Statistical analysis

Continuous variables were represented as mean ± standard deviation for symmetric distributions and median (lower quartile–upper quartile) for skewed distributions. Discrete variables were summarized as frequency (percentage). To compare between the time periods, for discrete variables, normal approximation and Fisher's exact test were used, and for continuous variables, Student's t-test and Mann–Whitney U-test were used. The resulting P values were adjusted by false discovery rate. P < 0.05 was considered statistically significant. Analyses were performed using SPSS ver. 25.0, (IBM SPSS Statistics, Version 25.0 Armonk, NY: IBM Corp.) Minitab 17 and R System for Statistical Computing.