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  3. SciScore for 10.1101/2022.04.14.22272888: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The COVASE trial was reviewed by an Independent Ethics Committee or Institutional Review Board: the South Central - Hampshire B Research Ethics Committee Level 3 Block B Whitefriars Lewins Mead Bristol BS1 2NT, chaired by Professor Vincenzo Libri (REC reference: 20/SC/0197, Protocol number: 132333, RAS project ID:283091) and the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA).
    IACUC: The trial was conducted in accordance with the principles of the Declaration of Helsinki and the ethical guidelines of the Council for International Organizations of Medical Sciences, applicable International Council for Harmonisation Good Clinical Practice guidelines, and applicable laws and regulations.
    Consent: All the randomized participants provided written informed consent.
    Sex as a biological variablenot detected.
    RandomizationAll the randomized participants provided written informed consent.
    Blindingnot detected.
    Power AnalysisA sample size of 90 participants was calculated to provide a power of 80% to determine a between-group difference of >40% in the primary outcome (CRP at day 7), a difference we considered both achievable and clinically relevant.

    Table 2: Resources

    Software and Algorithms
    Data were analysed using Microsoft Excel and Graph Pad Prism software.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)
    Graph Pad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    With the caveat that the small numbers of participants necessitate a degree of caution, we found that both CRP and D-dimers correlated with cf-DNA in all patients and that dornase alfa led to a reduction in both. Our finding that D-dimer is reduced back to normal levels over 7 days in participants in the BAC + dornase alfa group but not in participants on BAC alone, alongside the restoration of lymphocyte counts, suggest wider effects of dornase alpha that may be attributable, in part, to a reduction in cf-DNA. It is therefore tempting to propose that by promoting extracellular DNA degradation in the alveolar space, dornase alfa may be impacting favourably on coagulopathy and leukocyte trafficking in these patients (Radermecker et al., 2020). One surprising aspect of our study was the reduction of systemic levels of cf-DNA in the circulation in dornase alfa treated patients, given that the treatment is not systemic but localized to the lung due to the short half-life of nebulized dornase-alpha in the bloodstream. Hence, these results suggest that decreases in blood cf-DNA levels reflect decreases in pulmonary cf-DNA by enhanced local clearance of NETs and DNA released by other dying cell types. Furthermore, we noted an inverse correlation between the final readings of circulating cf-DNA and the magnitude of decrease in CRP within the 7-day treatment period, further supporting a functional link between chromatin levels and systemic inflammation in COVID-19 pneumonitis. Another...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    NCT04359654CompletedNebulised Dornase Alfa for Treatment of COVID-19
    NCT04432987RecruitingDornase Alpha for the Treatment of COVID-19
    NCT04387786CompletedDornase Alfa Administered to Patients With COVID-19 (DACOVID…
    NCT04409925RecruitingDISmantling COvid iNduced Neutrophil ExtraCellular Traps (DI…
    NCT0442970Trial number did not resolve on Is the number correct?NA
    NCT04402944RecruitingPulmozyme to Improve COVID-19 ARDS Outcomes
    NCT04445285RecruitingPhase 2 Trial Using rhDNase to Reduce Mortality in COVID-19 …
    NCT05139901Not yet recruitingUsefulness of DORNASE in COVID-19 on HFNO
    NCT04355364TerminatedEfficacy and Safety of aerosolizedDornase Alfa Administratio…
    NCT04459325CompletedTigerase® Efficacy and Safety as Part of Complex Therapy in …
    NCT04488081RecruitingI-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critica…
    NCT04402970CompletedDornase Alfa for ARDS in Patients With Severe Acute Respirat…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

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