Statistical analysis and graph settings
Data and statistical analyses were calculated with GraphPad Prism 9 (GraphPad Software, Inc., La Jolla, CA, USA) and are displayed as mean values ± SEM. Prior to performing the Shapiro-Wilk test, data were tested for normal distribution. For analysis of more than two groups that are unpaired the following tests were applied: 1. for normal distributed data one-way-ANOVA followed by a posthoc Tukey’s multiple comparison test, and 2. for non-normal distributed data Kruskal-Wallis test followed by Dunn’s test. For analysis of more than two groups that are paired the following tests were used: 1. for normal distributed data repeated measures one-way ANOVA (RM one-way ANOVA) followed by posthoc Tukey’s multiple comparison tests and 2. for non-normal distributed data Friedman test. A p-value ≤ 0.05 was considered as significant.To investigate whether the treatment of the first series has an effect on the outcome after cross-over (after tp5) (see 


If the p-value is higher than 0.05, there is no influence of the treatment in the first year on the second treatment one year later (after cross-over) and the data of the respective therapies were pooled (