Illicit cigarette purchasing after implementation of menthol cigarette bans in Canada: findings from the 2016-2018 ITC Four Country Smoking and Vaping Surveys.

OBJECTIVE: To examine the impact of menthol cigarette bans on use and purchasing of illicit cigarettes among menthol and non-menthol smokers in seven Canadian provinces. METHODS: Data from 1098 non-menthol smokers and 138 menthol smokers in Canada who completed the ITC Four Country Smoking and Vaping Survey in 2016 (pre-ban) and 2018 (post-ban). Brand validation analysis was conducted to (1) compare self-reported use of menthols versus actual use of menthols as regular brand, and verify self-reported purchasing of menthols among pre-ban menthol smokers at post-ban; and (2) assess pre-post ban changes in purchasing of illicit cigarettes from First Nations reserves among non-menthol smokers and menthol smokers. RESULTS: Among the subset of 138 pre-ban menthol smokers, 36 (19.5%) reported smoking menthols at post-ban. Brand validation analyses showed that 19 (9.0%) were actually using a non-menthol brand; of the 17 (10.5%) who were actually using a menthol brand, 13 (7.9%) bought a menthol brand at last purchase, and 4 (2.6%) bought a non-menthol brand. Among the full sample of smokers who purchased cigarettes from First Nations reserves at both pre-ban and post-ban, there was no change in purchasing of menthols (n=9 menthol smokers; 51.2% vs 51.2%, p=1.00), non-menthols (n=1024 non-menthol smokers; 9.1% vs 8.7%, p=0.69) or all cigarettes (menthol+non-menthol) (n=1086 smokers; 9.7% vs 9.2%, p=0.56). CONCLUSIONS: Actual rates of brand-verified menthol smoking were substantially lower than self-reported rates at post-ban. After Canada's menthol ban, there was no increase in illicit purchasing of menthol or non-menthol cigarettes from First Nations reserves.

Public support for tobacco endgame policies in South Korea: Findings from the 2020 International Tobacco Control Korea Survey.

BACKGROUND: Strong public support can increase the likelihood of adopting tobacco control policies. We assessed support for six commercial tobacco endgame policies in South Korea: limiting the nicotine in cigarettes, banning all additives in cigarettes, restricting the number of places where cigarettes are sold, and banning the manufacture and sales of cigarettes (unconditionally, with the provision of cessation support and with alternative tobacco products available). METHODS: Data were obtained from 4740 adults who completed the 2020 International Tobacco Control Korea Survey. Participants were categorised based on their nicotine use: (1) did not use any products, (2) vaped and/or used heated tobacco products (HTPs) but did not smoke cigarettes, (3) smoked cigarettes only and (4) smoked cigarettes and vaped and/or used HTPs. Attitudes towards the policies were classified as supportive, undecided or opposed. Weighted multinomial logistic regression models assessed support levels according to nicotine use. RESULTS: Support was highest for limiting the nicotine content in cigarettes (68.4%; 95% CI 64.6% to 72.3%) and restricting the number of retailers (68.1%; 95% CI 64.5% to 71.7%), and lowest for banning cigarette sales if alternative products are made available (45.0%; 95% CI 40.9% to 49.1%). People who did not use any products were most likely to support endgame policies, except for banning cigarette sales with alternatives available. The proportion of undecided participants exceeded 10% (range 13%-25%) for all policies. CONCLUSION: There is a strong public support for tobacco endgame policies in South Korea. Further research should prioritise the development of strategies to ensure the effective implementation of highly supported policies.

Optimising a product standard for banning menthol and other flavours in tobacco products.

In this paper, we highlight key issues that policymakers should consider when developing a product standard banning menthol and other flavours in tobacco products based on research evidence and experiences learnt from other countries. A flavour product standard may be optimised by (1) having a clear and comprehensive definition of flavour that includes a complete ban on additives that have flavour properties and/or evoke sensory/cooling effects (ie, menthol analogues and synthetic coolants that stimulate the cooling receptor of the brain) rather than only as a 'characterising flavour' and (2) applying the standard to all tobacco product categories as well as all components or parts of the tobacco product (ie, the tobacco, filter, wrapper or paper), including separate flavourings that can be added to the product.

Evaluating the impact of plain packaging among Canadian smokers: findings from the 2018 and 2020 ITC Smoking and Vaping Surveys.

BACKGROUND: In February 2020, Canada implemented plain packaging without any changes to the size and content of health warning labels (HWLs), which were last updated in 2012 (pictorial HWLs on 75% of the pack front and back). This pre-post evaluation study assessed the impact of plain packaging in Canada on: (1) pack appeal; (2) HWL effectiveness; and (3) support for plain packaging. Additionally, a quasi-experimental design was used to assess the Canadian results relative to two comparator countries: Australia, where plain packaging (with new larger HWLs) was implemented in 2012, and the United States (USA), where plain packaging has not been implemented and the same text warnings have appeared on cigarette packs since 1985. METHODS: Data are from adult smokers who participated in the 2018 and/or 2020 International Tobacco Control Smoking and Vaping Surveys in Canada (n=4600), Australia (n=1834) and the USA (n=3046). Online surveys were conducted before (February to July 2018) and after (February to June 2020) the implementation of plain packaging in Canada. Adjusted regression analyses were conducted on weighted data. RESULTS: Plain packaging was associated with a significant increase in the percentage of Canadian smokers who did not like the look of their cigarette pack (2018: 28.6% vs 2020: 44.7%, p<0.001), whereas no change in pack appeal was observed among smokers in Australia and the USA over the same period. Plain packaging was not associated with changes in HWL effectiveness in Canada. Support for plain packaging increased significantly among Canadian smokers (2018: 25.6% vs 2020: 33.7%, p<0.001). CONCLUSIONS: Plain packaging in Canada substantially reduced pack appeal and increased support for the policy among adult smokers; however, there was no increase in the effectiveness of Canada's 8-year-old HWLs. The impact of plain packaging on health warning effectiveness may depend on the design of the warnings and length of time since implementation.

Impact of Canada's menthol cigarette ban on quitting among menthol smokers: pooled analysis of pre-post evaluation from the ITC Project and the Ontario Menthol Ban Study and projections of impact in the USA.

INTRODUCTION: Between 2015 and 2018, Canada banned menthol cigarettes. This study pooled data from two pre-post cohort studies (the Ontario Menthol Ban Study, and the International Tobacco Control Policy Evaluation (ITC) Canada Survey, conducted in seven provinces) to derive more precise estimates of the impact of Canada's menthol ban on quitting and to apply these estimates to project the impact of a menthol ban in the USA. METHODS: Weighted multivariable logistic analyses compared post-ban quit success of menthol smokers with non-menthol smokers (for daily smokers and for all (daily + non-daily) smokers), controlling for sex, age, ethnicity, education, baseline smoking status, baseline cigarettes per day and study regions. Projections to the USA were created by multiplying the effect size of the Canadian menthol ban on quitting (percentage of increased quitting among menthol smokers) by the number of menthol smokers overall and among African Americans, from the 2019 National Survey on Drug Use and Health. RESULTS: After the menthol cigarette ban, menthol smokers were more likely than non-menthol smokers to have quit smoking among daily smokers (difference=8.0%; 95% CI: 2.4% to 13.7%,p=0.005) and all (daily+non-daily) smokers (difference=7.3%; 95% CI: 2.1% to 12.5%,p=0.006). The projected number of smokers who would quit after a US menthol ban would be 789 724 daily smokers (including 199 732 African Americans) and 1 337 988 daily+non-daily smokers (including 381 272 African Americans). CONCLUSIONS: This pooled analysis of Canada's menthol cigarette ban provides the foundation for estimating the impact of menthol bans in the USA and other countries. Projections suggest that a US menthol cigarette ban would have a substantial impact on increasing quitting.

Illicit purchasing and use of flavour accessories after the European Union menthol cigarette ban: findings from the 2020-21 ITC Netherlands Surveys.

BACKGROUND: The 2020 European Union (EU) menthol cigarette ban increased quitting among pre-ban menthol smokers in the Netherlands, but some reported continuing to smoke menthol cigarettes. This study examined three possible explanations for post-ban menthol use-(i) illicit purchasing, (ii) use of flavour accessories and (iii) use of non-menthol replacement brands marketed for menthol smokers. METHODS: Data were from the ITC Netherlands Cohort Surveys among adult smokers before the menthol ban (Wave 1: February-March 2020, N = 2067) and after the ban (Wave 2: September-November 2020, N = 1752; Wave 3: June-July 2021, N = 1721). Bivariate, logistic regression and generalized estimating equation model analyses were conducted on weighted data. RESULTS: Illicit purchasing remained low from pre-ban (2.4%, 95% CI: 1.8-3.2, Wave 1) to post-ban (1.7%, 1.2-2.5%, Wave 3), with no difference between menthol and non-menthol smokers from Wave 1 to Wave 3. About 4.4% of post-ban menthol smokers last purchased their usual brand outside of the EU and 3.6% from the internet; 42.5% of post-ban menthol smokers and 4.4% of smokers overall reported using flavour accessories, with greater odds among those aged 25-39 years vs. 55+ (aOR = 3.16, P = 0.002). Approximately 70% of post-ban smokers who reported using a menthol brand were actually using a non-menthol replacement brand. CONCLUSIONS: There was no increase in illicit purchasing or of smuggling outside the EU among menthol and non-menthol smokers in the Netherlands 1 year after the EU menthol cigarette ban. Use of flavour accessories and non-menthol replacement brands best explain post-ban menthol use, suggesting the need to ban accessories and ensure industry compliance.

The Thyroid Hormone Axis and Female Reproduction.

Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and polycystic ovarian syndrome. Thus, the complex molecular interplay between hormones involved in thyroid and reproductive functions is further compounded by the association of certain common autoimmune states with disorders of the thyroid and the HPG axes. Furthermore, in prepartum and intrapartum states, even relatively minor disruptions have been shown to adversely impact maternal and fetal outcomes, with some differences of opinion in the management of these conditions. In this review, we provide readers with a foundational understanding of the physiology and pathophysiology of thyroid hormone interactions with the female HPG axis. We also share clinical insights into the management of thyroid dysfunction in reproductive-aged women.

Questionnaire-based exposome-wide association studies (ExWAS) reveal expected and novel risk factors associated with cardiovascular outcomes in the Personalized Environment and Genes Study.

While multiple factors are associated with cardiovascular disease (CVD), many environmental exposures that may contribute to CVD have not been examined. To understand environmental effects on cardiovascular health, we performed an exposome-wide association study (ExWAS), a hypothesis-free approach, using survey data on endogenous and exogenous exposures at home and work and data from health and medical histories from the North Carolina-based Personalized Environment and Genes Study (PEGS) (n = 5015). We performed ExWAS analyses separately on six cardiovascular outcomes (cardiac arrhythmia, congestive heart failure, coronary artery disease, heart attack, stroke, and a combined atherogenic-related outcome comprising angina, angioplasty, atherosclerosis, coronary artery disease, heart attack, and stroke) using logistic regression and a false discovery rate of 5%. For each CVD outcome, we tested 502 single exposures and built multi-exposure models using the deletion-substitution-addition (DSA) algorithm. To evaluate complex nonlinear relationships, we employed the knockoff boosted tree (KOBT) algorithm. We adjusted all analyses for age, sex, race, BMI, and annual household income. ExWAS analyses revealed novel associations that include blood type A (Rh-) with heart attack (OR[95%CI] = 8.2[2.2:29.7]); paint exposures with stroke (paint related chemicals: 6.1[2.2:16.0], acrylic paint: 8.1[2.6:22.9], primer: 6.7[2.2:18.6]); biohazardous materials exposure with arrhythmia (1.8[1.5:2.3]); and higher paternal education level with reduced risk of multiple CVD outcomes (stroke, heart attack, coronary artery disease, and combined atherogenic outcome). In multi-exposure models, trouble sleeping and smoking remained important risk factors. KOBT identified significant nonlinear effects of sleep disorder, regular intake of grapefruit, and a family history of blood clotting problems for multiple CVD outcomes (combined atherogenic outcome, congestive heart failure, and coronary artery disease). In conclusion, using statistics and machine learning, these findings identify novel potential risk factors for CVD, enable hypothesis generation, provide insights into the complex relationships between risk factors and CVD, and highlight the importance of considering multiple exposures when examining CVD outcomes.

Evaluating the impact of menthol cigarette bans on cessation and smoking behaviours in Canada: longitudinal findings from the Canadian arm of the 2016-2018 ITC Four Country Smoking and Vaping Surveys.

OBJECTIVE: To evaluate the impact of menthol cigarette bans in seven Canadian provinces between 2016 and 2018. METHODS: Longitudinal data from the Canadian arm of the 2016 and 2018 ITC Four Country Smoking and Vaping Survey. 1098 non-menthol and 138 menthol smokers were surveyed pre-menthol and post-menthol cigarette bans. Multivariate logistic regression models examined associations between pre-post ban changes in smoking behaviour, including differences between menthol and non-menthol smokers in quit attempts and quitting. RESULTS: At follow-up, 59.1% of pre-ban menthol smokers switched to non-menthol cigarettes; 21.5% quit smoking and 19.5% still smoked menthols, primarily purchased from First Nations reserves. Menthol smokers were more likely than non-menthol smokers to make a quit attempt (adjusted OR (aOR)=1.61, 95% CI 1.03 to 2.51), and to remain quit (aOR=2.30, 95% CI 1.06 to 5.01). Menthol smokers did not differ significantly from non-menthol smokers in quit success (aOR=1.72, 95% CI 0.98 to 3.01); however, daily menthol smokers were more likely than daily non-menthol smokers to quit (aOR=2.21, 95% CI 1.15 to 4.24), and daily menthol smokers who quit before the ban were more likely than daily non-menthol smokers to remain quit (aOR=2.81, 95% CI 1.15 to 6.85). CONCLUSIONS: Although menthol smokers were most likely to switch to non-menthol cigarettes, the menthol ban was also significantly associated with higher rates of quit attempts and quit success among menthol smokers compared with non-menthol smokers, and may have helped to prevent relapse among menthol smokers who had quit smoking before the ban. Results confirm and extend evaluation of Ontario's menthol ban across provinces covering 83% of the Canadian population.

Impact of the European Union's menthol cigarette ban on smoking cessation outcomes: longitudinal findings from the 2020-2021 ITC Netherlands Surveys.

INTRODUCTION: To reduce the appeal of tobacco, the European Union (EU) banned menthol as a characterising flavour in cigarettes in May 2020. This pre/post-study evaluated the impact of the menthol ban on smoking cessation outcomes among a representative cohort of Dutch smokers. METHODS: Adult (18+ years) smokers were recruited at wave 1 (pre-ban) of the International Tobacco Control Netherlands Surveys (February-March 2020) and followed post-ban at wave 2 (September-November 2020) and wave 3 (June-July 2021) (N=1326 participated in all three waves). Weighted bivariate, logistic regression and generalised estimating equation model analyses were conducted. RESULTS: Usual menthol use decreased from pre-ban (7.8%) to post-ban (4.0% at wave 2 and 4.4% at wave 3) (p<0.001). Pre-ban menthol smokers had greater odds of making a post-ban quit attempt than non-menthol smokers (66.9% vs 49.6%, adjusted OR (aOR)=1.89, 95% CI: 1.13 to 3.16). Compared with pre-ban non-menthol smokers, a higher proportion of menthol smokers quit by wave 2 (17.8% vs 10.2%, p=0.025) and by wave 3 (26.1% vs 14.1%, p=0.002), although this was not significant after adjusting for other factors. Female pre-ban menthol smokers had greater odds of quitting by wave 3 than female non-menthol smokers (aOR=2.23, 95% CI: 1.10 to 4.51). Most pre-ban menthol smokers (n=99) switched to non-menthol cigarettes (40.0%) or reported that they continued to smoke menthol cigarettes (33.0%) at wave 3. CONCLUSIONS: The EU menthol ban was effective in reducing menthol use and in increasing quit attempts and quitting among pre-ban menthol smokers. Impact could be maximised by closing gaps that allow post-ban menthol cigarette use.

Scoping review of COVID-19-related systematic reviews and meta-analyses: can we really have confidence in their results?

AIM: The aim of this study was to systematically appraise the quality of a sample of COVID-19-related systematic reviews (SRs) and discuss internal validity threats affecting the COVID-19 body of evidence. DESIGN: We conducted a scoping review of the literature. SRs with or without meta-analysis (MA) that evaluated clinical data, outcomes or treatments for patients with COVID-19 were included. MAIN OUTCOME MEASURES: We extracted quality characteristics guided by A Measurement Tool to Assess Systematic Reviews-2 to calculate a qualitative score. Complementary evaluation of the most prominent published limitations affecting the COVID-19 body of evidence was performed. RESULTS: A total of 63 SRs were included. The majority were judged as a critically low methodological quality. Most of the studies were not guided by a pre-established protocol (39, 62%). More than half (39, 62%) failed to address risk of bias when interpreting their results. A comprehensive literature search strategy was reported in most SRs (54, 86%). Appropriate use of statistical methods was evident in nearly all SRs with MAs (39, 95%). Only 16 (33%) studies recognised heterogeneity in the definition of severe COVID-19 as a limitation of the study, and 15 (24%) recognised repeated patient populations as a limitation. CONCLUSION: The methodological and reporting quality of current COVID-19 SR is far from optimal. In addition, most of the current SRs fail to address relevant threats to their internal validity, including repeated patients and heterogeneity in the definition of severe COVID-19. Adherence to proper study design and peer-review practices must remain to mitigate current limitations.

Cadmium Exposure and Ovarian Reserve in Women Aged 35-49 Years: The Impact on Results From the Creatinine Adjustment Approach Used to Correct for Urinary Dilution.

Cadmium is toxic to the ovaries in animal studies, but its association with diminished ovarian reserve in women is not established. We investigated urinary cadmium, a biomarker of long-term exposure, in relation to diminished ovarian reserve, as indicated by elevated serum follicle-stimulating hormone concentrations (≥10 IU/L), in women aged 35-49 years (unweighted n = 1,681). Using data from the Third National Health and Nutrition Examination Survey (1988-1994), we conducted Poisson regression to estimate adjusted relative risks and 95% confidence intervals. Because the best approach to correcting for urinary dilution in spot samples with creatinine remains controversial, we employed 3 approaches: standardization, covariate adjustment, and covariate-adjusted standardization. Our data suggested a modest association with standardization (highest quartile vs. lowest: relative risk (RR) = 1.3, 95% confidence interval (CI): 0.8, 1.9; P for trend = 0.06) and covariate-adjusted standardization (highest quartile vs. lowest: RR = 1.3, 95% CI: 0.9, 1.9; P for trend = 0.05) and a stronger association with covariate adjustment (highest quartile vs. lowest: RR = 1.8, 95% CI: 1.2, 2.9; P for trend = 0.01). The stronger association with covariate adjustment may reflect bias from conditioning on urinary creatinine, a collider in the hypothesized causal pathway. We conclude that cadmium may contribute to ovarian aging in women and that careful consideration of the creatinine adjustment approach is needed to minimize bias.

Exploring the motivations of research participants who chose not to learn medically actionable secondary genetic findings about themselves.

PURPOSE: Proposals to return medically actionable secondary genetic findings (SFs) in the clinical and research settings have generated controversy regarding whether to solicit individuals' preferences about their "right not to know" genetic information. This study contributes to the debate by surveying research participants who have actively decided whether to accept or refuse SFs. METHODS: Participants were drawn from a large National Institutes of Health (NIH) environmental health study. Participants who had accepted SFs (n = 148) or refused SFs (n = 83) were given more detailed information about the types of SFs researchers could return and were given an opportunity to revise their original decision. RESULTS: Forty-one of 83 initial refusers (49.4%) opted to receive SFs following the informational intervention. Nearly 75% of these "reversible refusers" thought they had originally accepted SFs. The 50.6% of initial refusers who continued to refuse ("persistent refusers") demonstrated high levels of understanding of which SFs would be returned postintervention. The most prominent reason for refusing was concern about becoming worried or sad (43.8%). CONCLUSION: This study demonstrates the need for a more robust informed consent process when soliciting research participants' preferences about receiving SFs. We also suggest that our data support implementing a default practice of returning SFs without actively soliciting preferences.

Phenotypic continuum between Waardenburg syndrome and idiopathic hypogonadotropic hypogonadism in humans with SOX10 variants.

PURPOSE: SOX10 variants previously implicated in Waardenburg syndrome (WS) have now been linked to Kallmann syndrome (KS), the anosmic form of idiopathic hypogonadotropic hypogonadism (IHH). We investigated whether SOX10-associated WS and IHH represent elements of a phenotypic continuum within a unifying disorder or if they represent phenotypically distinct allelic disorders. METHODS: Exome sequencing from 1,309 IHH subjects (KS: 632; normosmic idiopathic hypogonadotropic hypogonadism [nIIHH]: 677) were reviewed for SOX10 rare sequence variants (RSVs). The genotypic and phenotypic spectrum of SOX10-related IHH (this study and literature) and SOX10-related WS cases (literature) were reviewed and compared with SOX10-RSV spectrum in gnomAD population. RESULTS: Thirty-seven SOX10-associated IHH cases were identified as follows: current study: 16 KS; 4 nIHH; literature: 16 KS; 1 nIHH. Twenty-three IHH cases (62%; all KS), had ≥1 known WS-associated feature(s). Moreover, five previously reported SOX10-associated WS cases showed IHH-related features. Four SOX10 missense RSVs showed allelic overlap between IHH-ascertained and WS-ascertained cases. The SOX10-HMG domain showed an enrichment of RSVs in disease states versus gnomAD. CONCLUSION: SOX10 variants contribute to both anosmic (KS) and normosmic (nIHH) forms of IHH. IHH and WS represent SOX10-associated developmental defects that lie along a unifying phenotypic continuum. The SOX10-HMG domain is critical for the pathogenesis of SOX10-related human disorders.

Which tobacco control policies do smokers support? Findings from the International Tobacco Control Four Country Smoking and Vaping Survey.

As governments consider policy action to reduce smoking, a key factor in creating political will is the level of public support, particularly among smokers who are most affected by the policies. The goal of this paper is to assess and compare the level of support in Canada, the United States, England, and Australia for five smoking control policies: 1) banning menthol in cigarettes, 2) banning cigarette additives, 3) reducing nicotine in cigarettes to make them less addictive, 4) raising the minimum age to purchase cigarettes to 21 years and older, and 5) requiring pictorial warning labels on cigarette packs (examined in the US only). Data for these analyses come from 8165 daily cigarette smokers who responded to the 2016 International Tobacco Control Four Country Smoking and Vaping Survey. In all countries, the highest level of support was for raising the legal age for purchase to 21 years and older (62-70%) and reducing the nicotine content of cigarettes to make them less addictive (57-70%). Smokers who were less dependent on cigarettes and those expressing interest in quitting were more likely to support all policies. When asked how they would respond to a nicotine reduction policy, the most common response given was to try the non-nicotine cigarettes to see how they liked them (42-48%), with the next most common response being to quit smoking entirely (16-24%). The high level of support for these proposed policies among daily smokers provides important evidence for policymakers to counteract claims that such policies would be unpopular.

Gender Differences in Reasons for Using Electronic Cigarettes and Product Characteristics: Findings From the 2018 ITC Four Country Smoking and Vaping Survey.

INTRODUCTION: Little is known about why males are more likely to use electronic cigarettes (ECs) compared with females. This study examined gender differences in reasons for vaping and characteristics of EC used (device type, device capacity, e-liquid nicotine strength, and flavor). METHODS: Data were obtained from 3938 current (≥18 years) at-least-weekly EC users who participated in Wave 2 (2018) ITC Four Country Smoking and Vaping Survey in Canada, the United States, England, and Australia. RESULTS: Of the sample, 54% were male. The most commonly cited reasons for vaping in females were "less harmful to others" (85.8%) and in males were "less harmful than cigarettes" (85.5%), with females being more likely to cite "less harmful to others" (adjusted odds ratio [aOR] = 1.64, p = .001) and "help cut down on cigarettes" (aOR = 1.60, p = .001) than males. Significant gender differences were found in EC device type used (χ  2 = 35.05, p = .043). Females were less likely to report using e-liquids containing >20 mg/mL of nicotine, and tank devices with >2 mL capacity (aOR = 0.41, p < .001 and aOR = 0.65, p = .026, respectively) than males. There was no significant gender difference in use of flavored e-liquids, with fruit being the most common flavor for both males (54.5%) and females (50.2%). CONCLUSION: There were some gender differences in reasons for vaping and characteristics of the product used. Monitoring of gender differences in patterns of EC use would be useful to inform outreach activities and interventions for EC use. IMPLICATIONS: Our findings provide some evidence of gender differences in reasons for vaping and characteristics of EC used. The most common reason for vaping reported by females was "less harmful to others," which may reflect greater concern by female vapers about the adverse effects of secondhand smoke compared with male vapers. Gender differences might be considered when designing gender-sensitive smoking cessation policies. Regarding characteristics of EC products used, we found gender differences in preferences for e-liquid nicotine strength and device capacity. Further studies should examine whether the observed gender differences in EC use reasons and product characteristics are predictive of smoking cessation. Furthermore, studies monitoring gender-based marketing of ECs may be considered.

Endocrine Conditions and COVID-19.

COVID-19 was declared a global pandemic by the WHO and has affected millions of patients around the world. COVID-19 disproportionately affects persons with endocrine conditions, thus putting them at an increased risk for severe disease. We discuss the mechanisms that place persons with endocrine conditions at an additional risk for severe COVID-19 and review the evidence. We also suggest precautions and management of endocrine conditions in the setting of global curfews being imposed and offer practical tips for uninterrupted endocrine care.

Support for Minimum Legal Sales Age Laws Set to Age 21 Across Australia, Canada, England, and United States: Findings From the 2018 ITC Four Country Smoking and Vaping Survey.

INTRODUCTION: Although the United States has seen a rapid increase in tobacco minimum legal sales age (MLSA) laws set to age 21, there is wide variation across high-income countries and less is known about policy support outside of the United States. We examined the prevalence of support for tobacco MLSA 21 laws as well as associations by sociodemographic, smoking, and household characteristics among current and former adult smokers. METHODS: In this cross-sectional analysis, we used the 2018 International Tobacco Control Four Country Smoking and Vaping Survey to examine support for MLSA 21 laws among 12 904 respondents from Australia, Canada, England, and United States. RESULTS: Support for raising the legal age of purchasing cigarettes/tobacco to 21 ranged from 62.2% in the United States to 70.8% in Canada. Endorsement also varied by age, such that 40.6% of 18-20 years old supported the policy compared with 69.3% of those aged ≥60 years. In the adjusted regression model, there was also higher support among respondents who were female than male, non-white than white, those who did not allow smoking in the household than those that did, and those who had children in the household than those that did not. There were no differences by household income, education, or smoking status. CONCLUSIONS: Most current and former smokers, including a sizable minority of those aged ≤20 years, support raising the legal age of purchasing cigarettes/tobacco to 21. IMPLICATIONS: There was strong support for MLSA 21 laws among smokers and former smokers across Australia, Canada, England, and the United States, providing evidence for the increasing public support of the passage of these laws beyond the United States.

Support for e-cigarette policies among smokers in seven European countries: longitudinal findings from the 2016-18 EUREST-PLUS ITC Europe Surveys.

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 = 9547; just after TPD) and 2018 (n = 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.

Smc5/6 Antagonism by HBx Is an Evolutionarily Conserved Function of Hepatitis B Virus Infection in Mammals.

Chronic infection with hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. HBVs (family Hepadnaviridae) have been associated with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions in genome maintenance, was identified as an antiviral restriction factor of human HBV. The virus has, however, evolved to counteract this defense mechanism by degrading the complex via its regulatory HBx protein. Whether the antiviral activity of the Smc5/6 complex against hepadnaviruses is an important and evolutionarily conserved function is unknown. In this study, we used an evolutionary and functional approach to address this question. We first performed phylogenetic and positive selection analyses of the Smc5/6 complex subunits and found that they have been conserved in primates and mammals. Yet, Smc6 showed marks of adaptive evolution, potentially reminiscent of a virus-host "arms race." We then functionally tested the HBx proteins from six divergent hepadnaviruses naturally infecting primates, rodents, and bats. We demonstrate that despite little sequence homology, these HBx proteins efficiently degraded mammalian Smc5/6 complexes, independently of the host species and of the sites under positive selection. Importantly, all HBx proteins also rescued the replication of an HBx-deficient HBV in primary human hepatocytes. These findings point to an evolutionarily conserved requirement for Smc5/6 inactivation by HBx, showing that Smc5/6 antiviral activity has been an important defense mechanism against hepadnaviruses in mammals. It will be interesting to investigate whether Smc5/6 may further be a restriction factor of other, yet-unidentified viruses that may have driven some of its adaptation.IMPORTANCE Infection with hepatitis B virus (HBV) led to 887,000 human deaths in 2015. HBV has been coevolving with mammals for millions of years. Recently, the Smc5/6 complex, which has essential housekeeping functions, was identified as a restriction factor of human HBV antagonized by the regulatory HBx protein. Here we address whether the antiviral activity of Smc5/6 is an important evolutionarily conserved function. We found that all six subunits of Smc5/6 have been conserved in primates, with only Smc6 showing signatures of an "evolutionary arms race." Using evolution-guided functional analyses that included infections of primary human hepatocytes, we demonstrated that HBx proteins from very divergent mammalian HBVs could all efficiently antagonize Smc5/6, independently of the host species and sites under positive selection. These findings show that Smc5/6 antiviral activity against HBV is an important function in mammals. They also raise the intriguing possibility that Smc5/6 may restrict other, yet-unidentified viruses.