Fig 2.

Adjusted hazard ratio (HR) of overall mortality according to time to treatment initiation (TTI) as a continuous variable by using restricted cubic splines with seven knots. The reference equals 1 at a TTI of 0 days. The restricted cubic spline allows for a nonlinear relationship of TTI with the log HR of mortality, estimated from the full Cox regression model adjusted for all covariates. The knots define change points where the cubic function can change. We found that the HR of death with respect to a TTI of zero decreased to a HR of less than 1 and then crossed the HR equivalent to 1 close to day 67, which was the cut point found in the recursive partitioning analysis. With a TTI greater than 67, the HR increased substantially.