Weekend delivery and maternal-neonatal adverse outcomes in low-risk pregnancies in the United States: A population-based analysis of 3-million live births.

BACKGROUND: Childbirth is the most common cause of hospital admission in the United States. Previous studies have shown that there might be a "weekend effect" in perinatal care, indicating that mothers and newborns whose deliveries occur during the weekends are at increased risk of having adverse outcomes. This study aims to isolate the association between the weekend delivery and maternal-neonatal adverse outcomes by investigating low-risk pregnancies in nationwide data. METHODS: A population-based study of all low-risk pregnancies (in-hospital, nonanomalous, term, normal birthweight, and singleton) was conducted based on US national natality data in 2017. Four maternal outcomes (ICU admission, uterine rupture, blood transfusion, and perineal laceration) and three neonatal outcomes (5-minute Apgar <7, NICU admission, and neonatal death) were defined as adverse outcomes. Logistic regression analyses were conducted to determine the association, adjusting for 23 maternal and neonatal characteristics and risk factors. RESULTS: Among 3 011 577 low-risk pregnancies, 6.0% were reported to have at least one of the maternal-neonatal adverse outcomes. Weekend deliveries were significantly associated with six maternal-neonatal adverse outcomes with an exception of neonatal death. In general, weekend deliveries were 1.13 times significantly as likely to have any of seven maternal-neonatal adverse outcomes than weekday deliveries (OR 1.13, 95% CI 1.11-1.14), being attributed to adverse outcomes of more than 4500 mother-newborn pairs. CONCLUSIONS: Weekend delivery is a consistent risk factor for both mothers and babies at the national level. Furthermore, studies are needed about possible modifiable factors that mediate these associations to ensure safe childbirth regardless of the day of delivery.

Dual Use of Cigarettes and JUUL: Trajectory and Cigarette Consumption.

Objectives: Many smokers who start using ENDS engage in dual use of cigarettes and ENDS. This paper examines time trends in dual use after a JUUL Starter Kit purchase, and changes in cigarette consumption among those remaining dual users. Methods: In the ADJUSST study, a cohort of adult smokers who purchased a JUUL Starter Kit were followed naturalistically 6 times over 12 months. Trends in dual use and reported complete switching away from cigarettes (ie, no past 30-day smoking), and changes in daily average cigarettes per day from baseline at 6 and 12 months were examined. Results: Dual use declined over time as complete switching increased. By 12 months, 43.2% reported dual using, and 51.2% reported switching away from cigarettes. Among dual users, approximately 60% reduced their cigarette consumption substantially (by ≥ 50%); average reductions in cigarette consumption were > 80%. Only a small minority (3%-10%) substantially increased cigarette consumption. Conclusions: Dual use of smoking and JUUL declines over time as switching away from smoking increases. This suggests that, for most smokers, dual use is a transitional state leading to switching completely away from cigarettes. Furthermore, dual use is often marked by substantial reductions in cigarette consumption.

Reducing the smoking-related health burden in the USA through diversion to electronic cigarettes: a system dynamics simulation study.

BACKGROUND: Electronic cigarettes ("e-cigarettes") have altered tobacco smoking trends, and their impacts are controversial. Given their lower risk relative to combustible tobacco, e-cigarettes have potential for harm reduction. This study presents a simulation-based analysis of an e-cigarette harm reduction policy set in the USA. METHODS: A system dynamics simulation model was constructed, with separate aging chains representing people in different stages of use (both of combustible cigarettes and e-cigarettes). These structures interact with a policy module to close the gap between actual (simulated) and goal numbers of individuals who smoke, chosen to reduce the tobacco-attributable death rate (i.e., mostly combustible cigarette-attributable, but conservatively allowing e-cigarette-attributable deaths) to that due to all accidents in the general population. The policy is two-fold, removing existing e-liquid flavor bans and providing an informational campaign promoting e-cigarettes as a lower-risk alternative. Realistic practical implementation challenges are modeled in the policy sector, including time delays, political resistance, and budgetary limitations. Effects of e-cigarettes on tobacco smoking occur through three mechanisms: (1) diversion from ever initiating smoking; (2) reducing progression to established smoking; and (3) increasing smoking cessation. An important unintended effect of possible death from e-cigarettes was conservatively included. RESULTS: The base-case model replicated the historical exponential decline in smoking and the exponential increase in e-cigarette use since 2010. Simulations suggest tobacco smoking could be reduced to the goal level approximately 40 years after implementation. Implementation obstacles (time delays, political resistance, and budgetary constraints) could delay and weaken the effect of the policy by up to 62% in the worst case, relative to the ideal-case scenario; however, these discrepancies substantially decreased over time in dampened oscillations as negative feedback loops stabilize the system after the one-time "shock" introduced by policy changes. CONCLUSIONS: The simulation suggests that the promotion of e-cigarettes as a harm-reduction policy is a viable strategy, given current evidence that e-cigarettes offset or divert from smoking. Given the strong effects of implementation challenges on policy effectiveness in the short term, accurately modeling such obstacles can usefully inform policy design. Ongoing research is needed, given continuing changes in e-cigarette use prevalence, new policies being enacted for e-cigarettes, and emerging evidence for substitution effects between combustible cigarettes and e-cigarettes.

Alcohol Use Disorder Symptoms Rather than Alcohol Exposure Predict Experiences of Cannabis Use Disorder Symptoms among Adolescents and Young Adults.

Background: Alcohol and cannabis use are highly comorbid. Objective: We evaluate if alcohol use and/or alcohol use disorder symptoms predict experiences of cannabis use disorder symptoms among adolescents and young adults and whether the relationships differ based on frequency of cannabis use, recency of cannabis initiation and age. Method: Data were drawn from five annual surveys of the National Survey on Drug Use and Health (2014-2018) to include adolescents and young adults (age 12 to 21 years) who reported using cannabis and alcohol at least once in the past 30 days. Results: Number of alcohol use disorder symptoms, over and above alcohol quantity or frequency, was positively associated with each of the cannabis use disorder symptoms as well as the total number of cannabis use disorder symptoms endorsed. The association between alcohol and cannabis use disorder symptoms was stronger among those who were younger and those who initiated cannabis use within the past 2 years. Conclusions: Treatment should consider these and other cross-over effects of substance disorder symptoms when addressing risk for chronic and dependent use.

Trends in electronic cigarette use and conventional smoking: quantifying a possible 'diversion' effect among US adolescents.

BACKGROUND AND AIMS: The impact of electronic cigarettes (ECs) on nicotine use is hotly debated: some fear that ECs are a 'catalyst' to conventional smoking, while others argue that they divert adolescents from the more harmful product. This study used simulation modeling to evaluate the plausibility of catalyst and diversion hypotheses against real-world data. DESIGN: A simulation model represented life-time exclusive EC use, exclusive conventional smoking and dual use as separate subpopulations. The 'catalyst' effect was modeled as EC use increasing dual use initiation (i.e. EC users also start smoking). The 'diversion' effect was modeled as EC use decreasing exclusive cigarette initiation. The model was calibrated using data from the US National Youth Tobacco Survey (NYTS). The plausibility of each scenario was evaluated by comparing simulated trends with NYTS data. This is the first study, to our knowledge, to estimate the magnitude of a diversion effect through simulation. SETTING: United States. PARTICIPANTS AND MEASUREMENTS: Adolescents aged 12-17 years in NYTS, a cross-sectional study from 2000 to 2019 (n = 12 500 to 31 000 per wave). Exclusive cigarette use, exclusive EC use and dual use of both products were defined using cumulative life-time criteria (100+ cigarettes smoked and/or > 100 days vaped). FINDINGS: A null model (no catalyst or diversion) over-predicts NYTS smoking by up to 87%. Under the conservative assumption that the catalyst effect accounts for all dual use, an exponential decay constant of 19.6% EC users/year initiating smoking is required; however, this further over-predicts actual smoking by up to 109%. A diversion effect with an exponential decay constant of 55.4%/year or 65.4%/year, with the maximum possible opposing catalyst effect also active, is required optimally to match NYTS smoking trends (root mean square error = 286 632 versus 391 396 in the null model). CONCLUSIONS: A simulation model shows that a substantial diversion effect is needed to explain observed nicotine use trends among US adolescents, and it must be larger than any possible opposing catalyst effect, if present.

Dynamic change in the association of a cigarettes-per-day polygenic risk score across the numeric range of its corresponding phenotype over adolescence and young adulthood.

The association between cigarettes per day (CPD) and CPD-calibrated polygenic risk scores (CPD-PGS) is positive, however, the shape of the association is unknown. CPD measurement is inconsistent across studies and different measurement can lead to different results. The pattern shape may also patterns may change over time, given differences in genetic influence on smoking. This study examines the dynamic pattern between number of cigarettes smoked and PGS-CPD over adolescence and young adulthood. A time-varying effects model in which CPD was the continuous dynamic variable, was estimated for ever-smokers in a nationally representative study tracking partiicpants over adolescence and young adulthood. Participants were genotyped and a CPD-PGS score was created using results from a large genome-wide study meta-analysis. Results indicated that the association between CPD and CPD-PGS changed over CPD. Low CPD-PGS related to higher odds of not smoking or smoking very low CPD. A flat positive association at 5-12 CPD suggeted a "low risk" group. The association peaked around 20 CPD, indicating that a high-risk score applied best to those smoking approximately 1 pack of cigarettes per day. Age also moderated the effect of CPD-PGS at specific CPD rates, such that CPD-PGS was stronger at later ages and higher CPD. The association between CPD and CPD-PGS should not be assumed to be linear or static over age; there seem to be CPD-PGS thresholds corresponding to significant CPD risk, although the effect of CPD-PGS also varies over age. More care and attention to measurement can improve behavior genetic addiction science.

Corrigendum: Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot.

[This corrects the article DOI: 10.3389/fcvm.2020.00008.].

Stability in effects of different smoking-related polygenic risk scores over age and smoking phenotypes.

PURPOSE: Polygenic risk scores (PRSs) for smoking behavior largely fail to consider the demonstrated developmental change in genetic influence over age and stage of smoking behaviors. Additionally, few studies have examined how stage-specific smoking PRSs (e.g. for initiation vs. smoking heaviness) generalize to other stages of risk. The current study examines the stability of PRS effects over age, and how specifically calibrated PRSs associate with other smoking phenotypes. METHODS: 7228 participants were from the National Longitudinal Study of Adolescent to Adult Health, who had calculated PRSs for two smoking phenotypes, Centers for Disease Control and Prevention (CDC) smoking initiation status, and cigarettes per day (CPD). Four time-varying effects models estimated associations between both PRSs and four smoking phenotypes (CDC status, cigarettes/day on smoking days, any past-30 day smoking, and past-30 day daily smoking) over adolescence and young adulthood. FINDINGS: The time-varying effects models demonstrated that both PRSs significantly associated with all four phenotypes age. PRS effects were similar, in both odds ratios and the overlap of 95 % confidence intervals. There were increases in PRS associations with quantity of smoking over age, and a decrease in PRS effects over age for the CDC smoking status phenotype over early to late adolescence. CONCLUSIONS: Smoking PRSs can be robust predictors of smoking behavior over age. However, the lack of differentiation between specific PRSs and multiple smoking phenotypes, as well as the added contribution of both PRSs to explaining genetic variance, indicates a need to reconceptualize phenotypic measurement used to calibrate smoking PRSs.

A key indicator of nicotine dependence is associated with greater depression symptoms, after accounting for smoking behavior.

INTRODUCTION: Depression is a global burden that is exacerbated by smoking. The association between depression and chronic smoking is well-known; however, existing findings contain possible confounding between nicotine dependence (ND), a latent construct measuring addiction, and objective smoking behavior. The current study examines the possible unique role of ND in explaining depression, independently of smoking behavior. METHODS: A nationally-representative sample of current adult daily smokers was drawn by pooling three independent, cross-sectional, biennial waves (spanning 2011-16) of the National Health and Nutrition Examination Survey (NHANES). The association between ND (operationally defined as time to first cigarette (TTFC) after waking) and the amount of depression symptoms was examined after adjusting for both current and lifetime smoking behaviors (cigarettes per day and years of smoking duration) and sociodemographic factors (gender, age, race, education and income to poverty ratio). RESULTS: Earlier TTFC was associated with more depression symptoms, such that those smoking within 5 minutes of waking had an approximately 1.6-fold higher depression score (PRR = 1.576, 95% CI = 1.324-1.687) relative to those who smoke more than 1 hour after waking. This relationship remained significant after adjusting for current and lifetime smoking behavior as well as sociodemographic factors (PRR = 1.370, 95% CI = 1.113, 1.687). CONCLUSIONS: The latent construct of ND, as assessed by TTFC, may be associated with an additional risk for depression symptoms, beyond that conveyed by smoking behavior alone. This finding can be used for more refined risk prediction for depression among smokers.

Electronic cigarettes, nicotine use trends and use initiation ages among US adolescents from 1999 to 2018.

BACKGROUND AND AIMS: Recent nicotine use trends raise concerns that electronic cigarettes (ECs) may act as a gateway to cigarettes among adolescents. The aims of this study were to examine prevalence trends of exclusive EC use, exclusive cigarette use and dual use to determine the corresponding ages of initiation and to investigate hypothetical trends in total nicotine use and cigarette use in the absence of ECs among US adolescents. DESIGN: Observational study using data from the National Youth Tobacco Survey (NYTS) to statistically model trends in the prevalences of each user group and their initiation ages. Projections from counterfactual models based on data from 1999 to 2009 (before EC introduction) were compared with actual trends based on data from 1999 to 2018. Rigorous error analyses were applied, including Theil proportions. SETTING: USA. PARTICIPANTS AND MEASUREMENTS: Adolescents aged 12-17 years who were established exclusive cigarette users (≥ 100 cigarettes smoked and ≤ 100 days vaped), established exclusive EC users (< 100 cigarettes smoked and > 100 days vaped) and established dual users (≥ 100 cigarettes smoked and > 100 days vaped), based on cumulative life-time exposure (n ≈ 12 500-31 000 per wave). FINDINGS: Exclusive cigarette use prevalence declined from 1999 to 2018, while exclusive EC use and dual use prevalences increased since their introduction in 2009. The age of cigarette initiation began a slight increase after 2014, whereas the age for EC use remained approximately constant and was higher than that of cigarettes. The counterfactual comparison results were consistent with ECs not increasing the number of US adolescent nicotine users, and in fact diverting adolescents from cigarettes. CONCLUSIONS: Electronic cigarettes may have offset conventional smoking among US adolescents between 2010 and 2018 by maintaining the total nicotine use prevalence and diverting them from more harmful conventional smoking. Additionally, electronic cigarette users appear to initiate at older ages relative to conventional smokers, which is associated with lower risk.

Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot.

Functional variants in nuclear envelope genes are implicated as underlying causes of cardiopathology. To examine the potential association of single nucleotide variants of nucleoporin genes with cardiac disease, we employed a prognostic scoring approach to investigate variants of NUP155, a nucleoporin gene clinically linked with atrial fibrillation. Here we implemented bioinformatic profiling and predictive scoring, based on the gnomAD, National Heart Lung and Blood Institute-Exome Sequencing Project (NHLBI-ESP) Exome Variant Server, and dbNSFP databases to identify rare single nucleotide variants (SNVs) of NUP155 potentially associated with cardiopathology. This predictive scoring revealed 24 SNVs of NUP155 as potentially cardiopathogenic variants located primarily in the N-terminal crescent-shaped domain of NUP155. In addition, a predicted NUP155 R672G variant prioritized in our study was mapped to a region within the alpha helical stack of the crescent domain of NUP155. Bioinformatic analysis of inferred protein-protein interactions of NUP155 revealed over representation of top functions related to molecular transport, RNA trafficking, and RNA post-transcriptional modification. Topology analysis revealed prioritized hubs critical for maintaining network integrity and informational flow that included FN1, SIRT7, and CUL7 with nodal enrichment of RNA helicases in the topmost enriched subnetwork. Furthermore, integration of the top 5 subnetworks to capture network topology of an expanded framework revealed that FN1 maintained its hub status, with elevation of EED, CUL3, and EFTUD2. This is the first study to report novel discovery of a NUP155 subdomain hotspot that enriches for allelic variants of NUP155 predicted to be clinically damaging, and supports a role for RNA metabolism in cardiac disease and development.

The Relationship Between Electronic Cigarette Use and Conventional Cigarette Smoking Is Largely Attributable to Shared Risk Factors.

INTRODUCTION: The growing popularity of electronic cigarettes (e-cigarettes) among youth raises concerns about possible causal effects on conventional cigarette smoking. However, past research remains inconclusive due to heavy confounding between cigarette and e-cigarette use. This study uses propensity score methods to robustly adjust for shared risk in estimating the relationship between e-cigarette use and conventional smoking. METHODS: Cross-sectional data from 8th and 10th graders were drawn from the 2015-2016 waves of Monitoring the Future (n = 12 421). The effects of (1) lifetime and (2) current e-cigarette use on (A) lifetime and (B) current conventional cigarette smoking were examined using logistic regression analyses with inverse propensity weighting based on 14 associated risk factors. RESULTS: After accounting for the propensity for using e-cigarettes based on 14 risk factors, both lifetime and current e-cigarette use significantly increased the risk of ever smoking a conventional cigarette (OR = 2.49, 95% CI = 1.77 to 3.51; OR = 2.32, 95% CI = 1.66 to 3.25, respectively). However, lifetime (OR = 2.17, 95% CI = 0.62 to 7.63) and current e-cigarette use (OR = 0.95, 95% CI = 0.55 to 1.63) did not significantly increase the risk of current conventional cigarette smoking. CONCLUSIONS: E-cigarette use does not appear to be associated with current, continued smoking. Instead, the apparent relationship between e-cigarette use and current conventional smoking is fully explained by shared risk factors, thus failing to support claims that e-cigarettes have a causal effect on concurrent conventional smoking among youth. E-cigarette use has a remaining association with lifetime cigarette smoking after propensity score adjustment; however, future research is needed to determine whether this is a causal relationship or merely reflects unmeasured confounding. IMPLICATIONS: This study examines the relationship between e-cigarette use and conventional smoking using inverse propensity score weighting, an innovative statistical method that produces less-biased results in the presence of heavy confounding. Our findings show that the apparent relationship between e-cigarette use and current cigarette smoking is entirely attributable to shared risk factors for tobacco use. However, e-cigarette use is associated with lifetime cigarette smoking, though further research is needed to determine whether this is a causal relationship or merely reflects unaccounted-for confounding. Propensity score weighting produced significantly weaker effect estimations compared to conventional regression control.

Youth smoking and anti-smoking policies in North Dakota: a system dynamics simulation study.

BACKGROUND: The current study utilizes system dynamics to model the determinants of youth smoking and simulate effects of anti-smoking policies in the context of North Dakota, a state with one of the lowest cigarette tax rates in the USA. METHODS: An explanatory model was built to replicate historical trends in the youth smoking rate. Three different policies were simulated: 1) an increase in cigarette excise taxes; 2) increased funding for CDC-recommended comprehensive tobacco control programs; and 3) enforcement of increased retailer compliance with age restrictions on cigarette sales. RESULTS: The explanatory model successfully replicated historical trends in adolescent smoking behavior in North Dakota from 1992 to 2014. The policy model showed that increasing taxes to $2.20 per pack starting in 2015 was the most effective of the three policies, producing a 32.6% reduction in youth smoking rate by 2032. Other policies reduced smoking by a much lesser degree (7.0 and 3.2% for comprehensive tobacco control program funding and retailer compliance, respectively). The effects of each policy were additive. CONCLUSIONS: System dynamics modeling suggests that increasing cigarette excise taxes are particularly effective at reducing adolescent smoking rates. More generally, system dynamics offers an important complement to conventional analysis of observational data.

Earlier smoking after waking and the risk of asthma: a cross-sectional study using NHANES data.

BACKGROUND: Recent research shows that nicotine dependence conveys additional health risks above and beyond smoking behavior. The current study examines whether smoking within 5 min of waking, an indicator of nicotine dependence, is independently associated with asthma outcomes. METHODS: Data were drawn from five pooled cross-sectional waves (2005-14) of NHANES, and the final sample consisted of N = 4081 current adult smokers. Weighted logistic regressions were run examining the relationship between smoking within 5 min of waking and outcomes of lifetime asthma, past-year asthma, and having had an asthma attack in the past year. Control variables included demographics, smoking behavior, family history of asthma, depression, obesity, and secondhand smoking exposure. RESULTS: After adjusting for smoking behavior, smoking within 5 min was associated with an approximately 50% increase in the odds of lifetime asthma (OR = 1.46, p = .008) and past-year asthma (OR = 1.47, p = .024), respectively. After additionally adjusting for demographics and other asthma risk factors, smoking within 5 min of waking was associated with a four-fold increase in the odds of lifetime asthma (OR = 4.05, p = .015). CONCLUSIONS: Smoking within 5 min of waking, an indicator of nicotine dependence, is associated with a significantly increased risk of lifetime asthma in smokers. These findings could be utilized in refining risk assessment of asthma among smokers.

The role of nicotinic receptor genes (CHRN) in the pathways of prenatal tobacco exposure on smoking behavior among young adult light smokers.

BACKGROUND: Prenatal tobacco exposure (PTE) is associated with more frequent smoking among young, light smokers. Little is known about how nicotinic acetylcholine receptor (CHRN) genes may contribute to this relationship. METHODS: Data were drawn from a longitudinal cohort of young light smokers of European ancestry (N = 511). Three single nucleotide polymorphisms (SNPs) among offspring, rs16969968 and rs6495308 in CHRNA5A3B4 and rs2304297 in CHRNB3A6, were analyzed with respect to whether they 1) predict PTE status; 2) confound the previously-reported effects of PTE on future smoking; 3) have effects on youth smoking frequency that are mediated through PTE; and 4) have effects that are moderated by PTE. RESULTS: rs2304297 and rs6495308 were associated with increased likelihood and severity of PTE, respectively. In a path analysis, rs16969968 directly predicted more frequent smoking in young adulthood (B = 1.50, p = .044); this association was independent of, and not mediated by, PTE. The risk of rs16969968 (IRR = 1.07, p = .015) and the protective effect of rs2304297 (IRR = 0.84, p < .001) on smoking frequency were not moderated by PTE. PTE moderated the effect of rs6495308, such that these alleles were protective against later smoking frequency only among non-exposed youth (IRR = 0.85, p < .001). CONCLUSIONS: The association between offspring CHRNB3A6 and PTE is a novel finding. The risk of rs16969968 on youth smoking is independent and unrelated to that of PTE among young, light smokers. PTE moderates the protective effect of rs6495308 on youth smoking frequency. However, PTE's pathway to youth smoking behavior was not explained by these genetic factors, leaving its mechanism(s) of action unclear.

Integrative Data Analysis of Gender and Ethnic Measurement Invariance in Nicotine Dependence Symptoms.

Little research has evaluated whether conflicting evidence for gender and racial/ethnic differences in nicotine dependence (ND) may be attributed to differences in psychometric properties of ND symptoms, particularly for young Hispanic smokers. Inadequate racial/ethnic diversity and limited smoking exposure variability has hampered research in young smokers. We used integrative data analysis (IDA) to pool DSM-IV ND symptom data for current smokers aged 12-25 (N = 20,328) from three nationally representative surveys (1999, 2000 National Surveys on Drug Use and Health (NSDUH) and Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Moderated nonlinear factor analysis (MNLFA) tested symptom measurement invariance in the pooled sample containing greater ethnic and smoking exposure variability. There was study noninvariance for most symptoms. NESARC participants were more likely to report tolerance, using larger amounts or for longer periods, inability to cut down/quit, and more time spent smoking at higher levels of ND severity, but reported emotional/physical health problems at lower ND severity. Four symptoms showed gender or race/ethnicity noninvariance, but observed differences were small. An ND severity factor score adjusting for symptom noninvariance related to study membership, gender, and race/ethnicity did not differ substantively from traditional DSM-IV diagnosis and number of endorsed symptoms in estimated gender and race/ethnicity differences in ND. Results were consistent with studies finding minimal gender and racial/ethnic differences in ND, and suggest that symptom noninvariance is not a major contributor to observed differences. Results support IDA as a potentially promising approach for testing novel ND hypotheses not possible in independent studies.

Evaluating the mutual pathways among electronic cigarette use, conventional smoking and nicotine dependence.

BACKGROUND AND AIMS: The implications of the rapid rise in electronic cigarette (e-cigarette) use remain unknown. We examined mutual associations between e-cigarette use, conventional cigarette use and nicotine dependence over time to (1) test the association between e-cigarette use and later conventional smoking (both direct and via nicotine dependence), (2) test the converse associations and (3) determine the strongest pathways predicting each product's use. DESIGN: Data from four annual waves of a prospective cohort study were analyzed. Path analysis modeled the bidirectional, longitudinal relationships between past-month smoking frequency, past-month e-cigarette frequency and nicotine dependence. SETTING: Chicago area, Illinois, USA. PARTICIPANTS: A total of 1007 young adult smokers and non-smokers (ages 19-23 years). MEASUREMENTS: Frequency of (1) cigarettes and (2) e-cigarettes was the number of days in the past 30 on which the product was used. The Nicotine Dependence Syndrome Scale measured nicotine dependence to cigarettes. FINDINGS: E-cigarette use was not associated significantly with later conventional smoking, either directly (ß = 0.021, P = 0.081) or through nicotine dependence (ß = 0.005, P = 0.693). Conventional smoking was associated positively with later e-cigarette use, both directly (ß = 0.118, P < 0.001) and through nicotine dependence (ß = 0.139, P < 0.001). The strongest predictors of each product's use was prior use of the same product; this pathway was strong for conventional cigarettes (ß = 0.604, P < 0.001) but weak for e-cigarettes (ß = 0.120, P < 0.001). Nicotine dependence moderately strongly predicted later conventional smoking (ß = 0.169, P < 0.001), but was a weak predictor of later e-cigarette use (ß = 0.069, P = 0.039). CONCLUSIONS: Nicotine dependence is not a significant mechanism for e-cigarettes' purported effect on heavier future conventional smoking among young adults. Nicotine dependence may be a mechanism for increases in e-cigarette use among heavier conventional smokers, consistent with e-cigarettes as a smoking reduction tool. Overall, conventional smoking and, to a lesser extent, its resulting nicotine dependence, are the strongest drivers or signals of later cigarette and e-cigarette use.

The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction.

Introduction: E-cigarettes (Electronic Nicotine Delivery Systems, or ENDS) are an increasingly popular tobacco product among youth. Some evidence suggests that e-cigarettes may be effective for harm reduction and smoking cessation, although these claims remain controversial. Little is known about how nicotine dependence may contribute to e-cigarettes' effectiveness in reducing or quitting conventional smoking. Methods: A cohort of young adults were surveyed over 4 years (approximately ages 19-23). Varying-coefficient models (VCMs) were used to examine the relationship between e-cigarette use and conventional smoking frequency, and how this relationship varies across users with different nicotine dependence levels. Results: Lifetime, but not recent, e-cigarette use was associated with less frequent concurrent smoking of conventional cigarettes among those with high levels of nicotine dependence. However, nondependent e-cigarette users smoked conventional cigarettes slightly more frequently than those who had never used e-cigarettes. Nearly half of ever e-cigarette users reported using them to quit smoking at the last measurement wave. For those who used e-cigarettes in a cessation attempt, the frequency of e-cigarette use was not associated with reductions in future conventional smoking frequency. Conclusions: These findings offer possible support that e-cigarettes may act as a smoking reduction method among highly nicotine-dependent young adult cigarette smokers. However, the opposite was found in non-dependent smokers, suggesting that e-cigarette use should be discouraged among novice tobacco users. Additionally, although a substantial proportion of young adults used e-cigarettes to help them quit smoking, these self-initiated quit attempts with e-cigarettes were not associated with future smoking reduction or cessation. Implications: This study offers potential support for e-cigarettes as a smoking reduction tool among highly nicotine-dependent young adult conventional smokers, although the extent and nature of this remains unclear. The use of e-cigarettes as a quit aid was not associated with reductions in conventional smoking, consistent with most other quit aids in this sample except for nicotine replacement therapy, which was only effective for the most dependent smokers. Notably, these findings highlight the necessity of accounting for smokers' nicotine dependence levels when examining tobacco use patterns.

Time-Varying Effects of Parental Alcoholism on Depression.

INTRODUCTION: Children of alcoholic parents are at increased risk for lifetime depression. However, little is known about how this risk may change in magnitude across age, especially in mid-adulthood and beyond. METHODS: We used a nationally representative sample (N = 36,057) of US adults from the National Epidemiologic Survey on Alcohol and Related Conditions, wave III. After adjusting for demographic characteristics, we examined the relationship between parental alcoholism and outcomes of 1) major depressive disorder, Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) and 2) DSM-5 persistent depressive disorder. To examine continuous moderation of this relationship across participants' age, we used time-varying effect models. RESULTS: Parental alcoholism was associated in general with a higher risk for both major depressive disorder (odds ratio [OR], 1.98, 95% confidence interval [CI], 1.85-2.11; P < .001) and persistent depressive disorder (OR, 2.28, 95% CI, 2.04-2.55; P < .001). The association between parental alcoholism and major depressive disorder was stable and positive across age, but the association with persistent depressive disorder significantly declined among older adults; respondents older than 73 years old were not at increased risk for persistent depressive disorder. CONCLUSIONS: Findings from this study show that the risk of parental alcoholism on depression is significant and stable among individuals of a wide age range, with the exception of a decline in persistent depressive risk among older adults. These findings highlight the importance of screening for depression among adults with parental alcoholism.

Time to first cigarette and serum cholesterol levels.

RATIONALE: Cigarette smoking is a primary cause of cardiovascular disease (CVD); however, prior research has rarely distinguished smoking behavior from nicotine dependence. OBJECTIVE: The current study presents a novel investigation into whether time to first cigarette (TTFC), a reliable proxy for nicotine dependence, is associated with lipid cholesterol, a biomarker for CVD, after controlling for smoking behavior and other risk factors. METHODS: In total, 3903 current adult smokers were drawn from four consecutive cross-sectional waves (2005-06, 2007-08, 2009-10, and 2011-12) of the National Health and Nutrition Survey (NHANES). Weighted regressions were used to examine whether earlier TTFC is associated with differences in a) numeric values; b) guideline-based binary outcomes of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the LDL/HDL ratio; and c) 10-year risk scores for CVD. RESULTS: Earlier TTFC (within 5, 30, or 60 min vs. >60 min) was significantly (p < 0.05) associated with lower HDL (2-3 mg/dL) and a lower odds ratio (OR = 0.70) of having optimal HDL levels, and a lower LDL/HDL ratio (0.14-0.32); these results were consistent across three models (unadjusted, adjusted for smoking behavior, and also adjusted for demographics and other CVD risk factors). Earlier TTFC was also associated (p < 0.05) with higher odds of having sub-optimal total cholesterol levels (OR = 1.55) and higher LDL values (8 mg/dL), but only in the models adjusting for smoking behavior. However, the association of TTFC with 10-year CVD risk scores did not reach significance (p > 0.05). CONCLUSION: More "addicted" smokers, as indicated by earlier TTFC, have less favorable lipid profiles, even after accounting for current and lifetime smoking history and other CVD risk factors. Future research should further explore whether TTFC could be a useful tool for refining clinically significant CVD risk among smokers.