Associations of per- and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones.

BACKGROUND/AIMS: Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development. METHODS: In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp). RESULTS: Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: -0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: -5.7; 95%CI: -10.3, -0.8, and %Δ: -4.1; 95%CI: -7.6, -0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: -5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: -7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: -9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: -17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: -16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: -3.7, 20.9). CONCLUSION: PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings.

Effect of early medication adherence on behavioral treatment utilization and smoking cessation among individuals with current or past major depressive disorder.

SIGNIFICANCE: Little is known about the mechanisms by which medication adherence promotes smoking cessation among adults with MDD. We tested the hypothesis that early adherence promotes abstinence by increasing behavioral treatment (BT) utilization. METHODS: Data for this post-hoc analysis were from a randomized trial of 149 adults with current or past MDD treated with BT and either varenicline (n = 81) or placebo (n = 68). Arms were matched on medication regimen. Early medication adherence was measured by the number of days in which medication was taken at the prescribed dose during the first six of 12 weeks of pharmacological treatment (weeks 2-7). BT consisted of eight 45-minute sessions (weeks 1-12). Bioverified abstinence was assessed at end-of-treatment (week 14). A regression-based approach was used to test whether the effect of early medication adherence on abstinence was mediated by BT utilization. RESULTS: Among 141 participants who initiated the medication regimen, BT utilization mediated the effect of early medication adherence on abstinencea) an interquartile increase in early medication days from 20 to 42 predicted a 4.2 times increase in abstinence (Total Risk Ratio (RR) = 4.24, 95% CI = 2.32-13.37; p <.001); b) increases in BT sessions predicted by such an increase in early medication days were associated with a 2.7 times increase in abstinence (Indirect RR = 2.73, 95% CI = 1.54-7.58; p <.001); and c) early medication adherence effects on abstinence were attenuated, controlling for BT (Direct RR = 1.55, 95% CI = 0.83-4.23, p =.17). CONCLUSIONS: The effect of early medication adherence on abstinence in individuals with current or past MDD is mediated by intensive BT utilization.

Changes over time in reasons for quitting vaping among treatment-seeking young people from 2019 to 2022.

Objectives: The landscape of availability, policies, and norms around e-cigarette use and cessation has changed rapidly in the last few years. There is also high interest in quitting vaping among teens and young adults. Understanding the motivation of those who want to quit vaping is important for effective intervention development. This analysis compares user-submitted reasons for quitting (RFQ) vaping from 2022 to a previous analysis from 2019 to determine whether motivations have shifted among young people. Methods: We reviewed 2000 RFQ submissions from users who enrolled in a vaping cessation text message program in 2022. Each response was coded by ≥ 2 researchers and categorized into one of 16 themes. Findings were compared to the 2019 analysis using item-wise comparisons. Results: The most frequent RFQ in 2022 were health (56.1%), social influence (15.8%), and other (11.7%). In comparison to 2019, health remained the top reason, but the rank order of all other reasons shifted. Theme prevalence changed significantly, with cost decreasing and health increasing. Among health-related sub-categories, current and mental health increased compared to 2019 submissions. Discussion: RFQ among young people shifted between 2019 and 2022. We observed greater concern about current and mental health, possibly from experiencing negative health impacts from vaping or from increased awareness of these impacts. The lower prevalence of cost may reflect the widespread availability of cheaper e-cigarettes. RFQ likely change rapidly with the fluctuating e-cigarette landscape and should be considered in cessation interventions, promotional campaigns, and policy.

Depression Severity Moderates Reward Learning Among Smokers with Current or Past Major Depressive Disorder in a Smoking Cessation Randomized Clinical Trial.

INTRODUCTION: Behavioral and pharmacological smoking cessation treatments are hypothesized to increase patients' reward learning to reduce craving. Identifying changes in reward learning processes that support effective tobacco dependence interventions among smokers who experience depression may guide patients towards efficient treatment strategies. The objective was to investigate the extent to which adult daily cigarette smokers with current or past major depressive disorder (MDD) learned to seek reward during 12 weeks of treatment combining behavioral activation and varenicline. We hypothesized that a decline in reward learning would be attenuated (least to most) in the following order: 1) Behavioral activation integrated with ST (BASC) + varenicline, 2) BASC + placebo, 3) Standard behavioral cessation treatment (ST) + varenicline, 4) ST + placebo. METHODS: We ran a Phase 4, placebo-controlled, randomized clinical trial with 300 participants receiving 12 weeks of one of four conditions across two urban medical centers. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI). Reward learning was ascertained at Weeks 1, 7, and 14 using the Probabilistic Reward Task (PRT), a laboratory task that uses an asymmetric reinforcement schedule to assess (a) learning to seek reward (response bias), (b) differentiate between stimuli, and (c) time to react to cues. RESULTS: There was a significant interaction of BDI group x PRT response bias. Response bias declined from Week 7 to 14 among participants with high baseline depression symptoms. The other two BDI groups showed no change in response bias. CONCLUSIONS: Controlling for baseline depression, participants showed a decrease in response bias from Week 1 to 14, and from Weeks 7 to 14. Treatment condition and abstinence status were unassociated with change in reward learning. IMPLICATIONS: Smokers who report greater depression severity show a decline in reward learning despite their participation in smoking cessation treatments, suggesting that depressed populations pose unique challenges with standard smoking cessation approaches.

Seeing Through the Blind: Belief about Treatment Randomization and Smoking Cessation Outcome among People with Current or Past Major Depressive Disorder who Smoke in a Placebo-Controlled Trial of Varenicline.

INTRODUCTION: Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial. METHODS: 175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed. RESULTS: Treatment arm belief was significantly associated with actual arm assignment (χ2(2)=13.0, p=0.002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, vs. "not sure" (RR=3.05 [1.41-6.60], p=0.005). Participants in the placebo arm were just as likely to believe they were taking placebo vs. "not sure" (χ2[2]=0.75, p=0.69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR=5.91 [2.06-16.92], p=0.001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline B=0.077 [0.002-0.192], p <0.05). CONCLUSIONS: Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.

Efficacy and safety of combination behavioral activation for smoking cessation and varenicline for treating tobacco dependence among individuals with current or past major depressive disorder: A 2 × 2 factorial, randomized, placebo-controlled trial.

BACKGROUND AND AIMS: Treatment of depression-related psychological factors related to smoking behavior may improve rates of cessation among adults with major depressive disorder (MDD). This study measured the efficacy and safety of 12 weeks of behavioral activation for smoking cessation (BASC), varenicline and their combination. DESIGN, SETTING, PARTICIPANTS: This study used a randomized, placebo-controlled, 2 × 2 factorial design comparing BASC versus standard behavioral treatment (ST) and varenicline versus placebo, taking place in research clinics at two urban universities in the United States. Participants comprised 300 hundred adult smokers with current or past MDD. INTERVENTIONS: BASC integrated behavioral activation therapy and ST to increase engagement in rewarding activities by reducing avoidance, withdrawal and inactivity associated with depression. ST was based on the 2008 PHS Clinical Practice Guideline. Both treatments consisted of eight 45-min sessions delivered between weeks 1 and 12. Varenicline and placebo were administered for 12 weeks between weeks 2 and 14. MEASUREMENTS: Primary outcomes were bioverified intent-to-treat (ITT) 7-day point-prevalence abstinence at 27 weeks and adverse events (AEs). FINDINGS: No significant interaction was detected between behavioral treatment and pharmacotherapy at 27 weeks (χ2 (1) = 0.19, P = 0.67). BASC and ST did not differ (χ2 (1) = 0.43, P = 0.51). Significant differences in ITT abstinence rates (χ2 (1) = 4.84, P = 0.03) emerged among pharmacotherapy arms (16.2% for varenicline, 7.5% for placebo), with results favoring varenicline over placebo (rate ratio = 2.16, 95% confidence interval = 1.08, 4.30). All significant differences in AE rates after start of medication were higher for placebo than varenicline. CONCLUSION: A randomized trial in smokers with major depressive disorder found that varenicline improved smoking abstinence versus placebo at 27 weeks without elevating rates of adverse events. Behavioral activation for smoking cessation did not outperform standard behavioral treatment, with or without adjunctive varenicline therapy.

Treatment adherence in a smoking cessation clinical trial for individuals with current or past major depressive disorder: Predictors and association with cessation.

INTRODUCTION: Individuals with major depressive disorder (MDD) exhibit high rates of tobacco use and lower responsiveness to tobacco cessation treatments. Treatment adherence is a strong predictor of treatment outcomes in the general population but has not been evaluated in this under-served community of smokers with MDD. METHODS: We used data from a randomized clinical trial on smoking cessation treatment among 300 smokers with MDD to examine the rate of adherence (medication and counseling), the association of adherence with cessation outcomes, and factors associated with adherence, including demographic and smoking characteristics, psychiatric characteristics, smoking cessation processes (e.g., withdrawal, reinforcers), and treatment-related side effects (e.g., nausea). RESULTS: Overall, 43.7% of participants were adherent with medication and 63.0% were adherent with counseling. Medication adherence was significantly associated with cessation, with 32.1% of adherent vs. 13.0% of non-adherent participants quitting smoking at EOT. Counseling adherence was also significantly associated with cessation, with 32.3% of adherent vs. 2.7% of non-adherent participants quitting smoking. Multivariate regression models showed that medication adherence was associated with higher engagement in complementary reinforcers and higher baseline smoking reward, while counseling adherence was associated with identifying as female, lower alcohol use and nicotine dependence, higher baseline smoking reward, and higher engagement in substitute and complementary reinforcers within the first weeks of medication use. CONCLUSIONS: As with the general population of smokers, non-adherence to treatment in smokers experiencing depression is widespread and a significant barrier to cessation. Interventions that target reinforcers may improve rates of treatment adherence.

Characterizing the use, preferences, and perceptions of flavors in cigars in pregnant women.

BACKGROUND: Flavors contribute to the appeal of tobacco products, but less is known about flavors in cigar products. The current study is the first to focus on characterizing the use and perceptions of flavors in cigar products among pregnant women. METHODS: Pregnant women (N = 124) reported their use, preferences (liking, attractiveness, smoothness, interest), perceptions of harm (general, pregnancy-specific, fetal), and postpartum intention to use eight flavor categories (menthol/mint, spices, fruit, chocolate, alcohol, other beverages, candy/sweet, tobacco). We utilized correspondence analysis of contingency tables to investigate clustering of preferences and perceptions of flavors across the sample, and examined how preferences and perceptions of flavors may differ based on history of cigar use (none vs. lifetime vs. prenatal). RESULTS: Overall, 37% reported never trying cigars, 51% reported lifetime use, and 12% reported prenatal use. Fruit (37%), tobacco (36%), and alcohol (14%) were the most common cigar flavors participants reported ever trying. Correspondence analysis revealed clustering in preferences for alcohol, fruit, and candy flavors compared to other flavors, and revealed lower intentions to use menthol/mint and tobacco flavors compared to other flavors. Participants who reported prenatal cigar use also reported more positive perceptions and greater intentions to use (1) spice and alcohol flavors compared to those who reported lifetime use (ps < .05); and (2) spice, alcohol, fruit, and tobacco cigar flavors compared to participants reporting never using cigars (ps < .04). CONCLUSIONS: Regulations to restrict the availability of flavors, especially fruit, spice, and alcohol, may reduce the appeal and use of cigar products in pregnant women.

Associations of individual and cumulative urinary phthalate and replacement biomarkers with gestational weight gain through late pregnancy.

BACKGROUND/AIMS: Phthalates and their replacements are endocrine/metabolic disruptors that may impact gestational weight gain (GWG) - a pregnancy health indicator. We investigated overall and fetal sex-specific associations of individual and cumulative phthalate/replacement biomarkers with GWG. METHODS: Illinois women (n = 299) self-reported their weight pre-pregnancy and at their final obstetric appointment before delivery (median 38 weeks). We calculated pre-pregnancy body mass index and gestational age-specific GWG z-scores (GWGz). We quantified 19 phthalate/replacement metabolites (representing 10 parent compounds) in pools of up-to-five first-morning urine samples, collected approximately monthly between 8 and 40 weeks gestation. We used linear regression, quantile-based g-computation (QGComp), and weighted quantile sum regression (WQSR) to evaluate associations of ten biomarkers (individual metabolites or parent molar-sums) individually or as mixtures (in interquartile range intervals) with GWGz. We evaluated associations in all women and stratified by fetal sex. RESULTS: Individually, sums of metabolites of di(2-ethylhexyl) phthalate (Æ©DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (Æ©DiNCH), and di(2-ethylhexyl) terephthalate (Æ©DEHTP) had consistent inverse associations with GWGz, and some associations were fetal sex-specific. When evaluating phthalates/replacements as a mixture, QGComp identified Æ©DEHP, Æ©DEHTP, and mono-(3-carboxypropyl) phthalate, along with sum of di(isononyl) phthalate metabolites (Æ©DiNP) and monobenzyl phthalate as notable contributors to lower and higher GWGz, respectively, resulting in a marginal inverse joint association in all women (ß: -0.29; 95% CI: -0.70, 0.12). In women carrying females, Æ©DEHP contributed to the marginal inverse joint association (ß: -0.54; 95% CI: -1.09, 0.03). However, there was no overall association in women carrying males (ß: 0.00; 95% CI: -0.60, 0.59), which was explained by approximately equal negative (driven by Æ©DEHTP) and positive (driven by Æ©DiNP) partial associations. WQSR analyses consistently replicated these QGComp findings. CONCLUSIONS: Biomarkers of phthalates/replacements were fetal sex-specifically associated with GWGz. Because Æ©DEHTP contributed substantively to mixture associations, additional studies in pregnant women may be needed around this plasticizer replacement.

An EHR-automated and theory-based population health management intervention for smoking cessation in diverse low-income patients of safety-net health centers: a pilot randomized controlled trial.

This study tested the preliminary effectiveness of an electronic health record (EHR)-automated population health management (PHM) intervention for smoking cessation among adult patients of a federally qualified health center in Chicago. Participants (N = 190; 64.7% women, 82.1% African American/Black, 8.4% Hispanic/Latino) were self-identified as smokers, as documented in the EHR, who completed the baseline survey of a longitudinal "needs assessment of health behaviors to strengthen health programs and services." Four weeks later, participants were randomly assigned to the PHM intervention (N = 97) or enhanced usual care (EUC; N = 93). PHM participants were mailed a single-page self-determination theory (SDT)-informed letter that encouraged smoking cessation or reduction as an initial step. The letter also addressed low health literacy and low income. PHM participants also received automated text messages on days 1, 5, 8, 11, and 20 after the mailed letter. Two weeks after mailing, participants were called by the Illinois Tobacco Quitline. EUC participants were e-referred following a usual practice. Participants reached by the quitline were offered behavioral counseling and nicotine replacement therapy. Outcome assessments were conducted at weeks 6, 14, and 28 after the mailed letter. Primary outcomes were treatment engagement, utilization, and self-reported smoking cessation. In the PHM arm, 25.8% of participants engaged in treatment, 21.6% used treatment, and 16.3% were abstinent at 28 weeks. This contrasts with no quitline engagement among EUC participants, and a 6.4% abstinence rate. A PHM approach that can reach all patients who smoke and address unique barriers for low-income individuals may be a critical supplement to clinic-based care.

Physical activity modifies the relation between gestational perfluorooctanoic acid exposure and adolescent cardiometabolic risk.

OBJECTIVE: Exposure to per- and polyfluoroalkyl substances (PFAS) - endocrine disrupting chemicals - may increase cardiometabolic risk. We evaluated whether adolescent lifestyle factors modified associations between gestational PFAS exposure and cardiometabolic risk using a prospective cohort study. METHODS: In 166 mother-child pairs (HOME Study), we measured concentrations of four PFAS in maternal serum collected during pregnancy. When children were age 12 years, we calculated cardiometabolic risk scores from visceral adiposity area, blood pressure, and fasting serum biomarkers. We assessed adolescent physical activity and Healthy Eating Index scores using the Physical Activity Questionnaire for Older Children (PAQ-C), actigraphy, and 24-h diet recalls. Using multivariable linear regression and weighted quantile sum regression, we examined whether physical activity or diet modified covariate-adjusted associations of PFAS and their mixture with cardiometabolic risk scores. RESULTS: Physical activity modified associations between perfluorooctanoic acid (PFOA) and cardiometabolic risk scores. Each doubling of PFOA was associated with worse cardiometabolic risk scores among children with PAQ-C scores < median (ß:1.4; 95% CI:0.5, 2.2, n = 82), but not among those with PAQ-C scores ≥ median (ß: 0.2; 95% CI: 1.2, 0.7, n = 84) (interaction p-value = 0.01). Associations were most prominent for insulin resistance, leptin-adiponectin ratio, and visceral fat area. We observed results suggesting that physical activity modified the association of PFAS mixture with cardiometabolic risk scores, insulin resistance, and visceral fat area (interaction p-values = 0.17, 0.07, and 0.10, respectively); however, the 95% CIs of the interaction terms included the null value. We observed similar, but attenuated patterns for PFOA and actigraphy-based measures of physical activity. Diet did not modify any associations. Physical activity or diet did not modify associations for other PFAS. CONCLUSIONS: Childhood physical activity modified associations of prenatal serum PFOA concentrations with children's cardiometabolic risk in this cohort, indicating that lifestyle interventions may ameliorate the adverse effects of PFOA exposure.

E-cigarette and combusted tobacco abstinence among young adults: Secondary analyses from a U.S.-based randomized controlled trial of vaping cessation.

OBJECTIVE: To examine patterns of abstinence from e-cigarettes, combusted tobacco products (CTPs), both, or neither among young adults enrolled in a U.S.-based randomized trial of a text message vaping cessation intervention. METHODS: At baseline, 1829 young adult e-cigarette users were categorized as Exclusive E-cigarette Users (no past 30-day CTP use; n = 1036, 56.6%) or Dual Users (past 30-day CTP use; n = 793, 43.4%). Four groups were defined at 7-months: 1) Dual Abstinent, 2) Exclusive Vaping, 3) Exclusive CTP Use, and 4) Dual Users. The proportion of participants who were Dual Abstinent was the outcome of interest. RESULTS: At follow-up, 22.1% (95% CI: 20.3, 24.1) of participants were Dual Abstinent, 44.8% (95% CI: 42.5, 47.1) reported Exclusive Vaping, 6.3% (95% CI: 5.2, 7.5) reported Exclusive CTP Use, and 26.8% (95% CI: 24.8, 28.9) were Dual Users. A higher proportion of participants randomized to Intervention were Dual Abstinent (25.9%, 95% CI 23.1, 28.9) compared to Control (18.5%, 95% CI 16.0, 21.1; p = .0002). Analyses of treatment effects on dual abstinence by baseline tobacco product use favored Intervention over Control among both Exclusive E-cigarette Users (p = .019) and Dual Users (p = .0014). CONCLUSION: A text message vaping cessation intervention was effective in promoting dual abstinence from e-cigarettes and CTPs among young adults. The advantage of treatment over control was equivalent for Exclusive E-cigarette Users and Dual Users. Rates of dual abstinence were higher among exclusive vapers than dual users, signaling the need for more research to optimize cessation programs for poly-tobacco users.

Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study.

BACKGROUND: DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation. OBJECTIVES: We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio). METHODS: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations. RESULTS: After adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q<0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children's age. DISCUSSION: In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118.

Maternal nicotine metabolism moderates the impact of maternal cigarette smoking on infant birth weight: A Collaborative Perinatal Project investigation.

BACKGROUND: Maternal cigarette smoking is an important modifiable risk factor for low birth weight in the US. We investigated the maternal nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine/cotinine) - a genetically-informed biomarker of nicotine clearance - as a moderator of links between prenatal cigarette use and birth weight. We also explored the role of race in these associations. METHODS: Participants were 454 pregnant women (Mage = 25 years; 11% Black) who smoked cigarettes and their 537 infants from the Collaborative Perinatal Project. Cigarettes smoked per day were assessed at each prenatal visit; maternal NMR was assayed from third trimester serum. Birth weight was obtained from medical records. Generalized estimating equations were used to evaluate associations between cigarette smoking, NMR, race, and birth weight. RESULTS: NMR moderated continuous associations between cigarettes per day over pregnancy and infant birth weight (p = .025). Among women who smoked at moderate levels (<15 cigarettes per day), those with slower NMR showed ~50-100 g decrements in birth weight versus those with faster NMR., while there were no significant associations between NMR and birth weight among women who smoked 15+ cigarettes per day. Although effects of NMR on birthweight were similar for Black and white women, Black women showed significantly slower NMR (p < .001). CONCLUSIONS: This is the first demonstration that the maternal nicotine metabolism phenotype moderates associations between maternal smoking during pregnancy and birth weight. Infants of women with slower nicotine metabolism - including disproportionate representation of Black women - may be at heightened risk for morbidity from maternal smoking.

Effectiveness of an optimized text message and Internet intervention for smoking cessation: A randomized controlled trial.

AIMS: To evaluate the effectiveness of a combined internet and text message intervention for smoking cessation compared with an internet intervention alone. The text message intervention was optimized for engagement in an earlier multiphase optimization (MOST) screening phase. DESIGN: A parallel, two-group, individually randomized clinical trial (RCT) was conducted in a MOST confirming phase. Recruitment spanned December 2018 to March 2019. Follow-up was conducted at 3 and 9 months, beginning March 2019 and ending January 2020. SETTING: United States: a digital study conducted among new registrants on a free tobacco cessation website. PARTICIPANTS: Eligible individuals were 618 adult current smokers in the United States, age 18 years or older who signed up for text messages during website registration (67.2% female, 70.4% white). INTERVENTIONS: The treatment arm (WEB+TXT; n = 311) received access to the website and text messaging. The control arm (WEB; n = 307) received access to the website alone. MEASUREMENTS: The primary outcome was self-reported 30-day point prevalence abstinence (ppa) at 9 months post-randomization analyzed under intent to treat (ITT), counting non-responders as smoking. Secondary outcomes included 3-month measures of 30-day ppa, intervention engagement and intervention satisfaction. FINDINGS: Abstinence rates at 9 months were 23.1% among WEB+TXT and 23.2% among WEB (OR = 1.00, 95% CI = 0.69-1.45; P = 0.99). WEB+TXT increased engagement with 5 of 6 interactive features (standardized mean difference (SMD) = 0.26-0.47, all P < 0.001) and repeat website visits (48.7% vs 38.9%, SMD = 0.14, P = 0.02). Satisfaction metrics favored WEB+TXT (satisfied: 96.3% vs 90.5%, SMD = 0.17, P = 0.008; recommend to friend: 95.9% vs 90.1%, SMD = 0.16, P = 0.028). CONCLUSIONS: A randomized controlled trial found no evidence that a combined internet and text message intervention for smoking cessation compared with an internet intervention alone increased 9-month abstinence rates among adult current smokers in the United States, despite evidence of higher levels of intervention engagement and satisfaction at 3 months.

Flavored waterpipe tobacco preferences, perceptions, and use in pregnant women: A latent factor mapping approach.

Waterpipe tobacco (WPT) use is increasingly common in young adults including pregnant and reproductive-age women. Sweet flavors contribute to the appeal of WPT and are a promising regulatory target. The present study utilized correspondence analysis of contingency tables, a latent factor mapping technique, to investigate preferences and perceptions of WPT flavors in a sample of racially/ethnically diverse, low-income pregnant women. One hundred pregnant women (mean age = 26 years, 65% racial/ethnic minorities) completed a detailed interview regarding their use, preferences, and perceptions of WPT flavors. Eighty-three percent of participants reported lifetime WPT use; 11% reported prenatal WPT use. Pregnant women reported greatest use of and stronger preferences for sweet (fruit, candy, alcohol) and menthol/mint flavors, and weaker preferences for tobacco flavored WPT. Latent factor mapping revealed clustering of preferred sweet (fruit, candy, alcohol) and menthol/mint flavors versus tobacco flavors, with pungent flavors (coffee, chocolate, spice) clustering between sweet and tobacco flavors. Preferences for sweet and menthol/mint flavors distinguished pregnant women who reported lifetime WPT versus no lifetime WPT use, and prenatal WPT use versus no prenatal WPT use. Harm perceptions did not vary by flavor. Regulations to restrict the availability of WPT flavors may reduce the appeal and use of WPT, especially among pregnant women.

Effectiveness of a Vaping Cessation Text Message Program Among Young Adult e-Cigarette Users: A Randomized Clinical Trial.

Importance: e-Cigarettes are the most commonly used tobacco product among young adults (YAs). Despite the harms of nicotine exposure among YAs, there are few, if any, empirically tested vaping cessation interventions available. Objective: To determine the effectiveness of a text message program for vaping cessation among YAs vs assessment-only control. Design, Setting, and Participants: A parallel, 2-group, double-blind, individually randomized clinical trial was conducted from December 2019 to November 2020 among YA e-cigarette users. Eligible individuals were US residents aged 18 to 24 years who owned a mobile phone with an active text message plan, reported past 30-day e-cigarette use, and were interested in quitting in the next 30 days. Participants were recruited via social media ads, the intervention was delivered via text message, and assessments were completed via website or mobile phone. Follow-up was conducted at 1 and 7 months postrandomization; follow-up data collection began January 2020 and ended in November 2020. The study was prespecified in the trial protocol. Interventions: All participants received monthly assessments via text message about e-cigarette use. The assessment-only control arm (n = 1284) received no additional intervention. The active intervention arm (n = 1304) also received This is Quitting, a fully automated text message program for vaping cessation that delivers social support and cognitive and behavioral coping skills training. Main Outcomes and Measures: The primary outcome was self-reported 30-day point prevalence abstinence (ppa) at 7 months analyzed under intention-to-treat analysis, which counted nonresponders as vaping. Secondary outcomes were 7-day ppa under intention-to-treat analysis and retention weighted complete case analysis of 30-day and 7-day ppa. Results: Of the 2588 YA e-cigarette users included in the trial, the mean (SD) age was 20.4 (1.7) years, 1253 (48.4%) were male, 2159 (83.4%) were White, 275 (10.6%) were Hispanic, and 493 (19.0%) were a sexual minority. Most participants (n = 2129; 82.3%) vaped within 30 minutes of waking. The 7-month follow-up rate was 76.0% (n = 1967), with no differential attrition. Abstinence rates were 24.1% (95% CI, 21.8%-26.5%) among intervention participants and 18.6% (95% CI, 16.7%-20.8%) among control participants (odds ratio, 1.39; 95% CI, 1.15-1.68; P < .001). No baseline variables moderated the treatment-outcome relationship, including nicotine dependence. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that a tailored and interactive text message intervention was effective in promoting vaping cessation among YAs. These results establish a benchmark of intervention effectiveness. Trial Registration: ClinicalTrials.gov Identifier: NCT04251273.

Evaluation of Naturalistic Driving Behavior Using In-Vehicle Monitoring Technology in Preclinical and Early Alzheimer's Disease.

Cognitive impairment is a significant risk factor for hazardous driving among older drivers with Alzheimer's dementia, but little is known about how the driving behavior of mildly symptomatic compares with those in the preclinical, asymptomatic phase of Alzheimer's disease (AD). This study utilized two in-car technologies to characterize driving behavior in symptomatic and preclinical AD. The goals of this pilot study were to (1) describe unsafe driving behaviors in individuals with symptomatic early AD using G-force triggered video capture and (2) compare the driving habits of these symptomatic AD drivers to two groups of cognitively normal drivers, those with and those without evidence of cerebral amyloidosis (CN/A+ and CN/A-) using a global positioning system (GPS) datalogger. Thirty-three drivers (aged 60+ years) were studied over 3 months. G-force triggered video events captured instances of near-misses/collisions, traffic violations, risky driver conduct, and driving fundamentals. GPS data were sampled every 30 s and all instances of speeding, hard braking, and sudden acceleration were recorded. For the early AD participants, video capture identified driving unbelted, late response, driving too fast for conditions, traffic violations, poor judgment, and not scanning intersections as the most frequently occurring safety errors. When evaluating driving using the GPS datalogger, hard breaking events occurred most frequently on a per trip basis across all three groups. The CN/A+ group had the lowest event rate across all three event types with lower instances of speeding. Slower psychomotor speed (Trail Making Part A) was associated with fewer speeding events, more hard acceleration events, and more overall events. GPS tracked instances of speeding were correlated with total number of video-captured near-collisions/collisions and driving fundamentals. Results demonstrate the utility of electronic monitoring to identify potentially unsafe driving events in symptomatic and preclinical AD. Results suggest that drivers with preclinical AD may compensate for early, subtle cognitive changes by driving more slowly and cautiously than healthy older drivers or those with cognitive impairment. Self-regulatory changes in driving behavior appear to occur in the preclinical phase of AD, but safety concerns may not arise until symptoms of cognitive impairment emerge and the ability to self-monitor declines.

Correction: Optimizing Text Messages to Promote Engagement With Internet Smoking Cessation Treatment: Results From a Factorial Screening Experiment.

[This corrects the article DOI: 10.2196/17734.].