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| 2. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Butler-Laporte, G, et al.
(författare)
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Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
- 2022
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
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Tidskriftsartikel (refereegranskat)abstract
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
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| 8. |
- Kroes, JA, et al.
(författare)
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Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
- 2023
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach.AimTo harmonize data from 10 national severe asthma registries and characterize patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.MethodsIn this observational cohort study, registry data (5871 patients) were extracted for harmonization. Where harmonization was possible, patients who initiated mepolizumab between 1-1-2016 and 31-12-2021 were examined. Changes of a 12 (range 11–18) months period in frequent (≥2) exacerbations, maintenance OCS use and dose were analyzed in a privacy-preserving manner using meta-analysis of generalized estimating equation parameters. Periods before and during the COVID-19 pandemic were analyzed separately.ResultsIn 912 patients who fulfilled selection criteria mepolizumab significantly reduced frequent exacerbations (OR;95%CI: 0.18;0.13–0.25), maintenance OCS use (OR;95%CI: 0.75;0.61–0.92) and dose (mean; 95%CI: −3.93 mg·day−1; −5.24–2.62) in the Pre-Pandemic group, with similar trends in the Pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.ConclusionsBy harmonizing patient-level registry data and applying federated analysis, SHARP demonstrated the real-wold effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
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| 13. |
- Ozkan, E., et al.
(författare)
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Current Smoking Determines the Levels of Circulating MPO and MMP-9 in Adults with Coronary Artery Disease and Obstructive Sleep Apnea
- 2023
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Ingår i: Journal of Clinical Medicine. - 2077-0383. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which a rupture of atherosclerotic plaques and oxidative stress play a role in the initiation and progression of the disorder. Circulating levels of myeloperoxidase (MPO), as an oxidative stress marker, as well as matrix metalloproteinase-9 (MMP-9), as a destabilizer of plaques, are known to be elevated in patients with CAD and are associated with worse prognosis. Some studies have suggested that OSA is associated with MPO and MMP-9, but the effect of OSA on these biomarkers in cardiac cohorts is unknown. (2) Aims: We addressed the determinants of high MPO and MMP-9 in a CAD cohort with concomitant OSA. (3) Materials and Methods: The current study was a secondary analysis of the RICCADSA trial that was conducted in Sweden between 2005 and 2013. A total of 502 revascularized CAD patients with OSA (apnea-hypopnea index [AHI] & GE; 15 events/h; n = 391) or no-OSA (AHI < 5 events/h; n = 101), based on a home sleep apnea test, and who had blood samples at baseline were included in the analysis. The patients were dichotomized into a high or low MPO and MMP-9 groups, based on the median cut-off values. (4) Results: The mean age of the participants was 63.9 (& PLUSMN;8.6), and 84% of the study cohort were men. Median values of MPO and MMP-9 levels were 116 ng/mL and 269 ng/mL, respectively. In different multivariate linear and logistic regression models, neither OSA nor OSA severity in terms of AHI and oxygenation indices were associated with the high MPO and MMP-9 levels. Current smoking was significantly associated with both high MPO (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06-2.84; p = 0.030) and high MMP-9 levels (OR 2.41, 95% CI 1.44-4.03; p < 0.001), respectively. Other significant determinants were revealed as beta blocker use (OR 1.81, 95% CI 1.04-3.16; p = 0.036) for high MPO as well as male sex (OR 2.07, 95% CI 1.23-3.50; p = 0.006) and calcium antagonist use (OR 1.91, 95% CI 1.18-3.09; p = 0.008) for high MMP-9 levels. (5) Conclusions: Current smoking, but not OSA, was significantly associated with high MPO and MMP-9 levels in this revascularized CAD cohort. Smoking status should be seriously taken into consideration while evaluating the effects of OSA and its treatment on long-term adverse cardiovascular outcomes in adults with CAD.
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| 14. |
- Ozkan, M., et al.
(författare)
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Early-Middle Jurassic metamorphic and non-metamorphic supra-subduction zone ophiolite fragments in a Late Cretaceous ophiolitic melange (northern Turkey): implications for long-lived and supra-subduction zone ophiolite formation
- 2022
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Ingår i: International Journal of Earth Sciences. - : Springer Science and Business Media LLC. - 1437-3254 .- 1437-3262. ; 111, s. 2391-2408
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Tidskriftsartikel (refereegranskat)abstract
- The Late Cretaceous accretionary complexes along the Izmir-Ankara-Erzincan (IAE) Neo-Tethyan suture zone in northern Turkey record the subduction-accretion processes of the oceanic lithosphere ranging in age from the Late Triassic to the Late Cretaceous. These accretionary complexes contain fragments of Early and Middle Jurassic metamorphic and non-metamorphic ophiolites. Here, we report new geochemical and geochronological data from the metamorphic and non-metamorphic ophiolitic rocks, which are observed in the Tekelidag melange (northern Sivas) of the IAE suture zone. Geochemical characteristics of these rocks point to formation in a subduction-related tectonic setting. Igneous zircons from meta-plagiogranite injected into the meta-ophiolitic rocks yielded zircon U-Pb age of 188 +/- 4 Ma (2 sigma, Early Jurassic), and those from a non-metamorphic plagiogranite crosscutting the non-metamorphic ophiolitic rocks gave an age value of 168 +/- 2 Ma (2 sigma, Middle Jurassic). The igneous crystallization age of the non-metamorphic plagiogranite is identical with the metamorphic age of meta-ophiolitic rocks, which has been dated as Middle Jurassic (166.7 +/- 2 Ma, 2 sigma) by the Ar-40-Ar-39 method. These age data indicate that (i) the supra-subduction zone ophiolite formation lasted about 20 Ma, (ii) the supra-subduction zone ophiolite and the meta-ophiolitic rocks formed simultaneously in the Middle Jurassic, and (iii) the meta-ophiolitic rocks are remnants of the metamorphosed equivalents of the Early Jurassic supra-subduction zone oceanic crust. The supra-subduction zone ophiolite formation probably occurred over an extended period of time in the Jurassic Neo-Tethys.
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| 16. |
- Peker, Yüksel, 1961, et al.
(författare)
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Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019 A Multicenter, Prospective, Observational Clinical Trial
- 2021
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Ingår i: Annals of the American Thoracic Society. - 1546-3222. ; 18:9, s. 1548-1559
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. Objectives: To determine the effect of OSA on clinical outcomes in patients with COVID-19. Methods: The current prospective observational study was conducted in three hospitals in Istanbul, Turkey from March 10 to June 22, 2020. The participants were categorized as high-risk or low-risk OSA according to the Berlin questionnaire that was administered in the out-patient clinic, in hospital, or shortly after discharge from hospital blinded to the clinical outcomes. A modified high-risk (mHR)-OSA score based on the snoring patterns (intensity and/or frequency), breathing pauses, and morning/daytime sleepiness, without taking obesity and hypertension into account, were used in the regression models. Results: The primary outcome was the clinical improvement defined as a decline of two categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death) on Days 7, 14, 21, and 28, respectively. Secondary outcomes included clinical worsening (an increase of 1 category), need for hospitalization, supplemental oxygen, and intensive care. In total, 320 eligible patients (median [interquartile range] age, 53.2 [41.3-63.0] yr; 45.9% female) were enrolled. In all, 121 (37.8%) were categorized as known (n = 3) or high-risk OSA (n = 118). According to the modified scoring, 70 (21.9%) had mHR-OSA. Among 242 patients requiring hospitalization, clinical improvement within 2 weeks occurred in 75.4% of the mHR-OSA group compared with 88.4% of the modified low-risk-OSA group (P = 0.014). In multivariate regression analyses, mHR-OSA (adjusted odds ratio [OR], 0.42; 95% confidence interval [CI], 0.19-0.92) and male sex (OR, 0.39; 95% CI, 0.17-0.86) predicted the delayed clinical improvement. In the entire study population (n = 320), including the nonhospitalized patients, mHR-OSA was associated with clinical worsening (adjusted hazard ratio, 1.55; 95% CI, 1.00-2.39) and with the need for supplemental oxygen (OR, 1.95; 95% CI, 1.06-3.59). Snoring patterns, especially louder snoring, significantly predicted delayed clinical improvement, worsening, need for hospitalization, supplemental oxygen, and intensive care. Conclusions: Adults with mHR-OSA in our COVID-19 cohort had poorer clinical outcomes than those with modified low-risk OSA independent of age, sex, and comorbidities.
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| 17. |
- Peker, Yüksel, 1961, et al.
(författare)
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Reliability of the Turkish version of the European Obstructive Sleep Apnea Screening (EUROSAS) questionnaire for drivers
- 2021
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Ingår i: Sleep and Breathing. - : Springer Science and Business Media LLC. - 1520-9512 .- 1522-1709. ; 25:2, s. 907-913
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The European Union Driver License Committee recently developed a questionnaire as a screening tool for obstructive sleep apnea (OSA) named the European Obstructive Sleep Apnea Screening (EUROSAS) questionnaire for drivers. We sought to address the reliability of the Turkish version of this questionnaire. Methods The EUROSAS was translated into Turkish. Using a "test-retest approach", data were collected twice with a 15-day interval among 150 participants (50 professional male drivers [PMD], 50 non-professional male drivers [NPMD], and 50 non-professional female drivers [NPFD]). The EUROSAS score ranges between 2 and 25, with scores >= 10 suggesting the presence of OSA. Results The median EUROSAS scores in the first test were 8.0 (interquartile range [IQR] 6.8-12.0) in PMD, 8.0 (IQR 6.0-11.0) in NPMD, and 5.0 (IQR 4.0-8.0) in NPFD (p< 0.001). Corresponding values in the retest were 9.5 (IQR 7.0-13.0), 8.0 (IQR 6.0-10.0), and 5.0 (IQR 4.0-8.0), respectively (p< 0.001). The EUROSAS score >= 10 was found among 34% in the first test and 50% in the retest in PMD (ns), 34% vs 24% in NPMD (ns), and 8% vs 16% in NPFD (ns). There was a positive correlation between the tests (r= 0.864,p< 0.001), and Cronbach's alpha value for the whole group was 0.477 (0.514 for PMD, 0.512 for NPMD, and 0.543 NPFD, respectively). Conclusions The EUROSAS-Turkish version is easy to understand and is reproducible. However, the test-retest reliability level is poor among the Turkish drivers. Further validation of the questionnaire by objective sleep studies and fitness-to-drive testing is necessary.
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| 19. |
- Sanches, Elijah E., et al.
(författare)
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Effects of Bariatric Surgery on Heart Rhythm Disorders : a Systematic Review and Meta-Analysis
- 2021
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Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 31:5, s. 2278-2290
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Forskningsöversikt (refereegranskat)abstract
- The aim of this systematic review is to provide an overview of the literature on the effects of bariatric surgery on obesity-associated electrocardiogram (ECG) abnormalities and cardiac arrhythmias. Fourteen studies were included with a methodological quality ranging from poor to good. Majority of the studies showed a significant decrease of QT interval and related measures after bariatric surgery. Seven studies were included in the meta-analysis on effects of bariatric surgery on QTc interval and a significant decrease in QTc interval of - 33.6 ms, 95%CI [- 49.8 to - 17.4] was seen. Bariatric surgery results in significant decrease in QTc interval and P-wave dispersion, i.e., a normalization of initial pathology. The effects on atrial fibrillation are conflicting and not yet fully understood.
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