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The perceived reduced formation of harmful chemicals (RF) or perceived reduced risk of harm (RH) of a smoke-free tobacco product relative to combustible tobacco products may influence its acceptance and use patterns among adult smokers and therefore impact public health. We analyzed whether and how the RF and/or RH of the heated tobacco product (HTP) IQOS™ impacted "exclusive" (100%) IQOS™ use in Japan, Italy, Germany, and Russia. Between 2016 and 2020, adult participants from longitudinal IQOS™ user cohorts in Japan (N = 6257), Italy (N = 8137), Germany (N = 8474), and Russia (N = 7231) repeatedly indicated the reasons for using IQOS™, including reasons referring to RF and RH, during their first 48 weeks in the cohort. Logistic and Cox regression were used to analyze the relationships between RF and/or RH indications for using IQOS™ and exclusive or stable exclusive IQOS™ use. At week 48, exclusive IQOS™ use in Japan (odds ratio [OR] = 1.89), Italy (OR = 3.35), Germany (OR = 3.48), and Russia (OR = 3.05) was more likely among participants who more frequently (highest vs. lowest category of number of RF and/or RH indications) indicated RF and/or RH as a reason for using IQOS™. In Japan, where other HTPs were also marketed, this was also true for the overall HTP category. Also, in Japan where RF and RH could be indicated separately as reasons for using IQOS™, indicating RH (OR = 2.92) compared to RF (OR = 1.81) resulted in a greater likelihood of exclusive IQOS™ use within the highest category of RF or RH indications. In Japan (hazard ratio [HR] = 0.74), Italy (HR = 0.80), Germany (HR = 0.72), and Russia (HR = 0.85), IQOS™ users who indicated RF and/or RH as a reason for using IQOS™ had a lower risk of becoming a stable nonexclusive than stable exclusive IQOS™ user as well as a 10–25% lower number of weeks until reaching stable exclusive IQOS™ use. Perceived reduced formation of harmful chemicals (RF) or perceived reduced risk of harm (RH) of IQOS™ have a significant impact on IQOS™ users' switching to exclusive IQOS™ use and the acceleration of stable exclusive IQOS™ use. This may also be true for the overall HTP category. Moreover, perceived RH of IQOS™ seems to be a stronger driver for exclusive IQOS™ use than perceived RF. [Contrib. Tob. Nicotine Res. 32 (2023) 50–64] [ABSTRACT FROM AUTHOR]

Objectives: Examine the prevalence of cognitive impairment within Wave 1 of the Irish Longitudinal Study on Aging (TILDA) cohort and its relationship with comorbidities and lifestyle factors. The effect of cognitive impairment on quality-of-life scores was also investigated. Methods: A secondary cross-sectional analysis of data from Wave 1 of the TILDA cohort was undertaken. Results: Prevalence of cognitive impairment ranged between 5.8% and 51.2%, depending on the instrument used (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA], respectively). Having hypertension (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.36–2.08), being a past or current smoker (OR 1.25; 95% CI 1.01–1.55) and having low physical activity (OR 2.04; 95% CI 1.64–2.53) increased the odds of being classified as cognitively impaired (MMSE <25). Similarly, being obese (OR 1.31; 95% CI 1.17–1.47), having hypertension (OR 1.42; 95% CI 1.27–1.57), and having diabetes (OR 1.71; 95% CI 1.40–2.09) increased the odds of cognitive impairment (MoCA <26). High cholesterol was associated with a protective effect (OR 0.79; 95% CI 0.63–0.98) under MMSE <25 classification while, problematic alcohol behavior reduced the odds of being classified as cognitively impaired using MoCA <26 by 35% (OR 0.65; 95% CI 0.55–0.76). Depression was not associated with increased odds of cognitive decline. Lastly, mean quality of life (QoL) scores decreases as severity of cognitive impairment increases from normal to moderate cognitive impairment (P < 0.001). Conclusions: Several modifiable risk factors for cognitive decline were identified, including smoking, low physical activity, hypertension, diabetes, and obesity. Policies aimed at reducing the prevalence of these risk factors in the population might reduce the impact of cognitive decline on public health. [ABSTRACT FROM AUTHOR]

Background: An ongoing outbreak of lung injury associated with e-cigarettes or vaping (also known as E-VALI or VALI) started in March, 2019, in the USA. The cause, diagnosis, treatment, and course of this disease remains unknown.Methods: In this multicentre, prospective, observational, cohort study, we collected data on all patients with lung injury associated with e-cigarettes or vaping seen in Intermountain Healthcare, an integrated health system based in Utah, USA, between June 27 and Oct 4, 2019. Telecritical care, based in Salt Lake City, UT, USA, was used as the central repository for case validation, public reporting, and system-wide dissemination of expertise, which included a proposed diagnosis and treatment guideline for lung injury associated with e-cigarettes or vaping. We extracted data on patient presentation, treatment, and short-term follow-up (2 weeks after discharge) from chart review and interviews with patients undertaken by the Utah Department of Health (Salt Lake City, UT, USA).Findings: 60 patients presented with lung injury associated with e-cigarettes or vaping at 13 hospitals or outpatient clinics in the integrated health system. 33 (55%) of 60 were admitted to an intensive care unit (ICU). 53 (88%) of 60 patients presented with constitutional symptoms, 59 (98%) with respiratory symptoms, and 54 (90%) with gastrointestinal symptoms. 54 (90%) of 60 were given antibiotics and 57 (95%) were given steroids. Six (10%) of 60 patients were readmitted to an ICU or hospital within 2 weeks, three (50%) of whom had relapsed with vaping or e-cigarette use. Of 26 patients who were followed up within 2 weeks, despite clinical and radiographic improvement in all, many had residual abnormalities on chest radiographs (ten [67%] of 15) and pulmonary function tests (six [67%] of nine). Two patients died and lung injury associated with e-cigarettes or vaping was thought to be a contributing factor, but not the cause of death, for both.Interpretation: Lung injury associated with e-cigarettes or vaping is an emerging illness associated with severe lung injury and constitutional and gastrointestinal symptoms. Increased awareness has led to identification of a broad spectrum of severity of illness in patients who were treated with antibiotics and steroids. Despite improvement, at short-term follow-up many patients had residual abnormalities. Lung injury associated with e-cigarettes or vaping remains a clinical diagnosis with symptoms that overlap infectious and other lung diseases. Maintaining a high index of suspicion for this disease is important as work continues in understanding the cause or causes, optimal therapy, and long-term outcomes of these patients.Funding: Intermountain Healthcare. [ABSTRACT FROM AUTHOR]

Background and aims: The long‐term population health impact of nicotine vaping products (NVPs) use among smokers is unknown, and subject to a range of plausible assumptions about the use and health consequences of NVPs. While NVPs use may substitute for cigarette smoking and thereby aid in quitting cigarette use, it is also possible that smokers who would have otherwise quit would instead delay quitting cigarettes. We aimed to develop a cohort‐specific simulation model of the impact of NVPs on smoking cessation by adult smokers and resulting premature deaths (PD) and life years lost (LYL). Design A cohort‐specific simulation model of the impact of NVPs on smoking cessation by adult smokers and resulting premature deaths (PD) and life years lost (LYL) was developed by gender for two birth cohorts, aged 30 and 50 years in 2012. Extensive sensitivity analyses were conducted. Setting: United States. Participants: Smokers in two birth cohorts, aged 30 and 50 years in 2012. Measurements Data were from the 1965–2012 National Health Interview Surveys and the 2014/15 Tobacco Use Supplement of the Current Population Survey. The model incorporated a range of plausible assumptions from published literature about transition rates from regular smoking to exclusive NVP and dual use, from dual use to exclusive NVP use and from exclusive NVP use to no use. Findings Compared with the no‐NVP scenario, the male (female) model projected 17.8% (19.3%) fewer PDs and 22.9% (26.6%) fewer LYL for the 1982 cohort and 5.4% (7.3%) fewer PDs and 7.9% (11.4%) fewer LYL for the 1962 cohort. These gains were sensitive to NVP use over time, age of initial NVP use, transitions from smoking to dual, exclusive NVP and no use and relative NVP mortality risks. Conclusions: Nicotine vaping product (NVP) use in the United States is projected to have a net positive impact on population health over a wide range of plausible levels of NVP use, transitions to dual, exclusive NVP and no use and NVP risks. However, net impact is sensitive to parameter estimates. [ABSTRACT FROM AUTHOR]

Background Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring. Methods A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999–2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. Results The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5–2.9; p  < 0.001; Kaplan-Meier log-rank test p  < 0.001). Conclusion Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring. [ABSTRACT FROM AUTHOR]

While smoking is the primary cause of lung cancer, only 11–24% of smokers develop the malignancy over their lifetime. The primary addictive agent in tobacco smoke is nicotine and variation in nicotine metabolism may influence the smoking levels of an individual. Therefore, inter-individual variation in lung cancer risk among smokers may be due in part to differences in the activity of enzymes involved in nicotine metabolism. In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes. We prospectively evaluated the association of urinary biomarkers of nicotine uptake (total nicotine equivalents [TNE]) and CYP2A6 activity (ratio of urinary total trans-3′-hydroxycotinine to cotinine) with lung cancer risk among 2,309 Multiethnic Cohort Study participants who were current smokers at time of urine collection; 92 cases were diagnosed during a mean follow-up of 9.5 years. We found that higher CYP2A6 activity and TNE was associated with increased lung cancer risk after adjusting for age, sex, race/ethnicity, body mass index, smoking duration, and urinary creatinine (p’s = 0.002). The association for CYP2A6 activity remained even after adjusting for self-reported cigarettes per day (CPD) (Hazard Ratio [HR] per unit increase in log-CYP2A6 activity = 1.52; p = 0.005) and after adjusting for TNE (HR = 1.46; p = 0.01). In contrast, the association between TNE and lung cancer risk was of borderline statistical significance when adjusted for CPD (HR = 1.53; p = 0.06) and not statistically significant when further adjusted for CYP2A6 activity (HR = 1.30; p = 0.22). These findings suggest that CYP2A6 activity provides information on lung cancer risk that is not captured by smoking history or a (short-term) biomarker of dose. CYP2A6 activity should be further studied as a risk biomarker for smoking-related lung cancer. [ABSTRACT FROM AUTHOR]

Introduction: Media presentations of e-cigarettes may affect perception of the devices which may influence use.Objectives: To assess in a cohort of past-year smokers (1) if perceived harm of e-cigarettes relative to cigarettes changed over time, (2) predictors of perceived relative harm, (3) if perceived relative harm predicted subsequent e-cigarette use among never-users.Methods: Longitudinal web-based survey of a general population sample of British smokers and ex-smokers, waves in 2012 (n=4553), 2013 and 2014 (44%, 31% response rate, respectively). Changes over time were assessed using Friedman and McNemar tests, n=1204. Perceived relative harm at wave 3 was regressed onto perceived relative harm at waves 1 and 2, while adjusting for socio-demographics and change in smoking and e-cigarette status, n=1204. Wave 2 e-cigarette use among 1588 wave 1 never-users was regressed onto wave 1 socio-demographics, smoking status and perceived relative harm.Results: Perceived relative harm changed (χ(2)=20.67, p<0.001); the proportion perceiving e-cigarettes to be less harmful than cigarettes decreased from 2013 to 2014 (χ(2)=16.55, p<0.001). Previous perception of e-cigarettes as less harmful, having tried e-cigarettes and having stopped smoking between waves predicted perceiving e-cigarettes as less harmful than cigarettes. Perceiving e-cigarettes to be less harmful than cigarettes predicted subsequent use, adjusting for other characteristics (OR=1.39; 95% CI: 1.08-1.80, p=0.011).Conclusion: Among a cohort of smokers and ex-smokers, accurately perceiving e-cigarettes as less harmful than smoking predicted subsequent e-cigarette use in never-users; this perception declined over time. Clear information on the relative harm of cigarettes and e-cigarettes is needed. [ABSTRACT FROM AUTHOR]

Objective Animal studies and human studies in small selected populations have shown a positive association between nicotine smoking and resting energy expenditure (REE), but data in large cohorts are lacking. We aimed to investigate the association between smoking behavior and REE in a large, population-based study. Design Population-based cross-sectional study. Methods In this cross-sectional analysis of baseline measurements from the Netherlands Epidemiology of Obesity (NEO) study (n = 6673), we included participants with REE measurement by indirect calorimetry who were not using lipid or glucose lowering drugs (n = 1189). We used linear regression analysis to examine the association of smoking status (never, former, occasional, current smoker) and smoking quantity (pack years) with REE per kilogram (kg) fat free mass (FFM) and with REE adjusted for FFM. Models were adjusted for age, sex, ethnicity, educational level, physical activity, energy intake and body mass index (BMI). Results Mean (standard deviation, SD) age was 55.2 (5.9) years and BMI was 26.3 (4.4) kg/m 2 . 60% of the participants were women. Mean (SD) REE/FFM (kcal/day/kg FFM) was for male never smokers 25.1 (2.0), male current smokers 26.4 (2.8), female never smokers 28.9 (2.5) and female current smokers 30.1 (3.7). After adjustment, only current smokers had a higher REE/FFM (mean difference 1.28, 95% CI 0.64, 1.92), and a higher REE adjusted for FFM (mean difference 60.3 kcal/day, 95% CI 29.1, 91.5), compared with never smokers. There was no association between pack years and REE/FFM (mean difference − 0.01, 95% CI − 0.06, 0.04) or REE adjusted for FFM (mean difference 0.2, 95% CI − 2.4, 2.8) in current smokers. Conclusion Current smoking is associated with a higher resting energy expenditure compared with never smoking in a large population-based cohort. [ABSTRACT FROM AUTHOR]

The Loeber Risk Score (LRS) was developed to predict early-onset cannabis use in adolescence from late childhood, facilitating early identification. However, the LRS was developed in non-representative historical samples, leaving uncertain its generalizability to children/adolescents across the U.S. today. We externally validated the LRS in a diverse, nationwide cohort (N = 4,898) weighted to the composition of the U.S. Census. Participants in 20 cities completed assessments when youth were approximately 5, 9, and 15 years old. Parents completed the LRS at the age ∼5 and ∼9 interviews. At the age ∼15 interview, youth reported on the onset of alcohol/drug use before age 15, monthly drinking/binge drinking at ages 14-16, and use of cannabis multiple times per month at ages 14-16. First, we validated the LRS measured at age ∼9. Area under the receiver operating curve was 0.62 for onset of cannabis use before age 15, 0.68 for onset of cigarette use before age 15, and 0.62 for use of cannabis multiple times per month at ages 14-16. For drinking outcomes, LRS performance could not be distinguished from chance prediction. The recommended screening cutoff of LRS ≥ 2 identified 24% of children, among whom early-onset cannabis/cigarette use outcomes occurred 1.4-2.2 times more frequently than the general population. The LRS' performance did not vary significantly by sex, race, or ethnicity. When the LRS was measured at age ∼5, AUROC was significantly lower for some outcomes. Together, findings support the LRS measure as a potential tool for identifying children in early or late childhood at risk of early-onset drug use in adolescence. [ABSTRACT FROM AUTHOR]

Abstract: Background: Contingency management (CM) is an efficacious intervention for reducing cigarette smoking. However, CM is rarely adopted as a smoking cessation treatment in the community. This study analyzed the effectiveness of a CM procedure in combination with a cognitive-behavioral treatment (CBT) for smoking cessation among treatment-seeking patients from the general population. Methods: A total of 92 patients were randomly assigned to one of two treatment conditions: CBT (N =49) or CBT+CM (N =43). The CM procedure included a voucher program through which nicotine abstinence was reinforced on a schedule of escalating magnitude of reinforcement with a reset contingency. Self-reported smoking status was confirmed with both carbon monoxide (CO) level in expired air and cotinine levels in urine. Results: Of the patients who received CBT+CM 97.7%, completed 6 weeks of treatment, versus 81.6% of those who received CBT (p =.03). At the post-treatment assessment, 95.3% of the patients assigned to the CBT+CM condition achieved abstinence in comparison to the 59.2% in the CBT group (p =.000). At the one-month follow-up, 72.1% of the patients who received CBT+CM maintained smoking abstinence, versus 34.7% in the CBT group (p =.001). At the six-month follow-up, 51.2% of the patients who received CBT+CM maintained smoking abstinence in comparison to the 28.6% in the CBT group (p =.04). Conclusions: Results from this randomized clinical trial showed that adding CM to a CBT is effective, and is feasible as an intervention approach with treatment-seeking patients in a community setting. [Copyright &y& Elsevier]

The objectives of this study were to: (i) to develop questionnaires that can identify never-smoking children and adults experiencing increased exposure to secondhand smoke (SHS+), (ii) to determine their validity against hair nicotine, and (iii) assess their reliability. A sample of 191 children (85 males; 106 females; 7–18 years) and 95 adult (23 males; 72 females; 18–62 years) never-smokers consented to hair nicotine analysis and answered a large number of questions assessing all sources of SHS. A randomly-selected 30% answered the questions again after 20–30 days. Prevalence of SHS+ in children and adults was 0.52±0.07 and 0.67±0.10, respectively (p<0.05). The Smoke Scale for Children (SS-C) and the Smoke Scale for Adults (SS-A) were developed via factor analysis and included nine questions each. Positivity criteria for SS-C and SS-A via receiver operating characteristics curve analysis were identified at >16.5 and >16, respectively. Significant Kappa agreement (p<0.05) was confirmed when comparing the SS-C and SS-A to hair nicotine concentration. Reliability analyses demonstrated that the SS-C and SS-A scores obtained on two different days are highly correlated (p<0.001) and not significantly different (p>0.05). Area under the curve and McNemar's Chi-square showed no pair-wise differences in sensitivity and specificity at the cutoff point between the two different days for SS-C and SS-A (p>0.05). We conclude that the SS-C and the SS-A represent valid, reliable, practical, and inexpensive instruments to identify children and adult never-smokers exposed to increased SHS. Future research should aim to further increase the validity of the two questionnaires. [ABSTRACT FROM AUTHOR]

Objective: To determine if maternal use of snuff (containing high levels of nicotine, low levels of nitrosamines and no combustion products) is associated with an increased risk of oral cleft malformations in the infant and whether cessation of snuff use or smoking before the antenatal booking influences the risk. Method: A population-based cohort study was conducted on all live born infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic regression analyses (using adjusted odds ratios, with 95% confidence intervals [CI]). Results: Among 975 866 infants that had information on maternal tobacco use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who used snuff or smoked three months prior pregnancy stopped using before the antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users, the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who continued to use snuff or to smoke were 1.48 [1.00–2.21] and 1.19 [1.01–1.41], respectively. In contrast, in infants of mothers who stopped using snuff or stopped smoking before the antenatal booking, the corresponding risks were not increased (adjusted odds ratios [95% CI] were 0.71 [0.44–1.14] and 0.88 [0.73–1.05], respectively). Conclusion: Maternal snuff use or smoking in early pregnancy is associated with an increased risk of oral clefts. Infants of mothers who stopped using snuff or stopped smoking before the antenatal booking had no increased risk of oral cleft malformations. Oral snuff or other sources of nicotine should not be recommended as an alternative for smoke-cessation during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: Nicotine replacement therapy (NRT) has been used to ameliorate nicotine withdrawal in the intensive care unit (ICU). Previous cohort studies have suggested an increased mortality with NRT use: methodological problems may call into question the validity of these findings. We undertook a retrospective cohort study to determine if NRT use was associated with adverse outcomes. Methods: This retrospective cohort study was conducted in a 30-bed, university affiliated, teaching hospital ICU. Results: We identified 423 smokers admitted over 2 years, of whom 73 received transdermal NRT. Cox proportional hazard regression models, with NRT modelled as a time-varying covariate, were used to test the hypothesis that NRT was associated with an altered ICU or hospital mortality. A second analysis utilized propensity scores. The unadjusted ICU and hospital mortalities were lower for the NRT group; although both differences were non-significant. The Cox models showed that, after adjustment for APACHE risk, age, sex and alcohol use, risk associated with NRT administration was not statistically different than non-administration for both ICU (hazard ratio 0.50, [95 % CI 0.20-1.24], p = 0.14) and hospital (hazard ratio 0.95, [95 % CI 0.52-1.75], p = 0.88) mortality. Similar findings occurred with the propensity matched analysis. Conclusion: We were unable to demonstrate any harm associated with NRT, with the ICU model actually trending towards benefit. We conclude that a randomised, blinded, placebo controlled trial is required to assess adequately the safety and efficacy of NRT as a treatment in critically ill smokers. [ABSTRACT FROM AUTHOR]

Abstract: Background: Adolescence is a period of development associated with a peak in an organism''s responsiveness to reward. Epidemiological data indicate that the initiation of smoking is high during adolescence and that earlier age of onset is associated with increased incidence of dependence as adults. In rats, nicotine is known to have primary reinforcing and reinforcement enhancing effects. Although the primary reinforcing effects of nicotine have been demonstrated in adolescent rats (self-administration), less is known about its reinforcement enhancing effects during this period. Moreover, the impact of adolescent nicotine exposure on its reinforcement enhancing effects during adulthood has not yet been examined. The objectives of this study were to assess whether (1) nicotine enhances operant responding for an unconditioned visual reinforcer (VS) in adolescent rats, and (2) exposure to nicotine during adolescence affects responsiveness to the VS in adulthood. Methods: Rats were exposed to nicotine (0.32mg/kg, subcutaneous injection) or saline during adolescence (postnatal day 29–42) and adulthood. Nose-poking for the VS was assessed under fixed and progressive ratio schedules. Results: Nicotine increased responding for the VS during adolescence. Adolescent nicotine exposure failed to significantly affect adult responsiveness for the VS, regardless of adult nicotine exposure, but early exposure to the VS affected responsiveness to the VS in adulthood. Conclusions: Nicotine exhibits reinforcement enhancing effects in adolescent rats. Long-term effects of adolescent nicotine on reinforcement enhancement are minimal, but the impact of early exposure to the VS and/or the primary reinforcing effects of nicotine requires further investigation. [Copyright &y& Elsevier]

Introduction: The α4β2 nicotinic receptor is of central importance in tobacco dependence, while the homomeric α7 receptor may also play a role. In this candidate gene study, we examine the association between 8 single nucleotide polymorphisms (SNPs) in genes coding for nicotinic acetylcholine receptor subunits α4 (rs1044396, rs2273504, rs2236196, and rs2273502), α7 (rs2133965 and rs4779969), and β2 (rs2072660 and rs2072661) and smoking abstinence in a cohort of quitters enrolled in a clinical trial of behavioral support. Methods: Data were obtained from the "Patch in Practice" study, involving 925 smokers in the United Kingdom. All participants were given an 8-week course of 15 mg of transdermal nicotine replacement therapy and blood was taken for genotyping. Results: Logistic regression analyses assessed the association between each selected SNP and smoking abstinence at 4, 12, 26, and 52 weeks. There were no statistically significant associations with smoking cessation success or nicotine intake assessed by plasma cotinine levels. However, rs2273502 was associated with a consistent (though nonsignificant) increase in the odds of abstinence. Conclusions: There was no compelling evidence that these SNPs were associated with a reduced or higher chance of abstinence. However, rs2273502 may be worth investigating in future studies. [ABSTRACT FROM AUTHOR]

Introduction: The role of the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25 in the etiology of nicotine dependence (ND) is still being defined. In this study, we included all 15 tagging single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster and tested associations with 30 smoking-related phenotypes. Methods: The study sample was ascertained from the Finnish Twin Cohort study. Twin pairs born 1938–1957 and concordant for a history of cigarette smoking were recruited along with their family members (mainly siblings), as part of the Nicotine Addiction Genetics consortium. The study sample consisted of 1,428 individuals (59% males) from 735 families, with mean age 55.6 years. Results: We detected multiple novel associations for ND. DSM-IV ND symptoms associated significantly with the proxy SNP Locus 1 (rs2036527, p = .000009) and Locus 2 (rs578776, p = .0001) and tolerance factor of the Nicotine Dependence Syndrome Scale (NDSS) showed suggestive association to rs11636753 (p = .0059), rs11634351 (p = .0069), and rs1948 (p = .0071) in CHRNB4. Furthermore, we report significant association with DSM-IV ND diagnosis (rs2036527, p = .0003) for the first time in a Caucasian population. Several SNPs indicated suggestive association for traits related to ages at smoking initiation. Also, rs11636753 in CHRNB4 showed suggestive association with regular drinking (p = .0029) and the comorbidity of depression and ND (p = .0034). Conclusions: We demonstrate novel associations of DSM-IV ND symptoms and the NDSS tolerance subscale. Our results confirm and extend association findings for other ND measures. We show pleiotropic effects of this gene cluster on multiple measures of ND and also regular drinking and the comorbidity of ND and depression. [ABSTRACT FROM PUBLISHER]

Objective: Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics. Methods: This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy. Results: Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences 20.23 mm (95%CI 20.45 to 20.00) and 20.41 mm (95%CI 20.69 to 20.13), respectively] and a smaller birth length [difference 22.61 mm (95%CI 25.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference -33 grams (95%CI -55 to -10)], and tended to be associated with birth weight [difference -38 grams (95%CI -89 to 13)]. This association persisted after adjustment for smoking quantity. Conclusions: Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene - fetal smoke exposure interactions. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (e-cigarettes) are battery-powered devices that deliver nicotine without any combustion or smoke. These devices have generated much publicity among the smoking-cessation community and support from dedicated users; however, little is known about the efficacy of the device as a smoking-cessation tool. Purpose: This study aimed to examine the effectiveness of e-cigarettes for smoking cessation using a survey of smokers who had tried e-cigarettes. Methods: Using as a sampling frame a cohort of all first-time purchasers of a particular brand of e-cigarettes during a 2-week period, a cross-sectional, online survey was conducted in 2010 to describe e-cigarette use patterns and their effectiveness as a smoking-cessation tool. There were 222 respondents, with a survey response rate of 4.5%. The primary outcome variable was the point prevalence of smoking abstinence at 6 months after initial e-cigarette purchase. Results: The primary finding was that the 6-month point prevalence of smoking abstinence among the e-cigarette users in the sample was 31.0% (95% CI=24.8%, 37.2%). A large percentage of respondents reported a reduction in the number of cigarettes they smoked (66.8%) and almost half reported abstinence from smoking for a period of time (48.8%). Those respondents using e-cigarettes more than 20 times per day had a quit rate of 70.0%. Of respondents who were not smoking at 6 months, 34.3% were not using e-cigarettes or any nicotine-containing products at the time. Conclusions: Findings suggest that e-cigarettes may hold promise as a smoking-cessation method and that they are worthy of further study using more-rigorous research designs. [ABSTRACT FROM AUTHOR]

Background: CHRNA5-CHRNA3-CHRNB4 and TTC12-ANKK1-DRD2 gene-clusters influence smoking behavior. Our aim was to test developmental changes in their effects as well as the interplays between them and with nongenetic factors. Methods: Participants included 4762 subjects from a general population-based, prospective Northern Finland 1966 Birth Cohort (NFBC 1966). Smoking behavior was collected at age 14 and 31 years. Information on maternal smoking, socioeconomic status, and novelty seeking were also collected. Structural equation modeling was used to construct an integrative etiologic model including genetic and nongenetic factors. Results: Several single nucleotide polymorphisms in both gene-clusters were significantly associated with smoking. The most significant were in CHRNA3 (rs1051730, p = 1.1 × 10−5) and in TTC12 (rs10502172, p = 9.1 × 10−6). CHRNA3-rs1051730[A] was more common among heavy/regular smokers than nonsmokers with similar effect-sizes at age 14 years (odds ratio [95% CI]: 1.27 [1.06–1.52]) and 31 years (1.28 [1.13–1.44]). TTC12-rs10502172[G] was more common among smokers than nonsmokers with stronger association at 14 years (1.33 [1.11–1.60]) than 31 years (1.14 [1.02–1.28]). In adolescence, carriers of three–four risk alleles at either CHRNA3-rs1051730 or TTC12-rs10502172 had almost threefold odds of smoking regularly than subjects with no risk alleles. TTC12-rs10502172 effect on smoking in adulthood was mediated by its effect on smoking in adolescence and via novelty seeking. Effect of CHRNA3-rs1051730 on smoking in adulthood was direct. Conclusions: TTC12-ANKK1-DRD2s seemed to influence smoking behavior mainly in adolescence, and its effect is partially mediated by personality characteristics promoting drug-seeking behavior. In contrast, CHRNA5-CHRNA3-CHRNB4 is involved in the transition toward heavy smoking in mid-adulthood and in smoking persistence. Factors related to familial and social disadvantages were strong independent predictors of smoking. [Copyright &y& Elsevier]

Objectives: To investigate the association of smoking with bruxism while controlling for genetic and environmental factors using a co-twin-control design. Especially, the role of nicotine dependence was studied in this context. Methods: The material derives from the Finnish Twin Cohort consisting of 12,502 twin individuals who responded to a questionnaire in 1990 (response rate of 77%). All were born in 1930–1957, the mean age being 44 years. The questionnaire covered 103 multiple choice questions, 7 dealing with tobacco use and 22 with sleep and vigilance matters, including perceived bruxism. In addition, a subsample derived from the Nicotine Addiction Genetics Finland Study containing 445 twin individuals was studied. Results: In age- and gender-controlled multinomial logistic regression, both monthly and rarely reported bruxism associated with both current cigarette smoking (odds ratio [OR] = 1.74 and 1.64) and former cigarette smoking (OR = 1.64 and 1.47). Weekly bruxism associated with current smoking (OR = 2.85). Current smokers smoking 20 or more cigarettes a day reported weekly bruxism more likely (OR = 1.61–1.97) than those smoking less. Among twin pairs (N = 142) in which one twin was a weekly bruxer and the cotwin a never bruxer, there were 13 monozygotic pairs in which one twin was a current smoker and the other twin was not. In all cases, the bruxer was the smoker (p = .0003). Nicotine dependence associated significantly with bruxism. Conclusions: Our twin study provides novel evidence for a possible causal link between tobacco use and bruxism among middle-aged adults. Nicotine dependence may be a significant predisposing factor for bruxism. [ABSTRACT FROM AUTHOR]

Background: Research on the comorbidity between cigarette smoking and major depression has not elucidated the pathways by which smoking is associated with depression.Aims: To examine the causal relationships between smoking and depression via fixed-effects regression and structural equation modelling.Method: Data were gathered on nicotine-dependence symptoms and depressive symptoms in early adulthood using a birth cohort of over 1000 individuals.Results: Adjustment for confounding factors revealed persistent significant (P<0.05) associations between nicotine-dependence symptoms and depressive symptoms. Structural equation modelling suggested that the best-fitting causal model was one in which nicotine dependence led to increased risk of depression. The findings suggest that the comorbidity between smoking and depression arises from two routes; the first involving common or correlated risk factors and the second a direct path in which smoking increases the risk of depression.Conclusions: This evidence is consistent with the conclusion that there is a cause and effect relationship between smoking and depression in which cigarette smoking increases the risk of symptoms of depression. [ABSTRACT FROM AUTHOR]

Abstract: Vaccination against nicotine is under investigation as a treatment for tobacco dependence. Passive immunization with nicotine-specific antibodies represents a complementary strategy to vaccination. A potential adverse effect of passive immunization in nicotine-dependent individuals is that it may lead to a rapid reduction in brain nicotine levels and trigger withdrawal. The goal of this study was to determine if passive immunization with the nicotine-specific monoclonal antibody Nic311 precipitated withdrawal in nicotine-dependent rats as measured by increases in brain reward thresholds and somatic signs. Another cohort of rats was used to measure brain nicotine levels after Nic311 administration. Nic311 30, 80 or 240 mg/kg reduced brain nicotine concentrations by 45, 83 or 92% compared to controls. None of these Nic311 doses precipitated withdrawal measured at intervals up to 72 h following antibody administration. Administration of the nicotinic antagonist mecamylamine precipitated a robust nicotine withdrawal syndrome. Therefore, a substantial, but not complete, acute reduction in brain nicotine levels following passive immunization was not sufficient to precipitate nicotine withdrawal in nicotine-dependent rats. The Nic311 doses used have been shown to attenuate the behavioral effects of nicotine, suggesting that the use of passive immunization to treat nicotine addiction is not likely to precipitate withdrawal. [Copyright &y& Elsevier]

Objective The objective of this study was to examine whether the use of nicotine replacement therapy (NRT) during pregnancy increases the risk of stillbirth. Design Cohort study with prospective data. Setting Denmark 1996–2002. Population A total of 87 032 singleton pregnancies enrolled in the Danish National Birth Cohort for which information on NRT use as well as smoking was available. Methods Outcome of pregnancy was identified by register linkage, with <1% loss to follow up. We conducted Cox regression analyses to estimate the hazard ratio (HR) and 95% CI of stillbirth according to the use of NRT, type of NRT use and a combination of NRT use and smoking. Main outcome measures Stillbirth, defined as delivery of a dead fetus after 20 completed weeks of gestation. Results A total of 495 pregnancies (5.7 in 1000 births) ended in stillbirth, 8 of which were among NRT users (4.2 in 1000 births). After adjustment for confounders, women who used NRT during pregnancy had a HR of 0.57 (95% CI 0.28–1.16) for stillbirth compared with those who did not use NRT. Smoking during pregnancy was associated with an increased risk of stillbirth (HR 1.46, 95% CI 1.17–1.82), while women who both smoked and used NRT had a HR of 0.83 (95% CI 0.34–2.00) compared with nonsmoking women who did not use NRT. Conclusion Our study does not indicate that use of NRT during pregnancy increases the risk of stillbirth. [ABSTRACT FROM AUTHOR]

Non-invasive biomonitoring of exposure to environmental tobacco smoke (ETS) by means of hair is attractive in children, although systematic evaluation is required in infants. The objective was to compare nicotine and cotinine concentrations in hair and plasma and parentally reported exposure to ETS in a birth cohort of 411 infants. Plasma was collected from 356 six-month-old infants and hair samples were collected from 368 one-year-old infants. Concentrations of nicotine and cotinine were measured by an optimized gas chromatography-mass spectrometry (GC/MS)-based method requiring 4 mg hair or 200 µl plasma. Information was obtained on the number of days with ETS exposure during the first year of life, the smoking habits of the parents, and the number of cigarettes smoked per day in the home. All three parentally reported indices of ETS exposure were significantly associated with the biomarkers, with clear dose–response relationships. There was a significant association between days with ETS exposure and nicotine in hair at relatively low exposure levels (10–99 days per year), whereas the other biomarkers only showed significant increases at higher exposure levels. In conclusion, nicotine in hair appears to be the biomarker most strongly associated with parental reports on exposure to ETS in infants. [ABSTRACT FROM AUTHOR]

The association of silica dust exposure with mortality among never smokers has not been well established. We aimed to evaluate the association of silica dust exposure with mortality among never smokers. We studied 17,130 workers employed for at least 1 year between January 1, 1960 and December 31, 1974, with follow-up until the end of 2013. Cumulative respirable silica dust exposure (CDE) was estimated by linking a job-exposure matrix to personal work history. We observed 3937 deaths during 589,357.26 person-years of follow-up. Significant positive exposure-response relationships were found between CDE and mortality from all cause (HR = 1.01, 95%CI = 1.01-1.02), respiratory tuberculosis (HR = 1.04, 95%CI = 1.02-1.06), CVDs (HR = 1.03, 95%CI = 1.02-1.04), and diseases of the respiratory system (HR = 1.06, 95%CI = 1.04-1.07). We found higher standardized mortality ratios for respiratory tuberculosis (2.62, 2.32-2.95), CVDs (1.43, 1.32-1.54), and pneumoconiosis (77.75, 68.21-88.25) among silica dust exposed workers. In addition, we estimated that 4.19%, 20.69%, 7.48% and 34.06% of deaths for all cause, respiratory tuberculosis, CVDs, and diseases of the respiratory system among Chinese workers were attributed to silica, after adjusting for other covariates. With regard to lung cancer, compared with unexposed group, the HRs and 95% CI were 0.94 (0.52-1.71), 1.86 (1.15-3.00), 1.65 (0.95-2.86) for low, medium, and high exposed workers, respectively. Long-term silica dust exposure is associated with increased mortality in the absence of cigarette smoking. [ABSTRACT FROM AUTHOR]

Objective: To determine whether exposure to secondhand smoke is associated with early prognosis following acute coronary syndrome. Design, setting and participants: We interviewed consecutive patients admitted to nine Scottish hospitals over 23 months. Information was obtained, via questionnaire, on age, sex, smoking status, postcode of residence and admission serum cotinine concentration was measured. Follow-up data were obtained from routine hospital admission and death databases. Results: Of the 5815 participants, 1261 were never-smokers. Within 30 days, 50 (4%) had died and 35 (3%) had a non-fatal myocardial infarction. All-cause deaths increased from 10 (2.1%) in those with cotinine ⩽0.1 ng/ml to 22 (7.5%) in those with cotinine >0.9 ng/ml (χ2 test for trend p<0.001). This persisted after adjustment for potential confounders (cotinine >0.9 ng/ml: adjusted OR 4.80, 95% CI 1.95 to 11.83, p = 0.003). The same dose response was observed for cardiovascular deaths and death or myocardial infarction. Conclusions: Secondhand smoke exposure is associated with worse early prognosis following acute coronary syndrome. Non-smokers need to be protected from the harmful effects of secondhand smoke. [ABSTRACT FROM AUTHOR]