Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial.

INTRODUCTION: Many oral nicotine pouch (ONP) brands use synthetic nicotine, which typically contains a racemic (50:50) mixture of nicotine's two stereoisomers: S-nicotine and R-nicotine. Because tobacco-derived nicotine contains more than 99% S-nicotine, the effects of R-nicotine in humans are not well known. We compared systemic nicotine exposure and product appeal of ONPs containing more than 99% S-nicotine versus racemic nicotine. AIMS AND METHODS: N = 18 adult smokers (Mage = 45 years, 66.7% male, 77.8% White) enrolled in a three-visit single-blind, randomized crossover study. During each visit, participants used one wintergreen-flavored, 3 mg nicotine ONP for 30 min following at least12 h nicotine abstinence. Study ONP #1 contained more than 99% S-nicotine and the other two study ONPs contained racemic nicotine (collapsed for analyses). Plasma nicotine assessments and measures of withdrawal relief occurred at t = 0, 5, 15, 30, 60, and 90 min; measures of product appeal were assessed following ONP use. RESULTS: Using the ONP with more than 99% S-nicotine resulted in greater plasma nicotine concentration from 15 to 90 min (p < .0001) and greater maximum plasma nicotine concentration than the ONPs with racemic nicotine (M = 9.9 ng/mL [SD = 2.5] vs. M = 5.7 ng/mL [SD = 2.8], respectively; p < .0001). Product liking and withdrawal relief were similar across ONPs, although participants reported more "bad effects" when using the ONP with more than 99% S-nicotine. CONCLUSIONS: Participants reported few subjective differences in ONPs according to nicotine stereoisomer, but plasma nicotine concentration was greater for ONPs using more than 99% S-nicotine. ONPs with more than 99% S-nicotine (vs. racemic nicotine) might be better substitutes for cigarettes, but research into other ONP characteristics (eg flavors, freebase nicotine) is needed to inform regulation. IMPLICATIONS: Little is known about the effects of racemic (vs. S-) nicotine in humans. In a sample of adults who smoke cigarettes, we identified that oral nicotine pouches containing racemic nicotine exposed participants to less nicotine than oral nicotine pouches containing only S-nicotine, but both types of oral nicotine pouches held similar, moderate appeal. Additional research evaluating the roles that flavorings, total nicotine concentration, and freebase nicotine play in the abuse liability of oral nicotine pouches would inform comprehensive product regulations to support public health.

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study.

BACKGROUND AND AIMS: Oral nicotine pouches (ONPs) probably offer reduced harm compared with cigarettes, but independent data concerning their misuse liability are lacking. We compared nicotine delivery and craving relief from ONPs with different nicotine concentrations to cigarettes. DESIGN: This was a single-blind, three-visit (≥ 48-hour washout), randomized-cross-over study. Participants were encouraged to complete all study visits in less than 1 month. SETTING: The study took place in Rural/Appalachian Ohio. PARTICIPANTS: Participants comprised 30 adults who smoke cigarettes. Participants (meanage = 34.5) were 60% men and 90% White. INTERVENTION: Participants who were ≥ 12-hour tobacco-abstinent used: (1) a 3-mg nicotine concentration ONP, (2) a 6-mg nicotine concentration ONP and (3) usual brand cigarette in separate visits. ONPs (wintergreen Zyn) were used for 30 minutes; cigarettes were puffed every 30 sec for 5 minutes. MEASUREMENTS: Plasma nicotine and self-reported craving were assessed at t = 0, 5, 15, 30, 60 and 90 minutes. The primary outcome was plasma nicotine concentration at t = 30 minutes. A secondary outcome was craving relief at t = 5 minutes. FINDINGS: At t = 30, mean [95% confidence interval (CI)] plasma nicotine was 9.5 ng/ml (95% CI = 7.1, 11.9 ng/ml) for the 3 mg nicotine ONP, 17.5 ng/ml (95% CI = 13.7, 21.3) for the 6 mg nicotine ONP and 11.4 ng/ml (95% CI = 9.2, 13.6 ng/ml) for the cigarette. Mean plasma nicotine at t = 30 minutes differed between the 3- and 6-mg nicotine ONPs (P = 0.001) and between the 6-mg nicotine ONP and cigarette (P = 0.002). Mean (95% CI) craving at t = 5 minutes was lower for the cigarette (mean = 1.00, 95% CI = 0.61, 1.39) than either the 3 mg (mean = 2.25, 95% CI = 1.68, 2.82; P < 0.0001) or 6 mg nicotine (mean = 2.19, 95% CI = 1.60, 2.79; P < 0.0001) ONP. CONCLUSIONS: Among adult smokers, using 6-mg nicotine concentration oral nicotine pouches (ONPs) was associated with greater plasma nicotine delivery at 30 minutes than 3-mg ONPs or cigarettes, but neither ONP relieved craving symptoms at 5 minutes as strongly as a cigarette. Accelerating the speed of nicotine delivery in ONPs might increase their misuse liability relative to cigarettes.

Effects of "Tobacco Free" Language in Warning Labels on Perceptions of Electronic Cigarettes and Nicotine Pouches among Young Adult Men: A Randomized Trial.

Background: Manufacturers of Puff Bar electronic cigarettes (e-cigarettes) and Fre nicotine pouches claim that their products contain synthetic nicotine. The packages for Puff Bar and Fre have modified versions of the warning labels required by the Food and Drug Administration (FDA) for tobacco products, which specify that Puff Bar and Fre products contain "tobacco free" or "non-tobacco" nicotine, respectively. We evaluated whether exposure to these "tobacco free" warning labels was associated with differing perceptions about the products. Method: N = 239 young adult men who were enrolled in a cohort study completed a short online experiment. Participants were randomly assigned to view either packages of Puff Bar and Fre nicotine pouches with the standard FDA warning or packages with the standard FDA warning + the tobacco free descriptor. We compared harm and addictiveness perceptions and products' perceived substitutability for cigarettes and smokeless tobacco (SLT) by exposure to a "tobacco free" warning. Results: Viewing a Puff Bar package with a "tobacco free" warning label was associated with increased perceived substitutability of the product for cigarettes and smokeless tobacco (p's<.05). Viewing a Fre package with a "non-tobacco" warning label was associated with thinking the product was less harmful than SLT (p<.01). Conclusions: "Tobacco free" descriptors in warning labels for e-cigarettes and nicotine pouches affect young adults' perceptions of the products. To date, it is unclear whether the FDA will continue to permit "tobacco free" descriptors in warning labels. As e-cigarettes and nicotine pouches are increasingly marketed with "tobacco free" language, urgent action is needed.

Adherence to COVID-19 Protective Measures in a Longitudinal Sample of Male Youth.

BACKGROUND: Adherence to COVID-19 protective measures is lowest for young people and males. The current study investigated characteristics associated with adherence to COVID-19 protective measures among male youth during the early months of the pandemic. METHOD: The study used data from a prospective cohort study among male youth with baseline assessment in 2015/2016 and follow-up measurements in 2019 and summer 2020. Attrition-weighted multivariable ordinal logistic and log-binomial regression models were used to assess factors associated with adherence to overall and specific adherence measures, respectively. RESULTS: Among 571 male youth (mean age 18.5), overall adherence was higher for those who were older (OR: 1.15; 95% CI: 1.03-1.30), non-White (OR: 1.96; 95% CI: 1.20-3.32), and residing in an urban area (OR: 2.06; 95% CI: 1.46-3.01). Overall adherence was lower for those who had a history of being drunk (OR: 0.65; 95% CI: 0.42-0.99). For outdoor mask-wearing, adherence was higher for youth with attention-deficit disorder or attention-deficit/hyperactivity disorder (RR: 1.58; 95% CI: 1.16-1.97) and lower for youth who currently used tobacco products (RR: 0.42; 95% CI: 0.21-0.70). Before a statewide mask mandate was issued, non-White youth were more likely to report wearing masks in outdoor spaces than their non-Hispanic White peers (RR: 2.34; 95% CI: 1.75-3.23). CONCLUSION: The study identified demographic, psychosocial, and behavioral factors associated with adherence to COVID-19 protective behaviors among male youth. The findings illustrate characteristics that could be leveraged for targeted preventive efforts during the ongoing pandemic and future outbreaks in a low-compliance group.

Associations between Cognitive and Affective Responses to Tobacco Advertisements and Tobacco Use Incidence: A Four-Year Prospective Study among Adolescent Boys.

Exposure to tobacco advertisements is associated with initiation of tobacco use among youth. The mechanisms underlying this association are less clear. We estimated longitudinal associations between youths' cognitive and affective responses to advertisements for cigarettes, e-cigarettes, and smokeless tobacco (SLT) and initiation of these products. N = 1220 Ohio-residing boys of ages 11-16 were recruited into a cohort in 2015 and 2016. Participants completed surveys every six months for four years. Surveys assessed cognitive and affective responses to tobacco advertisements (which included health warnings) and tobacco use after an advertisement viewing activity. We used mixed-effects Poisson regression models with robust standard errors to estimate risk of initiating use of each tobacco product according to participants' cognitive (i.e., memorability of health risks) and affective (i.e., likability of advertisement) responses to advertisements for that product. No associations between affective responses to advertisements and tobacco use outcomes were detected in adjusted models. However, finding health risks memorable was associated with reduced risk of ever smoking initiation (aRR = 0.57; 95% CI: 0.34, 0.95) and a reduced risk of ever SLT initiation that approached statistical significance (aRR = 0.61; 95% CI: 0.36, 1.05). Measures to increase saliency of health risks on cigarette and SLT advertisements might reduce use among youth.

Perceived Changes in Mood and Anxiety Among Male Youth During the COVID-19 Pandemic: Findings From a Mixed-Methods Study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has changed almost every aspect of our lives. Young adults are vulnerable to pandemic-related adverse mental health outcomes, but little is known about the impact on adolescents. We examined factors associated with perceived changes in mood and anxiety among male youth in urban and Appalachian Ohio. METHODS: In June 2020, participants in an ongoing male youth cohort study were invited to participate in an online survey that included questions about changes in mood, anxiety, closeness to friends and family, and the major impacts of the pandemic. Weighted log-binomial regression models were used to assess the risk of worsened mood and increased anxiety. Chi-square tests were used to examine the association between perceived changes in mood and anxiety and perceived changes in closeness to friends and family and open-ended responses to a question about COVID-19's impact on participants. RESULTS: Perceived worsened mood and increased anxiety during the pandemic were associated with higher household socioeconomic status, older age, feeling less close to friends and family, and reporting that COVID-19 negatively affected mental health. A perceived increase in anxiety was also associated with a history of symptoms of depression or anxiety. CONCLUSIONS: Specific subgroups of male youth may be at heightened risk of worsening mental health during the COVID-19 pandemic. Interventions should target vulnerable adolescents and seek to increase closeness to social contacts. Such efforts could involve novel programs that allow youth to stay connected to friends, which might mitigate the negative impact on mental health.

How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?

Myalgic encephalomyelitis/chronic fatigue syndrome has been a controversial diagnosis, resulting in tensions between patients and professionals providing them with care. A major constraint limiting progress has been the lack of a 'gold standard' for diagnosis; with a number of imperfect clinical and research criteria used, each defining different, though overlapping, groups of people with myalgic encephalomyelitis or chronic fatigue syndrome. We review basic epidemiological concepts to illustrate how the use of more specific and restrictive case definitions could improve research validity and drive progress in the field by reducing selection bias caused by diagnostic misclassification.

Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls.

BACKGROUND: People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continue to struggle to have their condition recognised as disabling in the face of public and professional prejudice and discrimination. OBJECTIVE: The aim of this study was to compare the functional status and well-being of people with well-characterised ME/CFS with people with multiple sclerosis (PWMS), as well as healthy controls (HCs). METHODS: In this cross-sectional study, we used data collected as part of the UK ME/CFS Biobank to compare actual participant scores from the Medical Outcomes Survey Short Form-36 v2™ (SF-36v2™) between groups, as a proxy for impact of disability, and from a bespoke questionnaire seeking data on employment and income. RESULTS: People with ME/CFS scored significantly lower than PWMS or HCs in almost all SF-36v2™ areas. Prominent were lower scores for people with ME/CFS in the Physical Component Summary and Role Physical and Social Function domains, while the smallest differences were seen in the Mental Health domain. Responses to the bespoke questionnaire indicated that people with ME/CFS in this study work fewer hours and have lower incomes compared with people in the other two groups. CONCLUSIONS: Using SF-36v2™ scores as a proxy, people with ME/CFS were measurably more disabled than PWMS or HCs in this study population. Furthermore, employment and income data are consistent with loss of functional status. These findings should encourage the health community to recognise the disabling effects of ME/CFS, to advocate for the needs of people with ME/CFS, and to investigate strategies to address the cost of the disease to both individuals and society.

The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis.

The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18-60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contains blood samples, aliquoted into serum, plasma, peripheral blood mononuclear cells (PBMC), red blood cells/granulocyte pellet, whole blood, and RNA (totalling 29,863 aliquots). Extensive dataset (700 clinical and socio-demographic variables/participant) enables comprehensive phenotyping. Potential reuse is conditional to ethical approval.