OBJECTIVE To review and critically appraise published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at increased risk of becoming infected with covid-19 or being admitted to hospital with the disease. DESIGNLiving systematic review and critical appraisal. DATA SOURCESPubMed and Embase through Ovid, Arxiv, medRxiv, and bioRxiv up to 7 April 2020.Cite this as: BMJ 2020;369:m1328 http://dx.
Objective To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19. Design Two stage individual participant data meta-analysis. Setting Secondary and tertiary care. Participants 46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021. Data sources Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ , and through PROSPERO, reference checking, and expert knowledge. Model selection and eligibility criteria Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor. Methods Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters. Main outcome measures 30 day mortality or in-hospital mortality. Results Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al’s model (0.96, 0.59 to 1.55, 0.21 to 4.28). Conclusion The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.
in some less diluted samples of the second test, raising the question whether a lower dilution (eg, 1:4) might be used to further improve the test sensitivity. A limitation of our study is the possibility that IgG 4 antibodiesnot measured in our samples-may have exerted competitive effects to IgE binding in our microarray. Also, the selected cutoff (ie, 0.03 ISU for diluted NasSec) cannot be automatically applied in other settings or to other microarrays. Large-scale studies are needed to confirm our promising findings. The technique should be investigated in more heterogeneous patient populations and with other airborne allergens. We thank Gabriele Holtappels (Upper Airway Research Laboratory, Ghent) for her advise on how to process NasSec and how to perform measurements in NasSec. We thank Alexander Rohrbach for his laboratory support (Charit e-Universit€ atsmedizin, Berlin). We thank Sander De Bruyne and Eveline van Mulders (2 medical students of Ghent University) for their help with patient recruitment and sample collection. Finally, we thank all patients for their participation in this study.
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