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Arts engagement is a health-related behavior that may be influenced by social inequalities. While the COVID-19 pandemic provided new opportunities for some people to engage in the arts, it might have created barriers for others. We aimed to examine whether there was social patterning in home-based arts engagement during the pandemic in the United States, and whether predictors of engagement differed according to the type of arts activity. We included 4,731 adults who participated in the United States COVID-19 Social Study between April and July 2020. Three types of home-based arts engagement were considered: reading for pleasure, arts or crafts activities, and digital arts activities. Using logistic regression models, we tested cross-sectional associations between a broad range of demographic, socioeconomic, psychosocial, and health-related factors as well as adverse events and worries during lockdown and each type of arts engagement. The factors most strongly associated with all three types of arts engagement were social support, social network size, age, race/ethnicity, keyworker status, and experiencing physical or psychological abuse during the pandemic. However, most socioeconomic and health-related factors were not associated with arts engagement, including household income and mental and physical health problems. Overall, our findings indicate that the social gradient in arts engagement was reduced in the first 4 months of the COVID-19 pandemic in the United States. Given the health benefits of arts engagement, the potential diversification of arts audiences during the pandemic is promising for both population-level health and wellbeing and the future of the arts and cultural sector.

Although substantial progress has been made in the pathophysiology and management of the post-thrombotic syndrome (PTS), several aspects still need clarification. Among them, the incidence and severity of PTS in the real world, the risk factors for its development, the value of patient's self-evaluation, and the ability to identify patients at risk for severe PTS. Eligible participants (n = 1107) with proximal deep-vein thrombosis (DVT) from the global GARFIELD-VTE registry underwent conventional physician's evaluation for PTS 36 months after diagnosis of their DVT using the Villalta score. In addition, 856 patients completed a Villalta questionnaire at 24 months. Variable selection was performed using stepwise algorithm, and predictors of severe PTS were incorporated into a multivariable risk model. The optimistic adjusted c-index was calculated using bootstrapping techniques. Over 36-months, 27.8% of patients developed incident PTS (mild in 18.7%, moderate in 5.7%, severe in 3.4%). Patients with incident PTS were older, had a lower prevalence of transient risk factors of DVT and a higher prevalence of persistent risk factors of DVT. Self-assessment of overall PTS at 24 months showed an agreement of 63.4% with respect to physician's evaluations at 36 months. The severe PTS multivariable model provided an optimistic adjusted c-index of 0.68 (95% CI 0.59-0.77). Approximately a quarter of DVT patients experienced PTS over 36 months after VTE diagnosis. Patient's self-assessment after 24 months provided added value for estimating incident PTS over 36 months. Multivariable risk analysis allowed good discrimination for severe PTS., (© 2023. The Author(s).)

Background: Economically developed countries continue to find that venous thromboembolism (VTE) is a major cause of morbidity and mortality., Objective: To compare baseline risk profiles and patient workflow patterns between the United States (U.S.) and Canadian management of VTE patients from 2014 to 2017., Methods: The Global Anticoagulant Registry in the FIELD (GARFIELD-VTE) is a prospective, observational study of 10,679 patients with objectively confirmed VTE, followed for 3 years. In total 1101 patients enrolled in the U.S. and Canada were included in this analysis., Results: Median age and body mass index were comparable between the U.S. (60.5; 30.2) and Canadian (59.7; 29) patients. A higher percentage of U.S. patients were black (n = 128, 24.1 %; n = 22, 3.9 %) and had a higher VTE-associated risk profile, including immobilization, hospitalization, and recent surgery. U.S. patients had a higher combined DVT and PE primary diagnoses (20.3 %) and were more likely to be treated in hospitals (77.2 %) than Canadians (13.3 %; 48.1 %). Direct oral anticoagulant therapy (DOAC) was nearly two-fold more frequent in Canadian patients (n = 218, 39.2 %) at the end of 3 years in comparison to the U.S. (n = 118, 23.0 %). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, the risk of all-cause mortality was 51.9 % higher in patients from the U.S. compared to those in Canada after 3 years. Patients from the U.S. also had a higher likelihood of hospitalization, major bleeding, and recurrent VTE after controlling for prior history and comorbid conditions., Conclusion: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies., Type of Research: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE)., Key Findings: 531 U.S. and 557 Canadians patients included in study. DOAC use more frequent in Canadian patients after 3 years than U.S. (39.2 % vs. 23.0 %, respectively). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, all-cause mortality risk remained higher in U.S. patients vs. Canadian patients after 3 years. U.S. patients had higher likelihood of hospitalization, major bleeding, and recurrent VTE., Take-Home Message: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and composition of specialists and their subsequent treatment strategies., Table of Contents Summary: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). Higher rates of adverse VTE-associated outcomes were observed in U.S. patients vs Canadian patients, which may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Samuel Z. Goldhaber: Research Support from Bayer Pharma AG, Boehringer-Ingelheim, BMS, BTG EKOS, Daiichi, Janssen, NHLBI, Thrombosis Research Institute. Consultancy fees from Bayer Pharma AG, Boehringer-Ingelheim. Marc Carrier: Grants from Pfizer/BMS, Canadian Institutes of Health Research, grants and personal fees from Leo Pharma, Bayer, personal fees from Sanofi Aventis, Pfizer, Bristol Myers Squibb. Alexander G. G. Turpie: Honoraria from Bayer Pharma AG, Janssen. Karen Pieper: Consultancy fee from Johnson & Johnson. Professor Ajay K Kakkar: Research grants from Bayer Pharma AG and Sanofi. Personal fees from Anthos Therapeutics, Bayer Pharma AG, Sanofi S.A. Alisha Oropallo, Adrian C. Chen, Amit S. Rao, Gloria Kayani, Uma Maheshwari: None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed., Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060., Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy., Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer., Funding: Erasmus MC., Competing Interests: All authors have completed the ICMJE uniform disclosure form. Luis Jara-Palomares: has received support for the present manuscript from MSD; grants from Leo Pharma; honoraria from Actelion Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Leo Pharma, MSD, Pfizer, ROVI, and Bristol-Myers Squibb. Isabelle Mahé: has received grants from BMS Pfizer; honoraria from BMS Pfizer, Leo Pharma, and Sanofi; support for attending meetings/travel from BMS Pfizer and Leo Pharma. Andrea Marshall: my institution received unrestricted educational grant from Bayer AG for the select-D trial. Remedios Otero Candelera: LEO-PHARMA was partially involved in the financial support to Hispalis Study without interfering in the intellectual conception, design and data analysis; received financial support for attendance to congresses and scientific meetings, payment to conferences or advisory board from BAYER HISPANIA, MSD, LEO-PHARMA and ROV; participated on a Data Safety Monitoring Board or Advisory Board. Frederikus Klok: has received research support from Bayer, Bristol-Myers Squibb, Actelion, Boston Scientific, Leo Pharma, PharmX, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe program, all outside this work and paid to his institution. Marieke Kruip: has received an unrestricted research grant from Sobi; research grants from Netherlands Thrombosis Foundation and the Netherlands Organization for Health Research and Development; speakers fee from Sobi, Roche, and BMS; all grants and fees are paid to her institution (Erasmus MC). Carin van der Rijt: has received a payment to the institution from the Netherlands Organization for Health Research and Development for a project on deprescription of medication at the end of life; is Chair of the Dutch Association for Professional Palliative Care (unpaid); is member of the Supervisory Board of the Foundation Roparun (attendance fee is paid). Eric Geijteman: has received an internal grant from the Erasmus MC (50.000 euro). This is a payment to finance this study (together with an interview- and questionnaire study about the perspectives of patient, caregivers and healthcare professionals on anticoagulation therapy). All other authors report no conflict of interest., (© 2023 The Author(s).)

Adolescent externalising behaviours are associated with numerous long-term negative outcomes, although most research is intervention-based as opposed to risk reduction. Arts engagement has been associated with numerous beneficial factors linked to externalising behaviours, yet direct evidence linking them in longitudinal studies is lacking. Data from the Early Childhood Longitudinal Study were used, with baseline at 5th grade and outcomes measured at 8th grade. Ordinary least squares (OLS) regression was used to examine individual-level associations between extracurricular and school-based arts engagement with externalising behaviours. OLS regression was also used to examine associations between school-level arts classes and facilities with an administrator-reported index of externalising behaviours in the school. All models were adjusted for sociodemographic factors. Individual-level analyses were clustered by school. At the individual level, engaging in a greater number of extracurricular arts activities was associated with fewer externalising behaviours, although there was no association for school-based arts engagement. There were no school-level associations between arts classes or adequate arts facilities and externalising behaviours. Our results suggest extracurricular arts activities may be beneficial in reducing the risk for externalising behaviours, but the relationship is seen at an individual-level of engagement rather than based on school-level provision or facilities., (© 2023. Springer Nature Limited.)

Objectives: There is a social gradient in both arts engagement and wellbeing that may have led to an overestimation of the impact of arts engagement on wellbeing. We tested whether participation in community arts groups was associated with wellbeing after removing confounding by demographic, socioeconomic, and health-related factors. Methods: Using propensity score matching, we analyzed data from 12,055 older adults in the Health and Retirement Study. We measured community arts groups participation and concurrent life satisfaction (evaluative wellbeing), positive and negative affect (experienced wellbeing), and purpose in life, constraints on personal control, and mastery (eudaimonic wellbeing). Results: After matching, arts group participation was associated with higher positive affect (average treatment effect on the treated [ATT] = 0.18, 95% CI = 0.12-0.24), life satisfaction (ATT = 0.09, 95% CI = 0.04-0.15), purpose in life (ATT = 0.07, 95% CI = 0.02-0.13), and mastery (ATT = 0.07, 95% CI = 0.01-0.14) than not participating. Participation was not associated with negative affect or constraints on personal control. In sensitivity analyses, these associations were maintained four years later. Conclusion: Arts group participation was associated with the positive elements of evaluative, experienced, and eudaimonic wellbeing. Facilitating participation in community arts groups could help to promote healthy aging, enabling a growing segment of the population to lead more fulfilling and satisfying lives.

Purpose: Although arts engagement holds promise for reducing loneliness and enhancing social support, previous research has focussed on older adults. We investigated whether arts engagement was associated with loneliness and social support during adolescence., Methods: We included 11,780 adolescents aged 11-21 years from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative cohort study. We measured whether adolescents engaged in school-based arts activities (band, book club, chorus, choir, cheerleading, dance, drama club, newspaper, orchestra) at wave one (1994-1995). Loneliness and perceived social support from peers were measured at waves one and two (1996). We used logistic regression to test whether arts engagement was associated with concurrent and subsequent loneliness and social support., Results: Arts engagement was not associated with concurrent or subsequent loneliness. Compared to not engaging, doing one or more school-based arts activities was associated with 59% higher odds of high social support concurrently (odds ratio [OR] = 1.59, 95% CI = 1.32-1.91). However, this cross-sectional association was attenuated after adjusting for demographic, socioeconomic, and health-related covariates (adjusted OR [AOR] = 1.16, 95% CI = 0.95-1.42). In contrast, doing arts activities was associated with 28% higher odds of reporting high social support one year later (AOR = 1.28, 95% CI = 1.03-1.59), independent of covariates and previous social support., Conclusions: Extracurricular arts activities are associated with increased odds of reporting good subsequent social support from peers. This may be because they provide opportunities for social engagement, developing friendships, and building a sense of community. Exploring these associations in more detail should be a priority, enabling better understanding of this strategy for enhancing social ties during adolescence., (© 2022. The Author(s).)

Introduction: We investigated whether changes in engagement in home-based creative activities were associated with changes in depressive symptoms, anxiety symptoms and life satisfaction during the COVID-19 pandemic, aiming to replicate findings from the UK in a USA sample., Methods: 3725 adults were included from the COVID-19 Social Study in the USA, a panel study collecting data weekly during the COVID-19 pandemic. We measured engagement in eight types of creative leisure activities on the previous weekday between April and September 2020. Data were analysed using fixed effects regression models., Results: Increased time spent gardening was associated with reductions in depressive and anxiety symptoms and enhanced life satisfaction. Spending more time doing woodwork/DIY and arts/crafts were also associated with enhanced life satisfaction. However, more time watching television, films or other similar media (not for information on COVID-19) was associated with increased depressive symptoms. Other creative activities were not associated with mental health or well-being., Conclusion: Some findings differ from evidence obtained in the UK, demonstrating the importance of replicating research across countries. Our findings should also be considered when formulating guidelines for future stay-at-home directives, enabling individuals to stay well despite the closure of public resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Arts and cultural engagement is a potential strategy for reducing or preventing reportedly antisocial or criminalized behaviors (those previously and problematically termed as "delinquent") in adolescence. However, most research to date has focused on arts-based interventions and has not tested arts and cultural engagement in large population-based longitudinal studies. This study investigated whether arts and cultural engagement reduced reportedly antisocial or criminalized behaviors in two large nationally representative cohorts, the National Longitudinal Study of Adolescent to Adult Health (n = 10,610; 50% female, 72% White, age range = 11-21 mean = 15.07) and the National Education Longitudinal Study of 1988 (n = 15,214; 50% female, 73% White, age range = 13-16 mean = 14.38). Structural equation modelling also allowed exploration of two potential mechanisms that might link arts and cultural engagement to reportedly antisocial or criminalized behaviors (self-control and attitudes towards these behaviors). More arts and cultural engagement was associated with fewer reportedly antisocial or criminalized behaviors, better self-control scores, and fewer positive perceptions of reportedly antisocial or criminalized behaviors concurrently and one to two years later. Arts and cultural engagement may provide opportunities for adolescents to realize positive developmental outcomes, reducing their risk of reportedly antisocial or criminalized behaviors., (© 2022. The Author(s).)

Background: Receptive cultural engagement (e.g. attending theaters and museums) can reduce depression in older adults. However, whether specific participatory leisure activities are associated with lower rates of depression remains unknown. We aimed to test whether engagement in a diverse range of leisure activities, all of which could involve artistic or creative elements, was associated with concurrent and subsequent depression., Methods: Using longitudinal data from 19,134 participants aged over 50 in the Health and Retirement Study, engagement in leisure activities was measured every four years, and depression every two years, between 2008 and 2016. Leisure activities included: reading books, magazines, or newspapers; writing; baking/cooking something special; making clothes, knitting, or embroidery (sewing); working on hobbies/projects; going to sport, social, or other clubs; and attending non-religious organization meetings. A score of three or more on the Center for Epidemiologic Studies Depression Scale indicated depression. We fitted population-averaged panel data models using generalized estimating equations with a logit link., Results: Engaging in some leisure activities, such as clubs, hobbies/projects, and baking/cooking was associated with reduced depression, independent of confounders. Concurrently, spending time on hobbies/projects (monthly OR = 0.80, 95% CI = 0.72-0.88; weekly OR = 0.81, 95% CI = 0.73-0.89) and clubs (monthly OR = 0.85, 95% CI = 0.77-0.94; weekly OR = 0.78, 95% CI = 0.69-0.88) was associated with lower odds of depression versus not engaging. Longitudinally, the odds of depression two years later were reduced amongst people engaging in weekly baking/cooking (OR = 0.85, 95% CI = 0.75-0.95), hobbies (OR = 0.81, 95% CI = 0.71-0.92), and clubs (OR = 0.82, 95% CI = 0.71-0.94). Writing, reading, sewing, and attending non-religious organizations were not consistently associated with depression., Conclusions: Engagement in some leisure activities is associated with reduced odds of depression. We should consider how older adults can be supported to actively participate in leisure activities as health-promoting behaviors., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

It is unclear whether links between religiosity and mental health are found in contexts outside the United States or are causal. We examined differences in mental wellbeing and associations between mental wellbeing and religiosity among the religiously unaffiliated, White and non-White Christians, Muslims of Pakistani, Bangladeshi, and other ethnicities, and other minority ethnoreligious groups. We used 4 waves of Understanding Society: the UK Household Longitudinal Study (2009-2013; n = 50,922). We adjusted for potential confounders (including socioeconomic factors and personality) and for household fixed effects to account for household-level unobserved confounding factors. Compared with those with no religious affiliation, Pakistani and Bangladeshi Muslims and members of other minority religions had worse wellbeing (as measured using the Shortened Warwick-Edinburgh Mental Wellbeing Scale and General Health Questionnaire). Higher subjective importance of religion was associated with lower wellbeing according to the General Health Questionnaire; associations were not found with the Shortened Warwick-Edinburgh Mental Wellbeing Scale. More frequent religious service attendance was associated with higher wellbeing; effect sizes were larger for those with religious affiliations. These associations were only partially attenuated by adjustment for potential confounding factors, including household fixed effects. Religious service attendance and/or its secular alternatives may have a role in improving population-wide mental wellbeing., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Engaging in the arts is a health-related behavior that may be influenced by social inequalities. While it is generally accepted that there is a social gradient in traditional arts and cultural activities, such as attending classical music performances and museums, previous studies of arts engagement in the US have not adequately investigated whether similar demographic and socioeconomic factors are related to other forms of arts engagement., Methods: Using cross-sectional data from the General Social Survey (GSS) in the US, we examined which demographic, socioeconomic, residential, and health factors were associated with attendance at arts events, participation in arts activities, membership of creative groups, and being interested in (but not attending) arts events. We combined data from 1993 to 2016 in four analytical samples with a sample size of 8684 for arts events, 4372 for arts activities, 4268 for creative groups, and 2061 for interested non-attendees. Data were analysed using logistic regression., Results: More education was associated with increased levels of all types of arts engagement. Parental education demonstrated a similar association. Being female, compared to male, was also consistently associated with higher levels of engagement. Attendance at arts events was lower in participants with lower income and social class, poorer health, and those living in less urban areas. However, these factors were not associated with participation in arts activities or creative groups or being an interested non-attendee., Conclusions: Overall, we found evidence for a social gradient in attendance at arts events, which was not as pronounced in participation in arts activities or creative groups or interest in arts events. Given the many benefits of engagement in the arts for education, health, and wider welfare, our findings demonstrate the importance of identifying factors to reduce barriers to participation in the arts across all groups in society.

Introduction: Disadvantaged socioeconomic position (SEP) in early and adult life has been repeatedly associated with premature mortality. However, it is unclear whether these inequalities differ across time, nor if they are consistent across different SEP indicators., Methods: British birth cohorts born in 1946, 1958 and 1970 were used, and multiple SEP indicators in early and adult life were examined. Deaths were identified via national statistics or notifications. Cox proportional hazard models were used to estimate associations between ridit scored SEP indicators and all-cause mortality risk-from 26 to 43 years (n=40 784), 26 to 58 years (n=35 431) and 26 to 70 years (n=5353)., Results: More disadvantaged SEP was associated with higher mortality risk-magnitudes of association were similar across cohort and each SEP indicator. For example, HRs (95% CI) from 26 to 43 years comparing lowest to highest paternal social class were 2.74 (1.02 to 7.32) in 1946c, 1.66 (1.03 to 2.69) in 1958c, and 1.94 (1.20 to 3.15) in 1970c. Paternal social class, adult social class and housing tenure were each independently associated with mortality risk., Conclusions: Socioeconomic circumstances in early and adult life show persisting associations with premature mortality from 1971 to 2016, reaffirming the need to address socioeconomic factors across life to reduce inequalities in survival to older age., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To assess whether educational differentials in three key physical activity (PA) domains vary by age, sex and ethnicity., Design: National cross-sectional survey., Setting: UK., Participants: Altogether 40 270 participants, aged 20 years and over, from the UK Household Longitudinal Study with information on education, PA and demographics collected in 2013-2015., Outcome Measures: Participation in active travel (AT), occupational activity (OA) and leisure time physical activity (LTPA) at the time of assessment., Results: Lower educational attainment was associated with higher AT and OA, but lower weekly LTPA activity; these associations were modified by sex, ethnicity and age. Education-related differences in AT were larger for women-the difference in predicted probability of activity between the highest and the lowest education groups was -10% in women (95% CI: -11.9% to 7.9%) and -3% in men (-4.8% to -0.4%). Education-related differences in OA were larger among men -35% (-36.9% to -32.4%) than women -17% (-19.4% to -15.0%). Finally, education-related differences in moderate-to-vigorous LTPA varied by ethnicity; for example, differences were 17% (16.2% to 18.7%) for white individuals compared with 6% (0.6% to 11.6%) for black individuals., Conclusions: Educational differences in PA vary by domain and are modified by age, sex and ethnicity. A better understanding of physically inactive subgroups may aid development of interventions to both increase activity levels and reduce health inequalities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Observational studies suggest childhood externalizing disorders are associated with increased smoking and earlier initiation. However, causality cannot be inferred from observational data alone. The current study uses two-sample MR to examine the causal relationship between externalizing behaviors and tobacco use. Single nucleotide polymorphisms (SNPs) associated with aggression were obtained from the Early Life Epidemiology Consortium (mean age 8), ADHD from the Integrative Psychiatric Research and Psychiatric Genomics Consortiums (age range 6-18), and tobacco initiation and age of onset from the Tobacco and Genetics Consortium. SNPs were combined using the inverse variance weighted approach, weighted median approach, and MR-Egger regression. There was no clear evidence of an effect of aggression on tobacco initiation or age of onset for childhood aggression (initiation: β -0.002, 95% CI -0.005, 0.001, P = 0.286; age: β -0.001 95% CI -0.002, 0.000, P = 0.310) or adolescent aggression (initiation: β -0.001, 95% CI -0.006, 0.003, P = 0.610; age: β 0.000, 95% CI 0.000, 0.001, P = 0.183)]. However, there was some evidence of an association of ADHD on tobacco initiation (OR 1.23, 95% CI 1.10, 1.35, P = 0.016), although no clear evidence of an effect of ADHD on age of onset (OR = 1.022, 95% CI 0.992, 1.052, P = 0.215). Our results provide some evidence that genetic risk of childhood ADHD is causally related to increased risk of tobacco initiation; however, the causal estimate is relatively small. We found no clear evidence that genetic risk of childhood aggression is causally related to the risk of tobacco initiation or age of onset., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Substance use is associated with impaired social cognition. Experimental studies have shown that acute intoxication of alcohol, tobacco, and cannabis decreases the performance in non-verbal, social communication and theory of mind tasks. However, in epidemiological studies the temporal direction of this association has gone relatively unstudied. We investigated both directions of association within an adolescent birth cohort: the association of social cognition with subsequent substance use, and the association of early substance use with subsequent social cognition. We used data from the Avon Longitudinal Study of Parents and Children, a UK birth cohort. Logistic regression indicated that poor childhood non-verbal communication was associated with decreased odds of adolescent alcohol (OR 0.70, 95% 0.54-0.91), tobacco (OR 0.62, 95% CI 0.47-0.83), and cannabis use (OR 0.62, 95% CI 0.46-0.83). Early adolescent substance use was associated with increased odds of poor social communication (alcohol: OR 1.46, 95% CI 0.99-2.14; tobacco: OR 1.95, 95% CI 1.33-2.86) and poor social reciprocity (alcohol: OR 1.57, 95% CI 1.18-2.09; tobacco: OR 1.92, 95% CI 1.43-2.58; cannabis: OR 1.54, 95% CI 1.16-2.05). Overall, the relationship between social cognition and substance use was different in each temporal direction. Poor non-verbal communication in childhood appeared protective against later substance use, while adolescent substance use was associated with decreased social cognitive performance.

The 7.5% carbon dioxide (CO2) inhalation model is used to provoke acute anxiety, for example to investigate the effects of anxiety on cognitive processes, or the efficacy of novel anxiolytic agents. However, little is known about the relationship of baseline anxiety sensitivity or trait anxiety (i.e., anxiety proneness), with an individual's response to the 7.5% CO2 challenge. We examined data from a number of 7.5% CO2 challenge studies to determine whether anxiety proneness was related to subjective or physiological response. Our findings indicate anxiety proneness is associated with greater subjective and physiological responses. However, anxiety-prone individuals also have a greater subjective response to the placebo (medical air) condition. This suggests that anxiety-prone individuals not only respond more strongly to the 7.5% CO2 challenge, but also to medical air. Implications for the design and conduct of 7.5% CO2 challenge studies are discussed., (© The Author(s) 2015.)

Background: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood., Methods and Results: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day., Conclusions: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate., (© 2015 American Heart Association, Inc.)

Objectives: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity., Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes., Participants: 148,731 current, former and never-smokers of European ancestry aged ≥ 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA)., Primary Outcome Measures: Waist and hip circumferences, and waist-hip ratio., Results: The data included up to 66,809 never-smokers, 43,009 former smokers and 38,913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele., Conclusions: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Objectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach., Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress., Participants: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA)., Primary Outcome Measures: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis., Results: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers., Conclusions: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)