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Sökning: WFRF:(Schilling J.) > (2020-2024)

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1.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Bakker, M. K., et al. (författare)
  • Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
  • 2020
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:12, s. 1303-1313
  • Tidskriftsartikel (refereegranskat)abstract
    • Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.
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4.
  • Burn, E., et al. (författare)
  • Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19. Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.
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5.
  • Pittman, S. J., et al. (författare)
  • Seascape ecology : identifying research priorities for an emerging ocean sustainability science
  • 2021
  • Ingår i: Marine Ecology Progress Series. - : INTER-RESEARCH. - 0171-8630 .- 1616-1599. ; 663, s. 1-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Seascape ecology, the marine-centric counterpart to landscape ecology, is rapidly emerging as an interdisciplinary and spatially explicit ecological science with relevance to marine management, bio-diversity conservation, and restoration. While important progress in this field has been made in the past decade, there has been no coherent prioritisation of key research questions to help set the future research agenda for seascape ecology. We used a 2-stage modified Delphi method to solicit applied research questions from academic experts in seascape ecology and then asked respondents to identify priority questions across 9 interrelated research themes using 2 rounds of selection. We also invited senior management/conservation practitioners to prioritise the same research questions. Analyses highlighted congruence and discrepancies in perceived priorities for applied research. Themes related to both ecological concepts and management practice, and those identified as priorities include seascape change, seascape connectivity, spatial and temporal scale, ecosystem-based management, and emerging technologies and metrics. Highest-priority questions (upper tercile) received 50% agreement between respondent groups, and lowest priorities (lower tercile) received 58% agreement. Across all 3 priority tiers, 36 of the 55 questions were within a +/- 10% band of agreement. We present the most important applied research questions as determined by the proportion of votes received. For each theme, we provide a synthesis of the research challenges and the potential role of seascape ecology. These priority questions and themes serve as a roadmap for advancing applied seascape ecology during, and beyond, the UN Decade of Ocean Science for Sustainable Development (2021-2030).
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  • Keilholz, U., et al. (författare)
  • ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee
  • 2020
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1435-1448
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment for brain metastases. The expert panel was divided into five working groups to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of metastatic melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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8.
  • Michielin, O., et al. (författare)
  • ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee
  • 2020
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1449-1461
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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9.
  • Prats-Uribe, A., et al. (författare)
  • Use of repurposed and adjuvant drugs in hospital patients with covid-19: Multinational network cohort study
  • 2021
  • Ingår i: The BMJ. - : BMJ. - 0959-8146. ; 373
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. Design Multinational network cohort study. Setting Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. Participants 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. Main outcome measures Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. Results Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. Conclusions Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19. ©
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10.
  • Le Grand, Q., et al. (författare)
  • Genetic Insights on the Relation of Vascular Risk Factors and Cervical Artery Dissection
  • 2023
  • Ingår i: Journal of the American College of Cardiology. - 0735-1097. ; 82:14, s. 1411-1423
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. OBJECTIVES This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS. METHODS This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections. RESULTS Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for f3-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD. CONCLUSIONS These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under f3-blockers. This may inform secondary prevention strategies and trial design for CeAD. (J Am Coll Cardiol 2023;82:1411-1423) <(c)> 2023 by the American College of Cardiology Foundation.
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