Effects of liquid nicotine concentration and flavour on the acceptability of electronic nicotine delivery systems (ENDS) among people who smoke participating in a randomised controlled trial to reduce cigarette consumption.

BACKGROUND: Research is needed to understand the acceptability of electronic nicotine delivery systems (ENDS) as a smoking reduction aid. This study examines the acceptability of ENDS by liquid nicotine concentration and flavour among people who smoke using ENDS to reduce their smoking. METHODS: People who smoke cigarettes but were naïve to ENDS participated in a double-blind randomised controlled trial to reduce conventional cigarette smoking. Participants were randomised to either a control cigarette substitute (CS) or one of three ENDS groups; 0 mg/mL, 8 mg/mL or 36 mg/mL nicotine concentration. ENDS flavour was chosen by the participant (tobacco or menthol). Participants reported their CS, ENDS and cigarettes per day (CPD) from the past 7 days at 1-month, 3-month and 6-month follow-up visits. Participants also reported side effects and measures of satisfaction, psychological reward, aversion and craving relief. Outcome variables were modelled using linear mixed effects by the following groups: liquid nicotine concentration, flavour and a flavour-nicotine concentration interaction. RESULTS: Participants (n=520) were 41.2% male, 67.3% white, had a mean age of 46.2 years and smoked a mean of 18.6 CPD (SD=7.74) at baseline. All flavour and concentration groups decreased CPD from baseline to all follow-up visits with the 36 mg/mL experiencing the greatest reduction, compared with the 0 mg/mL and 8 mg/mL groups. All groups except the 36 mg/mL group decreased their product use over time. The use of menthol flavour was associated with fewer side effects at 3 months (p=0.02) and lesser aversion at 1 month (p=0.03) compared with tobacco-flavoured ENDS. The 36 mg/mL group experienced the greatest craving relief and greatest aversion compared with other groups. CONCLUSIONS: Both nicotine concentration and flavour appear to have independent, as well as interactive, effects that influence ENDS acceptability among people who use cigarettes.

Nicotine Delivery of a Menthol-Flavored Heat-not-Burn Tobacco Product During Directed Use.

INTRODUCTION: IQOS was authorized by the U.S. Food and Drug Administration (FDA) as a modified-risk tobacco product. We conducted a pharmacokinetic study evaluating the nicotine delivery and subjective effects of IQOS use among current menthol cigarette smokers to better understand if IQOS is an acceptable cigarette alternative in light of the proposed menthol cigarette ban. AIMS AND METHODS: Participants were adult smokers of >4 menthol cigarettes per day. After 14-hour nicotine abstinence, participants were provided an IQOS device and menthol heatstick to puff every 20 seconds for a total of 14 puffs. Blood samples were collected at baseline and during active use to calculate nicotine boost from baseline to peak concentration. Nicotine withdrawal symptoms were collected before and after IQOS use. In addition, a modified Product Evaluation Scale for IQOS was collected after use. RESULTS: Participants (n = 8) were a mean age of 43.9 years, 63% were female, 88% identified as White, and they smoked a mean of 17.1 menthol cigarettes per day. After IQOS use, the mean nicotine boost obtained was 15.96 ng/mL (SD = 6.91) (range 9.31 to 30.55 ng/mL). Most (75%) participants reported enjoying use of the product "a lot" or greater and more than half (62.5%) reported reduced cigarette cravings. Most participants reported no side effects after use; however, two experienced dry mouth, three experienced dizziness, one experienced throat irritation, and one experienced headache. CONCLUSION: We found that directed use (14 puffs) of menthol IQOS delivered a mean nicotine boost of 15.96 ng/mL which reduced craving for a cigarette. The majority of participants enjoyed use of IQOS and reported mild side effects. IMPLICATIONS: Menthol IQOS delivered a sufficient dose of nicotine perceived as satisfying by menthol cigarette smokers and it reduced craving with mild side effects. Menthol IQOS has potential to serve as a less harmful alternative for menthol cigarette smokers. The availability of modified risk products like IQOS should be considered by FDA's Comprehensive Plan for Tobacco and Nicotine Regulation.

A Comparison of Mental Health Symptoms among Adults Who Vape Nicotine, Cannabis, or Both.

OBJECTIVES: Dual use of combustible cannabis and nicotine is related to worse mental health symptoms (MHS); however, little is known about MHS among those who vape cannabis and nicotine. The current study aimed to determine if dual use of cannabis and nicotine vapes is associated with worse MHS compared to single use and to identify correlates of MHS for dual users. METHODS: We used Amazon Mechanical Turk to survey adults (N = 492) who used nicotine or cannabis vapes in the past 30 days on stress, anxiety, depression, vape use behaviors and sociodemographic information. We conducted hierarchical linear regressions to compare MHS between dual vs. single substance vape use and to identify correlates of MHS, including sociodemographic variables and vape use characteristics. RESULTS: The final sample was 37.6% female, 87.6% White, and 11% Hispanic/Latinx with a mean age of 34.15 years. After controlling for sociodemographic characteristics and combustible product use, dual users had significantly higher mean MHS severity than single users. For dual users, younger age and being married were associated with higher symptoms of depression and stress. Holding a medical cannabis card was associated with higher anxiety symptoms. CONCLUSION: The findings suggest that dual use of cannabis and nicotine vapes is associated with worse MHS severity compared to single substance use.

Effectiveness of smoking cessation interventions among persons with cancer: A systematic review.

OBJECTIVES: Continued smoking after cancer diagnosis is associated with worse outcomes, however, many persons diagnosed with cancer who smoke are unable to quit successfully. Effective interventions are needed to promote quitting in this population. The purpose of this systematic review is to understand the most effective interventions for smoking cessation among persons with cancer and to identify gaps in knowledge and methodology to suggest directions for future research. METHODS: Three electronic databases (The Cochrane Central Register of Controlled trials, MEDLINE, and EMBASE) were searched for studies of smoking cessation interventions among persons with cancer, published up to 1 July 2021. Title and abstract screening, full-text review, and data extraction was completed by two independent reviewers, via Covalence software, with any discordance resolved by a third reviewer. A quality assessment was completed using the Cochrane Risk of Bias Tool Version 2. RESULTS: Thirty-six articles were included in the review, including 17 randomized-controlled trials (RCTs) and 19 non-RCT studies. Of the 36 studies, 28 (77.8%) utilized an intervention that included both counseling and medication, with 24 (85.7%) providing medication to participants at no cost. Abstinence rates in the RCT intervention groups (n = 17) ranged from 5.2% to 75%, while the non-RCTs found abstinence rates ranging from 15% to 46%. Overall, studies met a mean of 2.28 out of seven quality items, ranging from 0 to 6. CONCLUSIONS: Our study highlights the importance of utilizing intensive combined behavioral and pharmacological interventions for persons with cancer. While combined therapy interventions seem to be the most effective, more research is needed, as current studies have several quality issues, including the lack of biochemical verification for abstinence.

The Roswell eND scale: Brief, valid assessment of nicotine dependence adults seeking to discontinue e-cigarette use.

BACKGROUND: Most adults who regularly use e-cigarettes or Electronic Nicotine Delivery Systems (ENDS) desire to discontinue use. ENDS use can result symptoms of nicotine withdrawal and dependence which can make it more difficult to discontinue use. Brief, valid assessment of nicotine dependence among adults who use ENDS is needed to guide treatment for nicotine dependence in this group. We sought to develop a brief, valid instrument to measure nicotine dependence among adults seeking to discontinue ENDS in a busy Quitline. METHODS: In this cross-sectional design, we examined content, construct, and concurrent validity of the Roswell ENDS Nicotine Dependence Scale (Roswell eND Scale) and the Penn State E-Cigarette Dependence Index (Penn State eCDI). Participants who called the New York Quitline from November 2019 to June 2020 seeking to discontinue ENDS use were invited to participate. Construct validity was examined with exploratory and confirmatory factor analyses. Instrument and factor scores were then correlated with cotinine, a biomarker of nicotine exposure. RESULTS: All participants (n = 209) were highly dependent and co-used combustible cigarettes to varying degrees. Both instruments demonstrated content validity and construct validity, however only the 5-item Roswell eND Scale demonstrated criterion-related validity by showing a significant positive correlation with salivary cotinine levels. CONCLUSIONS: The 5-item Roswell eND Scale can briefly and effectively assess nicotine dependence among treatment-seeking adults who co-use ENDS and cigarettes. These preliminary psychometric findings have the potential to be generalizable to other adults seeking to discontinue ENDS use, many of whom currently or formerly smoked cigarettes.

Changes in Nicotine Dependence Among Smokers Using Electronic Cigarettes to Reduce Cigarette Smoking in a Randomized Controlled Trial.

INTRODUCTION: How nicotine dependence will be affected when current smokers initiate electronic cigarette (e-cigarette) use to reduce cigarette smoking is unknown. This study evaluated cigarette, e-cigarette, and total nicotine dependence more than 6 months among smokers reducing cigarette consumption by replacing with e-cigarettes. AIMS AND METHODS: Adult cigarette smokers were randomized to one of four conditions (36 mg/ml e-cigarette, 8 mg/ml e-cigarette, 0 mg/ml e-cigarette, or cigarette-substitute [CS] [provided at no cost]) and instructed to reduce their cigarette smoking by 75% at 1 month. Participants completed follow-up at 1, 3, and 6 months. The Penn State Nicotine Dependence Index (PSNDI) measured dependence on cigarettes (PSCDI) and e-cigarettes (PSECDI). Urine cotinine measured total nicotine exposure. Linear mixed effects models for each outcome were conducted and included interaction terms between visit and condition. RESULTS: Participants (n = 520) were 58.8% female, 67.3% White, and 48.0 years old. At baseline, the median number of cigarettes smoked per day was 17.3 and the mean PSCDI score was 13.4, with no significant differences between conditions. Participants in the e-cigarette conditions reported significantly lower PSCDI scores, compared with baseline, and with the CS condition at all follow-up visits. Those in the 36 mg/ml e-cigarette condition reported greater PSECDI scores at 6 months, compared with baseline and the 0 mg/ml and 8 mg/ml conditions. At all follow-up visits, there were no differences in total nicotine exposure compared to baseline, nor between any conditions. CONCLUSIONS: E-cigarette use was associated with reduced cigarette dependence, compared to the CS, without significant increases in total nicotine exposure. IMPLICATIONS: Initiation of electronic cigarette use while continuing to smoke could potentially increase nicotine dependence. In this randomized trial aimed at helping smokers to reduce their cigarette intake, we found that use of an e-cigarette was associated with a reduction in cigarette dependence and an increase in e-cigarette dependence (in the condition with the highest nicotine concentration only), with no long term increase in total nicotine dependence or nicotine exposure.

The effects of reduced nicotine content cigarettes on biomarkers of nicotine and toxicant exposure, smoking behavior and psychiatric symptoms in smokers with mood or anxiety disorders: A double-blind randomized trial.

BACKGROUND: The U.S. Food and Drug Administration and the government of New Zealand have proposed a reduction of the nicotine content in cigarettes to very low levels. This study examined the potential effects of this regulation in smokers with affective disorders. METHODS: In a randomized controlled parallel group trial conducted at two sites in the USA (Penn State University, Hershey, PA and Massachusetts General Hospital, Boston, MA) 188 adult smokers with a current (n = 118) or lifetime (n = 70) anxiety or unipolar mood disorder, not planning to quit in the next 6 months, were randomly assigned (1:1) to smoke either Usual Nicotine Content (UNC) (11.6 mg nicotine/cigarette) research cigarettes, or Reduced Nicotine Content (RNC) research cigarettes where the nicotine content per cigarette was progressively reduced to 0.2 mg in five steps over 18 weeks. Participants were then offered the choice to either receive assistance to quit smoking, receive free research cigarettes, or resume using their own cigarette brand during a 12-week follow-up period. Main outcomes were biomarkers of nicotine and toxicant exposure, smoking behavior and dependence and severity of psychiatric symptoms. The pre-registered primary outcome was plasma cotinine. RESULTS: A total of 143 (76.1%) randomized participants completed the randomized phase of the trial, 69 (73.4%) in the RNC group and 74 (78.8%) in the UNC group. After switching to the lowest nicotine content cigarettes, compared to smokers in the UNC group, at the last randomized visit the RNC group had significantly lower plasma cotinine (metabolite of nicotine): difference between groups, -175.7, 95% CI [-218.3, -133.1] ng/ml. Urine NNAL (metabolite of NNK, a lung carcinogen), exhaled carbon-monoxide, cigarette consumption, and cigarette dependence were also significantly lower in the RNC group than the UNC group. No between-group differences were found on a range of other biomarkers (e.g. 8-isoprostanes) or health indicators (e.g. blood pressure), or on 5 different psychiatric questionnaires, including the Kessler K6 measure of psychological distress. At the end of the subsequent 12-week treatment choice phase, those randomized to the RNC group were more likely to have quit smoking, based on initial intent-to-treat sample, n = 188 (18.1% RNC v 4.3% UNC, p = 0.004). CONCLUSION: Reducing nicotine content in cigarettes to very low levels reduces some toxicant exposures and cigarette addiction and increases smoking cessation in smokers with mood and/or anxiety disorders, without worsening mental health. TRIAL REGISTRATION: TRN: NCT01928758, registered August 21, 2013.

A Comparison of Vaping Behavior, Perceptions, and Dependence among Individuals Who Vape Nicotine, Cannabis, or Both.

Background: Electronic delivery systems (e.g., vapes, e-cigarettes) are now popular modes of cannabis and nicotine administration that are often used by the same individuals; however, we still know little about dual nicotine and cannabis vaping. Materials & Methods: An online convenience sample of adult nicotine and/or cannabis vape users residing in the United States completed a 60 min survey on sociodemographic characteristics, cannabis and/or nicotine vape use behaviors and dependence, reasons for vape use, and perceptions of benefits and harms. After data cleaning, we compared dual vs. nicotine-only and cannabis-only vape users with univariate statistics and step-wise hierarchical linear regression analyses. Additionally, we assessed the factor structure, internal consistency, and criterion and convergent validity of the Penn State Cannabis Vaping Dependence Index (PSCVDI). Results: The final sample included 357 dual, 40 cannabis, and 106 nicotine vape users. Compared to nicotine- and cannabis-only vapers, dual vapers started using their nicotine and cannabis vapes at a younger age (p < 0.001), used them for more years (p < 0.001), and were less likely to use their nicotine vape to replace combustible cigarettes (p = 0.047). Dual users vs. single-substance users did not have significantly higher nicotine or cannabis vape dependence scores after controlling for sociodemographic and use behaviors. The PSCVDI showed adequate validity for measuring cannabis vape dependence. Conclusions: This survey is the first to highlight important differences in vape use behaviors and reasons for use between dual vs. cannabis- and nicotine-only vape users.

Effect of menthol on nicotine reduction: Pooled results from two double-blind randomized controlled trials.

BACKGROUND: Menthol upregulates nicotinic acetylcholine receptors and is associated with tobacco dependence. The effects of menthol when smoking cigarettes with varying low nicotine content up to 98 % (e.g., non-addicting) less than commercial cigarettes is not well understood. The U.S. Food and Drug Administration is considering two tobacco product standards in cigarettes including banning menthol and reducing nicotine content. These new standards have the potential to significantly reduce smoking initiation and maintenance by limiting the mechanistic effects of nicotine and menthol on the brain. METHODS: We conducted two parallel randomized clinical trials of gradually reduced nicotine in cigarettes from 11.6 mg down to 0.2 mg nicotine/cigarette (very low nicotine content; VLNC) vs. usual nicotine content (11.6 mg; UNC) over an 18-week period in people who smoke cigarettes with low socioeconomic status (SES) and mental health conditions. RESULTS: Compared to UNC, VLNC was associated with significant reductions in cotinine, cigarettes per day, expired carbon monoxide levels, nicotine dependence and symptomology. These associations did not differ between menthol and non-menthol cigarettes, except people who smoke menthol cigarettes had less of a cotinine reduction in the SES trial. The pooled odds ratio of being adherent with using only VLNC study cigarettes in the gradual nicotine reduction arm for people who smoke non-menthol vs. menthol cigarettes was 2.6 (95 % CI:1.0, 6.4; p-value: 0.04). CONCLUSIONS: When nicotine is lowered to non-addicting levels, the results indicate an independent effect of menthol on the need to sustain nicotine intake in addicted people who smoke cigarettes.

Pilot randomized controlled trial evaluating the effect of random nicotine delivery on cigarettes per day and smoke exposure.

BACKGROUND: Many smokers report attempting to quit each year, yet most relapse, in part due to exposure to smoking-related cues. It is hypothesized that extinction of the cue-drug association could be facilitated through random nicotine delivery (RND), thus making it easier for smokers to quit. The current study aimed to evaluate the effects of RND on smoking cessation-related outcomes including cigarettes per day (CPD) and exhaled carbon monoxide (CO). METHODS: Participants were current smokers (>9 CPD) interested in quitting. Novel trans-mucosal, orally dissolving nicotine films, developed by Bionex Pharmaceuticals, were used in the study. The pharmacokinetic profile of these films was assessed in single (Experiment 1) and multiple-dose (Experiment 2) administrations prior to the smoking cessation study (Experiment 3). In Experiment 3, participants were randomized 1:1:1 to recieve 4 nicotine films per day of either: placebo delivery (0 mg), steady-state delivery (2 mg), or random nicotine delivery (RND) (0 mg or 4 mg). After two weeks, participants were advised to quit (target quit date, TQD) and were followed up 4 weeks later to collect CPD and CO and to measure dependence (Penn State Cigarette Dependence Index; PSCDI) and craving (Questionnaire of Smoking Urges; QSU-Brief). Means and frequencies were used to describe the data and repeated measures ANOVA was used to determine differences between groups. RESULTS: The pharmacokinetic studies (Experiment 1 and 2) demonstrated that the films designed for this study delivered nicotine as expected, with the 4 mg film delivering a nicotine boost of approximately 12.4 ng/mL across both the single and the multiple dose administration studies. The films reduced craving for a cigarette and were well-tolerated, overall, and caused no changes in blood pressure or heart rate. Using these films in the cessation study (Experiment 3) (n = 45), there was a significant overall reduction in cigarettes smoked per day (CPD) and in exhaled CO, with no significant differences across groups (placebo, steady-state, RND). In addition, there were no group differences in dependence or craving. Adverse events included heartburn, hiccups, nausea, and to a lesser extent, vomiting and anxiety and there were no differences across groups. CONCLUSION: Overall, this pilot study found that RND via orally dissolving films was feasible and well tolerated by participants. However, RND participants did not experience a greater reduction in self-reported CPD and exhaled CO, compared with participants in the steady-state and placebo delivery groups. Future studies to evaluate optimal RND parameters with larger sample sizes are needed to fully understand the effect of RND on smoking cessation-related outcomes.

Feasibility of Patient Navigation-Based Smoking Cessation Program in Cancer Patients.

Continued smoking after a cancer diagnosis is causally associated with increased risks of all-cause and cancer-specific mortality, and of smoking-related second primary cancers. Patient navigation provides individualized assistance to address barriers to smoking cessation treatment and represents a promising bridge to smoking cessation in persons with cancer who smoke cigarettes. We conducted a single-arm interventional cohort study of current smokers identified through prospective health record screening and recruited from Penn State Cancer Institute outpatient clinics. Consented participants received two telephone intervention sessions and gain-framed messaging-based smoking cessation educational materials designed for persons with cancer. The primary study outcome was the feasibility of the patient navigation-based intervention; the secondary outcome was the engagement in smoking cessation treatment at the two-month follow-up. Of 1168 unique screened Cancer Institute patients, 134 (11.5%) were identified as current cigarette smokers. Among 67 patients approached at outpatient clinics, 24 (35.8%) were interested in participating, 12 (17.9%) were enrolled, eight (11.9%) completed the intervention sessions and study assessments, and six engaged in smoking cessation treatment. The participants expressed satisfaction with the intervention sessions (median = 8.5, scale 0-10). The low recruitment rates preclude patient navigation as a feasible method for connecting cancer patients to smoking cessation treatment resources.

Intentions and Attempts to Quit JUUL E-Cigarette Use: The Role of Perceived Harm and Addiction.

INTRODUCTION: Research on electronic cigarette (e-cigarette) quit intentions and attempts is limited despite the potential health benefits of quitting, especially for long-term users. The current study aimed to investigate perceptions of harm and addictiveness and tobacco use characteristics associated with quit variables among users of a popular e-cigarette brand, JUUL. METHODS: We surveyed 301 US adult JUUL users on their tobacco use characteristics, perceptions of JUUL harm and addictiveness, and quit variables at 3 time points, from July 2019 to April 2020. We used logistic regression models to assess demographic characteristics, smoking characteristics, and perceptions of JUUL harm and addictiveness as correlates of e-cigarette quit intentions, attempts, importance, and confidence. RESULTS: Twenty-three percent of the sample had intentions to quit using JUUL within the year, and 22.6% reported making a lifetime quit attempt. The average rating of quit importance was 4.1 and quit confidence was 5.8 on a Likert scale of 1 to 10. More than 90% of the sample indicated that JUUL was at least moderately addictive, whereas less than one-quarter indicated that JUUL was as harmful or more harmful than smoking. Higher levels of perceived JUUL addictiveness were associated with more quit intentions, attempts, and importance. Higher levels of perceived JUUL harm compared with smoking were associated with more quit importance. CONCLUSION: Our findings suggest that a small proportion of adult JUUL users are interested in quitting. Self-reported perceptions of JUUL's addiction potential may be related to more quit attempts. Findings highlight the need for evidence-based information on e-cigarette addictiveness and effective strategies for cessation.

Quitting electronic cigarettes: Factors associated with quitting and quit attempts in long-term users.

Some electronic cigarette (e-cigarette) users are interested in quitting e-cigarette use, though few studies have assessed what factors contribute to this interest. This study aimed to identify factors associated with e-cigarette quitting interest and quitting behaviors in exclusive, long-term e-cigarette users. These e-cigarette users were surveyed in January 2017 (baseline) and June 2019 (follow-up), with an average follow-up period of 2.4 years. At baseline, the sample had been e-cigarette users for an average of 5.6 years. Among the 221 participants, 205 (92.8%) did not intend to quit using e-cigarettes at baseline. At follow-up, 196 (88.7%) continued exclusive e-cigarette use, 17 (7.7%) quit e-cigarettes, 8 (3.6%) became dual users, and none became exclusive smokers. At baseline, 16 users intended to quit e-cigarettes, 2 (12.5%) of whom quit at follow-up. Predictors of quitting e-cigarettes included no previous cigarette smoking (ß = -3.7, OR = 0.021, p < .01), lower Penn State Electronic Cigarette Dependence Index score (ß = -0.21, OR = 0.81, p = .011), and lower number of devices used per day (ß = -1.9, OR = 0.15, p = .015). Intending to quit e-cigarettes at baseline was not predictive of quitting at follow-up. At follow-up, 57 (25.8%) had tried to quit in the past. Overall predictors of trying to quit included interest in quitting at baseline (ß = 1.7, OR = 5.3, p < .01) and using a drip-fed atomizer (ß = 1.0, OR = 2.7, p = .022). These results suggest that long-term exclusive e-cigarette users generally have little interest in stopping e-cigarette use, and that type of device used, smoking history, e-cigarette dependence, number of devices used, and intention to quit are associated with e-cigarette quitting behaviors.

Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial.

INTRODUCTION: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute. METHODS: This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization. RESULTS: At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9-104.9] and 3.5 [95% CI = 1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130). CONCLUSIONS: When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute. IMPLICATIONS: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.

Evidence from an fMRI study that dessert-flavored e-cigarettes engage taste-related, but not smoking-related, brain circuitry for female daily smokers.

Regulations limiting the sale of flavored e-cigarette products are controversial for their potential to interfere with e-cigarette use as a cessation aid in addition to curbing youth use. Limited research suggests that flavor might enhance the addictive potential of e-cigarettes; however, the acute effects of flavored aerosols on brain function among humans have not been assessed. The present study aimed to isolate and compare the neural substrates of flavored and unflavored e-cigarette aerosols on brain function among nine female daily smokers. Participants inhaled aerosolized e-liquid with 36 mg/mL of nicotine with and without a strawberry-vanilla flavor while undergoing functional magnetic resonance imaging. We used general linear modeling to compare whole-brain mean neural activation and seed-to-voxel task-based functional connectivity between the flavored and unflavored inhalation runs. Contrary to our hypothesis, the flavored aerosol was associated with weaker activation than the unflavored aerosol in the brain stem and bilateral parietal-temporal-occipital region of the cortex. Instead, the flavor engaged taste-related brain regions while suppressing activation of the neural circuits typically engaged during smoking and nicotine administration. Alternatively, functional connectivity between subcortical dopaminergic brain seeds and cortical brain regions involved in motivation and reward salience were stronger during the flavored compared to unflavored aerosol run. The findings suggest that fruity and dessert-flavored e-cigarettes may dampen the reward experience of aerosol inhalation for smokers who initiate e-cigarette use by inhibiting activation of dopaminergic brain circuits. These preliminary findings may have implications for understanding how regulations on flavored e-cigarettes might impact their use as cessation aids. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effect of an electronic nicotine delivery system with 0, 8, or 36 mg/mL liquid nicotine versus a cigarette substitute on tobacco-related toxicant exposure: a four-arm, parallel-group, randomised, controlled trial.

BACKGROUND: Electronic nicotine delivery systems (ENDSs) are used by some smokers to reduce cigarette consumption, but their effectiveness is uncertain. We aimed to examine the extent to which ENDSs or a non-nicotine cigarette substitute influence tobacco-related toxicant exposure and cigarette consumption in smokers interested in smoking reduction. METHODS: We did a four-arm, parallel-group, randomised controlled trial at two sites in the USA (Penn State University, Hershey, PA, and Virginia Commonwealth University, Richmond, VA). We enrolled adults aged 21-65 years who smoked more than nine cigarettes per day (for at least the past year), with exhaled CO of more than 9 parts per million at screening, who were not currently using an ENDS, and who were interested in reducing smoking but not quitting. Participants were randomised (site-specific with allocation concealment; 1:1:1:1) to receive either a cartomiser-based, pen-style ENDS (eGo-style) paired with 0, 8, or 36 mg/mL liquid nicotine (participants and researchers masked to concentration) or a non-ENDS cigarette-shaped plastic tube that delivered no nicotine or aerosol (cigarette substitute; unmasked) for 24 weeks. Conditions were chosen to reflect a range of nicotine delivery including none (cigarette substitute and 0 mg/mL ENDS), low (8 mg/mL), and cigarette-like (36 mg/mL), and all conditions were paired with smoking reduction instructions. The primary outcome was concentration of the tobacco-specific carcinogen metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; urinary total) collected at randomisation and at 4, 12, and 24 weeks. Multiple imputation with and without covariate adjustment was used in addition to sensitivity analyses. This trial is registered with ClinicalTrials.gov, NCT02342795. FINDINGS: Between July 22, 2015, and Nov 16, 2017, 684 individuals were screened and 520 (76%) were enrolled and randomised. 188 (36%) of 520 participants were lost to follow-up by week 24; attrition did not differ by study group (39 [30%] of 130 in the cigarette substitute group, 56 [43%] of 130 in the ENDS with 0 mg/mL nicotine group, 49 [38%] of 130 in the ENDS 8 mg/mL group, and 44 [34%] of 130 in the ENDS 36 mg/mL group). Urinary total NNAL at 24 weeks in the ENDS with 36 mg/mL nicotine group was 210·80 pg/mg creatinine (95% CI 163·03-274·42) compared with 346·09 pg/mg creatinine (265·00-455·32) in the cigarette substitute group (p=0·0061). No other significant differences between groups were observed for any time point for urinary total NNAL. Serious adverse event frequency was similar across groups (12 events in 12 participants [9%] in the ENDS with 36 mg/mL nicotine group, seven events in six participants [5%] in the 8 mg/mL group, 11 events in ten participants [8%] in the 0 mg/mL group, and 13 events in 13 participants [10%] in the cigarette substitute group), and all of these were deemed unrelated or unlikely to be related to study product use. There was one death between randomisation and 24 weeks (suicide; in the ENDS with 0 mg/mL nicotine group). INTERPRETATION: Use of an ENDS with cigarette-like nicotine delivery can reduce exposure to a major pulmonary carcinogen, NNAL, even with concurrent smoking. Future ENDS trials should involve products with well characterised nicotine delivery, including those with nicotine delivery approaching that of a cigarette. FUNDING: National Institutes of Health, US Food and Drug Administration.

Tobacco Use Changes and Perceived Health Risks among Current Tobacco Users during the COVID-19 Pandemic.

COVID-19 has become a global pandemic, with over 81 million cases worldwide. To assess changes in tobacco use as a result of the pandemic, we surveyed a convenience sample of current tobacco users between April and June 2020. The sample was taken from a tobacco user research registry (n = 3396) from the Penn State College of Medicine in Hershey, Pennsylvania, USA. Participants who responded to the survey and were eligible for this study (n = 291) were 25.6% male, 93% white, and had a mean age of 47.3 (SD = 11.6) years. There were no reports of participants testing positive for COVID-19, but 21.7% reported experiencing symptoms associated with the virus. Most participants (67%) believed that their risk of contracting COVID-19 was the same as non-tobacco users, but 57.7% believed that their risk of serious complications, if infected, was greater compared to non-tobacco users. A total of 28% reported increasing their cigarette use during the pandemic. The most common reasons for increased use were increased stress, more time at home, and boredom while quarantined. Nearly 15% reported decreasing their tobacco use. The most common reasons for reduced use were health concerns and more time around non-smokers (including children). A total of 71 (24.5%) users reported making a quit attempt. Characterizing these pandemic-related changes in tobacco use may be important to understanding the full scope of subsequent health outcomes resulting from the pandemic. Tobacco cessation resources should be tailored to allow for safe, appropriate access for those interested in quitting.

Cataract Surgery Redesign: Meeting Increasing Demand, Training, Audit and Patient-Centered Care.

OBJECTIVE: The demand for cataract surgery in Fife (a well-defined region in southeast Scotland) was steadily increasing over 15 years. Cataract surgery was therefore being outsourced to meet demand with consequences on list mix, training needs, patient experience and staff morale. We aimed to redesign our services to meet local demand, retain a patient-centered service and continue to fulfil training needs. METHODS: We quantified cataract surgery delivery over an 18-month period: before, during and after redesign of services. We studied numbers of operations, trainee cases and number of outsourced cases. We also considered the economic implications of the redesign. RESULTS: We studied three periods (each of six months duration): before redesign (BR), redesign period (RP) and post-redesign (PR). Data were collected on total operation numbers, number of cases performed by trainees, and numbers performed out with normal working hours (weekend lists) and external providers. An economic analysis examined the cost of outsourcing cataracts during BR and RP and the costs of the redesign, including building, equipment and additional nursing staff. CONCLUSION: Regional fulfilment of cataract surgery provision remains a continuous challenge within the NHS. We show that with minimal investment, smart redesign process and collaborative working, increased local provision is possible while fulfilling trainee needs and achieving the necessary clinical audits and national standards.