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. 2021 Jul 14;16(7):e0253933. doi: 10.1371/journal.pone.0253933

Table 3. Mediation analysis.

Adjusted Absolute Difference (95% CI)a p value
Univariable Mediation Modelb
    Body height as mediator
        Total effect of sex -27.6 (-29.7 to -26.0) < 0.001
        Average causal mediation effect of body height -27.7 (-29.7 to -26.0) < 0.001
        Average direct effect of female sex 0.1 (-2.5 to 3.0) 0.940
    Body weight as mediator
        Total effect of sex -27.6 (-29.7 to -26.0) < 0.001
        Average causal mediation effect of body weight 1.0 (0.4 to 2.0) < 0.001
        Average direct effect of female sex -28.6 (-30.7 to -26.0) < 0.001
    Default VT as mediator
        Total effect of sex -27.7 (-29.8 to -26.0) < 0.001
        Average causal mediation effect of titrated VT 0.0 (-0.0 to 0.0) 0.150
        Average direct effect of female sex -27.7 (-29.9 to -26.0) < 0.001
    Body height, weight and titrated VT as mediators*
        Total effect of sex -28.0 (-32.2 to -23.9) < 0.001
        Average causal mediation effect of height -30.7 (-34.2 to -27.2) < 0.001
        Average causal mediation effect of weight 3.3 (2.7 to 4.0) < 0.001
        Average causal mediation effect of titrated VT 0.0 (-0.1 to 0.1) 0.818
        Average direct effect of female sex -0.7 (-3.8 to 2.5) 0.671
Multivariable Mediation Modelc
    Body height as mediator**
        Total effect of sex -28.4 (-30.7 to -26.0) < 0.001
        Average causal mediation effect of body height -28.4 (-30.4 to -26.0) < 0.001
        Average direct effect of female sex -0.0 (-2.8 to 3.0) 0.960
    Body weight as mediator***
        Total effect of sex -0.3 (-3.1 to 3.0) 0.820
        Average causal mediation effect of body weight -0.3 (-0.8 to 0.0) 0.310
        Average direct effect of female sex -0.0 (-2.8 to 3.0) 0.970
    Default VT as mediator****
        Total effect of sex 0.1 (-2.6 to 3.0) 0.939
        Average causal mediation effect of titrated VT 0.2 (0.0 to 0.0) 0.021
        Average direct effect of female sex -0.0 (-2.8 to 3.0) 0.968
    Body height, weight and titrated VT as mediators*
        Total effect of sex -27.0 (-31.3 to -22.7) < 0.001
        Average causal mediation effect of body height -30.1 (-33.5 to -26.6) < 0.001
        Average causal mediation effect of body weight 3.6 (2.9 to 4.4) < 0.001
        Average causal mediation effect of titrated VT 0.1 (-0.1 to 0.2) 0.459
        Average direct effect of female sex -0.7 (-3.9 to 2.5) 0.679

a All estimated generated after 10,000 simulations if not otherwise indicated.

b Mixed–effect mediation model with Quasi–Bayesian confidence intervals, with hospitals and year as random effects and dataset as fixed effect.

c Mixed–effect mediation model with Quasi–Bayesian confidence intervals, with hospitals and year as random effects and dataset as fixed effect and adjusted for: age, OASIS, SOFA, type of admission, pH and PaCO2.

* Confidence intervals estimated from robust clustered standard errors.

** Further adjusted by weight and titrated tidal volume.

*** Further adjusted by height and titrated tidal volume.

**** Further adjusted by weight and height.