Supplementary materials
Supplementary S1. Analysis methods of the lung ultrasound examinations
All examinations were performed by five investigators using a COVID-19 unit-restricted SonoSite-Edge II ultrasound machine. All measurements were performed using a 10-5 MHz linear transducer or 5-3 MHz curvilinear transducer with lung examination setting and a depth of >6 centimeters.
Offline analyses of all ultrasound images of 191 examinations were performed by two investigators (MLAH and AWEL) blinded to the patient’s baseline characteristics. The investigators determined the involvement per zone [1-3]:
0 = A-line pattern; 1 = Well-separated B-lines; 2 = Confluent B-lines; 3 = Consolidation.
In order to appropriately compare pulmonary involvement across protocols, a LUS index (LUSI = (total LUS / total LUS achievable) × 100) was calculated.
Supplementary S2. The calculation method for the smallest detectable change
Systematic and random error in measurements produce a difference in LUS that is not attributed to true changes in pulmonary involvement. These measurement errors can be quantified as the standard error of measurement (SEM). One can obtain a SEM by calculating a two-way mixed effects intraclass correlation coefficient model for absolute agreement (ICC) and using the following formula [4]:
SEMinterrater=σ ×
√
1−ICCinterraterThe SEM can then be used to calculate the smallest detectable change (SDC), which represents the minimal change a score must show to ensure that the observed change is true and not a result of measurement error. The following formula can be used:
SDCinterrater=1.96×
√
2× SEMinterraterA power calculation was performed to determine the required sample size for the ICC. A minimum acceptable reliability of 0.65, with an expected reliability of 0.89 based on previous research [5], a power of 0.90, and a significance level of 0.05 resulted in a sample size of 27 examinations for two raters.
Twenty-seven examinations were then selected from the total sample of 191 using a random number generator. These examinations were evaluated by both investigators (MLAH and AWEL). The interrater of the investigators ICC was 0.870, whereas the mean and standard deviation were 66.6±17.6. As a result the SEM was 6.3, and the SDC 17.4%. The 95% confidence interval for the SDC was 11.8-26.1%.
The Bland-Altman plot was created in accordance with previous literature [6]. In a linear model of the difference (Bland-Altman Y axis) as a function of the mean (Bland-Altman X-axis), the coefficient of the mean was 0.04, with a P-value > 0.05, indicating that the proportionality of the bias was neither significant nor clinically relevant. The constant bias was 1.9 with a 95% confidence interval of 1.12- 2.69 and the limits of agreement were 10.8 with a 95% confidence interval of 7.4-14.2.
The comparison between SDC and limits of agreement was estimated from 10,000 seeded bootstrapped comparisons in R language for statistical computing with the tidyverse suite of packages. The resulting p-value was 0.019.
References for supplementary materials
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