Background and aims
Most studies in English‐speaking countries have found a positive association between e‐cigarette experimentation and subsequent daily tobacco smoking among adolescents. However, ...this result may not be valid in other cultural contexts; in addition, few studies have assessed whether this association varies with the subject' age at the time of e‐cigarette experimentation. This study aimed to estimate the association between experimenting first with e‐cigarette (rather than tobacco) and subsequent daily smoking according to age at the time of experimentation.
Design
Secondary analysis; risk ratios (RRs) computed using modified Poisson regressions with inverse probability weighting.
Setting
A cross‐sectional nation‐wide representative survey performed in 2017 in France.
Participants
French adolescents (n = 24 111), aged 17 to 18.5 years, who had previously experimented with either e‐cigarettes or tobacco.
Measures
Exposure was defined as the experimentation with e‐cigarettes first (whether or not followed by experimentation with tobacco); the outcome as daily tobacco smoking at the time of data collection. Gender, age, literacy, socio‐economic status, pre‐exposure repeat school years and experimentation with drunkeness, 3 licit and 8 illicit drugs were adjusted for. Uncertainties about the sequence of events defining exposure were handled by the definition of three patterns of exposure, to avoid a misclassification bias.
Findings
Exposure reduced the risk of transition to daily smoking: RR = 0.58, 95% confidence interval (CI) = 0.54, 0.62. This effect increased in a linear manner with age at exposure (RR = 0.87, 95% CI = 0.78; 0.98 for 1 year, P < 0.001): from RR = 1.30, 95% CI = 1.09; 1.54 at age 9 to RR = 0.38, 95% CI = 0.32; 0.45 at age 17.
Conclusions
Experimenting with e‐cigarettes first (as opposed to tobacco first) appears to be associated with a reduction in the risk of daily tobacco smoking among French adolescents aged 17–18.5, but this risk varies negatively with age at experimentation, and early e‐cigarette experimenters are at higher risk.
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.
Despite its success with compliant or supervised patients, disulfiram has been a controversial medication in the treatment of alcoholism. Often, study designs did not recognize a pivotal factor in ...disulfiram research, the importance of an open-label design. Our objectives are: (1) to analyze the efficacy and safety of disulfiram in RCTs in supporting abstinence and (2) to compare blind versus open-label studies, hypothesizing that blinded studies would show no difference between disulfiram and control groups because the threat would be evenly spread across all groups.
We searched PubMed, EMBASE and the Cochrane Central Register for RCTs on disulfiram use with alcoholics in comparison to any alcoholic control group. The primary outcome was defined by the authors of each trial. Additional analyses included: blind vs. open-label, with or without supervision, cocaine study or not, and type of control. Overall, the 22 included studies showed a higher success rate of disulfiram compared to controls Hedges'g = .58 (95%CI = .35-.82). When comparing blind and open-label RCTs, only open-label trials showed a significant superiority over controls g = .70 (95%CI = .46-.93). RCTs with blind designs showed no efficacy of disulfiram compared to controls. Disulfiram was also more effective than the control condition when compared to naltrexone g = .77, 95%CI = .52-1.02, to acamprosate g = .76, 95%CI = .04-1.48, and to the no disulfiram groups g = .43, 95%CI = .17-.69. LIMITS INCLUDE: (1) a population of 89% male subjects and (2) a high but unavoidable heterogeneity of the studies with a substantial I-square in most subgroups of studies.
Blinded studies were incapable of distinguishing a difference between treatment groups and thus are incompatible with disulfiram research. Based on results with open-label studies, disulfiram is a safe and efficacious treatment compared to other abstinence supportive pharmacological treatments or to no disulfiram in supervised studies for problems of alcohol abuse or dependence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cannabis remains the most commonly used and trafficked illicit drug in the world. Its use is largely concentrated among young people (15- to 34-year-olds). There is a variety of cannabis use ...patterns, ranging from experimental use to dependent use. Men are more likely than women to report both early initiation and frequent use of cannabis. Due to the high prevalence of cannabis use, the impact of cannabis on public health may be significant. A range of acute and chronic health problems associated with cannabis use has been identified. Cannabis can frequently have negative effects in its users, which may be amplified by certain demographic and/or psychosocial factors. Acute adverse effects include hyperemesis syndrome, impaired coordination and performance, anxiety, suicidal ideations/tendencies, and psychotic symptoms. Acute cannabis consumption is also associated with an increased risk of motor vehicle crashes, especially fatal collisions. Evidence indicates that frequent and prolonged use of cannabis can be detrimental to both mental and physical health. Chronic effects of cannabis use include mood disorders, exacerbation of psychotic disorders in vulnerable people, cannabis use disorders, withdrawal syndrome, neurocognitive impairments, cardiovascular and respiratory and other diseases.
Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for ...the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients.
Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping.
The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed.
This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen.
Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen.
Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in ...methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double‐blind placebo‐controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d‐amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.
Summary
Background
The latest French good practice recommendations (GPRs) for the screening, prevention, and treatment of alcohol misuse were recently published in partnership with the European ...Federation of Addiction Societies (EUFAS). This article aims to synthesize the GPRs focused on the pharmacotherapy of alcohol dependence.
Methods
A four‐member European steering committee defined the questions that were addressed to an 18‐member multiprofessional working group (WG). The WG developed the GPRs based on a systematic, hierarchical, and structured literature search and submitted the document to two review processes involving 37 French members from multiple disciplines and 5 non‐French EUFAS members. The final GPRs were graded A, B, or C, or expert consensus (EC) using a reference recommendation grading system.
Results
The treatment of alcohol dependence consists of either alcohol detoxification or abstinence maintenance programs or drinking reduction programs. The therapeutic objective is the result of a decision made jointly by the physician and the patient.
For alcohol detoxification, benzodiazepines (BZDs) are recommended in first‐line (grade A). BZD dosing should be guided by regular clinical monitoring (grade B). Residential detoxification is more appropriate for patients with a history of seizures, delirium tremens, unstable psychiatric comorbidity, or another associated substance use disorder (grade B). BZDs are only justified beyond a 1‐week period in the case of persistent withdrawal symptoms, withdrawal events or associated BZD dependence (grade B). BZDs should not be continued for more than 4 weeks (grade C). The dosing and duration of thiamine (vitamin B1) during detoxification should be adapted to nutritional status (EC).
For relapse prevention, acamprosate and naltrexone are recommended as first‐line medications (grade A). Disulfiram can be proposed as second‐line option in patients with sufficient information and supervision (EC). For reducing alcohol consumption, nalmefene is indicated in first line (grade A). The second‐line prescription of baclofen, up to 300 mg/day, to prevent relapse or reduce drinking should be carried out according to the “temporary recommendation for use” measure issued by the French Health Agency (EC).
During pregnancy, abstinence is recommended (EC). If alcohol detoxification is conducted during pregnancy, BZD use is recommended (grade B). No medication other than those for alcohol detoxification should be initiated in pregnant or breastfeeding women (EC). In a stabilized pregnant patient taking medication to support abstinence, the continuation of the drug should be considered on a case‐by‐case basis, weighing the benefit/risk ratio. Only disulfiram should be always stopped, given the unknown risks of the antabuse effect on the fetus (EC).
First‐line treatments to help maintain abstinence or reduce drinking are off‐label for people under 18 years of age and should thus be considered on a case‐by‐case basis after the repeated failure of psychosocial measures alone (EC). Short half‐life BZDs should be preferred for the detoxification of elderly patients (grade B). The initial doses of BZDs should be reduced by 30 to 50% in elderly patients (EC). In patients with chronic alcohol‐related physical disorders, abstinence is recommended (EC). Any antidepressant or anxiolytic medication should be introduced after a psychiatric reassessment after 2–4 weeks of alcohol abstinence or low‐risk use (grade B). A smoking cessation program should be offered to any smokers involved in an alcohol treatment program (grade B).
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.
Abstract
Objectives
To investigate the link between smoking status, including childhood and adult passive exposure, and the risk of incident RA.
Methods
The French E3N cohort includes 98 995 female ...volunteers prospectively followed since 1990. Self-administered questionnaires sent every 2–3 years collected medical events, general, lifestyle and environmental characteristics. RA diagnoses were collected in three successive questionnaires and confirmed if women received reimbursement for an RA-specific medication. The risk of incident RA was estimated using an age-adjusted Cox model that considers smoking status as a time-dependent variable.
Results
Among 71 248 women, 371 incident RA cases were confirmed. Ever-smokers not exposed to passive smoking had an increased risk of RA 1.38 (95% CI 1.10, 1.74). In never-smokers, passive smoking exposure during childhood was associated with a borderline increased risk of RA in the same range as active smoking in adults, with an hazard ratio (HR) of 1.43 (95% CI 0.97, 2.11). Ever-smokers who also had childhood passive smoking exposure had a higher risk of RA than smokers not exposed during childhood HR 1.67 (95% CI 1.17, 2.39), but without a significant difference (P = 0.30). RA began earlier in smokers exposed to childhood passive smoking.
Conclusion
This study confirms that active smoking is associated with an increased risk of RA. It suggests for the first time that passive exposure to tobacco during childhood might also increase the risk of RA in future light smokers and probably non-smokers. Our results highlight the importance of avoiding any tobacco environment in children, especially in those with a family history of RA.
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