E-Cigarettes May Support Smokers With High Smoking-Related Risk Awareness to Stop Smoking in the Short Run: Preliminary Results by Randomized Controlled Trial

Abstract

IntroductionE-cigarettes may be positively used in tobacco cessation treatments. However, neither the World Health Organization nor the American Food and Drug Administration has recognized them as effective cessation aids. Data about the efficacy and safety of e-cigarettes are still limited and controversial.MethodsThis was a double-blind randomized controlled study. The main aim was to assess the efficacy of the use of e-cigarettes in a tobacco cessation program with a group of chronic smokers voluntarily involved in long-term lung cancer screening. Participants were randomized into three arms: e-cigarettes (Arm 1), placebo (Arm 2), and control (Arm 3). All subjects also received a low-intensity counseling.ResultsAbout 25% of participants who followed a cessation program based on the use of e-cigarettes (Arm 1 and Arm 2) were abstinent after 3 months. Conversely, only about 10% of smokers in Arm 3 stopped. Participants in Arm 1 also reported a higher reduction rate (M = −11.6441, SD = 7.574) than pa

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THIS IS A PRE-PRINT PARTIAL VERSION
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Full article may be find in:
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Nicotine & Tobacco Research, nty047,https://doi.org/10.1093/ntr/nty047
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Nicotine & Tobacco Research (2018). DOI: 10.1093/ntr/nty047.
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Nicotine & Tobacco Research, nty175, https://doi.org/10.1093/ntr/nty175
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CORRECTED PROOF
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E-Cigarettes May Support Smokers With High
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Smoking-Related Risk Awareness to Stop
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Smoking in the Short Run: Preliminary
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Results by Randomized Controlled Trial
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Marianna Masiero Claudio Lucchiari Ketti Mazzocco Giulia VeronesiPatrick
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Maisonneuve Costantino Jemos Emanuela Omodeo Salè Stefania SpinaRaffaella
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Bertolotti Gabriella Pravettoni
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Abstract
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Method: The main focus of this article is on a secondary outcome of the study, that is,
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the assessment of effectiveness and safety of e-cigarettes in achieving smoking cessation
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in a group of chronic smokers voluntarily involved in long-term lung cancer screening.
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Participants were randomized into three arms with a 1:1:1 ratio: e-cigarettes (arm 1),
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placebo (arm 2), and control (arm 3). All subjects also received a low intensity
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counseling.
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Results: Two hundred ten smokers were randomized (70 to nicotine e-cigarettes, 70 to
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nicotine-free placebo e-cigarettes, and 70 to control groups). About 25% of participants
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who followed a cessation program based on the use of e-cigarettes (arms 1 and 2) were
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abstinent after 3 months. Conversely, only about 10% of smokers in arm 3 stopped. A
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Kruskal–Wallis test showed significant differences in daily cigarettes smoking across the
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three arms (K-W = 6.277, p = .043). In particular, participants in arm 1 reported a higher
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reduction rate (M = −11.6441, SD = 7.574) than participants in arm 2 (M =
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−10.7636, SD = 8.156) and arm 3 (M = −9.1379, SD = 8.8127).
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The primary outcome of this trial was the assessment of the impact of a 3-month e-
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cigarettes program to reduce smoking-related respiratory symptoms (dry cough, breath
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shortness, mouth irritation, and phlegm) as a consequence of reduced tobacco cigarette
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consumption. The secondary outcomes included the assessment of the success rate of
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smoking cessation attempts and daily smoking reduction in the three arms, and the
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monitoring of safety and toxicity during the study in arms 1 and 2. The present work
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illustrates data at 3 months, where the primary outcome was not measured yet. So, we
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focused here on smoking stopping, smoking reduction, and safety issues.
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We hypothesized that e-cigarette filled with nicotine liquid (arm 1) would be more
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effective than nicotine-free e-cigarette (arm 2) and the control group (arm 3) for smoking
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reduction and would have no greater risk of side-effects.
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A sample size of 210 participants was chosen to assess smoking reduction. Starting with
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the expected intrinsic motivation of participants, the study aimed to have at least 80%
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retention at 6 months and 70% at 12 months. Considering these figures, we expected to
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maintain a statistical power to detect a reduction of 5 cigarettes/day in our smokers
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(being the cigarettes per day mean about 20 in the COSMOS population). Thus, using a
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two-sided two-sample t-test with a significance level (alpha) of 0.05, a sample size of 49
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participants per arm we expected to achieve 80% power to detect a mean reduction of 5
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cigarettes/day between any of the two experimental arms and the control arm, assuming
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a mean consumption of 20 cigarettes/day in the control arm and common standard
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deviation within group of 8.7.
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…
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Results
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At the baseline, the levels of anxiety and depression were not significantly different
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between the three groups. Generally, participants reported normal values, indicating the
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absence of clinical depression. Likewise, no differences among groups were found in the
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physical and psychological domains based on the LCQ scores. Some common e-
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cigarette side effects were reported.
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At month 3, we collected complete data about 170 participants. No statistical differences
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in the number of missing data were present between arms (χ2(2) = .835, p = .659).
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Participants in Arm 1 and Arm 2 had a similar compliance in the use of e-cigarettes. In
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fact, considering the number of empty flacons they gave back at the end of the study we
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dind’t find any significant difference, though the placebo group used on average less
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liquid (Arm 1 M = 10.9 empty flacons; Arm 2 M = 9.8 empty flacons).
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Across study arms, 20% of participants (N = 34) stopped smoking at month 3. The
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percentage was significantly higher in the nicotine (N = 15; 25.4%) and nicotine-free (N
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= 13; 23.4%) e-cigarette groups than in the control group (N = 6; 10.34%) (χ2(2) =
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4.899, p = .044).
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Next, we compared reduction of cigarette consumption in participants who had used e-
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cigarettes (Arm 1 and Arm 2) and those who only received counseling (Arm 3). The
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Mann-Whitney U test reported significant differences between conditions (e-cigarettes
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vs. control) at month 1 (U = 2.508, p < .010) and at month 3 (U = 2.130, p < .022). The
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use of the electronic device actually helped participants reduce daily cigarettes. At
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month 3, also the reduction rate showed interesting results. Participants in Arm 3
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reported smoking an average of 10.034 cigarettes/day, while participants in Arm 1 and
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Arm 2 showed a lower consumption (7.671 and 9.091, respectively). However, while the
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difference between Arm 1 and Arm 3 was statistically significant, differences between
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Arms 1 and 2 and between Arms 2 and 3 were not.
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Considering the mean difference in cigarette consumption between the baseline and
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month 3, the Kruskal-Wallis H test for 3 independent samples showed a significant
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difference among Arms 1, 2, and 3 (see table 2): Participants in Arm 1 reported a higher
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reduction rate (M = -11.644, SD = 7.574) than participants in Arm 2 (M = -10.763, SD =
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8.156) and Arm 3 (M = -9.138, SD = 8.8127).
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Table 2 here
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However, excluding from the reduction analysis the participants who discontinued
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smoking, we failed to find any statistical difference, even though in Arm 1 we found the
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highest reduction (M = - 9.164 in Arm1; M = -8.262 in Arm2; M = -7.875 in Arm3).
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Considering respiratory symptoms, a significant reduction in all conditions was found,
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probably due to the decreased number of daily cigarettes smoked by most participants,
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independent of study arms. In particular, about 21.5% of participants reported a decrease
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in coughing, about 18.50% reported less catarrh, and about 14.5% reported an
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improvement in breathing.
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Focusing on e-cigarettes tolerability, our participants reported few side effects (see table
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3). In particular, at month 1 the most relevant complain was “burning throat”. It was
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reported by about 23% of participants using liquid containing nicotine (while only about
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4% of participant reported the same complain using nicotine-free liquid). However, at
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month 3 we observed a drastic decrease of the symptom. Cough was also reported at
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month 1 by about 10% of participants, both using nicotine and nicotine-free liquid. Also
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in this case, the symptom decreased during time.
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Discussion
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In this study, we tested the efficacy of e-cigarettes as cessation treatment in a sample of
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chronic smokers involved in a screening program. Our main result is that the use of e-
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cigarettes helped participant stop smoking since about one-quarter of participants who
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followed a cessation program based on e-cigarettes (both with and without nicotine) and
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a low-intensity counseling were abstinent after three months. Conversely, about 10% of
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smokers stopped following a program based only on a low-intensity counseling.
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Furthermore, e-cigarettes increased the reduction rate in participants who continued
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smoking. In fact, although all participants reported a significant reduction of daily
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cigarette consumption compared to the baseline, the use of e-cigarettes (including those
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without nicotine) allowed smokers achieving a better result. The few side effects
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reported, which were also reported in other studies,36-39 were well managed by
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participants and showed no increase during the treatment. Consequently, our findings
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confirm the efficacy as well as the safety of e-cigarettes in a short-term period.
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Although participants in Arm 1 generally achieved better results, the placebo condition
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was effectively as well, in some case leading to comparable outcomes. This result has
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not been described before and provides suggestions for potentially fruitful new lines of
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research.
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Future studies should analyze costs and benefits related to the use of nicotine-free e-
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cigarettes in high-risk patients who smoke. In particular, the efficacy of combining
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clinical counseling and nicotine-free e-cigarettes for high-risk patients should be
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discussed. In our view, it could have pivotal implications in clinical practice. We believe
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that nicotine-free e-cigarettes might be a first-line choice, particularly for subjects who
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have severe diseases (for example, those with heart problems) and cannot use nicotine or
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receive other medical treatments. However, the lack of differences between nicotine and
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nicotine-free device effects on smoking might also be linked to the low dosage of
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nicotine we adopted. In fact, using a device working at 10 W with an 8 mg/mL nicotine
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concentration we obtained quite a low dosage (less than 0.1 mg per puff) with respect to
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the nicotine normally assumed daily by a chronic smoker40. This may explain why
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results in Arm 1 (nicotine e-cigarettes) and Arm 2 (nicotine-free e-cigarettes) are so
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similar. Increasing nicotine concentration probably may enlarge this difference, although
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we need targeted research to establish which protocol may optimize the risk/benefits
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ratio.
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In conclusion, taking into consideration the perspective of personalized medicine, e-
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cigarettes based protocols associated with new ICT-driven models of self-management
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may be implemented to support people to better handle behavioral changes and side
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effects.41-45 This is true for ready-to-quit smokers (such as our participants) but could
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also be advantageous for less motivated smokers engaged in clinical settings.
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Limits of the Study
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The number of initial dropouts, i.e., participants who explicitly declared the willingness
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not to continue within the first month (1 participant in Arm 1, 2 in Arm 2, and 6 in Arm
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3) was particularly high in in the control group. It might suggest that motivation to
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participate to the study was related to the possibility of using the e-cigarettes rather than
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an actual willingness to stop smoking. During the study we had some missing data
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(12.4% at month 1; 21.9% at month 2; 18.1% at month 3) that limit our results.
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Monthly, we monitored the use of e-cigarettes during the counseling calls and the
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follow-up to manage potential problems. However, we didn’t assess systemically any
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quantitative measure about the actual use. For this reason, only qualitative considerations
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can be done about the different use of e-cigarettes between subjects in Arm 1 and Arm 2.
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Furthermore, the number of smoked cigarettes was recorded as participants’ self-reports,
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which might have led to a measurement bias. The impossibility of assessing carbon
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monoxide in an expired breath at month 3 because of the study design cannot
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disambiguate the aforementioned possible explanation. However, if present, this effect
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was constant in all 3 arms, thus not affecting the exhibited effects. Finally, this paper
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focused on a secondary outcome, since the primary one was supposed to be assessed at
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six months.
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Protocol
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Clinicaltrials.gov NCT02422914; https://clinicaltrials.gov/ct2/show/NCT02422914
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Funding
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This study was supported by a grant from Fondazione Umberto Veronesi (FUV).
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