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.

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.

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.

Self-Directed Learning among Internal Medicine Residents in the Information Age.

OBJECTIVES: The revolution in information technology and a rapidly expanding evidence base are changing residency training. Understanding the habits and preferences of trainees' self-directed learning (SDL) has never been more important. Our goal was to provide a contemporary description of residents' SDL practices. METHODS: Internal medicine residents at four university-affiliated programs were surveyed in Spring 2017. Residents estimated the number of hours in their typical week spent in SDL on service and after hours when on inpatient and noninpatient rotations, how often they used specific educational resources for SDL, and the percentage of time that they used four different modes to access resources. RESULTS: Of 384 residents, a total of 254 (66%) responded. Residents spent more total hours in SDL on noninpatient services (median 11, interquartile range 8-17) than on inpatient services (median 7, interquartile range 4-10) and the same median number of hours in SDL on clinical duty as off hours for both inpatient (median 3 hours) and noninpatient (median 5 hours) rotations. Nearly all of the respondents (99%) reported using online point-of-care resources for SDL at least once per week. Most (77%) never used printed textbooks. Desktop/laptop was the most commonly used (47% of the time) medium to access resources. CONCLUSIONS: Although the resident learning environment and resource use are changing, residents engage in as much or more time in SDL as in previous studies, with a large proportion occurring during clinical service. Understanding residents' current SDL habits will better prepare educators to support and guide our trainees.

Measurement of Electronic Cigarette Frequency of Use Among Smokers Participating in a Randomized Controlled Trial.

BACKGROUND: The United States Food and Drug Administration has prioritized understanding the dependence potential of electronic cigarettes (e-cigs). Dependence is often estimated in part by examining frequency of use; however measures of e-cig use are not well developed because of varying product types. This study used an e-cig automatic puff counter to evaluate the value of self-reported e-cig use measures in predicting actual use (puffs). METHODS: Data were collected from a two-site randomized placebo-controlled trial evaluating the effects of e-cigs on toxicant exposure in smokers attempting to reduce their cigarette consumption. Participants randomized to an e-cig condition self-reported their e-cig frequency of use (times per day-one "time" consists of around 15 puffs or lasts around 10 minutes) on the Penn State Electronic Cigarette Dependence Index (PSECDI) and kept daily diary records of the number of puffs per day from the e-cig automatic puff counter. A linear mixed-effects model was used to determine the predictive value of the times per day measure. Correlations were used to further investigate the relationship. RESULTS: A total of 259 participants with 1165 observations of e-cig use were analyzed. Self-reported e-cig use in times per day was a significant predictor of e-cig puffs per day (p < .01). The Spearman correlation between measures was r equal to .58. Examination of individual participant responses revealed some potential difficulties reporting and interpreting times per day because of the difference in use patterns between cigarettes and e-cigs. CONCLUSION: This study provides evidence that the self-reported PSECDI measure of times per day is a significant predictor of actual frequency of e-cig puffs taken. IMPLICATIONS: Self-reported measures of e-cig frequency of use are predictive of actual use, but quantifying e-cig use in patterns similar to cigarettes is problematic.

Automating Vancomycin Monitoring to Improve Patient Safety.

INTRODUCTION: Intravenous vancomycin is a frequently used antibiotic and a common cause of medication-related harm because of its narrow therapeutic range. Improving monitoring of drug levels with automation in the electronic health record (EHR) may decrease this harm. METHODS: After examining the existing state of vancomycin ordering, administration, and monitoring, an automated process was created in the EHR that, on initiation of a new vancomycin order, automatically ordered a vancomycin trough level 30 minutes before the fourth dose. In addition, a nursing alert was integrated into the bar coding medication administration process that, if no trough level had been drawn by the time of the administration of the fourth dose, prompted the nurse to draw a trough level. Data from a three-month, post-implementation period was compared to data from a preceding three-month period. RESULTS: The frequency of trough levels drawn between the third and fourth dose increased from 58.6% to 75.8% (p < 0.01). However, the percentage of trough levels drawn within one hour of the fourth dose remained unchanged, possibly because nursing staff waited for the result of the level prior to administering the next dose of vancomycin. A minority of patients in both groups had trough levels that were in range (difference between groups, p = 0.46). CONCLUSION: Automation of vancomycin monitoring was associated with improvement in the frequency of monitoring and only delayed medication dosing by six minutes. Because vancomycin is high risk, this type of process should be broadly implemented, and outcomes should be assessed to identify unexpected outcomes and necessary further refinements.

Influence of electronic cigarette liquid flavors and nicotine concentration on subjective measures of abuse liability in young adult cigarette smokers.

BACKGROUND: A rapidly evolving tobacco marketplace highlights the timeliness of the FDA's authority to regulate tobacco, specifically the role that flavorings in nicotine-containing electronic cigarette (ECIG) liquids have on public health. This study aimed to evaluate the extent to which ECIG liquid flavor and nicotine concentration influenced subjective measures of abuse liability among young adult cigarette (cig) smokers. METHODS: Young adult (18-21 y.o.) smokers (M = 10.1 cig/day, no regular ECIG use history) completed 7 Latin-square ordered conditions each preceded by 12 h. nicotine/tobacco abstinence. Conditions were own brand cig (OB) and eGo-style ECIG paired with three liquid flavors (cream, tropical fruit, tobacco/menthol) varying in nicotine concentration (0 or 36 mg/ml). Products were administered in two 10-puff bouts in each condition. Heart rate/blood pressure (HR/BP) and tobacco/nicotine abstinence symptoms, nicotine/general drug effects, and acceptability measures were assessed repeatedly throughout sessions. Mixed linear models were followed-up with Tukey's HSD t-tests. RESULTS: HR/BP indicated nicotine exposure during nicotine-containing conditions. OB and tobacco/menthol 36 mg/ml conditions produced significant decreases in ratings of cig smoking urges. Nicotine/drug effects were elevated significantly for OB and 36 mg/ml ECIG conditions with one exception noted for the tobacco/menthol 0 mg/ml condition. OB had the highest acceptability ratings, and ECIG condition results varied by acceptability item. CONCLUSIONS: Among young adult smokers, ECIG conditions containing nicotine were positively associated with several subjective measures of abuse liability but not all. Flavors did not consistently mask/enhance effects observed. Results reinforce continued examination of ECIG-delivered nicotine and liquid flavors in relationship to abuse liability.

Pulmonary and other health effects of electronic cigarette use among adult smokers participating in a randomized controlled smoking reduction trial.

BACKGROUND: There is limited evidence about the effects of dual electronic cigarette (e-cig) and combustible cigarette use on lung health or other health outcomes. Studies that have evaluated these outcomes have not included estimates of e-cig or cigarette exposure in the analyses. MATERIALS AND METHODS: Data analyzed were from 263 smokers participating in a randomized controlled trial designed to encourage participants to reduce their combustible cigarette use by substituting with an e-cig or a non-electronic cigarette substitute (cig-sub). t-tests were used to evaluate changes from baseline at 1 month and 3 months in lung function, blood pressure, pulse, exhaled carbon monoxide, and weight. Linear mixed effects models were used to test associations between health outcomes and study product group, including exposure to the study products (e-cig and cig-sub times used and days used in the past 7 days) and cigarettes per day (CPD). RESULTS: There were few significant differences between the groups for lung function indices at any time point in the unadjusted analyses. There were significant reductions in diastolic blood pressure and pulse at 1 month in the unadjusted analyses for those in the e-cig group compared to the cig-sub group. CPD decreased significantly more for the e-cig group than for the cig-sub group at both time points. There were no significant associations between any measured health outcomes and group in the linear mixed effects models. CONCLUSION: E-cig use did not contribute to significant changes in health outcome markers as compared with use of a non-electronic cig-sub.

Change implementation: the association of adaptive reserve and burnout among inpatient medicine physicians and nurses.

Adaptive Reserve (AR) is positively associated with implementing change in ambulatory settings. Deficits in AR may lead to change fatigue or burnout. We studied the association of self-reported AR and burnout among providers to hospitalized medicine patients in an academic medical center. An electronic survey containing a 23-item Adaptive Reserve scale, burnout inventory, and demographic questions was sent to a convenience sample of nurses, house staff team members, and hospitalists. A total of 119 self-administered, online surveys collected from June 2014 to March 2015 were analyzed. Ordinal regression analyses were used to examine the association between AR and burnout. Eighty percent of participants reported either level 1 or 2 burnout. Additionally, 10.9% of participants responded level 0% and 7.6% of participants reported level 3. Participants reporting higher burnout were about three times more likely to report lower AR levels. AR is strongly associated with self-reported burnout by physicians and nurses providing inpatient care at this academic medical center. Growing evidence supports the positive association of AR to successful change implementation in ambulatory settings. Similar studies are needed to determine whether certain levels of AR can predict successful change in hospital settings.

Nurse-physician collaboration in an academic medical centre: The influence of organisational and individual factors.

Ineffective physician-nurse collaboration has been recognised to adversely impact patient and organisational outcomes, and some studies suggest an underlying factor may be that nurses and physicians have different perceptions of interprofessional collaboration (IPC). The objectives of this study were to evaluate for a difference in the perception of IPC between physicians and nurses and to explore potential contributing factors at the individual and organisational levels to any observed difference. Data including measures of perceptions of IPC were collected from a convenience sample of resident physicians (n = 47), attending physicians (n = 18), and nurses (n = 54) providing care for internal medicine patients in a large tertiary care academic medical centre. Regression analysis revealed significantly lower perceptions of IPC scores for nurses in comparison to the scores of both the resident and attending physician groups (p = .0001 for both). Although demographic and workload factors also differed by profession, only profession and workload remained significant in regression analysis. Given the known relationships between effective physician-nurse collaboration and superior patient and organisational outcomes, better defining the individual and organisational predictors of IPC scores may support development of more effective interventions targeting improvements in IPC.

A transdisciplinary model to inform randomized clinical trial methods for electronic cigarette evaluation.

BACKGROUND: This study is a systematic evaluation of a novel tobacco product, electronic cigarettes (ECIGs) using a two-site, four-arm, 6-month, parallel-group randomized controlled trial (RCT) with a follow-up to 9 months. Virginia Commonwealth University is the primary site and Penn State University is the secondary site. This RCT design is important because it is informed by analytical work, clinical laboratory results, and qualitative/quantitative findings regarding the specific ECIG products used. METHODS: Participants (N = 520) will be randomized across sites and must be healthy smokers of >9 cigarettes for at least one year, who have not had a quit attempt in the prior month, are not planning to quit in the next 6 months, and are interested in reducing cigarette intake. Participants will be randomized into one of four 24-week conditions: a cigarette substitute that does not produce an inhalable aerosol; or one of three ECIG conditions that differ by nicotine concentration 0, 8, or 36 mg/ml. Blocked randomization will be accomplished with a 1:1:1:1 ratio of condition assignments at each site. Specific aims are to: characterize ECIG influence on toxicants, biomarkers, health indicators, and disease risk; determine tobacco abstinence symptom and adverse event profile associated with real-world ECIG use; and examine the influence of ECIG use on conventional tobacco product use. Liquid nicotine concentration-related differences on these study outcomes are predicted. Participants and research staff in contact with participants will be blinded to the nicotine concentration in the ECIG conditions. DISCUSSION: Results from this study will inform knowledge concerning ECIG use as well as demonstrate a model that may be applied to other novel tobacco products. The model of using prior empirical testing of ECIG devices should be considered in other RCT evaluations. TRIAL REGISTRATION: TRN: NCT02342795 , registered December 16, 2014.

Peak Bone Mass and Patterns of Change in Total Bone Mineral Density and Bone Mineral Contents From Childhood Into Young Adulthood.

The literature has not reached a consensus on the age when peak bone mass is achieved. This study examines growth patterns of total bone mineral content (TBMC) and total bone mineral density (TBMD), peak bone mass, effect of concurrent anthropometry measures, and physical activity on growth patterns in a sample of 312 white males and 343 females aged 8-30 yr. We analyzed data from participants enrolled in Fels Longitudinal Study. Descriptive analysis was used to ascertain characteristics of participants and growth patterns of TBMC and TBMD. Mixed effects models were applied to predict ages at attainment of peak TBMC and TBMD and assess the effects of height, weight, body mass index (BMI), and habitual physical activity on the attainment. Significant differences between sexes were observed for measures of TBMC and TBMD, and differences varied with age. For females, predicted median ages at peak TBMC and TBMD attainments are 21.96 yr (interquartile range [IQR]: 21.81-22.21) and 22.31 yr (IQR: 21.95-22.59), respectively. For males, predicted median ages are 23.34 yr (IQR: 24.34-26.19) and 26.86 yr (IQR: 25.14-27.98) respectively. For females, height, weight, and BMI, but not physical activity, had significant influences on attainment of TBMC and TBMD (p<0.01). For males, weight and BMI, but not height and physical activity, exerted significant influence on attainment of TBMC and TBMD (p<0.01), and also modified correlations between age and peak TBMC and TBMD. Our results suggest that (1) for both sexes, trajectories of TBMC and TBMD follow a curvilinear pattern between ages 8 and 30 yr; (2) predicted ages at peak TBMC and TBMD are from early to late 20s for both white males and females, with females reaching their peaks significantly earlier than males; and (3) concurrent height, weight, and BMI, but not habitual physical activity, exert significant effects on trajectories of TBMC and TBMD.

Associations between childhood body size, composition, blood pressure and adult cardiac structure: the Fels Longitudinal Study.

OBJECTIVES: To determine whether childhood body size, composition and blood pressure are associated with adult cardiac structure by estimating childhood "age of divergence." METHODS: 385 female and 312 male participants in the Fels Longitudinal Study had echocardiographic measurements of left ventricular mass, relative wall thickness, and interventricular septal thickness. Also available were anthropometric measurements of body mass index, waist circumference, percentage body fat, fat free mass, total body fat, and systolic and diastolic blood pressures, taken in both childhood and adulthood. The age of divergence is estimated as the lowest age at which childhood measurements are significantly different between patients with low and high measurements of adult cardiac structure. RESULTS: Childhood body mass index is significantly associated with adult left ventricular mass (indexed by height) in men and women (ages of divergence: 7.5 years and 11.5 years, respectively), and with adult interventricular septal thickness in boys (age of divergence: 9 years). Childhood waist circumference indexed by height is associated with left ventricular mass (indexed by height) in boys (age of divergence: 8 years). Cardiac structure was in general not associated with childhood body composition and blood pressure. CONCLUSIONS: Though results are affected by adult body size, composition and blood pressure, some aspects of adult cardiac structure may have their genesis in childhood body size.