Associations of a Prenatal Serum Per- and Polyfluoroalkyl Substance Mixture with the Cord Serum Metabolome in the HOME Study.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous and persistent chemicals associated with multiple adverse health outcomes; however, the biological pathways affected by these chemicals are unknown. To address this knowledge gap, we used data from 264 mother-infant dyads in the Health Outcomes and Measures of the Environment (HOME) Study and employed quantile-based g-computation to estimate covariate-adjusted associations between a prenatal (∼16 weeks' gestation) serum PFAS mixture [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] and 14,402 features measured in cord serum. The PFAS mixture was associated with four features: PFOS, PFHxS, a putatively identified metabolite (3-monoiodo-l-thyronine 4-O-sulfate), and an unidentified feature (590.0020 m/z and 441.4 s retention time; false discovery rate <0.20). Using pathway enrichment analysis coupled with quantile-based g-computation, the PFAS mixture was associated with 49 metabolic pathways, most notably amino acid, carbohydrate, lipid and cofactor and vitamin metabolism, as well as glycan biosynthesis and metabolism (P(Gamma) <0.05). Future studies should assess if these pathways mediate associations of prenatal PFAS exposure with infant or child health outcomes, such as birthweight or vaccine response.

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.

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.

Prenatal exposure to famine and the development of diabetes later in life: an age-period-cohort analysis of the China health and nutrition survey (CHNS) from 1997 to 2015.

PURPOSE: Prenatal exposure to famine has been linked to increased diabetes risk in adulthood. However, one fundamental issue to be addressed is that the reported famine-diabetes relation may be confounded by the age differences between the exposed and non-exposed groups. We aimed to determine the association between prenatal exposure to the Chinese famine of 1959-1962 and risk of diabetes by applying age well-controlled strategies. METHODS: Among 20,535 individuals born in 1955-1966 who participated in the China Health and Nutrition Survey from 1997 to 2015, we constructed age-matched exposed vs. non-exposed groups to investigate the role of prenatal exposure to the Chinese famine of 1959-1962 in relation to diabetes. We also built a hierarchical age-period-cohort (HAPC) model to specifically examine the relation of famine to diabetes risk independent of age. RESULTS: Compared to the age-balanced men in the non-exposed group, the exposed men born in 1961 had a 154% increased risk of diabetes [odds ratio (OR) 2.54 (95% CI 1.07-6.03), P = 0.04). In the HAPC analysis, the predicted probabilities of diabetes peaked in the 1961-birth cohort of men [3.4% (95% CI 2.4%-5.0%)], as compared to the average probability of diabetes (reference) of 1.8% for men overall. Neither analytical strategy revealed any strong relation between famine exposure and diabetes risk in women. CONCLUSION: Among the pre-defined Chinese famine period of 1959-1962, early-life exposure to famine was associated with increased diabetes risk in men but not in women, and these relations were independent of age.

Results from the Strong Families Start at Home/Familias Fuertes Comienzan en Casa: feasibility randomised control trial to improve the diet quality of low-income, predominantly Hispanic/Latinx children.

OBJECTIVE: To describe the feasibility, acceptability and results of Strong Families Start at Home, a 6-month pilot trial of a home-based food parenting/nutrition intervention. DESIGN: Pilot randomised controlled trial. SETTING: Participants received six visits with a community health worker trained in motivational interviewing (three home visits, three phone calls); an in-home cooking or reading activity; personalised feedback on a recorded family meal or reading activity; text messages and tailored printed materials. PARTICIPANTS: Parents and their 2-5-year-old child were randomised into intervention (responsive food parenting practices/nutrition) or control (reading readiness) groups. RESULTS: Parents (n 63) were mostly mothers (90 %), Hispanic/Latinx (87 %), born outside the USA (62 %), with household incomes <$25 k (54 %). Despite delivery during COVID-19, 63 % of dyads were retained at 6 months. The intervention was delivered with high fidelity. All parents in the intervention group (n 24) expressed high levels of satisfaction with the intervention, which produced positive treatment effects for whole and total fruit component Healthy Eating Index-2015 scores (point estimate (PE) = 2·14, 95 % CI (0·17, 1·48); PE = 1·71, 95 % CI (0·16, 1·47), respectively) and negative treatment effects for sodium (PE = -2·09, 95 % CI (-1·35, -0·04)). Positive treatment effects also resulted for the following food parenting practices: regular timing of meals and snacks (PE = 1·08, 95 % CI (0·61, 2·00)), reducing distractions during mealtimes (PE = -0·79, 95 % CI (-1·52, -0·19)), using food as a reward (PE = -0·54, 95 % CI (-1·35, -0·04)) and providing a supportive meal environment (PE = 0·73, 95 % CI (0·18, 1·51)). CONCLUSION: Given the continued disparities in diet quality among low-income and diverse families, continued efforts to improve child diet quality in fully powered intervention trials are needed.

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.

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.

Gestational perfluoroalkyl substance exposure and body mass index trajectories over the first 12 years of life.

BACKGROUND/OBJECTIVES: Gestational exposure to perfluoroalkyl substances (PFAS), a ubiquitous class of persistent endocrine disrupting chemicals, is associated with increased risk of obesity and cardiometabolic disease. However, it is unclear if gestational PFAS exposure is associated with adiposity trajectories related to adult obesity and cardiometabolic health. SUBJECTS/METHODS: We measured perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononaoic acid, and perfluorohexanesulfonic acid (PFHxS) concentrations in maternal serum collected between 16 weeks gestation and delivery in a cohort of 345 mother-child pairs in Cincinnati, OH (enrolled 2003-06). From age 4 weeks to 12 years, we measured weight and length or height up to eight times and calculated child body mass index (BMI) (1865 repeated measures). Using covariate-adjusted linear mixed models and splines to account for repeated BMI measures and nonlinear BMI patterns, respectively, we estimated the age/magnitude of infancy BMI zenith (~1 year) and childhood BMI nadir (~5 years), BMI accrual from 8 to 12 years, and BMI at age 12 years by PFAS terciles. RESULTS: BMI trajectories varied by PFOA concentrations (age × PFOA interaction p value = 0.03). Children born to women with higher PFOA concentrations had lower infancy and early childhood BMI, earlier BMI nadir, accelerating BMI gains in mid-childhood and adolescence, and higher BMI at age 12 years. Some of these associations were non-monotonic. PFOS and PFHxS were not associated with alterations in BMI trajectories, but were monotonically associated with lower BMI across infancy, childhood, and adolescence. Compared to children in the first PFOS tercile, those in the second (ß: -0.83; 95% confidence interval (CI): -2.11, 0.51 kg/m2), and third (ß: -1.41; 95% CI: -2.65, -0.14 kg/m2) had lower BMI at age 12 years. CONCLUSIONS: These results suggest that gestational PFOA exposure may be associated with BMI trajectories related to adult obesity and cardiometabolic disease, while PFOS and PFHxS exposure is associated with lower BMI in the first 12 years of life.

Effects of prenatal bacterial infection on cognitive performance in early childhood.

BACKGROUND: Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up. OBJECTIVES: We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection. METHODS: We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models. RESULTS: ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters. CONCLUSIONS: We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring.

Exposure to Per- and Polyfluoroalkyl Substances and Adiposity at Age 12 Years: Evaluating Periods of Susceptibility.

Per- and polyfluoroalkyl substances (PFAS) exposure may increase adiposity and obesity risk in children. However, no studies have extended these findings into adolescence or identified periods of heightened susceptibility. We estimated associations of repeated pre- and postnatal serum PFAS concentrations with adolescent adiposity and risk of overweight/obesity. We studied 212 mother-offspring pairs from the HOME Study. We quantified serum concentrations of four PFAS in mothers at ∼16 week gestation and their children at birth and ages 3, 8, and 12 years. We assessed adiposity at 12 years using anthropometry and dual-energy X-ray absorptiometry. Using multiple informant models, we estimated covariate-adjusted associations of an interquartile range (IQR) increase in log2-transformed PFAS for each time period with adiposity measures and tested differences in these associations. Serum perfluorooctanoate (PFOA) and perfluorohexane sulfonate (PFHxS) concentrations during pregnancy were associated with modest increases in central adiposity and risk of overweight/obesity, but there was no consistent pattern for postnatal concentrations. We observed nonlinear associations between PFOA in pregnancy and some measures of adiposity. Overall, we observed a pattern of modest positive associations of gestational PFOA and PFHxS concentrations with central adiposity and the risk of obesity in adolescents, while no pattern was observed for postnatal PFAS concentrations.

Prenatal antidepressant exposures and gastrointestinal complaints in childhood: A gut-brain axis connection?

Selective serotonin/norepinephrine reuptake inhibitors (collectively, SRIs) are the most commonly prescribed antidepressant agents for the treatment of depression in pregnancy. SRIs affect maternal and placental serotonin signaling, which might impact fetal brain development. Alterations in serotonin signaling might also impact the developing gut-brain axis (GBA) via alterations in the fetal enteric nervous system (ENS). Emerging evidence suggests that gestational SRI exposure may be associated with offspring gastrointestinal problems. However, prospective human studies of the effects of fetal SRI exposure on the ENS and function are absent in the literature. In this paper we present data demonstrating significant associations between prenatal SRI exposure and children's gastrointestinal (GI) problems in two well-characterized, prospective cohorts of preschool and later childhood individuals. The results support the hypothesis that prenatal SRI exposure can increase the risk for childhood GI difficulties. Further research is warranted on the potential SRI-induced changes to the child gut including the role of the microbiome and the GBA in the development of GI problems.

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.].

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

BACKGROUND: Smoking remains a leading cause of preventable death and illness. Internet interventions for smoking cessation have the potential to significantly impact public health, given their broad reach and proven effectiveness. Given the dose-response association between engagement and behavior change, identifying strategies to promote engagement is a priority across digital health interventions. Text messaging is a proven smoking cessation treatment modality and a powerful strategy to increase intervention engagement in other areas of health, but it has not been tested as an engagement strategy for a digital cessation intervention. OBJECTIVE: This study examined the impact of 4 experimental text message design factors on adult smokers' engagement with an internet smoking cessation program. METHODS: We conducted a 2×2×2×2 full factorial screening experiment wherein 864 participants were randomized to 1 of 16 experimental conditions after registering with a free internet smoking cessation program and enrolling in its automated text message program. Experimental factors were personalization (on/off), integration between the web and text message platforms (on/off), dynamic tailoring of intervention content based on user engagement (on/off), and message intensity (tapered vs abrupt drop-off). Primary outcomes were 3-month measures of engagement (ie, page views, time on site, and return visits to the website) as well as use of 6 interactive features of the internet program. All metrics were automatically tracked; there were no missing data. RESULTS: Main effects were detected for integration and dynamic tailoring. Integration significantly increased interactive feature use by participants, whereas dynamic tailoring increased the number of features used and page views. No main effects were found for message intensity or personalization alone, although several synergistic interactions with other experimental features were observed. Synergistic effects, when all experimental factors were active, resulted in the highest rates of interactive feature use and the greatest proportion of participants at high levels of engagement. Measured in terms of standardized mean differences (SMDs), effects on interactive feature use were highest for Build Support System (SMD 0.56; 95% CI 0.27 to 0.81), Choose Quit Smoking Aid (SMD 0.38; 95% CI 0.10 to 0.66), and Track Smoking Triggers (SMD 0.33; 95% CI 0.05 to 0.61). Among the engagement metrics, the largest effects were on overall feature utilization (SMD 0.33; 95% CI 0.06 to 0.59) and time on site (SMD 0.29; 95% CI 0.01 to 0.57). As no SMD >0.30 was observed for main effects on any outcome, results suggest that for some outcomes, the combined intervention was stronger than individual factors alone. CONCLUSIONS: This factorial experiment demonstrates the effectiveness of text messaging as a strategy to increase engagement with an internet smoking cessation intervention, resulting in greater overall intervention dose and greater exposure to the core components of tobacco dependence treatment that can promote abstinence. TRIAL REGISTRATION: ClinicalTrials.gov NCT02585206; https://clinicaltrials.gov/ct2/show/NCT02585206. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2015-010687.

Metabolomics of childhood exposure to perfluoroalkyl substances: a cross-sectional study.

INTRODUCTION: Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAS toxicity. OBJECTIVE: To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. METHODS: We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate < 20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. RESULTS: Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. CONCLUSIONS: In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health.

Discussions of Alcohol Use in an Online Social Network for Smoking Cessation: Analysis of Topics, Sentiment, and Social Network Centrality.

BACKGROUND: Few Internet smoking cessation programs specifically address the impact of alcohol use during a quit attempt, despite its common role in relapse. This study used topic modeling to describe the most prevalent topics about alcohol in an online smoking cessation community, the prevalence of negative sentiment expressed about alcohol use in the context of a quit attempt (i.e., alcohol should be limited or avoided during a quit attempt) within topics, and the degree to which topics differed by user social connectivity within the network. METHODS: Data were analyzed from posts from the online community of a larger Internet cessation program, spanning January 1, 2012 to May 31, 2015 and included records of 814,258 online posts. Posts containing alcohol-related content (n = 7,199) were coded via supervised machine learning text classification to determine whether the post expressed negative sentiment about drinking in the context of a quit attempt. Correlated topic modeling (CTM) was used to identify a set of 10 topics of at least 1% prevalence based on the frequency of word occurrences among alcohol-related posts; the distribution of negative sentiment and user social network connectivity was examined across the most salient topics. RESULTS: Three salient topics (with prevalence ≥10%) emerged from the CTM, with distinct themes of (i) cravings and temptations; (ii) parallel between nicotine addiction and alcoholism; and (iii) celebratory discussions of quit milestones including "virtual" alcohol use and toasts. Most topics skewed toward nonnegative sentiment about alcohol. The prevalence of each topic differed by users' social connectivity in the network. CONCLUSIONS: Future work should examine whether outcomes in Internet interventions are improved by tailoring social network content to match user characteristics, topics, and network behavior.

Inferring Smoking Status from User Generated Content in an Online Cessation Community.

Introduction: User generated content (UGC) is a valuable but underutilized source of information about individuals who participate in online cessation interventions. This study represents a first effort to passively detect smoking status among members of an online cessation program using UGC. Methods: Secondary data analysis was performed on data from 826 participants in a web-based smoking cessation randomized trial that included an online community. Domain experts from the online community reviewed each post and comment written by participants and attempted to infer the author's smoking status at the time it was written. Inferences from UGC were validated by comparison with self-reported 30-day point prevalence abstinence (PPA). Following validation, the impact of this method was evaluated across all individuals and time points in the study period. Results: Of the 826 participants in the analytic sample, 719 had written at least one post from which content inference was possible. Among participants for whom unambiguous smoking status was inferred during the 30 days preceding their 3-month follow-up survey, concordance with self-report was almost perfect (kappa = 0.94). Posts indicating abstinence tended to be written shortly after enrollment (median = 14 days). Conclusions: Passive inference of smoking status from UGC in online cessation communities is possible and highly reliable for smokers who actively produce content. These results lay the groundwork for further development of observational research tools and intervention innovations. Implications: A proof-of-concept methodology for inferring smoking status from user generated content in online cessation communities is presented and validated. Content inference of smoking status makes a key cessation variable available for use in observational designs. This method provides a powerful tool for researchers interested in online cessation interventions and establishes a foundation for larger scale application via machine learning.

Identifying periods of susceptibility to the impact of phthalates on children's cognitive abilities.

BACKGROUND: Early-life phthalate exposures may adversely affect children's neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering fatty acid concentrations in the brain. This study aimed to identify periods of heightened susceptibility during gestation, infancy, and childhood to the impact of phthalates on children's cognitive abilities. METHODS: We used data from 253 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio), a longitudinal pregnancy and birth cohort. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation and 6 times during study visits when children were aged 1-8 years using a modified method of on-line solid phase extraction coupled with isotope dilution-high performance liquid chromatography-tandem mass spectrometry. We assessed children's intelligence (IQ) at ages 5 and 8 years using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV, respectively. We estimated covariate-adjusted associations between a 1-standard deviation increase in log10-transformed urinary phthalate metabolite concentrations at each visit and children's IQ, adjusting for demographic, perinatal, and child factors; we tested for differences in these associations across visits using multiple informant models. RESULTS: Associations between some phthalate metabolites and IQ varied by visit (phthalate x visit interaction p-values<0.20). The sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), mono(3-carboxypropyl) phthalate, and monoethyl phthalate at age 3 years, and monobenzyl phthalate at 16 weeks gestation and child ages 3, 5, and 8 years were inversely associated with children's full-scale IQ. For example, each 1-standard deviation increase in ΣDEHP at age 3 was associated with a 1.9-point decrease in full-scale IQ (95% confidence interval: -3.7, -0.2). Mono-n-butyl phthalate and mono-isobutyl phthalate at age 4 years were positively associated with children's full-scale IQ. CONCLUSION: Urinary concentrations of several phthalate metabolites at age 3 years, compared to other time periods, were more strongly associated with decreased cognitive abilities in these children.

Mining User-Generated Content in an Online Smoking Cessation Community to Identify Smoking Status: A Machine Learning Approach.

Online smoking cessation communities help hundreds of thousands of smokers quit smoking and stay abstinent each year. Content shared by users of such communities may contain important information that could enable more effective and personally tailored cessation treatment recommendations. This study demonstrates a novel approach to determine individuals' smoking status by applying machine learning techniques to classify user-generated content in an online cessation community. Study data were from BecomeAnEX.org, a large, online smoking cessation community. We extracted three types of novel features from a post: domain-specific features, author-based features, and thread-based features. These features helped to improve the smoking status identification (quit vs. not) performance by 9.7% compared to using only text features of a post's content. In other words, knowledge from domain experts, data regarding the post author's patterns of online engagement, and other community member reactions to the post can help to determine the focal post author's smoking status, over and above the actual content of a focal post. We demonstrated that machine learning methods can be applied to user-generated data from online cessation communities to validly and reliably discern important user characteristics, which could aid decision support on intervention tailoring.

Associations of early life urinary triclosan concentrations with maternal, neonatal, and child thyroid hormone levels.

BACKGROUND: Triclosan, an antimicrobial agent used in some consumer products, reduces endogenous thyroid hormone concentrations in rodents. Despite ubiquitous triclosan exposure and the importance of thyroid hormones for normal fetal development, few human studies have examined the impact of triclosan exposure on maternal, neonatal, or child thyroid hormones. METHODS: In the HOME Study, a prospective cohort from Cincinnati, OH, we measured urinary triclosan concentrations up to three times in pregnant women between 16weeks and delivery, and up to three times in children between age 1-3years. We quantified serum concentrations of thyroid stimulating hormone and total and free thyroxine and triiodothyronine in mothers at 16-weeks gestation (n=202), neonates at delivery (n=274), and children at age 3years (n=153). We estimated covariate-adjusted differences in thyroid hormones with a 10-fold increase in triclosan using linear regression and multiple informants models. RESULTS: Triclosan was not associated with thyroid hormones during pregnancy. We observed a few associations of triclosan concentrations with thyroid hormone concentrations in neonates at delivery and children at age 3years. Higher gestational triclosan, particularly around the time of delivery, was associated with lower cord serum total thyroxine (ß: 0.3µg/dL; 95% CI: -0.6, -0.0). Childhood triclosan, particularly at age 1year, was positively associated with total thyroxine at age 3years (ß: 0.7µg/dL; 95% CI: 0.3, 1.2). CONCLUSION: Our findings suggest that triclosan exposure may influence some features of neonatal and early child thyroid function. Given the large number of comparisons we made, these findings should be replicated in other cohorts.

Improving Adherence to Smoking Cessation Treatment: Smoking Outcomes in a Web-based Randomized Trial.

Background: Partial adherence in Internet smoking cessation interventions presents treatment and evaluation challenges. Increasing adherence may improve outcomes. Purpose: To present smoking outcomes from an Internet randomized trial of two strategies to encourage adherence to tobacco dependence treatment components: (i) a social network (SN) strategy to integrate smokers into an online community and (ii) free nicotine replacement therapy (NRT). In addition to intent-to-treat analyses, we used novel statistical methods to distinguish the impact of treatment assignment from treatment utilization. Methods: A total of 5,290 current smokers on a cessation website (WEB) were randomized to WEB, WEB + SN, WEB + NRT, or WEB + SN + NRT. The main outcome was 30-day point prevalence abstinence at 3 and 9 months post-randomization. Adherence measures included self-reported medication use (meds), and website metrics of skills training (sk) and community use (comm). Inverse Probability of Retention Weighting and Inverse Probability of Treatment Weighting jointly addressed dropout and treatment selection. Propensity weights were used to calculate Average Treatment effects on the Treated. Results: Treatment assignment analyses showed no effects on abstinence for either adherence strategy. Abstinence rates were 25.7%-32.2% among participants that used all three treatment components (sk+comm +meds).Treatment utilization analyses revealed that among such participants, sk+comm+meds yielded large percentage point increases in 3-month abstinence rates over sk alone across arms: WEB = 20.6 (95% CI = 10.8, 30.4), WEB + SN = 19.2 (95% CI = 11.1, 27.3), WEB + NRT = 13.1 (95% CI = 4.1, 22.0), and WEB + SN + NRT = 20.0 (95% CI = 12.2, 27.7). Conclusions: Novel propensity weighting approaches can serve as a model for establishing efficacy of Internet interventions and yield important insights about mechanisms. Clinical Trials.gov: NCT01544153.