Does misclassification of former tobacco smokers explain the 'smoker's paradox' in the risk of COVID-19? Insights from the Stockholm Public Health Cohort.

BACKGROUND: The association between tobacco smoking and the risk of COVID-19 and its adverse outcomes is controversial, as studies reported contrasting findings. Bias due to misclassification of the exposure in the analyses of current versus non-current smoking could be a possible explanation because former smokers may have higher background risks of the disease due to co-morbidity. The aim of the study was to investigate the extent of this potential bias by separating non-, former, and current smokers when assessing the risk or prognosis of diseases. METHODS: We analysed data from 43,400 participants in the Stockholm Public Health Cohort, Sweden, with information on smoking obtained prior to the pandemic. We estimated the risk of COVID-19, hospital admissions and death for (a) former and current smokers relative to non-smokers, (b) current smokers relative to non-current smokers, that is, including former smokers; adjusting for potential confounders (aRR). RESULTS: The aRR of a COVID-19 diagnosis was elevated for former smokers compared with non-smokers (1.07; 95% confidence interval (CI) =1.00-1.15); including hospital admission with any COVID-19 diagnosis (aRR= 1.23; 95% CI = 1.03-1.48); or with COVID-19 as the main diagnosis (aRR=1.23, 95% CI= 1.01-1.49); and death within 30 days with COVID-19 as the main or a contributory cause (aRR=1.40; 95% CI=1.00-1.95). Current smoking was negatively associated with risk of COVID-19 (aRR=0.79; 95% CI=0.68-0.91). CONCLUSIONS: Separating non-smokers from former smokers when assessing the disease risk or prognosis is essential to avoid bias. However, the negative association between current smoking and the risk of COVID-19 could not be entirely explained by misclassification.

Prevalence of cannabis use among young adults in Sweden comparing randomized response technique with a traditional survey.

BACKGROUND AND AIMS: The prevalence of cannabis use based on self-reports is likely to be underestimated in population surveys, especially in contexts where its use is a criminal offence. Indirect survey methods ask sensitive questions ensuring that answers cannot be identified with an individual respondent, therefore potentially resulting in more reliable estimates. We aimed to measure whether the indirect survey method 'randomized response technique' (RRT) increased response rate and/or increased disclosure of cannabis use among young adults compared with a traditional survey. DESIGN: We conducted two parallel nation-wide surveys during the spring and the summer of 2021. The first survey was a traditional questionnaire-based one (focusing on substance use and gambling). The second survey applied an indirect survey method known as 'the cross-wise model' to questions related to cannabis use. The two surveys employed identical procedures (e.g. invitations, reminders and wording of the questions) SETTING AND PARTICIPANTS: The participants were young adults (aged 18-29 years) living in Sweden. The traditional survey had 1200 respondents (56.9% women) and the indirect survey had 2951 respondents (53.6% women). MEASUREMENTS: In both surveys, cannabis use was assessed according to three time-frames: life-time use; use during the past year; and use during the past 30 days. FINDINGS: The estimated prevalence of cannabis use was two- to threefold higher on all measures when estimated using the indirect survey method compared with the traditional survey: use during life-time (43.2 versus 27.3%); during the past year (19.2 versus 10.4%); and during the past 30 days (13.2 versus 3.7%). The discrepancy was larger among males and individuals with an education shorter than 10 years, who were unemployed, and who were born in non-European countries. CONCLUSIONS: Indirect survey methods may provide more accurate estimates than traditional surveys on prevalence of self-reported cannabis use.

A weighted blanket increases pre-sleep salivary concentrations of melatonin in young, healthy adults.

Weighted blankets have emerged as a potential non-pharmacological intervention to ease conditions such as insomnia and anxiety. Despite a lack of experimental evidence, these alleged effects are frequently attributed to a reduced activity of the endogenous stress systems and an increased release of hormones such as oxytocin and melatonin. Thus, the aim of the present in-laboratory crossover study (26 young and healthy participants, including 15 men and 11 women) was to investigate if using a weighted blanket (~12% of body weight) at bedtime resulted in higher salivary concentrations of melatonin and oxytocin compared with a light blanket (~2.4% of body weight). We also examined possible differences in salivary concentrations of the stress hormone cortisol, salivary alpha-amylase activity (as an indicative metric of sympathetic nervous system activity), subjective sleepiness, and sleep duration. When using a weighted blanket, the 1 hour increase of salivary melatonin from baseline (i.e., 22:00) to lights off (i.e., 23:00) was about 32% higher (p = 0.011). No other significant differences were found between the blanket conditions, including subjective sleepiness and total sleep duration. Our study is the first to suggest that using a weighted blanket may result in a more significant release of melatonin at bedtime. Future studies should investigate whether the stimulatory effect on melatonin secretion is observed on a nightly basis when frequently using a weighted blanket over weeks to months. It remains to be determined whether the observed increase in melatonin may be therapeutically relevant for the previously described effects of the weighted blanket on insomnia and anxiety.

Country differences in the cross-sectional associations between smoking and depressive symptoms in adolescence.

BACKGROUND: The aim of the present study was to compare the cross-sectional association between smoking and depressive symptoms among adolescents between Sweden and Italy, two countries historically characterized by different norms about tobacco use and different tobacco control efforts. METHODS: A cross-sectional study including 3283 adolescents 15-16 years of age participating in the Swedish KUPOL study and 1947 same-age adolescents from the Italian BE-TEEN study. Current smoking was defined as any smoking in the past 30 days. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and the internalizing score of the Strengths and Difficulties Questionnaire (SDQ). Country differences were explored in stratified and interaction analyses. RESULTS: Current smoking was associated with a 2- to 3-fold increased odds of depressive symptoms among Swedish adolescents using both CES-DC and SDQ internalizing scale. Among Italian adolescents, slightly lower increased odds of 1.5-2.5 for depressive symptoms with smoking were found using the CES-DC but not the SDQ scale. Both multiplicative and additive interactions for country were significant. The association between smoking and depressive symptoms was weaker among Italian compared with Swedish adolescents for both scores. CONCLUSIONS: Countries with different tobacco norms and control show different associations between smoking and depressive symptoms in adolescence, probably due to different psychosocial profiles of smokers. These findings need to be considered when planning tobacco prevention programmes, e.g. by focusing on early detection of mental health distress among adolescents in settings with declining smoking prevalence and restrictive tobacco control environments.

Compositional characteristics of neighbourhoods and of schools as correlates of youths' mental health: A cross-sectional study among Swedish adolescents.

AIMS: The study aimed to analyse the association between neighbourhood- and school-level socio-demographic factors and self-reported mental health among adolescents. METHODS: The study population consisted of 3959 adolescents in southern and central Sweden (the KUPOL study), surveyed in the seventh grade (13 years old) and again in the ninth grade (15 years old). Cross-sectional associations were studied between socio-demographic indicators at neighbourhood level (proportion of adults with high education, without employment, of foreign-born residents) and at school level (proportion of students with at least one parent with high education, of students with a foreign background, mean qualification points in ninth grade) and mental health problems. These were assessed through the Strengths and Difficulties Questionnaire (SDQ). We derived odds ratios (OR) and corresponding 95% confidence intervals (CI) of scale scores above the threshold using multilevel logistic regression models. RESULTS: After adjustment for individual- and family-level socio-demographic factors, there was an indication of higher OR of mental health problems with increasing proportions of foreign-born and residents without employment, especially among girls and in public schools. Stronger associations in the expected direction were found with the internalising subscale. Socio-demographic factors at the school level were not associated with adolescents' mental health, except in private schools, where increasing proportions of students with highly educated parents were significantly associated with SDQ scores under the threshold (OR=0.91; 95% CI 0.85-0.97). CONCLUSIONS: The results indicate that equal living conditions may represent important cues to improve the mental health of adolescents. Longitudinal studies are needed to determine any causality.

Randomised controlled study of two counselling models at the Swedish alcohol helpline: Effectiveness and sustainability outcomes at 12-month follow-up.

Aim: This two-arm parallel randomised controlled trial explored the effectiveness of a brief counselling model compared with the usual multi-session counselling at an alcohol telephone helpline. Methods: A total of 320 callers who contacted the Swedish Alcohol Helpline (SAH) because of hazardous or harmful alcohol use were randomised to either brief structured intervention (self-help booklet plus one proactive call) or usual care (multi-session telephone counselling). The primary outcome was a downward shift in risk level at 12-month follow-up compared with baseline, based on self-reports. Sustained risk level reduction throughout the whole follow-up was also assessed as secondary outcome. Results: Both interventions were significantly associated with a shift to a lower level of risky alcohol use (75% among participants in the brief structured intervention, and 70% in the usual care group) after 12 months. There was no difference between the two interventions in the proportions changing alcohol use or sustaining risk level reduction. Conclusion: In the context of telephone helplines, minimal and extended interventions appear to be equally effective in promoting long-term change in alcohol use.

What works to improve school lunch nutritional quality - legislation or self-audit?

OBJECTIVE: Sweden updated its legislation on universal free school meals in 2011 and nutrition was explicitly mentioned. This study i) describes cross-sectional changes in school lunch nutritional quality during the following eight years, and ii) examines if repeated self-auditing, using a fully automated, online tool (School Food Sweden), based on the implementation strategy of audit and feedback, was associated with improvements. DESIGN: Both repeated cross-sectional and longitudinal design. Factors associated with meeting nutritional criteria were examined using variance weighted least squares regression and logistic regression. SETTING: Sweden. PARTICIPANTS: Primary schools who self-selected to audit meal quality between March 2012 and July 2019. RESULTS: Almost half of all (ca 4800) primary schools signed up to use the tool, and 1500 audited nutritional quality at least once. Repeated cross-sectional analyses showed the proportion meeting the nutritional criteria increased significantly between 2012/13 (11%) and 2018/19 (34%). Longitudinally, each additional audit completed increased the odds of meeting the nutritional criteria by 1.30 (CI 1.20-1.41), controlling for region and time elapsed since the legislative change. In 774 schools with repeat audits, both number of audits and frequency of accessing feedback predicted meeting the nutritional criteria (OR 2.02, CI 1.23-3.31), even after adjusting for time since the legislative change and days elapsed since previous audit. CONCLUSIONS: Both legislation and self-audit with automatic feedback appear effective in helping schools to improve school meal quality. Self-audit with feedback may be an effective complement to legislation, or a promising alternative in settings where regulation is not an option.

DNA methylation of the glucocorticoid receptor gene predicts substance use in adolescence: longitudinal data from over 1000 young individuals.

Early life stress has been linked to increased methylation of the Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) gene, which codes for the glucocorticoid receptor. Moreover, early life stress has been associated with substance use initiation at a younger age, a risk factor for developing substance use disorders. However, no studies to date have investigated whether NR3C1 methylation can predict substance use in young individuals. This study included adolescents 13-14 years of age that reported no history of substance use at baseline, (N = 1041; males = 46%). Participants contributed saliva DNA samples and were followed in middle adolescence as part of KUPOL, a prospective cohort study of 7th-grade students in Sweden. Outcome variables were self-reports of (i) recent use, (ii) lifetime use, and (iii) use duration of (a) alcohol, (b) tobacco products, (c) cannabis, or (d) any substance. Outcomes were measured annually for three consecutive years. The predictor variable was DNA methylation at the exon 1 F locus of NR3C1. Risk and rate ratios were calculated as measures of association, with or without adjustment for internalizing symptoms and parental psychiatric disorders. For a subset of individuals (N = 320), there were also morning and afternoon salivary cortisol measurements available that were analyzed in relation to NR3C1 methylation levels. Baseline NR3C1 hypermethylation associated with future self-reports of recent use and use duration of any substance, before and after adjustment for potential confounders. The overall estimates were attenuated when considering lifetime use. Sex-stratified analyses revealed the strongest association for cigarette use in males. Cortisol analyses revealed associations between NR3C1 methylation and morning cortisol levels. Findings from this study suggest that saliva NR3C1 hypermethylation can predict substance use in middle adolescence. Additional longitudinal studies are warranted to confirm these findings.

No association of cigarette smoking and depressive symptoms with cortisol concentration in adolescents. Results from a population-based Swedish cohort.

Several studies have shown that smoking increases the risk of depressive symptoms, and suggested a possible role of the hypothalamic-pituitary-adrenal axis in the smoking-depression pathway. This study aimed to assess if smokers have higher cortisol levels than non-smokers, and if higher cortisol levels are associated with depressive symptoms. Saliva samples were collected from a subgroup of 409 participants at enrolment (13-14 years old) and two years later (15-16 years old). First, we examined the association between smoking phenotypes and cortisol concentration. Second, we evaluated whether these associations differed between adolescents with and without depressive symptoms. The mean difference between smokers and non-smokers in cortisol concentrations was close to zero at both time points. For instance, the adjusted mean difference for morning cortisol concentration between current and non-current smokers was 0.000 µg/dl [95% CI -0.055, 0.056]. In addition, there were no differences in cortisol concentration at the second time-point between those who had smoked and those who did not during the two previous years. Moreover, cortisol levels were not associated with depressive symptoms. The hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis might be involved in the association between smoking behavior and depressive symptoms during adolescence was not supported by this data.

The Importance of Pedagogical and Social School Climate to Bullying: A Cross-Sectional Multilevel Study of 94 Swedish Schools.

BACKGROUND: Bullying is a public health issue with long-term effects for victims. This study investigated if there was an association between pedagogical and social school climate and student-reported bullying victimization, which dimensions of pedagogical and social school climate were associated with bullying, and if these associations were modified by individual-level social factors. METHODS: The study had a cross-sectional multilevel design with individual-level data on bullying from 3311 students nested in 94 schools over 3 consecutive school years. School climate was measured with student and teacher questionnaires, aggregated at the school level. The association between school climate and bullying victimization was estimated with multilevel mixed-model logistic regression. RESULTS: In schools with the most favorable school climate, fewer students reported being bullied. This was especially evident when school climate was measured with the student instrument. Students in schools with favorable climate had an adjusted odds ratio of bullying of 0.74 (95% CI: 0.55-1.00) compared to students in schools with the worst climate. Results from the teacher instrument were in the same direction, but less consistent. CONCLUSIONS: Improvement in school climate has the potential to affect students both academically, and socially, as well as decrease the prevalence of bullying.

Social Media and Mental Health Among Early Adolescents in Sweden: A Longitudinal Study With 2-Year Follow-Up (KUPOL Study).

PURPOSE: The aim of this study is to assess the longitudinal associations between the frequency of social media use and symptoms of mental ill-health among Swedish adolescents. METHODS: Data came from KUPOL, a Swedish school-based longitudinal cohort accrued in 101 participating schools in 8 regions of Sweden. The study sample consisted of 3,501 adolescents in grade 8 (14-15 years, 51.5%, n = 1,765 girls) followed for 2 consecutive years. Daily social media use was measured as weighted average of self-reported use in weekdays and weekend days. Mental health was measured with the Strength and Difficulties Questionnaire (SDQ). A Random-Intercept Cross-Lagged Panel Model was applied to distinguish between-person from within-person associations between social media use and symptoms of mental ill-health. RESULTS: Median SDQ score at baseline was 9 (interquartile range [IQR] 6-14). Median social media use was 1.7 hours at baseline (interquartile range .6-3.0) and increased over the 3-year period. Adolescents with more social media use also reported higher SDQ scores, B (95% confidence interval [CI]) = 2.40 (2.03-2.77). On a within-person level, no cross-lagged associations were found between changes in social media use and subsequent changes in symptoms of mental ill-health after 1 year, B (95% CI) = .02 (-.12 to .16) or vice versa B (95% CI) = .00 (-.02 to .02). Weak cross-sectional associations were found between changes in social media use and concurrent changes in symptoms of mental ill-health, B (95% CI) = .24 (.00-.48). CONCLUSIONS: Adolescents with higher use of social media report more symptoms of mental health problems, but there is no evidence for a longitudinal association between increased use and mental health problems. This suggests that social media may be rather an indicator than a risk factor for symptoms of mental ill-health.

Cortisol Concentration as Predictor of Tobacco Initiation in Adolescents: Results From a Population-Based Swedish Cohort.

PURPOSE: Stress potentiates the smoking reward, decreases the ability to resist smoking, and increases the risk of smoking relapse in adulthood. This study aimed to clarify if salivary cortisol, as an indicator of stress, may be prospectively associated with the onset and phenotype of tobacco use in adolescents. METHODS: This study was based on a cohort of Swedish adolescents, among whom saliva specimens were collected from a nested sample. We included adolescents with salivary cortisol measurements and without a history of tobacco use (n = 381, aged 13-14 years). Quartiles of morning and afternoon cortisol concentration and cortisol area under the curve were considered as predictors. We categorized tobacco use according to the product mainly used: cigarette smoking, snus use, or either type of tobacco. For each product use, two outcomes were considered: initiation and duration of use. Poisson regression models were used to calculate rate ratios. RESULTS: A quartile increase in morning cortisol levels and cortisol area under the curve was consistently associated with a 1.2- to 1.4-fold increased risk of initiation of cigarette smoking snus use, or any tobacco use. Similar results were obtained examining the dose-response relationship and using the duration of use as outcome. No associations were apparent between afternoon cortisol concentration and any of the outcomes. All associations were similar between sexes. CONCLUSIONS: Morning cortisol concentration, an indicator of hypothalamic-pituitary-adrenal axis activation, is prospectively associated with tobacco use in adolescents. Whether this activation indicates the cumulative effect of stressors during the life course remains to be elucidated.

School climate and mental health among Swedish adolescents: a multilevel longitudinal study.

BACKGROUND: School is one of the most formative institutions for adolescents' development, but whether school environment affects mental health is uncertain. We investigated the association between the school's pedagogical and social climate and individual-level mental health in adolescence. METHODS: We studied 3416 adolescents from 94 schools involved in KUPOL, a longitudinal study conducted in eight regions in Sweden. School climate was reported by the school's teaching personnel and by the final year students using the teacher and the student versions of the Pedagogical and Social Climate Questionnaire, respectively. Index persons' mental health was assessed with the Center for Epidemiological Studies Depression Scale for Children and the Strengths and Difficulties Questionnaire. We performed multilevel logistic regression models adjusted for individual, familial and school-level confounders measured in grade 7 and exposure and outcome measured in grades 8 and 9. RESULTS: The adjusted odds ratios and 95% confidence intervals comparing the middle and the high to the lowest tertile of the total teacher school climate score were 1.47 (1.10-1.97) and 1.52 (1.11-2.09) for depressive symptoms and 1.50 (1.08-2.08) and 1.64 (1.16-2.33) for the total strengths and difficulties score. In contrast, there was no association between total student school climate score and mental health. CONCLUSIONS: We found that teacher-, but not student-rated school climate was associated with an increased risk of poor mental health at the student level; the association was most pronounced for internalizing problems. Given schools' importance for adolescents' development, further studies are needed to clarify the mechanisms underlying the observed association.

NR3C1 hypermethylation in depressed and bullied adolescents.

The disruption of key epigenetic processes during critical periods of brain development can increase an individual's vulnerability to psychopathology later in life. For instance, DNA methylation in the glucocorticoid receptor gene (NR3C1) in adulthood is known to be associated with early-life adversities and has been suggested to mediate the development of stress-related disorders. However, the association between NR3C1 methylation and the emergence of internalizing symptoms in childhood and adolescence has not been studied extensively. In the present report, we used saliva DNA from a cohort of Swedish adolescents (13-14 years old; N = 1149) to measure NR3C1 methylation in the exon 1F region. Internalizing psychopathological symptoms were assessed using the Center for Epidemiologic Studies Depression Scale for Children (CES-DC). We found that NR3C1 hypermethylation was cross-sectionally associated with high score for internalizing symptoms in the whole group as well as among the female participants. In addition, an analysis of social environmental stressors revealed that reports of bullied or lacking friends were significantly associated with NR3C1 hypermethylation. This cross-sectional association of NR3C1 exon 1F hypermethylation with internalizing psychopathology in adolescents, as well as with bullying and lack of friends are novel results in this field. Longitudinal studies are needed to address whether NR3C1 methylation mediates the link between social stressors and psychopathology in adolescence.