ROBO2 could be a potential novel locus for ICS response in Europeans.
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| 18. |
- Loth, Daan W, et al.
(author)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Journal article (peer-reviewed)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 19. |
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| 20. |
- Verhamme, A., et al.
(author)
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Recovering the systemic redshift of galaxies from their Lyman alpha line profile
- 2018
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966 .- 1745-3925 .- 1745-3933. ; 478:1, s. L60-L65
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Journal article (peer-reviewed)abstract
- The Lyman alpha (Ly alpha) line of Hydrogen is a prominent feature in the spectra of star-forming galaxies, usually redshifted by a few hundreds of km s(-1) compared to the systemic redshift. This large offset hampers follow-up surveys, galaxy pair statistics, and correlations with quasar absorption lines when only Ly alpha is available. We propose diagnostics that can be used to recover the systemic redshift directly from the properties of the Ly alpha line profile. We use spectroscopic observations of Ly alpha emitters for which a precise measurement of the systemic redshift is available. Our sample contains 13 sources detected between z approximate to 3 and z approximate to 6 as part of various multi-unit spectroscopic explorer guaranteed time observations. We also include a compilation of spectroscopic Ly alpha data from the literature spanning a wide redshift range (z approximate to 0-8). First, restricting our analysis to double-peaked Ly alpha spectra, we find a tight correlation between the velocity offset of the red peak with respect to the systemic redshift, V-peak(red), and the separation of the peaks. Secondly, we find a correlation between V-peak(red) and the full width at half-maximum of the Ly alpha line. Fitting formulas to estimate systemic redshifts of galaxies with an accuracy of <= 100 km s(-1), when only the Ly alpha emission line is available, are given for the two methods.
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