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Sökning: WFRF:(Hills Thomas)

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  • Axfors, Cathrine, et al. (författare)
  • Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
  • 2021
  • Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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  • Axfors, Cathrine, et al. (författare)
  • Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
  • 2021
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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  • Schnabel, Renate B, et al. (författare)
  • Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation : the 8th AFNET/EHRA consensus conference
  • 2023
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:1, s. 6-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.
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  • Aaberge, Rolf, et al. (författare)
  • Tony Atkinson and his Legacy
  • 2017
  • Ingår i: The Review of Income and Wealth. - : Wiley. - 0034-6586 .- 1475-4991. ; 63:3, s. 411-444
  • Tidskriftsartikel (refereegranskat)abstract
    • Tony Atkinson is universally celebrated for his outstanding contributions to the measurement and analysis of inequality, but he never saw the study of inequality as a separate branch of economics. He was an economist in the classical sense, rejecting any sub-field labelling of his interests and expertise, and he made contributions right across economics. His death on 1 January 2017 deprived the world of both an intellectual giant and a deeply committed public servant in the broadest sense of the term. This collective tribute highlights the range, depth and importance of Tony's enormous legacy, the product of almost fifty years’ work.
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  • Hills, Richard G., et al. (författare)
  • Validation Challenge Workshop
  • 2008
  • Ingår i: Computer Methods in Applied Mechanics and Engineering. - : Elsevier BV. - 0045-7825 .- 1879-2138. ; 197:29-32, s. 2375-2380
  • Tidskriftsartikel (refereegranskat)abstract
    • This special issue presents the results of the Sandia organized Model Validation Challenge Workshop, held May 2006. The workshop brought together researchers from different fields to present various approaches to model validation, and focused on the methodological elements of model validation rather than on model building. Three problems were defined in the disciplines of structural statics, structural dynamics, and heat transfer, all with a uniform structure. The workshop was specifically designed to investigate the relative merits of different approaches to hierarchal model validation through application to these problems. This paper describes a hierarchal approach in the challenge problems, presents the uniform conceptual framework that was used for the challenge problem definitions, and provides an overview of the organization of this special issue.
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