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Without accounting for these limitations, the data on legal sales of tobacco products from the European countries analyzed in this case study (Italy, Lithuania, and Latvia) suggests that the introduction of heated tobacco products coincided with the acceleration of combustible tobacco product volume declinesin particular, cigaretteswhen comparing annual average declines between 2011 and 2020 with the period between the year in which the share of HTUs in all tobacco products reached at least 1% and 2020 (which was in 2018 for Italy and Lithuania and in 2019 for Latvia)

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Additionally, we observed a characteristic eddy suggestive of proliferating cells in clusters #1 and #4 from both vehicle and chronic nicotine samples (Fig