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Makinen KK – Studies have also been conducted on compounds that have turned out to display synergistic effects. When long–term and synergistic effects are simultaneously present in trials involving a crossover design, difficulties may arise in the interpretation of results. This communication uses as an example the long–term clinical and microbiological effects of xylitol and suggests that inclusion of the crossover practice in clinical trials should be separately and carefully contemplated in each instance.

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