The Impact of Three Alternate Nicotine-Delivery Products on Combusted Cigarette Use: A Randomized Controlled Trial.

INTRODUCTION: Smoking cessation is a critical public health goal. This study examined the ability of e-cigarettes and very low nicotine cigarettes (VLNCs) to serve as cigarette substitutes and whether a substitution was supported by steady-state nicotine from a nicotine patch. AIMS AND METHODS: This mixed design experiment with study product (between-subjects) and patch (within-subjects) factors recruited adults smoking cigarettes daily and not motivated to quit (N = 160). Participants were randomized to 4 weeks of: (1) VLNCs; (2) e-cigarettes; or (3) no product. During two switch weeks, one with an active nicotine patch and one with a placebo patch (in a double-blind and counterbalanced fashion), participants were told to not smoke their usual cigarettes. RESULTS: During the switch weeks, participants in the VLNC (M = 2.88, SD = .65) and e-cigarette (M = 3.20, SD = .63) groups smoked fewer of their own cigarettes per day than did no product group participants who continued to smoke their own cigarettes (M = 5.48, SD = .63); the VLNC and e-cigarette groups did not differ. There was no main effect of patch on mean usual brand cigarettes smoked per day (P = .09), nor was there a product × patch interaction (P = .51). There was a product × age interaction (P = .03); smokers aged 60-74 smoked more of their own cigarettes if they were randomized to no product group. CONCLUSIONS: VLNCs and e-cigarettes appear to reduce usual brand cigarettes smoked per day to a similar degree, regardless of patch condition. Behavioral factors, in addition to nicotine dependence, play an important role in sustaining smoking behavior and need to be addressed in smoking cessation treatment. IMPLICATIONS: This study found that behavioral substitutes for cigarettes, whether or not they delivered nicotine, reduced the number of usual brand cigarettes smoked. Specifically, both e-cigarettes delivering nicotine and VLNCs equally reduce usual brand cigarettes smoked among adults who smoke daily and do not want to quit.

Predictive utility of the P3 event-related potential (ERP) response to alcohol cues for ecologically assessed alcohol craving and use.

Neural measures of alcohol cue incentive salience have been associated with retrospective reports of riskier alcohol use behaviour and subjective response profiles. This study tested whether the P3 event-related potential (ERP) elicited by alcohol-related cues (ACR-P3) can forecast alcohol use and craving during real-world drinking episodes. Participants (N = 262; Mage = 19.53; 56% female) completed a laboratory task in which they viewed images of everyday objects (Neutral), non-alcohol drinks (NonAlc) and alcohol beverages (Alc) while EEG was recorded and then completed a 21-day ecological momentary assessment (EMA) protocol in which they recorded alcohol craving and consumption. Anthropometrics were used to derive estimated blood alcohol concentration (eBAC) throughout drinking episodes. Multilevel modelling indicated positive associations between P3 amplitudes elicited by all stimuli and within-episode alcohol use measures (e.g., eBAC, cumulative drinks). Focal follow-up analyses indicated a positive association between AlcP3 amplitude and eBAC within episodes: Larger AlcP3 was associated with a steeper rise in eBAC. This association was robust to controlling for the association between NonAlcP3 and eBAC. AlcP3 also was positively associated with episode-level measures (e.g., max drinks, max eBAC). There were no associations between any P3 variables and EMA-based craving measures. Thus, individual differences in neural measures of alcohol cue incentive salience appear to predict the speed and intensity of alcohol consumption but not reports of craving during real-world alcohol use episodes.

Correlates of improved outcomes in patients with COVID-19 treated in US emergency departments.

BACKGROUND: The COVID-19 pandemic was managed in part by the rapid development of vaccines, diagnostics, and therapeutics including antiviral agents and advances in emergency airway and ventilatory management. The impact of these therapeutic advances on clinically pertinent metrics of emergency care have not been well-studied. METHODS: We abstracted data from emergency department (ED) visits made to 21 US health systems during the first two years of the pandemic, from February 1, 2020 to January 31, 2022. These health systems were participants in the NIH-supported COVID EHR Cohort, in which the University of Wisconsin served as the coordinating site. Limited patient-level data files were submitted monthly. Data elements included demographic and clinical variables, as well as standard measures of ED outcomes including 72-h returns, 72-h returns leading to readmission, and in-hospital mortality. Multivariable models were fitted to identify correlates of each of the dependent variables. A test for trend was used to detect changes in outcomes over time. RESULTS: During the two-year period, 150,357 individuals aged 18 years or older visited the ED. The median age was 45.4 years (IQR 27), 58.1 % were female, 49 % were White, 18.3 % Hispanic/Latino, and 45 % were publicly insured or uninsured. The prevalence of 72-h ED returns, readmissions, and in-hospital mortality significantly declined across the two-year period. SARS-CoV-2 vaccination was associated with reduced ED returns and mortality. Therapeutic agents were associated with increased mortality risk but were likely confounded by unmeasured covariates. CONCLUSIONS: Operational and clinical outcomes of ED-based treatment of individuals with COVID-19 improved in the first two years of the pandemic. This improvement is likely multifactorial and includes the development and deployment of SARS-CoV-2-specific vaccines, therapeutic agents, and improved healthcare delivery in the ED and elsewhere addressing management of airway and ventilatory status, as well as increased innate immunity in the general population.

COVID-19 outcomes among patients with dementia and age-matched controls who were hospitalized in 21 US health-care systems.

INTRODUCTION: COVID-19 had devastating impacts worldwide. However, most research examining the impact of dementia on COVID-19 outcomes has been conducted in Europe and Asia and has not examined dementia subtypes. METHODS: A retrospective analysis of electronic health record data from 21 US health-care systems examined relationships of all-cause dementia, Alzheimer's disease (AD), and vascular dementia with in-hospital mortality, intensive care unit (ICU) admission, and hospital stay duration. RESULTS: All-cause dementia, but not AD or vascular dementia independently, was associated with increased mortality risk, the inclusion of discharge to hospice as a mortality equivalent increased risk for mortality for all-cause dementia, and AD and vascular dementia. Patients with all-cause dementia and AD were less likely to be admitted to the ICU than patients without. Patients with any form of dementia had longer hospital stays than patients without. DISCUSSION: Dementia was associated with increased mortality or hospice discharge, decreased ICU admissions, and longer hospital stays. HIGHLIGHTS: Only all-cause dementia was associated with increased mortality risk. This risk was lower than what has been published in previous research. Combining mortality and hospice discharge increased risk for all dementia subtypes. All-cause and Alzheimer's disease (AD) dementia were associated with decreased intensive care unit admissions. All-cause, vascular, and AD dementia were associated with longer hospital stays.

Factors associated with 60-day readmission among inpatients with COVID-19 at 21 United States health systems.

Identifying patients at risk for readmission after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could facilitate care planning and prevention. This retrospective cohort study of 60-day readmission included 105 543 COVID-19 patients at 21 US healthcare systems who were discharged alive between February 2020 and November 2021. Generalized linear mixed regression analyses tested predictors of 60-day readmission and severity. The all-cause readmission rate was 15% (95% confidence interval [CI] = 10%-21%), with 22% (95% CI = 18%-26%) of readmitted patients needing intensive care, and 6% (95% CI = 05%-07%) dying. Factors associated with readmission included male sex, government insurance, positive smoking history, co-morbidity burden, longer index admissions, and diagnoses at index admission (e.g., cancer, chronic kidney disease, and liver disease). Death and intensive care rates at readmission declined postvaccine availability. Receiving at least two COVID-19 vaccine doses, which were more common among older patients and those with comorbid conditions, was not independently associated with readmission but predicted a reduced risk of death at readmission. This retrospective cohort study identified factors associated with all-cause readmission for patients re-admitted to the same health system after hospitalization with SARS-CoV-2 infection. Patients who are male, who smoke, who have a higher comorbidity burden, and have government insurance may benefit from additional postacute care planning.

The Relationship of COVID-19 Vaccination with Mortality Among 86,732 Hospitalized Patients: Subpopulations, Patient Factors, and Changes over Time.

BACKGROUND: Information on COVID-19 vaccination effects on mortality among patients hospitalized with COVID-19 could inform vaccination outreach efforts and increase understanding of patient risk. OBJECTIVE: Determine the associations of vaccination status with mortality in adult patients hospitalized with COVID-19. DESIGN: This retrospective cohort study assessed the characteristics and mortality rates of adult patients hospitalized with COVID-19 across 21 healthcare systems in the USA from January 1, 2021, to January 31, 2022. PARTICIPANTS: Adult patients admitted to participating hospitals who had COVID-19 diagnoses and/or positive PCR tests and completed their hospital stay via discharge or death. MAIN MEASURE: In-hospital mortality vs. discharge (outcome) and patient age, sex, race, ethnicity, BMI, insurance status, comorbidities, and vaccination status extracted from the electronic health record (EHR). KEY RESULTS: Of 86,732 adult patients hospitalized with COVID-19, 45,082 (52%) were female, mean age was 60 years, 20,800 (24%) were Black, and 22,792 (26.3%) had one or more COVID-19 vaccinations. Statistically adjusted mortality rates for unvaccinated and vaccinated patients were 8.3% (95% CI, 8.1-8.5) and 5.1% (95% CI, 4.8-5.4) respectively (7.9% vs. 4.5% with no immune compromise). Vaccination was associated with especially large reductions in mortality for obese (OR = 0.67; 95% CI 0.56-0.80) and severely obese (OR = 0.52; 95% CI, 0.41-0.67) patients and for older patients (OR = 0.99; 95% CI, 0.98-0.99). Mortality likelihood was higher later in the study period (August 2021-January 31, 2022) than earlier (January 1, 2021-July 30, 2021) (OR = 1.10; 95% CI = 1.04-1.17) and increased significantly for vaccinated patients from 4.6% (95% CI, 3.9-5.2%) to 6.5% (95% CI, 6.2-6.9%). CONCLUSIONS: Patients vaccinated for COVID-19 had reduced mortality, especially for obese/severely obese and older individuals. Vaccination's protective effect against mortality declined over time and hospitalized obese and older individuals may derive especially great benefit from prior vaccination against SARS-CoV-2.

Disordered gambling in a longitudinal birth cohort: from childhood precursors to adult life outcomes.

BACKGROUND: Despite its introduction into the diagnostic nomenclature over four decades ago, there remain large knowledge gaps about disordered gambling. The primary aims of the present study were to document the long-term course, childhood precursors, and adult life outcomes associated with disordered gambling. METHODS: Participants enrolled in the population-representative Dunedin Study were prospectively followed from birth through age 45. Disordered gambling was assessed six times from age 18; composite measures of childhood social class, general intelligence, and low self-control were based on assessments obtained from birth through age 15; adult socioeconomic, financial, and legal outcomes were obtained through age 45. Lifetime disordered gambling was predicted from the three childhood precursors and the adult outcomes were predicted from lifetime disordered gambling. RESULTS: Past-year disordered gambling usually occurred at only a single time point and recurrence was relatively uncommon. Lower childhood social class, general intelligence, and self-control significantly predicted lifetime disordered gambling in adulthood. In turn, lifetime disordered gambling in adulthood significantly predicted occupational, educational, and financial problems in adulthood (ds = 0.23-0.41). These associations were markedly reduced and sometimes rendered nonsignificant after adjusting for childhood precursors (ds = 0.04-0.32). CONCLUSIONS: Socioeconomic, financial, and legal outcomes in adulthood are not merely consequences of disordered gambling, but also are predicted from childhood precursors. Deflecting the trajectories of young people at risk for developing disordered gambling may help to ameliorate not just the development of later disordered gambling, but also other associated adverse outcomes.

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Effects of alcohol sensitivity on alcohol-induced blackouts and passing out: An examination of the alcohol sensitivity questionnaire among underage drinkers.

BACKGROUND: The role of alcohol sensitivity in the experience of blacking out and passing out has not been well established. Here, we examined the relation between individual differences in alcohol sensitivity (i.e., numbers of drinks required to experience various effects of alcohol) and reports of blacking out and passing out in the past year. METHODS: Participants (925 healthy, underage college student drinkers) completed the Alcohol Sensitivity Questionnaire (ASQ) and reported on their past year blacking out and passing out experiences. RESULTS: The fit of the ASQ's 2-factor structure was fair (CFI = 0.90, RMSEA = 0.09) in this sample of underage drinkers. In unadjusted models, higher ASQ scores (i.e., requiring more drinks to experience effects, indicating lower alcohol sensitivity) were associated with experiencing more blackouts (IRR = 1.68 [1.31-2.15]) and passing out (IRR = 2.25 [1.59-3.18]) in the past year. After controlling for typical consumption, however, higher ASQ scores were associated with fewer past-year blackouts (IRR = 0.76 [0.60-0.98]). Total ASQ scores moderated the relationship between typical alcohol consumption and blackout occurrence (interaction IRR = 0.96 [0.93-0.98]), but not passing out occurrence (interaction IRR = 0.95 [0.89-1.01]), with the quantity of alcohol consumed more strongly associated with blackout occurrence among higher-sensitivity than lower-sensitivity drinkers. CONCLUSIONS: These findings are consistent with prior work suggesting that low sensitivity may act as a paradoxical risk factor for certain heavy drinking effects, contributing to higher levels of alcohol consumption and more frequent negative consequences while also conferring protection (relative to high-sensitivity peers) at a given level of alcohol exposure.

Prospective Study Examining the Effects of Extreme Drinking on Brain Structure in Emerging Adults.

BACKGROUND: Emerging adulthood is a critical neurodevelopment period in which extreme drinking has a potentially pronounced neurotoxic effect. Therefore, extreme drinking, even a single episode, could be particularly harmful to the developing brain's structure. Relatedly, heavy alcohol use in emerging adults has been associated with structural brain damage, especially in the corpus callosum. However, it is unclear whether and how much a single extreme drinking episode would affect brain morphometry. METHODS: For the first time in the literature, the current study prospectively examined the impact of an extreme drinking episode (i.e., twenty-first birthday celebration) on the brain morphometry of emerging adults immediately following their birthday celebration (n = 50) and approximately 5 weeks post-birthday celebration (n = 29). RESULTS: We found evidence that a single extreme drinking episode was associated with structural changes immediately post-birthday celebration. Specifically, higher twenty-first birthday estimated blood-alcohol concentration was associated with decreased volume of the posterior and central corpus callosum immediately post-birthday celebration. This extreme drinking episode was not associated with further structural changes, or recovery, 5 weeks post-twenty-first birthday celebration. CONCLUSIONS: Overall, results suggest that a single episode of heavy drinking in emerging adulthood may be associated with immediate structural changes of the corpus callosum. Thus, emerging adulthood, which is characterized by high rates of extreme drinking, could be a critical period for targeted prevention and intervention.

Neighborhood alcohol outlet density and genetic influences on alcohol use: evidence for gene-environment interaction.

BACKGROUND: Genetic influences on alcohol involvement are likely to vary as a function of the 'alcohol environment,' given that exposure to alcohol is a necessary precondition for genetic risk to be expressed. However, few gene-environment interaction studies of alcohol involvement have focused on characteristics of the community-level alcohol environment. The goal of this study was to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to drink in a genetically-informed national survey of United States young adults. METHODS: The participants were 2434 18-26-year-old twin, full-, and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Participants completed in-home interviews in which alcohol use was assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level to derive the density of outlets. RESULTS: There was evidence that the estimates of genetic and environmental influences on alcohol use varied as a function of the density of alcohol outlets in the community. For example, the heritability of the frequency of alcohol use for those residing in a neighborhood with ten or more outlets was 74% (95% confidence limits = 55-94%), compared with 16% (95% confidence limits = 0-34%) for those in a neighborhood with zero outlets. This moderating effect of alcohol outlet density was not explained by the state of residence, population density, or neighborhood sociodemographic characteristics. CONCLUSIONS: The results suggest that living in a neighborhood with many alcohol outlets may be especially high-risk for those individuals who are genetically predisposed to frequently drink.

Assessment of Alcohol Use in the Natural Environment.

The current article critically reviews 3 methodological options for assessing drinking episodes in the natural environment. Ecological momentary assessment (EMA) typically involves using mobile devices to collect self-report data from participants in daily life. This technique is now widely used in alcohol research, but investigators have implemented diverse assessment strategies. This article focuses on "high-resolution" EMA protocols that oversample experiences and behaviors within individual drinking episodes. A number of approaches have been used to accomplish this, including using signaled follow-ups tied to drinking initiation, asking participants to log entries before and after individual drinks or drinking episodes, and delivering frequent signaled assessments during periods of the day when alcohol use is most common. Transdermal alcohol sensors (TAS) are devices that are worn continuously and are capable of detecting alcohol eliminated through the skin. These methods are appealing because they do not rely upon drinkers' self-report. Studies using TAS have been appearing with greater frequency over the past several years. New methods are making the use of TAS more tractable by permitting back-translation of transdermal alcohol concentration data to more familiar estimates of blood alcohol concentration or breath alcohol concentration. However, the current generation of devices can have problems with missing data and tend to be relatively insensitive to low-level drinking. An emerging area of research investigates the possibility of using mobile device data and machine learning to passively detect the user's drinking, with promising early findings. EMA, TAS, and sensor-based approaches are all valid, and tend to produce convergent information when used in conjunction with one another. Each has a unique profile of advantages, disadvantages, and threats to validity. Therefore, the nature of the underlying research question must dictate the method(s) investigators select.

Interactive Effects of Naturalistic Drinking Context and Alcohol Sensitivity on Neural Alcohol Cue-Reactivity Responses.

BACKGROUND: Considerable evidence indicates that a low level of subjective response to alcohol's acute effects (i.e., low sensitivity) is associated with enhanced risk for alcohol use disorder (AUD). Recent work suggests that the highest risk response profile consists of blunted sensitivity to alcohol's sedation-like effects, coupled with enhanced sensitivity to alcohol's stimulation-like effects (i.e., differential sensitivity). A largely separate body of work indicates that enhanced reactivity to alcohol-related cues is associated with increased AUD risk. AIMS: The current research examined the extent to which variability in alcohol response phenotypes is associated with enhanced P3 event-related potential (ERP) responses to alcohol-related pictures (ACR-P3), and whether this reactivity varies according to depicted drinking contexts. METHODS: Eighty young adults (aged 18 to 33 years) completed a self-report measure of alcohol sensitivity (the Alcohol Sensitivity Questionnaire) and viewed images depicting drinking in naturalistic contexts, alcohol and nonalcohol beverages in isolation (devoid of naturalistic drinking context), and neutral nonbeverage control images while ERPs were recorded. RESULTS: Results indicated that blunted sensitivity to alcohol's sedative-like effects was differentially associated with enhanced ACR-P3 but reduced P3 reactivity to nonalcohol cues. Variation in sensitivity to alcohol's stimulant-like effects was not associated with differential ACR-P3. Contrary to predictions, these effects were not potentiated by drinking contexts. CONCLUSIONS: The current results replicate and extend previous work linking low alcohol sensitivity with enhanced incentive salience for alcohol-related cues and suggest that cues depicting drinking contexts are less likely to differentiate high-risk from low-risk drinkers.

In-the-Moment Drinking Characteristics: An Examination Across Attention-Deficit/Hyperactivity Disorder History and Race.

BACKGROUND: Adults with a history of childhood attention-deficit/hyperactivity disorder (ADHD) and Black drinkers are at elevated risk for alcohol problems and alcohol use disorder. Processes that increase risk for these distinct populations have not focused on in-the-moment behaviors that occur while drinking. The present study examined in-the-moment drinking characteristics (i.e., location, social context, day, time, drink type, speed of consumption) that may differ for individuals with and without ADHD histories or for Black and White drinkers. We also examined the interplay among these in-the-moment drinking characteristics to further understanding of contexts when risk may be momentarily increased. METHODS: As part of a larger study, 135 individuals (Mage  = 27.81, 69.6% male, 45.9% ADHD, 69.6% White) completed a 10-day ecological momentary assessment protocol that included self-initiated reports following consumption of an alcoholic drink. Hypotheses were tested using multilevel modeling. RESULTS: Controlling for multiple demographic covariates, Black drinkers drank significantly more quickly than White drinkers and were more likely to consume hard liquor-containing beverages. Differences in drinking speed remained significant when adjusting for Black drinkers' greater likelihood to consume liquor-containing beverages and momentary experience of discrimination; however, Black drinkers' increased likelihood to consume liquor-containing beverages was no longer significant when adjusting for momentary experience of discrimination. Individuals with ADHD histories did not differ from those without ADHD histories in any in-the-moment drinking characteristics. ADHD and race did not interact to predict any drinking characteristic. CONCLUSIONS: Differences in speed of alcohol consumption and propensity to consume liquor-containing beverages may contribute to increased risk for alcohol problems experienced by Black drinkers compared to White drinkers.

Polygenic Risk Scores for Psychiatric Disorders Reveal Novel Clues About the Genetics of Disordered Gambling.

Disordered gambling (DG) is a rare but serious condition that results in considerable financial and interpersonal harms. Twin studies indicate that DG is heritable but are silent with respect to specific genes or pathways involved. Existing genomewide association studies (GWAS) of DG have been substantially underpowered. Larger GWAS of other psychiatric disorders now permit calculation of polygenic risk scores (PRSs) that reflect the aggregated effects of common genetic variants contributing risk for the target condition. The current study investigated whether gambling and DG are associated with PRSs for four psychiatric conditions found to be comorbid with DG in epidemiologic surveys: major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). Genotype data and survey responses were analyzed from the Wave IV assessment (conducted in 2008) of the National Longitudinal Study of Adolescent to Adult Health, a representative sample of adolescents recruited in 1994-1995 and followed into adulthood. Among participants classified as having European ancestry based on genetic analysis (N = 5215), 78.4% reported ever having gambled, and 1.3% reported lifetime DG. Polygenic risk for BD was associated with decreased odds of lifetime gambling, OR = 0.93 [0.87, 0.99], p = .045, pseudo-R2(%) = .12. The SCZ PRS was associated with increased odds of DG, OR = 1.54 [1.07, 2.21], p = .02, pseudo-R2(%) = .85. Polygenic risk scores for MDD and ADHD were not related to either gambling outcome. Investigating features common to both SCZ and DG might generate valuable clues about the genetically influenced liabilities to DG.

The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings.

Introduction: Human genetic research has succeeded in definitively identifying multiple genetic variants associated with risk for nicotine dependence and heavy smoking. To build on these advances, and to aid in reducing the prevalence of smoking and its consequent health harms, the next frontier is to identify genetic predictors of successful smoking cessation and also of the efficacy of smoking cessation treatments ("pharmacogenomics"). More broadly, additional biomarkers that can be quantified from biosamples also promise to aid "Precision Medicine" and the personalization of treatment, both pharmacological and behavioral. Aims and Methods: To motivate ongoing and future efforts, here we review several compelling genetic and biomarker findings related to smoking cessation and treatment. Results: These Key results involve genetic variants in the nicotinic receptor subunit gene CHRNA5, variants in the nicotine metabolism gene CYP2A6, and the nicotine metabolite ratio. We also summarize reports of epigenetic changes related to smoking behavior. Conclusions: The results to date demonstrate the value and utility of data generated from biosamples in clinical treatment trial settings. This article cross-references a companion paper in this issue that provides practical guidance on how to incorporate biosample collection into a planned clinical trial and discusses avenues for harmonizing data and fostering consortium-based, collaborative research on the pharmacogenomics of smoking cessation. Implications: Evidence is emerging that certain genotypes and biomarkers are associated with smoking cessation success and efficacy of smoking cessation treatments. We review key findings that open potential avenues for personalizing smoking cessation treatment according to an individual's genetic or metabolic profile. These results provide important incentive for smoking cessation researchers to collect biosamples and perform genotyping in research studies and clinical trials.

Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision Medicine: Why and How.

Implications: This article outlines a framework for the consistent integration of biological data/samples into smoking cessation pharmacotherapy trials, aligned with the objectives of the recently unveiled Precision Medicine Initiative. Our goal is to encourage and provide support for treatment researchers to consider biosample collection and genotyping their existing samples as well as integrating genetic analyses into their study design in order to realize precision medicine in treatment of nicotine dependence.

Women's Alcohol Sensitivity Predicts Alcohol-Related Regretted Sex.

BACKGROUND: Low sensitivity (LS) to alcohol's acute effects is a known risk factor for heavy drinking and its negative consequences. However, LS could be protective due to LS drinkers being less impaired at a given level of consumption. Here, we tested whether LS is associated with differences in men's and women's reports of alcohol-related regretted sex. METHODS: Eight hundred and one young adults (393 women) aged 21 to 35 (M = 23.11 years) recruited for a study of alcohol's effects on cognition completed self-report measures of alcohol sensitivity, typical alcohol use, and alcohol consequences (including regretted sex). RESULTS: Participants whose alcohol sensitivity scores classified them as LS were more likely to experience alcohol-related regretted sex than were high-sensitivity (HS) participants. However, when controlling for typical alcohol use and experience of alcohol consequences in general, alcohol sensitivity was negatively associated with risk of alcohol-related regretted sex, but only among women. CONCLUSIONS: At a given level of consumption, and controlling for experience of alcohol consequences other than regretted sex, reduced sensitivity to certain effects of alcohol may be a protective factor for women against risk for alcohol-related regretted sexual situations. This study provides insight on the unique risks of drinking among LS and HS women.

WISDM Primary and Secondary Dependence Motives: Associations With Smoking Rate, Craving, and Cigarette Effects in the Natural Environment.

INTRODUCTION: The Wisconsin Inventory of Smoking Dependence Motives (WISDM) is a multidimensional measure of smoking motives that was developed to facilitate research aiming to refine the nomological network surrounding tobacco dependence. Recent evidence suggests that a composite of four subscales, termed the Primary Dependence Motives (PDM), may represent core features of advanced addiction, while the remaining nine subscales (Secondary Dependence Motives; SDM) represent instrumental motives for cigarette use that may be relevant at any stage of smoking. METHODS: A sample of 255 smokers (all regular alcohol users) participated in an ecological momentary assessment study in which they monitored smoking behavior and related experiences for 21 days. Multilevel regression analyses tested how PDM and SDM predicted daily smoking rate, cigarette craving, and appraisals of pleasure and relief of unpleasant feelings from smoking. RESULTS: When PDM and SDM were entered simultaneously, only PDM was related to daily cigarette count, and only SDM predicted reports of craving and relief from unpleasant feelings from smoking. SDM was associated with reports of greater pleasure from smoking and PDM was associated with lower pleasure ratings. The Fagerström Test for Nicotine Dependence (FTND) was related to daily smoking rate and craving, but WISDM composites contributed incremental prediction. CONCLUSIONS: The findings confirm that PDM indexes heavier use that is relatively unrelated to immediate consequences of smoking. SDM is not uniquely related to smoking heaviness, but is associated with craving and reports of pleasure and relief of unpleasant feelings derived from smoking during ad lib use. IMPLICATIONS: This study extends the evidence for the distinction between the WISDM PDM and SDM. PDM scores are associated with heavier smoking and are relatively unrelated to immediate consequences of smoking. SDM is more strongly related to craving and reports of smoking-derived pleasure and relief of unpleasant feelings during ongoing use in daily life.

Countering Craving with Disgust Images: Examining Nicotine Withdrawn Smokers' Motivated Message Processing of Anti-Tobacco Public Service Announcements.

There is a lack of research examining whether smoking cues in anti-tobacco advertisements elicit cravings, or whether this effect is moderated by countervailing message attributes, such as disgusting images. Furthermore, no research has examined how these types of messages influence nicotine withdrawn smokers' cognitive processing and associated behavioral intentions. At a laboratory session, participants (N = 50 nicotine-deprived adults) were tested for cognitive processing and recognition memory of 12 anti-tobacco advertisements varying in depictions of smoking cues and disgust content. Self-report smoking urges and intentions to quit smoking were measured after each message. The results from this experiment indicated that smoking cue messages activated appetitive/approach motivation resulting in enhanced attention and memory, but increased craving and reduced quit intentions. Disgust messages also enhanced attention and memory, but activated aversive/avoid motivation resulting in reduced craving and increased quit intentions. The combination of smoking cues and disgust content resulted in moderate amounts of craving and quit intentions, but also led to heart rate acceleration (indicating defensive processing) and poorer recognition of message content. These data suggest that in order to counter nicotine-deprived smokers' craving and prolong abstinence, anti-tobacco messages should omit smoking cues but include disgust. Theoretical implications are also discussed.