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Tissue-resident memory T (TRM) cells function as alarming sensors providing a long-term local memory that can spread widely when re-infected with the same antigen or when suppressing cancer. However, when dysfunctional, skin located TRM cells can have a profound role in various skin disorders, including psoriasis, allergic contact dermati-tis, cutaneous T cell lymphoma and vitiligo. Therefore, targeting TRM cells appears to be an attractive treatment strategy for vitiligo. The evidence on the contribution of TRM cells in cancer suppression also shows how the mani-pulation of TRM cells can be beneficial in optimizing the anti-tumor immunity. Vaccination strategies have success-fully generated TRM cell populations that have effectively suppressed tumor growth in mouse models of melanoma. With more knowledge becoming available on the involve-ment of TRM cells in autoimmunity and cancer, future research will hopefully overcome barriers to effectively block or to promote effective responses of TRM cells to vitiligo and melanoma.

Background: Tobacco product packaging is a key part of marketing efforts to make tobacco use appealing. In contrast, large, prominent health warnings are intended to inform individuals about the risks of smoking. In the European Union, since May 2016, the Tobacco Products Directive 2014/40/EU (TPD2) requires tobacco product packages to carry combined health warnings consisting of a picture, a text warning and information on stop smoking services, covering 65% of the front and back of the packages. Methods: Key measures of warning label effectiveness (salience, cognitive reactions and behavioural reaction) before and after implementation of the TPD2, determinants of warning labels’ effectiveness and country differences were examined in a longitudinal sample of 6011 adult smokers from Germany, Greece, Hungary, Poland, Romania and Spain (EUREST-PLUS Project) using longitudinal Generalized Estimating Equations (GEE) models. Results: In the pooled sample, the warning labels’ effectiveness increased significantly over time in terms of salience (adjusted OR ¼ 1.18; 95% CI: 1.03–1.35), while cognitive and behavioural reactions did not show clear increases. Generally, among women, more highly educated smokers and less addicted smokers, the effectiveness of warning labels tended to be higher. Conclusion: We found an increase in salience, but no clear increases for cognitive and behavioural reactions to the new warning labels as required by the TPD2. While it is likely that our study underestimated the impact of the new pictorial warning labels, it provides evidence that health messages on tobacco packaging are more salient when supported by large pictures. ......................................................................................................... © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: Advertising, promotion and sponsorship of electronic cigarettes (ECAPS) have increased in recent years. Since May 2016, the Tobacco Products Directive 2014/40/EU (TPD2) prohibits ECAPS in various advertising channels, including media that have cross-border effects. The objective of this study was to investigate changes in exposure to ECAPS in a cohort of smokers from six European Union member states after implementation of TPD2. Methods: Self-reported exposure to ECAPS overall and in various media and localities was examined over two International Tobacco Control Policy Evaluation survey waves (2016 and 2018) in a cohort of 6011 adult smokers from Germany, Greece, Hungary, Poland, Romania and Spain (EUREST-PLUS Project) using longitudinal generalized estimating equations models. Results: Self-reported ECAPS exposure at both timepoints varied between countries and across examined advertising channels. Overall, there was a significant increase in ECAPS exposure [adjusted odds ratio (aOR): 1.25, 95% CI: 1.09–1.44]. Between waves, no consistent patterns of change in ECAPS exposure across countries and different media were observed. Generally, ECAPS exposure tended to decline in some channels regulated by TPD2, particularly on television and radio, while exposure tended to increase in some unregulated channels, such as at points of sale. Conclusions: The findings suggest that the TPD2 was generally effective in reducing ECAPS in regulated channels. Nonetheless, further research is warranted to evaluate its role in reducing ECAPS exposure, possibly by triangulation with additional sources of data. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Glut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism. The increasing complexity of Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment. International experts (n = 23) developed a consensus statement utilizing their collective professional experience, responses to a standardized questionnaire, and serial discussions of wide-ranging issues related to Glut1DS. Key clinical features signaling the onset of Glut1DS are eye-head movement abnormalities, seizures, neurodevelopmental impairment, deceleration of head growth, and movement disorders. Diagnosis is confirmed by the presence of these clinical signs, hypoglycorrhachia documented by lumbar puncture, and genetic analysis showing pathogenic SLC2A1 variants. KDT represent standard choices with Glut1DS-specific recommendations regarding duration, composition, and management. Ongoing research has identified future interventions to restore Glut1 protein content and function. Clinical manifestations are influenced by patient age, genetic complexity, and novel therapeutic interventions. All clinical phenotypes will benefit from a better understanding of Glut1DS natural history throughout the life cycle and from improved guidelines facilitating early diagnosis and prompt treatment. Often, the presenting seizures are treated initially with antiseizure drugs before the cause of the epilepsy is ascertained and appropriate KDT are initiated. Initial drug treatment fails to treat the underlying metabolic disturbance during early brain development, contributing to the long-term disease burden. Impaired development of the brain microvasculature is one such complication of delayed Glut1DS treatment in the postnatal period. This international consensus statement should facilitate prompt diagnosis and guide best standard of care for Glut1DS throughout the life cycle. © 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Background: The prevalence of roll-your-own tobacco (RYO) in Europe has been increasing. The aim of this study was to investigate transitions between factory-made (FM) cigarettes and RYO in a longitudinal sample of European smokers, and their perceptions of relative harmfulness and knowledge of health effects. Methods: We used data collected from the EUREST-PLUS ITC 6 European Country (6E) Surveys in 2016 (n ¼ 6011 smokers) and in 2018 (n ¼ 6027) in Germany, Greece, Hungary, Poland, Romania and Spain. A total of 3195 cohort respondents were interviewed in both years. Use of RYO and FM, knowledge of health effects of smoking as well as perceptions about RYO were assessed. We used logistic regression models to explore sociodemographic correlates of transitions from one product to the other, of perceptions and knowledge related to smoking health effects. Results: Approximately 7.4% of exclusive FM smokers transitioned to RYO and 29.5% of exclusive RYO smokers transitioned to FM cigarettes from 2016 to 2018. RYO use in 2018 was more frequent among smokers of low education and income, but none of these factors were associated with transitions. Most RYO smokers perceived RYO as cheaper than FM and 21.7% of them considered RYO to be less harmful than FM. Knowledge of the health effects of smoking was not associated with type of product smoked. Conclusions: RYO is popular among European smokers; its lower cost seems to be a major factor for RYO users; reasons for transitions to and from RYO are less clear and need to be further investigated. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association.

Background: The European (EU) Tobacco Product Directive (TPD) was implemented in May 2016 to regulate the design and labelling of cigarettes and roll-your-own tobacco. At the same time, the UK introduced standardized packaging measures, whereas Germany, Greece, Hungary, Poland, Romania and Spain did not. This study examines the impact of introducing standardized packaging in England using a quasi-experimental design. Methods: Data from adult smokers in Waves 1 (2016; N¼9547) and 2 (2018; N¼9724) from the International Tobacco Control Policy Evaluation surveys (England) and EUREST-PLUS surveys (Germany, Greece, Hungary, Poland, Romania and Spain) were used. Generalized estimating equations were used to estimate changes in pack/brand appeal, salience of health-warning labels (HWLs) and perceived relative harm of different brands in England (where larger HWLs and standardized packaging were implemented), vs. each EU country (where only larger HWLs were implemented). Results: There was an increase in the percentage of respondents from Germany, Hungary and Poland reporting they did not like the look of the pack (4.7%, 9.6%, and 14.2%, respectively), but the largest increase was in England (41.0%). Moreover, there was a statistically significant increase in the salience of HWLs in Hungary, Poland and Romania (17.0%, 13.9%, and 15.3%, respectively), but the largest increase was in England (27.6%). Few differences were observed in cross-country comparisons of the perceived relative harm of different brands. Conclusions: Findings suggest that standardized packaging reduces pack appeal and enhances the salience of HWLs over and above the effects of larger HWLs. Findings provide additional evidence and support for incorporating standardized packaging into the EU TPD. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

The European Tobacco Products Directive (TPD) introduced a ban on characterizing flavours in cigarettes (2016), including menthol (2020). The longitudinal data analysis of the EUREST-PLUS International Tobacco Control (ITC) Project Europe Surveys (n ¼ 16 534; Wave 1 in 2016 and Wave 2 in 2018) found significant but small declines in the weighted prevalence of menthol (by 0.94%; P ¼ 0.041) and other flavoured cigarette use (by 1.32%; P < 0.001) following the 2016 TPD. The declines tended to be driven primarily by the menthol and flavoured cigarette (MFC) smokers switching to unflavoured tobacco. Cigarette consumption declined between waves, but there were no statistically significant difference in decline between MFC and unflavoured tobacco smokers on smoking and cessation behaviours between the waves. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: The emergence of new types of tobacco and tobacco-related products on the European Union (EU) market has precipitated the possibility for both poly-tobacco use and transitions between products. In the EU, the regulatory environment has shifted with the implementation of the European Tobacco Products Directive (TPD) in May 2016, which may influence consumer transitions between products. Methods: The aim of this paper was to examine trends and transitions in tobacco products from 2016 to 2018 -before and after implementation of the TPD in the EU. Data come from Wave 1 (pre-TPD) and Wave 2 (post-TPD) of the EUREST-PLUS ITC Six European Country Survey, a cohort study of adults who at the time of recruitment were smokers from six EU countries-Germany, Greece, Hungary, Poland, Romania, and Spain. D (N ¼ 3195). Bivariate and logistic regression analyses of weighted data was conducted using SAS-callable SUDAAN Results: Overall, among those who smoked factory-made cigarettes (FM) only at Wave 1, 4.3% switched to roll-your-own tobacco (RYO) only. Among RYO only users at Wave 1, 17.0% switched to FM only, however compared to all other countries, respondents from Hungary had the highest percentage of FM only users at Wave 1 switch to RYO only at Wave 2 (18.0%). Conclusions: The most prominent transition overall was from smoking RYO exclusively at Wave 1 to smoking FM tobacco exclusively at Wave 2, however this varied across countries. As the tobacco control regulatory environment of the EU develops, it is important to continue to monitor transitions between types of products, as well as trends in cessation. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: The European Tobacco Products Directive (TPD), which went into effect in May 2016, regulates packaging design and labelling of cigarettes and roll-your-own (RYO) tobacco. The aim of the current study was to examine whether smokers and recent quitters in six European Union (EU) countries (Germany, Greece, Hungary, Poland, Romania and Spain) reported noticing TPD-related changes to packaging, and correlates of noticing these changes. Methods: Cross-sectional data from the Wave 2 of the ITC 6 European Country Survey in 2018 after implementation of the TPD. Bivariate analyses included adult smokers (n ¼ 5597) and recent quitters (n ¼ 412). Adjusted logistic regression analyses were restricted to the subset of current smokers (n ¼ 5597) and conducted using SAS-callable SUDAAN. Results: Over half of smokers (58.2%) and 30% of quitters noticed at least one of five types of TPD-related pack changes. Over one-quarter of all respondents noticed changes to health warnings (30.0%), standardized openings (27.7%), minimum pack unit size (27.9%), and the removal of tar, nicotine and carbon monoxide information (26.7%) on packaging. Cross-country differences were observed across all measures, with noticing all pack changes markedly lower in Spain than the other countries. Correlates of noticing specific pack changes included sociodemographic characteristics, smoking behaviours and related to packaging. Conclusions: This is one of the first cross-country studies to examine the extent to which TPD changes to cigarette and RYO tobacco packaging are being noticed by smokers and recent quitters. Findings indicate that the majority of smokers noticed at least one type of pack change, but this varied across countries and sub-populations. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: The 2016 European Tobacco Products Directive (TPD) required Member States (MS) to implement new regulations for electronic cigarettes (ECs). We conducted a longitudinal study to assess changes over 2 years in smokers’ support for EC policies and identify predictors of support in seven European countries after TPD implementation. Methods: Prospective cohort surveys were conducted among adult smokers in Germany, Greece, Hungary, Poland, Romania, Spain and England in 2016 (n ¼ 9547; just after TPD) and 2018 (n ¼ 10 287; 2 years after TPD). Multivariable logistic regression models employing generalized estimating equations assessed changes in support for four EC policies, and tested for country differences and strength of key predictors of support. Results: Banning EC use in smoke-free places was supported by 53.1% in 2016 and 54.6% in 2018 with a significant increase in Greece (51.7–66.0%) and a decrease in Spain (60.1–48.6%). Restricting EC/e-liquid nicotine content was supported by 52.2 and 47.4% in 2016 and 2018, respectively, with a significant decrease in England (54.2–46.5%) and Romania (52.5–41.0%). An EC promotion ban was supported by 41.1 and 40.2%. A flavour ban was supported by 33.3% and 32.3% with a significant increase in Hungary (34.3–43.3%). Support was generally higher in Poland, Hungary and Greece vs. England. Support was lower among dual and EC-only users, and low-income smokers. Conclusions: Smokers in all countries strongly supported banning EC use in smoke-free places and restricting nicotine content after TPD implementation, with no clear trends for changes in policy support. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: The study assessed awareness and use of heated tobacco products (HTPs) and factors that influenced these issues among cigarette smokers from six European countries in 2016 (Wave 1) and 2018 (Wave 2). Methods: A survey was conducted among a nationally representative sample of cigarette smokers aged 18 years or older from Germany, Greece, Hungary, Poland, Romania and Spain in 2016 (N ¼ 6011) and 2018 (N ¼ 6027; 53% of smokers from the previous wave were retained, regardless of smoking status and dropouts were replaced by a replenishment sample of smokers). Data were collected through face-to-face interviews. Estimates were produced using weighted data. The study presents the cross-sectional results. Results: Awareness of HTPs increased from 8% to 17% between the two waves. At Wave 1, 1.1% of the smokers declared having used HTPs at least once during their lifetime; and at Wave 2, this increased to 1.9% (around 1% or less in four countries, except for Greece and Romania where it was around 4%). Factors associated with HTPs use among those who had ever heard about these products at Wave 1 were country of residence, being a daily cigarette smoker and ever use of electronic cigarettes. At Wave 2, ever use of HTPs was significantly higher among those who had tried to quit smoking combustible cigarettes in the last 12 months, had tried electronic cigarettes during lifetime and perceived HTPs as less dangerous than combustible cigarettes; the country of residence was also associated with HTPs use. Conclusion: This study offers insights into the behaviours and perceptions of European adult smokers regarding HTPs, an important emerging issue in the field of tobacco control. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: The EUREST-PLUS ITC Europe surveys aim to evaluate the impact of the European Union’s Tobacco Products Directive (EU TPD) implementation within the context of the WHO FCTC. This article describes the methodology of the 2016 (Wave 1) and 2018 (Wave 2) International Tobacco Control 6 European (6E) Country Survey in Germany, Greece, Hungary, Poland, Romania and Spain; the England arm of the 2016 (Wave 1) and 2018 (Wave 2) ITC 4 Country Smoking and Vaping (4CV) Survey; and the 2016 (Wave 10) and 2017 (Wave 11) ITC Netherlands (NL) Survey. All three ITC surveys covering a total of eight countries are prospective cohort studies with nationally representative samples of smokers. Methods: In the three surveys across the eight countries, the recruited respondents were cigarette smokers who smoked at least monthly, and were aged 18 and older. At each survey wave, eligible cohort members from the previous waves were retained, regardless of smoking status, and dropouts were replaced by a replenishment sample. Results: Retention rates between the two waves of the ITC 6E Survey by country were 70.5% for Germany, 41.3% for Greece, 35.7% for Hungary, 45.6% for Poland, 54.4% for Romania and 71.3% for Spain. The retention rate for England between ITC 4CV1 and ITC 4CV2 was 39.1%; the retention rates for the ITC Netherlands Survey were 76.6% at Wave 10 (2016) and 80.9% at Wave 11 (2017). Conclusion: The ITC sampling design and data collection methods in these three ITC surveys allow analyses to examine prospectively the impact of policy environment changes on the use of cigarettes and other tobacco products in each country, to make comparisons across the eight countries. ß The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: Social norms have received little attention in relation to electronic cigarettes (EC). The current study examine social norms for EC use and smoking tobacco, and their associations with (i) initiation of EC use, (ii) intention to quit smoking and (iii) attempts to quit smoking. Methods: Cross-sectional and longitudinal data analysis from Waves 1 and 2 of the ITC 6 European Country Survey and corresponding waves from England (the ITC Four Country Smoking and Vaping Survey). Current smokers at baseline, who heard of ECs and provided data at both waves were included (n ¼ 3702). Complex samples logistic regression examined associations between the outcomes and descriptive (seeing EC use in public, close friends using ECs/smoking) and injunctive (public approves of ECs/smoking) norms, adjusting for country, demographics, EC use and heaviness of smoking. Results: In longitudinal analyses, seeing EC use in public at least some days was the only social norm that predicted initiation of EC use between waves (OR ¼ 1.66, 95%CI ¼ 1.08–2.56). In the cross-sectional analysis, having an intention to quit was associated with seeing EC use in public (OR ¼ 1.37, 95%CI ¼ 1.04–1.81) and reporting fewer than three close friends smoke (OR ¼ 0.59, 95%CI ¼ 0.44–0.80). There was no association between any social norm and making a quit attempt between waves. Conclusions: Initiation of EC use is predicted by seeing EC use in public, which was also associated with greater intention to quit smoking. Friends’ smoking was associated with lower intention to quit. These findings may allay concerns that increased visibility of ECs is renormalizing smoking amongst current smokers. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: We examined quit attempts, use of cessation assistance, quitting beliefs and intentions among smokers who participated in the 2018 International Tobacco Control (ITC) Europe Surveys in eight European Union Member States (England, Germany, Greece, Hungary, the Netherlands, Poland, Romania and Spain). Methods: Cross-sectional data from 11 543 smokers were collected from Wave 2 of the ITC Six European Country (6E) Survey (Germany, Greece, Hungary, Poland, Romania and Spain—2018), the ITC Netherlands Survey (the Netherlands—late 2017) and the Four Countries Smoking and Vaping (4CV1) Survey (England—2018). Logistic regression was used to examine associations between smokers’ characteristics and recent quit attempts. Results: Quit attempts in the past 12 months were more frequently reported by respondents in the Netherlands (33.0%) and England (29.3%) and least frequently in Hungary (11.5%), Greece (14.7%), Poland (16.7%) and Germany (16.7%). With the exception of England (35.9%), the majority (56–84%) of recent quit attempts was unaided. Making a quit attempt was associated with younger age, higher education and income, having a smoking-related illness and living in England. In all countries, the majority of continuing smokers did not intend to quit in the next 6 months, had moderate to high levels of nicotine dependence and perceived quitting to be difficult. Conclusions: Apart from England and the Netherlands, smokers made few quit attempts in the past year and had low intentions to quit in the near future. The use of cessation assistance was sub-optimal. There is a need to examine approaches to supporting quitting among the significant proportion of tobacco users in Europe and increase the use of cessation support as part of quit attempts. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: There is currently no comprehensive legislation protecting non-smokers and children from secondhand smoke (SHS) exposure in private cars at the European Union (EU) level. This study aims to assess smokers’ support for smoke-free cars legislation in six EU countries. Methods: Data come from the EUREST-PLUS ITC Europe Surveys: Wave 1 (2016, n ¼ 6011) and Wave 2 (2018, n ¼ 6027) conducted in Germany, Greece, Hungary, Poland, Romania and Spain. Support for smoke-free cars carrying pre-school children and non-smokers and voluntary implementation of smoke-free cars were assessed among adult smokers. Generalized estimating equations models were used to assess changes in support between waves. Results: In 2018, 96.3% [95% confidence interval (CI) 95.4–97.0%] of the overall sample supported smoke-free legislation for cars carrying pre-school children, representing an increase of 2.4 percentage points in comparison to 2016. Smoke-free legislation for cars transporting non-smokers was supported by 85.2% (95% CI 83.1–87.1%) of smokers’ in 2016 and 90.2% (95% CI 88.6–91.7%) in 2018. Among smokers who owned cars, there was a significant 7.2 percentage points increase in voluntary implementation of smoke-free cars carrying children from 2016 (60.7%, 95% CI 57.2–64.0%) to 2018 (67.9%, 95% CI 65.1–70.5%). All sociodemographic groups of smokers reported support higher than 80% in 2018. Conclusion: The vast majority of smokers in all six EU countries support smoke-free legislation for cars carrying pre-school children and non-smokers. This almost universal support across countries and sociodemographic groups is a clear indicator of a window of opportunity for the introduction of comprehensive legislation to protect non-smokers and children from SHS exposure in cars. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Background: This study presents perceptions of the harmfulness of electronic cigarettes (e-cigarettes) relative to combustible cigarettes among smokers from six European Union (EU) countries, prior to the implementation of the EU Tobacco Products Directive (TPD), and 2 years post-TPD. Methods: Data were drawn from the EUREST-PLUS ITC Europe Surveys, a cohort study of adult smokers (≥18 years) from Germany, Greece, Hungary, Poland, Romania and Spain. Data were collected in 2016 (pre-TPD: N ¼ 6011) and 2018 (post-TPD: N ¼ 6027). Weighted generalized estimating equations were used to estimate perceptions of the harmfulness of e-cigarettes compared to combustible cigarettes (less harmful, equally harmful, more harmful or ‘don’t know’). Results: In 2016, among respondents who were aware of e-cigarettes (72.2%), 28.6% reported that they perceived e-cigarettes to be less harmful than cigarettes (range 22.0% in Spain to 34.1% in Hungary). In 2018, 72.2% of respondents were aware of e-cigarettes, of whom 28.4% reported perceiving that e-cigarettes are less harmful. The majority of respondents perceived e-cigarettes to be equally or more harmful than cigarettes in both 2016 (58.5%) and 2018 (61.8%, P > 0.05). Overall, there were no significant changes in the perceptions that e-cigarettes are less, equally or more harmful than cigarettes, but ‘don’t know’ responses significantly decreased from 12.9% to 9.8% (P ¼ 0.036). The only significant change within countries was a decrease in ‘don’t know’ responses in Spain (19.3–9.4%, P ¼ .001). Conclusions: The majority of respondents in these six EU countries perceived e-cigarettes to be equally or more harmful than combustible cigarettes. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association.