Electronic Nicotine-Delivery Systems for Smoking Cessation.

BACKGROUND: Electronic nicotine-delivery systems - also called e-cigarettes - are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed. METHODS: In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy. The primary outcome was biochemically validated, continuous abstinence from smoking at 6 months. Secondary outcomes included participant-reported abstinence from tobacco and from any nicotine (including smoking, e-cigarettes, and nicotine-replacement therapy) at 6 months, respiratory symptoms, and serious adverse events. RESULTS: A total of 1246 participants underwent randomization; 622 participants were assigned to the intervention group, and 624 to the control group. The percentage of participants with validated continuous abstinence from tobacco smoking was 28.9% in the intervention group and 16.3% in the control group (relative risk, 1.77; 95% confidence interval, 1.43 to 2.20). The percentage of participants who abstained from smoking in the 7 days before the 6-month visit was 59.6% in the intervention group and 38.5% in the control group, but the percentage who abstained from any nicotine use was 20.1% in the intervention group and 33.7% in the control group. Serious adverse events occurred in 25 participants (4.0%) in the intervention group and in 31 (5.0%) in the control group; adverse events occurred in 272 participants (43.7%) and 229 participants (36.7%), respectively. CONCLUSIONS: The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking-cessation counseling alone. (Funded by the Swiss National Science Foundation and others; ESTxENDS ClinicalTrials.gov number, NCT03589989.).

Changes in biomarkers of endothelial function, oxidative stress, inflammation and lipids after smoking cessation: A cohort study.

BACKGROUND: Tobacco use is known to be involved in the development of cardiovascular diseases, which leads to premature mortality. Endothelial dysfunction, the first step in this process, was shown induced by smoking. It is reported that quitting smoking could reduce the risk of diseases, but the implied mechanisms are still unclear. This study aimed to evaluate the biological markers of endothelial function in smokers when actively smoking and after cessation. METHODS: Quantification of several biomarkers reflecting inflammation, endothelium activation, oxidative stress, and lipids was performed in 65 smokers when actively smoking and after cessation (median abstinence duration of 70 days). RESULTS: A possible decrease of inflammation was observed through the concentration reduction of a proinflammatory cytokine (interleukine-6) on quitting. A decrease of endothelium activation was visible by the reduced level of the soluble intercellular adhesion molecule. Two antioxidants, uric acid and vitamin C, were found at higher concentration than before the cessation, potentially reflecting the decrease of oxidative stress on quitting. Lipid profile was improved post-quit since HDL level was increased and LDL level was decreased. All these effects were visible at short term with abstinence duration less than 70 days. No sex-specific difference was observed and no additional changes were observed for longer abstinence duration. CONCLUSION: These observations suggest that some adverse effects of smoking on endothelial function could be reversible on quitting smoking. It could encourage smokers to enter a cessation program to reduce the risk for cardiovascular diseases development.

Effect of the Nicotine Replacement Therapy on Biomarkers of Inflammation, Endothelial Dysfunction, Oxidative Stress, and Lipids in Smokers Who Quit Smoking.

INTRODUCTION: Our previous study showed major changes in biomarkers on quitting compared to the smoking state. They reflected a decrease in inflammation, endothelial activation, and oxidative stress, as well as an improved lipid profile. Nicotine replacement therapy (NRT) is effective to increase the rate of successful quitting, but healthcare professionals may have concerns to prescribe this first-line smoking cessation treatment because its effect on inflammation and related processes is controversial. AIMS AND METHODS: The present study assessed the influence of NRT on biomarkers of inflammation, endothelial function, oxidative stress, and lipids, in people who quit smoking. Sixty-five subjects who daily smoke cigarettes were recruited and followed on quitting. Thirty-five quit using NRT and thirty quit without NRT. Biomarkers of inflammation, endothelial function, oxidative stress, and lipids were quantified at baseline when actively smoking and after cessation in the presence of NRT or not. RESULTS: Changes in biomarkers on quitting did not differ according to the treatment used. No difference was found when comparing participants who were exposed to NRT and those who were not. CONCLUSIONS: These results may indicate that NRT has no effect on inflammation, endothelial function, oxidative stress, and lipids, when used as a medication aid for quitting smoking. IMPLICATIONS: This study provides new evidence to support the safety profile of NRT products regarding the biomarkers of endothelial function, oxidative stress, inflammation, and lipids.

Changes in smoking and alcohol consumption during COVID-19-related lockdown: a cross-sectional study in France.

BACKGROUND: In many countries, lockdown measures were implemented to curb the COVID-19 pandemic. This situation may have an impact on mental health, tobacco smoking and alcohol consumption. The aim of this research report is therefore to describe changes in tobacco and alcohol consumption in the general French population during the first 2 weeks of lockdown and identify any associated factors. METHODS: Self-reported changes in smoking and alcohol consumption following the lockdown implemented in France on 17 March 2020 were collected from 2003 respondents aged 18 years and older in an online cross-sectional survey carried out from 30 March to 1 April 2020. Anxiety and depression levels were assessed using the Hospital Anxiety and Depression Scale. RESULTS: Among current smokers, 26.7% reported an increase in their tobacco consumption since lockdown and 18.6% reported a decrease, while it remained stable for 54.7%. The increase in tobacco consumption was associated with an age of 18-34 years, a high level of education, and anxiety. Among alcohol drinkers, 10.7% reported an increase in their alcohol consumption since lockdown and 24.4% reported a decrease, while it remained stable for 64.8%. The increase in alcohol consumption was associated with an age of 18-49 years, living in cities of more than 100 000 inhabitants, a high socio-professional category, and a depressive mood. CONCLUSIONS: The national lockdown implemented in France during the COVID-19 pandemic influenced tobacco and alcohol consumption in different ways according to sociodemographic group and mental health.

[Three approaches to doctor-patient communication and prevention : Which model for which situation ?] / Trois approches de communication médecin-patient et prévention : quel modèle pour quelle situation ?

Doctors learn different communication approaches for use during prevention consultations to promote healthy habits, so as to set up a partnership and to promote patient autonomy. Three of these approaches are shared decision making, when there is more than one reasonable choice, motivational interviewing, principally for behaviour change and therapeutic education, a pedagogical approach helping patients develop skills so that they may have a better management of their chronic illness. This article presents an overview of the commonalities and the differences between these approaches, often considered separately, nevertheless they are complementary and in practice, using elements of all three during a consultation could improve preventative care.

Les médecins apprennent différentes approches de communication utilisées lors des consultations de prévention afin de promouvoir des comportements sains, créer un partenariat avec le patient et favoriser son autonomie. Trois des approches les plus courantes sont : la décision partagée lorsqu'il y a plus d'un choix raisonnable, l'entretien motivationnel pour le changement de comportement et l'éducation thérapeutique, une approche pédagogique visant le développement de compétence des patients pour une gestion optimale des maladies chroniques. Nous présentons ici une vision d'ensemble des similarités et des différences entre ces approches, car, souvent considérées en silos, elles sont néanmoins complémentaires et, en pratique, utiliser des éléments tirés des trois durant une consultation pourrait améliorer la prise en charge.

Using Trial Sequential Analysis for estimating the sample sizes of further trials: example using smoking cessation intervention.

BACKGROUND: Assessing benefits and harms of health interventions is resource-intensive and often requires feasibility and pilot trials followed by adequately powered randomised clinical trials. Data from feasibility and pilot trials are used to inform the design and sample size of the adequately powered randomised clinical trials. When a randomised clinical trial is conducted, results from feasibility and pilot trials may be disregarded in terms of benefits and harms. METHODS: We describe using feasibility and pilot trial data in the Trial Sequential Analysis software to estimate the required sample size for one or more trials investigating a behavioural smoking cessation intervention. We show how data from a new, planned trial can be combined with data from the earlier trials using trial sequential analysis methods to assess the intervention's effects. RESULTS: We provide a worked example to illustrate how we successfully used the Trial Sequential Analysis software to arrive at a sensible sample size for a new randomised clinical trial and use it in the argumentation for research funds for the trial. CONCLUSIONS: Trial Sequential Analysis can utilise data from feasibility and pilot trials as well as other trials, to estimate a sample size for one or more, similarly designed, future randomised clinical trials. As this method uses available data, estimated sample sizes may be smaller than they would have been using conventional sample size estimation methods.

Pharmacological interventions for promoting smoking cessation during pregnancy.

BACKGROUND: Tobacco smoking in pregnancy causes serious health problems for the developing fetus and mother. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion, and varenicline) are effective for increasing smoking cessation, however their efficacy and safety in pregnancy remains unknown. Electronic cigarettes (ECs) are becoming widely used, but their efficacy and safety when used for smoking cessation in pregnancy are also unknown. OBJECTIVES: To determine the efficacy and safety of smoking cessation pharmacotherapies and ECs used during pregnancy for smoking cessation in later pregnancy and after childbirth, and to determine adherence to smoking cessation pharmacotherapies and ECs for smoking cessation during pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 May 2019), trial registers, and grey literature, and checked references of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) conducted in pregnant women, comparing smoking cessation pharmacotherapy or EC use with either placebo or no pharmacotherapy/EC control. We excluded quasi-randomised, cross-over, and within-participant designs, and RCTs with additional intervention components not matched between trial arms. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. The primary efficacy outcome was smoking cessation in later pregnancy; safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being. We also collated data on adherence to trial treatments. We calculated the risk ratio (RR) or mean difference (MD) and the 95% confidence intervals (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate. MAIN RESULTS: We included 11 trials that enrolled a total of 2412 pregnant women who smoked at enrolment, nine trials of NRT and two trials of bupropion as adjuncts to behavioural support, with comparable behavioural support provided in the control arms. No trials investigated varenicline or ECs. We assessed four trials as at low risk of bias overall. The overall certainty of the evidence was low across outcomes and comparisons as assessed using GRADE, with reductions in confidence due to risk of bias, imprecision, and inconsistency. Compared to placebo and non-placebo (behavioural support only) controls, there was low-certainty evidence that NRT increased the likelihood of smoking abstinence in later pregnancy (RR 1.37, 95% CI 1.08 to 1.74; I² = 34%, 9 studies, 2336 women). However, in subgroup analysis by comparator type, there was a subgroup difference between placebo-controlled and non-placebo controlled RCTs (test for subgroup differences P = 0.008). There was unclear evidence of an effect in placebo-controlled RCTs (RR 1.21, 95% CI 0.95 to 1.55; I² = 0%, 6 studies, 2063 women), whereas non-placebo-controlled trials showed clearer evidence of a benefit (RR 8.55, 95% CI 2.05 to 35.71; I² = 0%, 3 studies, 273 women). An additional subgroup analysis in which studies were grouped by the type of NRT used found no difference in the effectiveness of NRT in those using patches or fast-acting NRT (test for subgroup differences P = 0.08). There was no evidence of a difference between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities, or neonatal death. In one study infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' at two years of age compared to the placebo group. Non-serious adverse effects observed with NRT included headache, nausea, and local reactions (e.g. skin irritation from patches or foul taste from gum), but data could not be pooled. Adherence to NRT treatment regimens was generally low. We identified low-certainty evidence that there was no difference in smoking abstinence rates observed in later pregnancy in women using bupropion when compared to placebo control (RR 0.74, 95% CI 0.21 to 2.64; I² = 0%, 2 studies, 76 women). Evidence investigating the safety outcomes of bupropion use was sparse, but the existing evidence showed no difference between the bupropion and control group. AUTHORS' CONCLUSIONS: NRT used for smoking cessation in pregnancy may increase smoking cessation rates in late pregnancy. However, this evidence is of low certainty, as the effect was not evident when potentially biased, non-placebo-controlled RCTs were excluded from the analysis. Future studies may therefore change this conclusion. We found no evidence that NRT has either positive or negative impacts on birth outcomes; however, the evidence for some of these outcomes was also judged to be of low certainty due to imprecision and inconsistency. We found no evidence that bupropion may be an effective aid for smoking cessation during pregnancy, and there was little evidence evaluating its safety in this population. Further research evidence on the efficacy and safety of pharmacotherapy and EC use for smoking cessation in pregnancy is needed, ideally from placebo-controlled RCTs that achieve higher adherence rates and that monitor infants' outcomes into childhood. Future RCTs of NRT should investigate higher doses than those tested in the studies included in this review.

Effectiveness of a Fully Automated Internet-Based Smoking Cessation Program: A Randomized Controlled Trial (STAMP).

Introduction: The Internet offers an interesting alternative to face-to-face and telephone-based support for smoking cessation. This study was designed to assess the effectiveness of a personalized and automated Internet-based program. Methods: French current adult smokers willing to quit within 2 weeks were recruited for a randomized controlled trial. The intervention consisted of an automated program of 45 e-mails ("e-coaching") sent over a 3-month period. The control group received a PDF version of a booklet on smoking cessation. Self-reported 7-day point prevalence smoking abstinence was measured at 6 months (primary outcome), at 3 and 12 months of follow-up (secondary outcomes). Results: 2478 smokers were randomized (1242 for e-coaching, 1236 for the booklet). Cessation rate in the intention-to-treat population was not significantly different between the two groups at 6 and 12 months, but was higher in the e-coaching group at 3 months than in the control group (27.5% vs. 23.5%, p = .02, odds ratio [OR] = 1.24, confidence interval [CI] = [1.03-1.49]). After adjustment for baseline conditions, the effect of the intervention in the per-protocol (PP) sample was significant at 3 months (adjusted odds ratio [aOR] = 1.72 [1.31-2.28], p < .001, N = 1042) and at 6 months (aOR = 1.27 [1.00-1.60], p = .05, N = 1082). GLM repeated measure analyses showed significant group by time interaction in the intent-to-treat and a significant group effect in the PP population. Conclusions: Analyzed intention-to-treat, e-coaching was superior to a booklet at 3 months (end of intervention) but no more superior at 6 and 12 months follow-up. Among those who actually followed the program, the effectiveness is also observed 3 months after the intervention is stopped. Implications: Analyzed intention-to-treat, our French tailored and personalized Internet-based cessation program was superior to a smoking cessation booklet at 3 months (end of intervention) but no more superior at 6 months follow-up. Among those who actually followed the program (PP population), the effectiveness is observed in the short-term but also 3 months after the intervention is stopped.

Cigarette Smoking During Pregnancy: Do Complete Abstinence and Low Level Cigarette Smoking Have Similar Impact on Birth Weight?

OBJECTIVES: Despite awareness of negative health outcomes associated with smoking, pregnant smokers might reduce their tobacco consumption thinking that a low smoking rate reduces smoking-related negative birth outcomes. We aimed to assess in a clinical sample whether there is a smoking rate that would not impact on birth weight (BW). METHODS: Pregnant smokers ≥18 years, gestational age of 9-20 weeks of amenorrhea, motivated to quit smoking, smoking ≥5 cigarettes/day (cpd) and their newborns (381 singleton, live births) were included in this secondary analysis of a French smoking cessation trial. RESULTS: The mean BW when the mother quit smoking was 3417 g (95 % CI: 3098-3738 g); when smoking >0<5 cpd, 3081g (3003-3159 g); when smoking 5-9 cpd, 3043 g (2930-3157 g); and when smoking ≥10 cpd, 2831 g (2596-3157 g) (p = .006). The corresponding effect sizes ranged from medium to large (Cohen's d for BW: 0.54, 0.57 and 0.85) compared to BW when the mother quit. In the multivariable analysis, adjusted for all significant confounders, when the mother smoked on average >0<5 cpd, the loss in BW was 228 g; when smoking 5-9 cpd, 251 g; and when smoking ≥10 cpd, 262 g (all p ≤ .02) compared to newborns' BW of mothers who stopped smoking since quit date. CONCLUSIONS: Even low cigarette consumption during pregnancy is associated with BW loss. All efforts should be made to help pregnant smokers quit completely during their pregnancy. IMPLICATIONS: As an alternative to quitting smoking, pregnant smokers reduce their smoking rate thinking that this diminishes smoking-related negative health outcomes. No study has established whether low smoking rate (more than 0 but less than 5 cpd) during pregnancy impacts BW compared to abstinence from smoking. Among treatment-seeking pregnant smokers BW of newborns of mothers who smoked even less than 5 cpd was significantly lower than of those whose mothers quit; effect sizes of different consumption levels on BW ranged from moderate (>0<5 cpd) to large (≥10 cpd). Even low smoking rate is associated with reduced BW compared to complete maternal smoking abstinence.

A Comparison of the Fagerström Test for Cigarette Dependence and Cigarette Dependence Scale in a Treatment-Seeking Sample of Pregnant Smokers.

INTRODUCTION: Valid and reliable brief measures of cigarette dependence are essential for research purposes and effective clinical care. Two widely-used brief measures of cigarette dependence are the six-item Fagerström Test for Cigarette Dependence (FTCD) and five-item Cigarette Dependence Scale (CDS-5). Their respective metric characteristics among pregnant smokers have not yet been studied. METHODS: This was a secondary analysis of data of pregnant smokers (N = 476) enrolled in a smoking cessation study. We assessed internal consistency, reliability, and examined correlations between the instruments and smoking-related behaviors for construct validity. We evaluated predictive validity by testing how well the measures predict abstinence 2 weeks after quit date. RESULTS: Cronbach's alpha coefficient for the CDS-5 was 0.62 and for the FTCD 0.55. Measures were strongly correlated with each other, although FTCD, but not CDS-5, was associated with saliva cotinine concentration. The FTCD, CDS-5, craving to smoke, and withdrawal symptoms failed to predict smoking status 2 weeks following the quit date. CONCLUSIONS: Suboptimal reliability estimates and failure to predict short-term smoking call into question the value of including either of the brief measures in studies that aim to explain the obstacles to smoking cessation during pregnancy.

Relationships between nicotine and cotinine concentrations in maternal milk and saliva.

AIM: Breastfeeding may be impaired due to nicotine excreted into the milk of smoking mothers. We investigated the relationships between nicotine and cotinine concentrations in maternal milk and saliva among breastfeeding smokers. METHODS: The 41 mothers reported their cigarette consumption between waking up and milk and saliva sampling. The median sampling time took place four days after delivery. Nicotine and cotinine concentrations were determined by liquid chromatography and UV detection, after a single-step saliva or three-step milk liquid-to-liquid extraction. RESULTS: The median (interquartile range) concentrations in milk and saliva were 7 (6-22) and 27 (4-207) µg/L for nicotine and 24 (5-111) and 22 (4-120) µg/L for cotinine, respectively. Milk cotinine was positively associated with saliva cotinine (p < 0.0001) and cigarette consumption (p = 0.039) and inversely associated with the time since the last cigarette (p = 0.0004, model R(2) = 0.90). Milk nicotine was associated with saliva nicotine concentration (p = 0.0017) and cigarette consumption (p = 0.0023, model R(2) = 0.63). CONCLUSION: Saliva nicotine concentration was not a very good estimate of milk nicotine concentration in breastfeeding mothers. Saliva cotinine concentration may be used instead of milk cotinine concentration to estimate tobacco or nicotine exposure among breastfed neonates or infants.

[SMOKING CESSATION IN PREGNANCY]. / Sevrage tabagique chez la femme enceinte.

Smoking during pregnancy is the leading preventable cause of perinatal morbidity. Half of smokers are weaned during pregnancy resulting in 15% of female smokers at time of delivery. Most often, women spontaneously withdraw at the announcement of pregnancy. Thus, the action of professionals has a modest effect. But this effect is real and should encourage us to take care for patients who smoke. They should feel free with guilty. The spouse must be included in this support to create an enabling environment. Every action has its effectiveness. Nicotine prescription should be reserved for cases where it reduces consumption and keep the medicalized link. It is possible to smoke with a nicotine patch in place; the substitution then reduces the cosumption of each cigarette.

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice.

Strategies for assisting smoking cessation include behavioural counselling to enhance motivation and to support attempts to quit and pharmacological intervention to reduce nicotine reinforcement and withdrawal from nicotine. Three drugs are currently used as first line pharmacotherapy for smoking cessation, nicotine replacement therapy, bupropion and varenicline. Compared with placebo, the drug effect varies from 2.27 (95% CI 2.02, 2.55) for varenicline, 1.69 (95% CI 1.53, 1.85) for bupropion and 1.60 (95% CI 1.53, 1.68) for any form of nicotine replacement therapy. Despite some controversy regarding the safety of bupropion and varenicline, regulatory agencies consider these drugs as having a favourable benefit/risk profile. However, given the high rate of psychiatric comorbidity in dependent smokers, practitioners should closely monitor patients for neuropsychiatric symptoms. Second-line pharmacotherapies include nortriptyline and clonidine. This review also offers an overview of pipeline developments and issues related to smoking cessation in special populations such as persons with psychiatric comorbidity and pregnant and adolescent smokers.

Do smoking abstinence periods among pregnant smokers improve birth weight? A secondary analysis of a randomised, controlled trial.

OBJECTIVES: Maternal smoking during pregnancy is associated with low birth weight (LBW). Reduction of cigarette consumption does not seem to improve birth weight but it is not known whether implementation of periods of smoking abstinence improves it. We assessed whether the number of 7-day periods of smoking abstinence during pregnancy may help reduce the number of newborns with LBW. DESIGN AND SETTING: Secondary analysis of a randomised, controlled, multicentre, smoking cessation trial among pregnant smokers. PARTICIPANTS: Pregnant women were included at <18 weeks of gestational age and assessed at face-to-face, monthly visits. Data of 407 singleton live births were analysed. PRIMARY OUTCOME MEASURE: Newborns with low birth weight. RESULTS: 40 and 367 newborns were born with and without LBW, respectively. Adjusted for all available confounders, 3 or more periods of at least 7 days' smoking abstinence during pregnancy was associated with reduced likelihood of LBW compared with no abstinence periods (OR = 0.124, 95% CI 0.03 to 0.53, p = 0.005). Reduction of smoking intensity by at least 50% was not associated with birth weight. CONCLUSION: Aiming for several periods of smoking abstinence among pregnant smokers unable to remain continuously abstinent from smoking may be a better strategy to improve birth weight than reducing cigarette consumption. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02606227.

Tobacco smoking and diabetes. A comparative survey among diabetologists and smoking cessation specialists.

AIMS: Because tobacco smoking is a major risk factor of mortality in diabetes and guidelines suggest evaluating smoking behavior among individuals with diabetes and helping smokers quit, we aimed to assess knowledge about the tobacco smoking - diabetes relationship among diabetologists and smoking cessation specialists (SCS). METHODS: An online cross sectional survey was conceived by the Working Group on Smoking and Diabetes, France. The questionnaire was tested by the members of the Working Group and deemed to be completed in less than 5 min. Only questions receiving the highest number of approval ratings were kept for the survey. The questionnaire was sent to all members of the French Language Society of Diabetes (Société Francophone du Diabète, SFD), N = 969 and the French Language Society on Tobacco (Société Francophone de Tabacologie, SFT), N = 307. The mailing lists of members were obtained with the previous agreement of the societies' board. RESULTS: 225 diabetologists and 97 SCS (response rate 23.2% and 31.5%, respectively) completed the questionnaire. Over 90% of the diabetologists reported recording smoking status of their patients. Although diabetologists were aware that smoking increases all-cause mortality of individuals with diabetes, only 29.3% were aware that smoking is a risk factor for type 2 diabetes (76.3% among SCS), for poor glycemic control: 32.9% (86.6% among SCS). Significantly less diabetologists (64%) than SCS (76.3%) were aware of smoking being a risk factor for microangiopathy. More diabetologists considered that smoking cessation is more important than optimizing glycemic control among individuals with type 2 (69.3%) than among those with type 1 diabetes (47.1%). Few diabetologists (11.1%) and SCS (14.4%) reported to be trained for smoking cessation among persons with diabetes. CONCLUSION: Specific knowledge about the negative tobacco smoking - diabetes association seems to be insufficient among French diabetologists. Diabetologists but also other health care professionals should be trained to help individuals with diabetes who smoke to quit smoking.

Prazosin and cyproheptadine in combination in the treatment of alcohol use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Pre-clinical studies suggest that the simultaneous blockade of the α1b and 5HT2A receptors may be effective in reducing alcohol consumption. This study aimed to assess the efficacy and safety of prazosin (α1b blocker) and cyproheptadine (5HT2A blocker) combination in decreasing total alcohol consumption (TAC) in alcohol use disorder (AUD). DESIGN, SETTING AND PARTICIPANTS: This was a double-blind, parallel group, placebo-controlled, Phase 2, randomized clinical trial conducted in 32 addiction treatment centres in France. A total of 108 men and 46 women with severe AUD took part. INTERVENTION: Participants were randomly assigned to one of the following 3-month treatments: (1) low-dose group (LDG) receiving 8 mg cyproheptadine and 5 mg prazosin extended-release (ER) formulation daily; (2) high-dose group (HDG) receiving 12 mg cyproheptadine and 10 mg prazosin ER daily; and (3) placebo group (PG) receiving placebo of cyproheptadine and prazosin ER. A total of 154 patients were randomized: 54 in the PG, 54 in the LDG and 46 in the HDG. MEASUREMENTS: The primary outcome was TAC change from baseline to month 3. FINDINGS: A significant main treatment effect in the change in TAC was found in the intent-to-treat population (P = 0.039). The HDG and LDG showed a benefit in the change in TAC from baseline to month 3 compared with PG: -23.6 g/day, P = 0.016, Cohen's d = -0.44; -18.4 g/day, P = 0.048 (Bonferroni correction P < 0.025), Cohen's d = -0.36. In a subgroup of very high-risk drinking-level participants (> 100 g/day of pure alcohol for men and > 60 g/day for women), the difference between the HDG and the PG in the primary outcome was -29.8 g/day (P = 0.031, Cohen's d = -0.51). The high and low doses were well-tolerated with a similar safety profile. CONCLUSIONS: A randomized controlled trial of treatment of severe alcohol use disorder with a cyproheptadine-prazosin combination for 3 months reduced drinking by more than 23 g per day compared with placebo. A higher dose combination was associated with a larger magnitude of drinking reduction than a lower dose combination while showing similar safety profile.