Diminishing benefit of smoking cessation medications during the first year: a meta‐analysis of randomized controlled trials

Background and aims

Although smoking cessation medications have shown effectiveness in increasing abstinence in randomized controlled trials (RCTs), it is unclear to what extent benefits persist over time. This paper assesses whether the benefits of smoking cessation medications decline over the first year.

Methods

We selected studies from three systematic reviews published by the Cochrane Collaboration. RCTs of first‐line smoking cessation medications, with 6‐ and 12‐month follow‐up, were eligible for inclusion. Meta‐analysis was used to synthesize information on sustained abstinence (SA) at 6 versus 12 months and 3 versus 6 months, using the risk difference (RD) (‘net benefit’) between intervention and control group quit rates, the relative risk (RR) and the odds ratio (OR).

Results

Sixty‐one studies (27 647 participants) were included. Fewer than 40% of intervention group participants were sustained abstinent at 3 months (bupropion: 37.1%; nicotine replacement therapy (NRT): 34.8%; varenicline: 39.3%); approximately a quarter were sustained abstinent at 6 months (bupropion: 25.9%; NRT: 26.6%; varenicline: 25.4%), and approximately a fifth were sustained abstinent at 12 months (bupropion: 19.9%; NRT: 19.8%%; varenicline: 18.7%). There was only a small decline in RR (3 months: 1.95 [95% confidence interval (CI) = 1.74–2.18, P < 0.0001]; 6 months: 1.87 (95% CI = 1.67–2.08 P < 0.0001); 12 months: 1.75 (95% CI = 1.56–1.95, P < 0.0001) between intervention and control groups over time, but a substantial decline in net benefit [3 months: RD = 17.3% (14.5–20.1%); 6 months: RD = 11.8% (10.0–13.7%); 12 months: RD = 8.2% (6.8–9.6%)]. The decline in net benefit was statistically significant between 3 and 6 [RD = 4.95% (95% CI = 3.49–6.41%), P < 0.0001] and 6 and 12 months [RD = 3.00% (95% CI = 2.36%–3.64%), P < 0.0001)] for medications combined and individual medications.

Conclusions

The proportion of smokers who use smoking cessation medications who benefit from doing so decreases during the course of the first year, but a net benefit still remains at 12 months.     

Education is the strongest socio‐economic predictor of smoking in pregnancy

Aims

To investigate socio‐economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions.

Design

Cross‐sectional analysis with linked survey and register data.

Setting

South‐western Finland.

Participants

A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study.

Measurements

The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire‐based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio‐economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated.

Findings

Mother's education was the strongest socio‐economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2–3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1–9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95% CI = 1.4–6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0–18.2; P < 0.001) for vocational secondary education and 14.4 (95% CI = 6.3–33.0; P < 0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1–3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4–2.8; P < 0.001), but did not attenuate its socio‐economic disparities.

Conclusions

In Finland, socio‐economic disparities in smoking in pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general).     

Assessment of factors associated with smoking cessation at diagnosis or during follow‐up of Crohn's disease

Background and Aim

Smoking cessation is known to improve the course of Crohn's disease (CD). However, the factors associated with smoking cessation after CD diagnosis have not been well established.

Methods

Clinical characteristics and change in smoking status were evaluated in 445 current smokers at the time of CD diagnosis. Patients were classified into three subgroups based on their final smoking status and time of smoking cessation: non‐quitters, quitters at diagnosis, and quitters during follow‐up.

Results

The overall smoking cessation rate was 55.7% (248 of 445 patients). The diagnosis of CD was the main reason for quitting (41.5%, 103 of 248 patients). Smoking cessation at the time of CD diagnosis was associated with intestinal resection within 3 months from CD diagnosis (odds ratio [OR] 2.355, 95% confidence interval [CI] 1.348–4.116, P = 0.003), light smoking (OR 2.041, 95% CI 1.157–3.602, P = 0.014), and initiation of smoking before 18 years of age (OR 0.570, 95% CI 0.327–0.994, P = 0.047). Light smoking (OR 1.762, 95% CI 1.019–3.144, P = 0.043) and initiation of smoking before 18 years (OR 0.588, 95% CI 0.381–0.908, P = 0.017) were also associated with overall smoking cessation.

Conclusion

Quitters after CD diagnosis, including quitters at diagnosis and quitters during follow‐up, had features distinct from those of non‐quitters. Given the motivation at CD diagnosis, a detailed history of smoking habits should be taken and all current smokers should be encouraged to quit smoking at the time of CD diagnosis.     

Combination bupropion SR and varenicline for smoking cessation: a systematic review

ABSTRACT

Background: Tobacco is the leading cause of preventable death in the world. Current cessation medications include nicotine replacement therapy (NRT), varenicline, and bupropion, while combination therapy primarily entails NRT with either varenicline or bupropion. However, recent studies have examined varenicline and bupropion in combination. Objectives: A systematic review assessing the efficacy and safety of combination varenicline and bupropion was conducted. Methods: PubMed and Clinicaltrials.gov were searched using terms: “varenicline combination”, “bupropion combination”, “bupropion AND varenicline”, and “bupropion AND varenicline combination smoking cessation”, yielding four studies including 1193 total patients. Results: Combination therapy yielded greater efficacy than varenicline monotherapy in two randomized controlled trials and one retrospective outcomes study. One single-arm Phase II trial provided additional efficacy and safety data. Of the prospective trials, one displayed a greater 4-week smoking abstinence for weeks 8–11 with combination (39.8%) versus monotherapy (25.9%) (OR = 1.89; 95% CI = 1.07–3.35). The other demonstrated greater prolonged abstinence (continuous abstinence from week 2) at 12 weeks (OR = 1.49; 95% CI = 1.05–2.12) and 26 weeks (OR = 1.52; 95% CI = 1.04–2.22), though results were not significant at 52 weeks in this study. The retrospective study displayed higher success rates (continuous abstinence rates at 52 weeks) with combination varenicline and bupropion (55.0%; compared to varenicline monotherapy (32.1%), p < 0.001). Subgroup analyses suggest that this combination may be more beneficial in males and patients with higher baseline nicotine dependence. Conclusion: To the authors’ knowledge, this is the first review conducted to compile current literature on this novel pharmacotherapy combination for smoking cessation. Combination bupropion SR and varenicline displayed greater efficacy in smoking cessation than varenicline monotherapy, though further safety analysis is warranted to rule out additive psychiatric adverse effects.     

Prescribing of smoking cessation medication in England since the introduction of varenicline

Aims To estimate the effect of the introduction of a new smoking cessation medication, varenicline, and the publication of guidance related to its use, on trends in prescribing of smoking cessation medications in England. Design Interrupted time series analysis of primary care data on prescribing of smoking cessation medication using autoregressive integrated moving average (ARIMA) modelling. Setting A total of 446 general practices included in The Health Improvement Network (THIN), a database of UK electronic primary care records. Participants All primary care patients registered with a THIN practice in England. Measurements Monthly rates of prescribing of varenicline, nicotine replacement therapy (NRT) and bupropion per 100 000 patients registered with a THIN practice between June 2000 and June 2009. Findings NRT was the most commonly prescribed stop smoking medication, and bupropion the least frequently prescribed. After its introduction in December 2006 varenicline rapidly became the second most commonly prescribed drug. There was no statistically significant change in overall prescribing for smoking cessation medications after its introduction (P = 0.760), or after the publication of the related guidance in July 2007 (P = 0.134). Conclusions Soon after being introduced in England, varenicline was widely prescribed; after nicotine replacement therapy it was the most commonly prescribed cessation medication. However, this does not appear to have increased overall rates of prescribing for smoking cessation medication.     

Excess overdose mortality immediately following transfer of patients and their care as well as after cessation of opioid substitution therapy

Aims

To investigate clustering of all‐cause and overdose deaths after a transfer of patients and their care to alternative treatment provider and after the end of opioid substitution therapy (OST) in opioid‐dependent individuals in specialist addiction treatment.

Design, Setting and Participants

Mortality data were identified within a sample of 5335 patients with opioid use disorder who had received OST treatment between 1 April 2008 and 31 December 2013 from a large mental health‐care provider in the United Kingdom. We investigated the circumstances and distribution of the 332 deaths identified within the observation window with a specific focus on overdose deaths (n = 103) after a planned discharge, dropout and transfer between services.

Measurements

Crude mortality rates for overdose mortality 14 days, 28 days and more than 1 month after the end of treatment/transfer for overdose mortality.

Findings

Of 47 individuals who died from overdose after having been transferred between services, nine died during the first 2 weeks [crude mortality rate (CMR) = 136.4, 95% confidence interval (CI) = 64.3–243.1] and a further five died during the first month post‐transfer (CMR= 79.5, 95% CI = 44.2–129.7). Of the 32 individuals who died from overdose after planned OST cessation, five died during the first 2 weeks (CMR = 151.5, 95% CI = 51.1–319.0) and a further four died during the first month post‐discharge (CMR = 82.6, 95% CI = 38.4–151.0).

Conclusions

In the United Kingdom, opioid‐dependent people who are transferred to an alternative treatment provider for continuation of their opioid substitution therapy experience high overdose mortality rates, with substantially higher rates during the first month (especially during the first 14 days) following transfer.     

Effects of comorbid substance use disorders on outcomes in a Housing First intervention for homeless people with mental illness

Background and Aims

Evidence supports the effectiveness of Housing First (HF) programmes for people who are experiencing homelessness and mental illness; however, questions remain about its use in people with comorbid substance use disorders (SUD). The aim of this project was to test whether SUD modifies the effectiveness of an HF intervention.

Design

Secondary analysis of data from a randomized controlled trial of HF versus treatment‐as‐usual (TAU) with 24‐month follow‐up, comparing those with and without SUD at trial entry.

Setting

Vancouver, Toronto, Winnipeg, Moncton and Montreal, Canada.

Participants

A total of 2154 participants recruited from 2009 to 2013 and randomized to HF versus TAU (67% male, mean age 40.8 ± 11.2, 25% ethno‐cultural minority). All were homeless and had a mental disorder at baseline; 35% reported symptoms consistent with SUD.

Intervention

Housing paired with Intensive Case Management or Assertive Community Treatment.

Measurements

Primary outcomes were days housed and community functioning. Secondary outcomes were general and health‐related quality of life and mental health symptoms. Predictors were SUD status crossed with intervention group (HF versus TAU).

Findings

People with SUD in both the HF and TAU groups spent less time in stable housing, but the effect of HF did not vary by SUD status [odds ratio (OR) = 1.17, 95% confidence interval (CI) = ?0.77, 1.76]. Similarly, there was no difference between those with and without SUD in the effect of HF (over TAU) on community functioning (b = 0.75, 95% CI = ?0.36, 1.87), quality of life (b = ?1.27, 95% CI = ?4.17, 1.63), health‐related quality of life (b = ?0.01, 95% CI = ?0.03, 0.02) or mental health symptoms (b = 0.43, 95% CI = ?0.99, 1.86).

Conclusions

Housing First programs in Canada are equally effective in people with and without comorbid substance use disorder (SUD). Overall, the intervention appears to be able to engage people with SUD and is reasonably successful at housing them, without housing being contingent upon abstinence or treatment.     

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis,based on measurements of plaque and intima–media thickness

Purpose

To examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima–media thickness (IMT).

Methods

This cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1–2, ≥3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8–1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors.

Results

MMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01–24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1–78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7–64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5–65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5–132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14–245.66, p = 0.01).

Conclusions

Elevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.     

Cost effectiveness of interventions to reduce relapse to smoking following smoking cessation

Aims To determine the incremental cost effectiveness of nicotine replacement therapy (NRT), bupropion and varenicline for preventing relapse to smoking when used by abstinent smokers Design setting and participants Cohort simulation and sensitivity analyses combining cost and health service data with systematic review estimates for the effectiveness of NRT, bupropion and varenicline when used by abstinent quitters to prevent their relapse to smoking. Measurements Incremental health gain in Quality Adjusted Life Years (QALYs) generated by each drug compared to ‘no intervention’. Findings Bupropion resulted in an incremental QALY increase of 0.07 with a concurrent cost saving of £68; NRT and varenicline both caused incremental QALYs increases of 0.04 at costs of £12 and £90 respectively, although varenicline findings were based on data from a single clinical trial and require cautious interpretation. Even after extensive sensitivity analyses with substantial varying of key model parameters, cost effectiveness of all drugs remained. Cost effectiveness ratios only exceeded the UK National Institute of Clinical Excellence (NICE) benchmark of £20 000 per QALY when drug treatment effects were postulated to last for no longer than 1 year; or, for NRT and varenicline, efficacy was reduced to 10% of that observed in clinical trials. Conclusions Bupropion, nicotine replacement therapy and varenicline appear cost effective at preventing relapse to smoking by smokers who are in quit attempts and have recently become abstinent; they have comparable cost effectiveness to smoking cessation interventions. Widespread use of these effective relapse prevention treatments could promote substantial health gain at an acceptable cost to health providers.     

Childhood traumatic experiences and the association with marijuana and cocaine use in adolescence through adulthood

Background and aims

Examination of longitudinal relationships between childhood traumatic experiences and drug use across the life‐course at the national level, with control of confounding by other forms of trauma, is needed. We aimed to estimate the prevalence of nine typologies of childhood traumas and the cumulative number experienced, correlation between traumas and associations between individual and cumulative number of traumas with drug use during adolescence, emerging adulthood and adulthood.

Design

Secondary data analysis using the National Longitudinal Study of Adolescent to Adult Health.

Setting

United States.

Participants

A nationally representative sample of individuals in grades 7–12 (aged 11–21 years) during 1994–95, who were re‐interviewed during emerging adulthood (2001–02; aged 18–28) and adulthood (2007–08; aged 24–34). The analytical sample comprised 12 288 participants with data at all three waves.

Measurements

Nine typologies of childhood traumas: neglect; emotional, physical and sexual abuse; parental incarceration and binge drinking; and witnessing, being threatened with and experiencing violence. Indicators of each were summed to measure cumulative dose. Outcomes were marijuana and cocaine use during adolescence, emerging adulthood and adulthood.

Findings

Approximately half experienced at least one childhood trauma; traumas were not highly correlated. We observed a dose–response relationship between the number of traumas and drug use in adolescence [marijuana, adjusted odds ratio (aOR) one trauma versus none = 1.65, 95% confidence interval (CI) = 1.42, 1.92; two traumas = 2.58, 95% CI = 2.17, 3.06; ≥ four traumas = 6.92, 95% CI = 5.17, 9.26; cocaine, aOR one trauma = 1.87, 95% CI = 1.23, 2.84; two traumas = 2.80, 95% CI = 1.74, 4.51; ≥ four traumas = 9.54, 95% CI = 5.93, 15.38]. Similar dose–response relationships with drug use were observed in emerging adulthood and adulthood. Each individual trauma was associated independently with either marijuana or cocaine use in adolescence, emerging adulthood and/or adulthood.

Conclusions

Childhood trauma is prevalent in the United States, and individual types as well as the total number experienced are associated significantly with marijuana and cocaine use throughout the life‐course.     

Extended‐release injectable naltrexone for opioid use disorder: a systematic review

Aims

To review systematically the published literature on extended‐release naltrexone (XR‐NTX, Vivitrol^®), marketed as a once‐per‐month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR‐NTX; (2) what are adherence rates to XR‐NTX; and (3) does XR‐NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined.

Methods

We searched PubMed and used Google Scholar for forward citation searches of peer‐reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR‐NTX were included.

Results

We identified and included 34 studies. Pooled estimates showed that XR‐NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5–70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0–90.1%); 44.2% (95% CI = 33.1–55.9%) of individuals took all scheduled injections of XR‐NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6‐month rates: 46.7%, 95% CI = 34.5–59.2% versus 10.5%, 95% CI = 4.6–22.4%, respectively). Compared with referral to treatment, XR‐NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR‐NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR‐NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification.

Conclusions

Many individuals intending to start extended‐release naltrexone (XR‐NTX) do not and most who do start XR‐NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR‐NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.     

Social participation and incident disability and mortality among frail older adults: A JAGES longitudinal study

Background

Frailty is the highest risk factor for incident disability and mortality. Social participation is a modifiable factor for reducing adverse outcomes among independent older adults. However, the association between social participation and incident disability and mortality among frail older adults remains unclear. Therefore, we examined the association between various social activities and incident disability and mortality.

Methods

This nationwide prospective cohort study (The Japan Gerontological Evaluation Study) recruited older adults with frailty, aged 65 years and older (N = 9090) who were followed up for 6 years (2010–2016). We examined incident disability and all-cause mortality at the end of the follow-up period. Frailty was assessed using the Kihon Checklist. The independent variable was social participation in 2010, grouped into the following seven categories: hobby groups, sports groups or clubs, volunteer groups, senior citizens' clubs, industries, neighborhood communities, and paid work.

Results

The incidence of disability among participants was 19.5% (1770) and that of mortality was 19.2% (1753). Belonging to sports groups or clubs (Hazard Ratios [HR] = 0.74; 95% Confidence Interval [CI] = 0.57, 0.98) or hobby groups (HR = 0.77; 95% CI = 0.60, 0.98) was significantly associated with a lower risk of incident disability. Meanwhile, hobby groups (HR = 0.68; 95% CI = 0.56, 0.83), sports groups or clubs (HR = 0.71; 95% CI = 0.57, 0.88), volunteer groups (HR = 0.69; 95% CI = 0.54, 0.88), and senior citizens' club (HR = 0.75; 95% CI = 0.61, 0.90) were associated with lower risk of incident mortality.

Conclusions

Social participation was associated with a lower risk of incident disability and mortality, not only in healthy older adults but also in frail older adults who are at higher risk of incident disability and mortality. This suggests that frail older adults should be encouraged to participate in all the seven types of social participation examined in this study, as this may lower the risk of subsequent disability and mortality.     

Sickness absence diagnoses among abstainers,low‐risk drinkers and at‐risk drinkers: consideration of the U‐shaped association between alcohol use and sickness absence in four cohort studies

Aims

To estimate differences in the strength and shape of associations between alcohol use and diagnosis‐specific sickness absence.

Design

A multi‐cohort study. Participants (n = 47 520) responded to a survey on alcohol use at two time‐points, and were linked to records of sickness absence. Diagnosis‐specific sickness absence was followed for 4–7 years from the latter survey.

Setting and participants

From Finland, we had population cohort survey data from 1998 and 2003 and employee cohort survey data from 2000–02 and 2004. From France and the United Kingdom, we had employee cohort survey data from 1993 and 1997, and 1985–88 and 1991–94, respectively.

Measurements

We used standard questionnaires to assess alcohol intake categorized into 0, 1–11 and > 11 units per week in women and 0, 1–34 and > 34 units per week in men. We identified groups with stable and changing alcohol use over time. We linked participants to records from sickness absence registers. Diagnoses of sickness absence were coded according to the International Classification of Diseases. Estimates were adjusted for sex, age, socio‐economic status, smoking and body mass index.

Findings

Women who reported drinking 1–11 units and men who reported drinking 1–34 units of alcohol per week in both surveys were the reference group. Compared with them, women and men who reported no alcohol use in either survey had a higher risk of sickness absence due to mental disorders [rate ratio = 1.51, 95% confidence interval (CI) = 1.22–1.88], musculoskeletal disorders (1.22, 95% CI = 1.06–1.41), diseases of the digestive system (1.35, 95% CI = 1.02–1.77) and diseases of the respiratory system (1.49, 95% CI = 1.29–1.72). Women who reported alcohol consumption of > 11 weekly units and men who reported alcohol consumption of > 34 units per week in both surveys were at increased risk of absence due to injury or poisoning (1.44, 95% CI = 1.13–1.83).

Conclusions

In Finland, France and the United Kingdom, people who report not drinking any alcohol on two occasions several years apart appear to have a higher prevalence of sickness absence from work with chronic somatic and mental illness diagnoses than those drinking below a risk threshold of 11 units per week for women and 34 units per week for men. Persistent at‐risk drinking in Finland, France and the United Kingdom appears to be related to increased absence due to injury or poisoning.     

The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom

Aims

To estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all‐cause mortality (ACM) and opioid drug‐related poisoning (DRP) mortality.

Design

Cohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register.

Setting

UK primary care.

Participants

A total of 11 033 opioid‐dependent patients who received OST from 1998 to 2014, followed‐up for 30 410 person‐years.

Measurements

Exposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed‐up for 16 363 person‐years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone and buprenorphine. Inverse probability weights were included to adjust for confounding and balance characteristics of patients prescribed methadone or buprenorphine.

Findings

ACM and DRP rates were 1.93 and 0.53 per 100 person‐years, respectively. DRP was elevated during the first 4 weeks of OST [incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97–3.82], the first 4 weeks off OST (IRR = 8.15, 95% CI = 5.45–12.19) and the rest of time out of OST (IRR = 2.13, 95% CI = 1.47–3.09) compared with mortality risk from 4 weeks to end of treatment. Patients on buprenorphine compared with methadone had lower ACM rates in each treatment period. After adjustment, there was evidence of a lower DRP risk for patients on buprenorphine compared with methadone at treatment initiation (IRR = 0.08, 95% CI = 0.01–0.48) and rest of time on treatment (IRR = 0.37, 95% CI = 0.17–0.79). Treatment duration (mean and median) was shorter on buprenorphine than methadone (173 and 40 versus 363 and 111, respectively). Model estimates suggest that there was a low probability that methadone or buprenorphine reduced the number of DRP in the population: 28 and 21%, respectively.

Conclusions

In UK general medical practice, opioid substitution treatment with buprenorphine is associated with a lower risk of all‐cause and drug‐related poisoning mortality than methadone. In the population, buprenorphine is unlikely to give greater overall protection because of the relatively shorter duration of treatment.     

戒烟药物的研究和应用进展

吸烟是引发许多疾病的重要危险因素,戒烟是减少烟草相关疾病的重要手段。戒烟药物有助于吸烟者戒烟。常用一线戒烟药物包括尼古丁替代疗法(NRT)制剂、安非他酮缓释制剂和伐尼克兰。该文对以上戒烟药物的研究和应用进展进行综述。     

The short‐term impact of the alcohol act on alcohol‐related deaths and hospital admissions in Scotland: a natural experiment

Background and aim

The introduction of the Alcohol Act in Scotland on 1 October 2011, which included a ban on multi‐buy promotions, was probably associated with a fall in off‐trade alcohol sales in the year after its implementation. The aim of this study was to test if the same legislation was associated with reduced levels of alcohol‐related deaths and hospital admissions in the 3‐year period after its introduction.

Design

A natural experiment design using time–series data to assess the impact of the Alcohol Act legislation in Scotland. Comparisons were made with unexposed populations in the rest of Great Britain.

Setting

Scotland with comparable data obtained for geographical control groups in other parts of Great Britain.

Participants

For alcohol‐related deaths, a total of 17 732 in Scotland and 88 001 in England and Wales throughout 169 4‐week periods between January 2001 and December 2013 and for alcohol‐related hospital admissions, a total of 121 314 in Scotland and 696 892 in England throughout 182 4‐week periods between January 2001 and December 2014.

Measurements

Deaths and hospital admissions in Scotland and control groups that were wholly attributable to alcohol for consecutive 4‐week periods between January 2001 and December 2014. Data were obtained by age, sex and area‐based socio‐economic position.

Findings

There was no evidence to suggest that the Alcohol Act was associated with changes in the overall rate of alcohol‐related deaths [incidence rate ratio (IRR) = 0.99, 95% confidence interval (CI) = 0.91–1.07)] or hospital admissions (IRR = 0.98, 95% CI = 0.95–1.02) in Scotland. In control group analyses, the pseudo intervention variable was not associated with a change in alcohol‐related death rates in England/Wales (IRR = 0.99, 95% CI = 0.95–1.02), but was associated with an increase in alcohol‐related hospital admission rates in England (IRR = 1.05, 95% CI = 1.03–1.07). In combined models, the interaction analysis did not provide support for a ‘net effect’ of the legislation on alcohol‐related deaths in Scotland compared with England/Wales (IRR 0.99, 95% CI = 0.95–1.04), but suggested a net reduction in hospital admissions for Scotland compared with England (IRR = 0.93, 95% CI = 0.87–0.98).

Conclusion

The implementation of the Alcohol Act in Scotland has not been associated clearly with a reduction in alcohol‐related deaths or hospital admissions in the 3‐year period after it was implemented in October 2011.