Tobacco endgame goals and measures in Europe: current status and future directions.

The European Union (EU) aims for a tobacco use prevalence of less than 5% by 2040 with its Tobacco-Free Generation goal, aligning with the tobacco endgame approach. In the Joint Action on Tobacco Control 2 (JATC-2) -project, we examined adopted and planned endgame goals and measures as well as preparedness to counter tobacco industry interference in the process. We surveyed key informants in 24 out of 50 countries in the WHO European Region (19 of the 27 EU Member States, MS). Altogether, eight countries (7 EU MS) had official governmental endgame goals, and an additional six EU MS had similar proposals from government, civil society or research entities. Movement towards tobacco endgame was most evident in retail-oriented and consumer-oriented policies. These include restricting the sales of tobacco and related products and raising the age limit above 18 years. Product standards were used especially to regulate flavours but no measures to substantially reduce addictiveness were reported. Market-oriented measures that tap into industry profits were predominantly missing, and countries often lacked concrete tools to prevent industry interference. Respondents' concerns around tobacco endgame were related to high smoking prevalence in some population groups, non-combustible and new nicotine products, cross-border marketing, political will, challenges with the existing regulations and industry interference. Results indicate both momentum and challenges in adopting and disseminating measures that facilitate achieving tobacco endgame goals. The EU goal can be used to advocate for national endgame goals and measures, and for the strengthened implementation of the WHO Framework Convention on Tobacco Control.

Genetic drivers and cellular selection of female mosaic X chromosome loss.

Mosaic loss of the X chromosome (mLOX) is the most common clonal somatic alteration in leukocytes of female individuals1,2, but little is known about its genetic determinants or phenotypic consequences. Here, to address this, we used data from 883,574 female participants across 8 biobanks; 12% of participants exhibited detectable mLOX in approximately 2% of leukocytes. Female participants with mLOX had an increased risk of myeloid and lymphoid leukaemias. Genetic analyses identified 56 common variants associated with mLOX, implicating genes with roles in chromosomal missegregation, cancer predisposition and autoimmune diseases. Exome-sequence analyses identified rare missense variants in FBXO10 that confer a twofold increased risk of mLOX. Only a small fraction of associations was shared with mosaic Y chromosome loss, suggesting that distinct biological processes drive formation and clonal expansion of sex chromosome missegregation. Allelic shift analyses identified X chromosome alleles that are preferentially retained in mLOX, demonstrating variation at many loci under cellular selection. A polygenic score including 44 allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile. Our results support a model in which germline variants predispose female individuals to acquiring mLOX, with the allelic content of the X chromosome possibly shaping the magnitude of clonal expansion.

Nicotine pouch use by sex, school type and tobacco product use among Finnish adolescents during the 2023 change in regulatory scheme with deregulated sales.

BACKGROUND AND AIMS: In Finland, nicotine pouches entered the national market abruptly in 2023, following a change in April 2023 from medicinal product classification into less regulated tobacco surrogate status. This study aimed to measure adolescent nicotine pouch use and associated characteristics. DESIGN AND SETTING: A cross-sectional, nationwide school-based survey among students in comprehensive schools (COMP), general upper secondary schools (GEN) and vocational institutes (VOC) in 2023 in Finland. PARTICIPANTS: A total of 151 224 respondents aged 14-20 years (mean age 16.18 years, standard deviation 1.20 years). MEASUREMENTS: Nicotine pouch use was used as the outcome variable. Demographics included age, sex, school type and tobacco product use (smoking, snus use and e-cigarette use). Covariates included parental education and parental smoking. All measures were self-reported. FINDINGS: Unadjusted results showed that current nicotine pouch use was more common among boys (11.3%) than among girls (3.3%), adolescents in VOC (15.4%) compared with COMP (6.8%) and GEN (4.3%), whereas daily use of other tobacco and nicotine products was associated with current nicotine pouch use compared with never using such products and the association was especially strong for snus use. The fully adjusted estimates of current nicotine pouch use remained strong for daily use of other tobacco and nicotine products (snus use: adjusted prevalence ratio [aPR] = 74.95, 95% confidence interval [CI] = 65.65-84.25; smoking: aPR = 1.43, 95% CI = 1.36-1.50; e-cigarette use: aPR = 2.15, 95% CI = 2.04-2.27) and for sex (boys aPR = 1.53, 95% CI = 1.48-1.57). There was no clear evidence of differences in current nicotine pouch use by school type, age or parental factors in the fully adjusted model. CONCLUSIONS: In Finland in 2023, during which the availability of nicotine pouches became less regulated, nicotine pouch use appeared to be more common among boys and adolescents who used other nicotine products.

Patterns and Determinants of Exclusive Smokeless Tobacco (Snus) Use, Exclusive Smoking and Dual Use in General Population During 20 Years.

BACKGROUND: We investigate smokeless tobacco (snus) use and its correlates over 20 years in a country where selling snus is prohibited but a large import quota and illicit market exists. METHODS: Repeated cross-sectional population-based surveys during 2000 to 2020 in Finland, including N = 57 111 adults aged 20 to 64 years. The outcome measures were current tobacco use (exclusive snus use, dual use, exclusive smoking, no tobacco use) and snus use (daily, occasional, no snus use). Study years, gender, age, education, marital status, self-rated health, body mass index, and binge drinking were used as explanatory variables. RESULTS: Exclusive snus use and dual use increased 3.6% units and 2.6% units from 2000 to 2005 and from 2018 to 2020, respectively. Overall decrease of tobacco use was led by decreasing exclusive smoking from 30.1% to 18.2%. The shared risk factors for snus use and dual use were male gender, age group 20 to 34 years, and binge drinking. The increases in snus and dual use over time were also most prevalent among these groups. Among men, occasional smoking increased the likelihood of daily (relative risk ratio [RRR] 2.38, 95% confidence interval [CI] 1.42, 3.99) and occasional (RRR 3.11, 95% CI 1.93, 5.03) snus use. CONCLUSIONS: Snus use has increased among the general adult population in Finland during 2000 to 2020 yet remains less common than smoking. Snus use and dual use share some common risk factors. Snus use should be considered in cessation services, with support for quitting developed and targeted predominantly for men, younger adults, and persons drinking to intoxication.

Tobacco endgame measures and their adaptation in selected European countries: A narrative review synthesis.

Due to the continued detrimental effects of tobacco use, a growing number of countries are embracing the idea of tobacco endgame, meaning ending the tobacco epidemic instead of controlling it. This narrative review aims to synthesize and update the evidence from earlier scientific reviews on effective tobacco endgame measures, as well as to assess their integration to current national strategies among European countries with official tobacco endgame goals. The synthesis of the prior scientific literature found most evidence on product-focused and some evidence for supply-focused policies. Little evidence was detected for user- and institutional-focused measures. An update for the tobacco-free generation measure showed uncertainty in reducing smoking prevalence, especially for adolescents' reactions to age-restrictive laws. All the countries that established a tobacco endgame strategy have included product standards in their measures, predominantly based on European Union regulations on conventional tobacco products, yet standards above this level and considering other products were also common. Cessation measures were given strong emphasis in strategies, yet none of the countries linked these to specific endgame measures. Despite commonly mentioning vulnerable groups, such as youth and pregnant women, adoption of measures to reduce tobacco use among these groups was scarce. Lastly, the decline in tobacco use seems to be modest, implying challenges in meeting the endgame goals. To meet these goals, European countries should reinforce the implementation of known effective tobacco control measures such as tax increases. Furthermore, new innovative strategies and measures to meet the objective of an endgame should be explored.

An immunogenetic basis for lung cancer risk.

Cancer risk is influenced by inherited mutations, DNA replication errors, and environmental factors. However, the influence of genetic variation in immunosurveillance on cancer risk is not well understood. Leveraging population-level data from the UK Biobank and FinnGen, we show that heterozygosity at the human leukocyte antigen (HLA)-II loci is associated with reduced lung cancer risk in smokers. Fine-mapping implicated amino acid heterozygosity in the HLA-II peptide binding groove in reduced lung cancer risk, and single-cell analyses showed that smoking drives enrichment of proinflammatory lung macrophages and HLA-II+ epithelial cells. In lung cancer, widespread loss of HLA-II heterozygosity (LOH) favored loss of alleles with larger neopeptide repertoires. Thus, our findings nominate genetic variation in immunosurveillance as a critical risk factor for lung cancer.

Cross-sectional study of the associations between the implementation of the WHO FCTC tobacco advertising, promotion and sponsorship bans and current e-cigarette use among youth from countries with different income levels.

BACKGROUND: The WHO Framework Convention on Tobacco Control (WHO FCTC) Article 13 requires countries to ban tobacco advertising, promotion and sponsorship (TAPS), and bans are recommended to cover electronic cigarettes (e-cigarettes). We examined youth e-cigarette prevalence by TAPS regulations in countries with different income levels. METHODS: We analysed data on 165 299 respondents from 48 countries with 2016/2018 WHO FCTC implementation reports and 2016-2019 Global Youth Tobacco Survey. We used multilevel logistic regressions to examine associations between TAPS regulations and current e-cigarette use, stratified by country income. RESULTS: About 1 in 10 respondents was currently using e-cigarettes. Respondents in countries with TAPS bans on the internet were less likely to use e-cigarettes (adjOR=0.58; 95% CI 0.39 to 0.86) than youth in countries without such bans. In lower middle-income and low-income countries, bans on displaying tobacco products at the point of sale (adjOR=0.55; 95% CI 0.34 to 0.90), bans on product placement (adjOR=0.44; 95% CI 0.28 to 0.69) and strength of additional TAPS measures were associated with lower prevalence of e-cigarette use among students. Being taught about the dangers of the use of tobacco in school was associated with lower odds of e-cigarette use. No differences in the use of e-cigarettes were observed by types of TAPS among respondents in high-income countries. CONCLUSIONS: Strengthening implementation of TAPS policies and assuring they cover new and emerging products, online channels and points of sales are essential, especially in lower income countries. Maintaining tobacco health education is also important to protect youth from e-cigarette use.

Have there been changes in daily smoking and cigarette consumption among adolescents? Investigation between 1999 and 2019 among Finnish adolescents.

BACKGROUND AND AIMS: It is postulated that due to decreased smoking rates and increased denormalisation of smoking, those who start and maintain smoking have more socially disadvantaged characteristics and are more dependent on nicotine than those who do not (the so-called 'hardening' hypothesis). The aim of this study was to measure changes in daily smoking and cigarette consumption among Finnish adolescents according to background factors. DESIGN AND SETTING: A repeated cross-sectional study using data from European School Survey Project on Alcohol and other Drugs (ESPAD) on six representative cross-sections of 15- to 16-year-old students between 1999 and 2019 in Finland. PARTICIPANTS: A total of 11 377 males and 12 247 females. MEASUREMENTS: The outcome measures included the proportion of daily smokers among current smokers, daily smoking and the estimated mean number of smoked cigarettes per day (CPD). Substance use, parental monitoring and school performance were used as independent variables. All measures were self-reported. FINDINGS: Daily smoking decreased over time and daily smokers constituted a smaller part of current smokers in 2019 compared with 1999 (the ratio among boys 0.68 and 0.43, respectively; among girls 0.59 and 0.43). Boys using cannabis (interaction between cannabis*survey year: P = 0.020; in 2019 odds ratio [OR]: 3.68, 95% confidence interval [CI] 2.23-6.08) and girls with heavy episodic drinking (interaction between heavy episodic drinking*survey year: P = 0.006, in 2019 OR: 9.00, 95% CI 5.61-14.42) had elevated adjusted odds for daily smoking over time. The estimated mean number of CPD decreased among daily smokers from 9.0 in 1999 to 7.2 in 2019 (P = 0.0002) and the differences diminished between groups based on gender, snus/alcohol use and parental monitoring. The between-group differences remained with regard to cannabis use (P = 0.0233 in 2019) and school performance (P = 0.0111 in 2019). CONCLUSIONS: Among currently smoking Finnish adolescents, the proportion of daily smokers decreased between 1999 and 2019, as did the number of cigarettes smoked per day (CPD) among daily smokers, suggesting an absence of 'hardening' in this group. However, differences were observed related to the odds of daily smoking and the mean number of CPD, indicating the change has been less favorable among some adolescent groups than others.

Implementation of the Article 13 WHO FCTC measures and changes in cigarette smoking among youth in 42 countries.

INTRODUCTION: Despite a decline in global smoking prevalence among adolescents, around 21 million youth report current cigarette smoking. Exposure to tobacco advertising, promotion and sponsorship (TAPS) is a risk factor for smoking initiation, and therefore the Article 13 of the WHO Framework Convention on Tobacco Control (WHO FCTC) requires comprehensive TAPS bans. We examined the associations between changes in youth cigarette smoking and implementation of Article 13. METHODS: We used two rounds of cross-sectional data from the Global Youth Tobacco Survey (GYTS) for 42 countries: first between 2006 and 2015, and second between 2017 and 2020. The GYTS data were linked with the WHO FCTC implementation reports from 2016 and 2018. The outcome was current smoking. Multilevel binary logistic regression models, stratified by country income level, were used to test the prevalence differences between the latest and previous GYTS rounds and their associations with TAPS bans with postestimations using marginal analyses. RESULTS: The percentage of students currently smoking decreased from 10.0% (95% CI 8.0 to 12.1) to 7.7% (95% CI 6.1 to 9.3) from first to second GYTS rounds (p<0.001), adjusting for country clustering. In low-income and lower-middle-income countries, the degree of decrease significantly differed between countries with versus without bans on display, partial internet TAPS ban, ban on depiction of tobacco products and by number of TAPS measures, adjusting for age and sex of the respondents. In high-income and upper-middle-income countries, the degree of decrease significantly differed by presence (or absence) of partial or full internet TAPS ban, ban on product placement and by number of TAPS measures. CONCLUSION: Implementation of TAPS bans is associated with decreased smoking among adolescents both in high-income and low-income countries. Enhanced and continuous efforts are necessary to protect youth from the promotion of tobacco and nicotine products.

SIRPα controls CD47-dependent platelet clearance in mice and humans.

Over the last decade, more data has revealed that increased surface expression of the "don't eat me" CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 is critical in regulating cell homeostasis and clearance, as binding of CD47 to the inhibitory receptor SIRPα can prevent phagocytosis and macrophage-mediated cell clearance. The purpose of this study was to examine the role of the CD47-SIRPα signal in platelet homeostasis and clearance. Therapeutic reagents targeting the CD47-SIRPα axis are very promising for treatment of hematologic malignancies and solid tumors, but lead to transient anemia or thrombocytopenia in a subset of patients. We found that platelet homeostatic clearance is regulated through the CD47-SIRPα axis and that therapeutic blockade to disrupt this interaction in mice and in humans has a significant impact on platelet levels. Furthermore, we identified genetic variations at the SIRPA locus that impact platelet levels in humans such that higher SIRPA gene expression is associated with higher platelet levels. SIRPA expression at either end of the normal range may affect clinical outcomes of treatment with anti-CD47 therapy.

Tobacco endgame in the WHO European Region: Feasibility in light of current tobacco control status.

INTRODUCTION: To assess the feasibility of developing World Health Organization (WHO) European Region countries' goals and measures in line with tobacco endgame objectives, information on the current tobacco control context and capacity is needed. The aim of this study was to assess the implementation of the Framework Convention on Tobacco Control (WHO FCTC) and MPOWER measures in the region. METHODS: In this cross-sectional study we used data from the WHO FCTC implementation reports and MPOWER from 2020 in 53 WHO European Region countries. Six domains (i.e. capacity, taxation and price policies, other national key regulations, public awareness raising and communication, tobacco use cessation, and monitoring) were formed. Subsequently, available indicators under these domains were scored and the level of implementation was computed for each country. Mann-Whitney tests were carried out to compare the scores between the group of countries with and without official endgame goals. RESULTS: Overall, implementation of the WHO FCTC with the selected indicators at the country level ranged from 28% to 86%, and of MPOWER from 31% to 96%. Full implementation was achieved by 28% of WHO FCTC Parties in the region in taxation and price policies, 12% in public awareness raising and communication, and 42% in monitoring. In capacity, tobacco use cessation and other national key regulations, none of the Parties in the region reached full implementation. Overall median WHO FCTC scores were significantly higher in countries with official endgame goals than in those without (p<0.001). CONCLUSIONS: There is unequal implementation of both WHO FCTC and MPOWER measures among WHO European Region countries. MPOWER and WHO FCTC provide all the measures for the necessary first steps, followed by innovative measures, to accomplish tobacco endgame goals.

Changes in smoking due to COVID-19 pandemic among persons of migrant origin compared with the general population: a population-based study.

AIMS: Prior studies have implied that smokers may have changed their smoking behaviour during the COVID-19 pandemic. However, little is known about changes in smoking behaviour and correlates of change due to the pandemic among persons of migrant origin compared with the general population. METHODS: Population-based cross-sectional studies with comparable study protocols and measures, one focusing on persons of migrant origin living in Finland (n = 3587, response rate 60%) and the other on the general Finnish population (n = 3444, response rate 56%), were utilised. The outcome measure was self-reported change in smoking behaviour due to COVID-19 among current smokers. Explanatory factors included sociodemographic-, health-, and COVID-19-related factors. Multinomial logistic regression was used in the analyses. RESULTS: Most of the current smokers reported no change in their smoking behaviour. In the adjusted model, younger age was positively associated with increased smoking, while region of origin (Russia, Africa, Asia, and Latin America) and worrying about getting infected with COVID-19 were associated with decreased smoking among persons of migrant origin. In the general population, younger age, female sex, being other than employed/student, increased loneliness, and decreased contact with close ones were associated with increased smoking, while reduced working capacity and worries that someone close to the respondent will be infected with COVID-19 were associated with decreased smoking. CONCLUSIONS: The findings of this study contribute to better identification of at-risk populations in future crises situations. This will allow for more efficient targeting and tailoring of health promotion services, including smoking cessation.

Changes in prevalence and sociodemographic correlates of tobacco and nicotine use in Finland during the COVID-19 pandemic.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on tobacco and nicotine use remains debated. We examined whether the prevalence of tobacco and nicotine use and nicotine-replacement therapy (NRT) changed during the COVID-19 pandemic and whether changes differed by sociodemographic groups. METHODS: Repeated cross-sectional study of three national surveys in Finland (2018, 2019 and 2020; n = 58 526 adults aged 20 and over). Outcomes were daily and occasional smoking, smokeless tobacco (snus) use, e-cigarettes use, total tobacco or nicotine use and NRT use. We examined changes for each outcome by sex, age, educational tertiles, marital status, mother tongue and social participation. RESULTS: Daily smoking decreased among males by 1.15 percentage points (pp) [95% confidence interval (CI) -2.10 to -0.20] between 2018 and 2020 and 0.86 pp among females (95% CI -1.58 to -0.15). Daily snus use remained stable in both sexes. Daily e-cigarette use was below 1% and remained stable. We found weak evidence of a reduction in total tobacco or nicotine use between 2018 and 2020 (males -1.18 pp, 95% CI -2.68 to 0.32 and females -0.8 pp, 95% CI -1.81 to 0.22). NRT use remained stable. Snus and NRT use decreased among 60- to 74-year-olds but remained stable in other age groups. We did not find evidence of interactions by subgroup for other outcomes. CONCLUSIONS: Daily smoking decreased in Finland between 2018 and 2020, but other forms of tobacco use did not experience a reduction. The COVID-19 pandemic does not seem to have altered the sustained reduction of smoking in Finland, although substantial sociodemographic differences persist.

Exclusive and dual use of electronic cigarettes among European youth in 32 countries with different regulatory landscapes.

BACKGROUND: The Tobacco Products Directive (2014/40/EU) partially harmonised the regulation of electronic cigarettes (e-cigarettes) in Europe, but individual countries maintain jurisdiction over bans on use in public places, domestic advertising, taxation and flavour regulations. Their association with youth e-cigarette use has not been examined. METHODS: We used the cross-sectional 2019 European School Survey Project on Alcohol and Other Drugs data from 32 countries with 98 758 students aged 15-16 years and the 2020 WHO's assessment of the e-cigarette regulations. Multilevel logistic regression models on ever (vs never) and current (vs non-current) exclusive e-cigarette use, exclusive cigarette use and dual use by e-cigarette regulations' composite score were adjusted for age, gender, parental education, perceived family's financial well-being, perceived difficulty of obtaining cigarettes, country income level and general progress in tobacco control. RESULTS: Of the respondents, 13.3% had ever used cigarettes, 10.6% e-cigarettes and 27.3% both; 13.0% currently used cigarettes, 6.0% e-cigarettes and 6.4% both. Higher composite country score in the e-cigarette regulations was associated with lower current exclusive e-cigarette use (OR=0.78; 95% CI 0.65 to 0.94) and current dual use (OR=0.80; 95% CI 0.67 to 0.95). Youth perceiving more difficulties in obtaining cigarettes were less likely to use cigarettes, e-cigarettes and both ever and currently (OR from 0.80 (95% CI 0.76 to 0.85) to 0.94 (95% CI 0.92 to 0.96)). CONCLUSIONS: More comprehensive e-cigarette regulations and enforcement of age-of-sale laws may be protective of e-cigarette and dual use among adolescents.

Area-level sociodemographic differences in tobacco availability examined with nationwide tobacco product retail licence data in Finland.

BACKGROUND: Differences in tobacco retailer density between areas by sociodemographic composition have been observed. However, little research comes from European jurisdictions and from countries with a tobacco retail licensing system. In Finland, the system consists of criteria for retailers and supervision fees. METHODS: The tobacco product retail licence data and sociodemographic data were retrieved from corresponding Finnish authorities. Area-level tobacco availability was measured as the presence of a retailer and as the number of retailers per 1000 inhabitants by postcode area. Sociodemographic indicators included median income, percentage of inhabitants in the lowest income tertile, percentage of adults with higher education and unemployment rate. Analyses were based on logistic regression and Ordinary Least Squares regression with log-transformed density. RESULTS: Lower area-level sociodemographic composition was mainly associated with higher tobacco availability. Income was the strongest correlate of the tobacco retailer availability: areas with higher median income had lower odds of having a tobacco retailer (OR 0.54, 95% CI 0.48 to 0.61 per €1000) and lower retailer density (-4.4% per €1000, Cohen's f=0.51). Areas with a greater proportion of people in the lowest income category had higher densities of tobacco retailers (+2.8% per percentage point, Cohen's f=0.07). Other sociodemographic indicators showed inconsistent associations with retailer presence and density. CONCLUSION: Tobacco availability can be higher in areas with lower sociodemographic composition also in a country with a comprehensive tobacco retail licensing system and small income inequalities. Retailing policies should be further developed to reduce tobacco availability and narrow inequalities in tobacco use.

Population analyses of mosaic X chromosome loss identify genetic drivers and widespread signatures of cellular selection.

Mosaic loss of the X chromosome (mLOX) is the most commonly occurring clonal somatic alteration detected in the leukocytes of women, yet little is known about its genetic determinants or phenotypic consequences. To address this, we estimated mLOX in >900,000 women across eight biobanks, identifying 10% of women with detectable X loss in approximately 2% of their leukocytes. Out of 1,253 diseases examined, women with mLOX had an elevated risk of myeloid and lymphoid leukemias and pneumonia. Genetic analyses identified 49 common variants influencing mLOX, implicating genes with established roles in chromosomal missegregation, cancer predisposition, and autoimmune diseases. Complementary exome-sequence analyses identified rare missense variants in FBXO10 which confer a two-fold increased risk of mLOX. A small fraction of these associations were shared with mosaic Y chromosome loss in men, suggesting different biological processes drive the formation and clonal expansion of sex chromosome missegregation events. Allelic shift analyses identified alleles on the X chromosome which are preferentially retained, demonstrating that variation at many loci across the X chromosome is under cellular selection. A novel polygenic score including 44 independent X chromosome allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile. Collectively our results support a model where germline variants predispose women to acquiring mLOX, with the allelic content of the X chromosome possibly shaping the magnitude of subsequent clonal expansion.

Towards Tobacco-Free Generation: implementation of preventive tobacco policies in the Nordic countries.

AIMS: Europe's Beating Cancer Plan set a goal of creating a Tobacco-Free Generation in Europe by 2040. Prevention is important for achieving this goal. We compare the Nordic countries' preventive tobacco policies, discuss the possible determinants for similarities and differences in policy implementation, and provide strategies for strengthening tobacco prevention. METHODS: We used the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) to identify the key policies for this narrative review. We focused on Articles 6, 8, 9, 11, 13 and 16 of the WHO FCTC, and assessed the status of the required (core) and recommended (advanced) policies and their application to novel tobacco and nicotine products. Information on the implementation of strategies, acts and regulations were searched from global and national tobacco control databases, websites and scientific articles via PubMed and MEDLINE. RESULTS: The WHO FCTC and European regulations have ensured that the core policies are mostly in place, but also contributed to the shared deficiencies that are seen especially in the regulations on smokeless tobacco and novel products. Strong national tobacco control actors have facilitated countries to implement some advanced policies - even as the first countries in the world: point-of-sale display bans (Iceland), outdoor smoking bans (Sweden), flavour bans on electronic cigarettes (Finland), plain packaging (Norway), and plain packaging on electronic cigarettes (Denmark). CONCLUSIONS: Collaboration and participation in reinforcing the European regulations, resources for national networking between tobacco control actors, and national regulations to provide protection from the tobacco industry's interference are needed to strengthen comprehensive implementation of tobacco policies in the Nordic countries.

Large registry-based analysis of genetic predisposition to tuberculosis identifies genetic risk factors at HLA.

Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment resistant strains. Therefore, it is important to identify mechanisms that contribute to risk and prognosis of tuberculosis as this may provide tools to understand disease mechanisms and provide novel treatment options for those with severe infection. Our goal was to identify genetic risk factors that contribute to the risk of tuberculosis and to understand biological mechanisms and causality behind the risk of tuberculosis. A total of 1895 individuals in the FinnGen study had International Classification of Diseases-based tuberculosis diagnosis. Genome-wide association study analysis identified genetic variants with statistically significant association with tuberculosis at the human leukocyte antigen (HLA) region (P < 5e-8). Fine mapping of the HLA association provided evidence for one protective haplotype tagged by HLA DQB1*05:01 (P = 1.82E-06, OR = 0.81 [CI 95% 0.74-0.88]), and predisposing alleles tagged by HLA DRB1*13:02 (P = 0.00011, OR = 1.35 [CI 95% 1.16-1.57]). Furthermore, genetic correlation analysis showed association with earlier reported risk factors including smoking (P < 0.05). Mendelian randomization supported smoking as a risk factor for tuberculosis (inverse-variance weighted P < 0.05, OR = 1.83 [CI 95% 1.15-2.93]) with no significant evidence of pleiotropy. Our findings indicate that specific HLA alleles associate with the risk of tuberculosis. In addition, lifestyle risk factors such as smoking contribute to the risk of developing tuberculosis.