Pre‐cessation nicotine replacement therapy: pragmatic randomized trial

Aims To determine the effectiveness of 2 weeks' pre‐cessation nicotine patches and/or gum on smoking abstinence at 6 months. Design Pragmatic randomized controlled trial. Setting New Zealand. Participants Eleven hundred adult, dependent smokers who called the New Zealand Quitline between March 2006 and May 2007 for support to stop smoking were randomized to 2 weeks of nicotine patches and/or gum prior to their target quit day followed by usual care (8 weeks of patches and/or gum plus support calls from a Quitline adviser), or to usual care alone. Measurements The primary outcome was self‐reported 7‐day point prevalence smoking abstinence 6 months after quit day. Secondary outcomes included continuous abstinence, cotinine‐verified abstinence, daily cigarette consumption, withdrawal symptoms and adverse events. Findings Six months after quit day 125 (22.7%) participants in the pre‐cessation group and 116 (21.0%) in the control group reported 7‐day point prevalence abstinence (relative risk 1.08 95% CI: 0.86, 1.35, P = 0.4, risk difference 1.7%, 95% CI: ?3.2%, 6.6%). However, when pooled in a meta‐analysis with other pre‐cessation trials a moderate benefit of about a one‐quarter increase in cessation rates was evident. There was no difference in adverse events between groups. Conclusions In this, the largest pre‐cessation NRT trial to date, using NRT 2 weeks before the target quit day was safe and well tolerated but offered no benefit over usual care. However, in conjunction with previous pre‐cessation trials there appears to be a moderate benefit, but not as large as that seen in most smaller trials.     

The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial

Aim To determine the combined effect of very low nicotine content (VLNC) cigarettes and usual Quitline care [nicotine replacement therapy (NRT) and behavioural support] on smoking abstinence, in smokers motivated to quit. Design Single‐blind, parallel randomized trial. Setting New Zealand. Participants Smokers who called the Quitline for quitting support were randomized to either VLNC cigarettes to use whenever they had an urge to smoke for up to 6 weeks after their quit date, in combination with usual Quitline care (8 weeks of NRT patches and/or gum or lozenges, plus behavioural support) or to usual Quitline care alone. Measurements The primary outcome was 7‐day point‐prevalence smoking abstinence 6 months after quit day. Secondary outcomes included continuous abstinence, cigarette consumption, withdrawal, self‐efficacy, alcohol use, serious adverse events and views on the use of the VLNC cigarettes at 3 and 6 weeks and 3 and 6 months. Findings A total of 1410 participants were randomized (705 in each arm), with a 24% loss to follow‐up at 6 months. Participants in the intervention group were more likely to have quit smoking at 6 months compared to the usual care group [7‐day point‐prevalence abstinence 33 versus 28%, relative risk (RR) = 1.18, 95% confidence interval (CI): 1.01, 1.39, P = 0.037; continuous abstinence 23 versus 15%, RR = 1.50, 95% CI: 1.20, 1.87, P = 0.0003]. The median time to relapse in the intervention group was 2 months compared to 2 weeks in the usual care group (P < 0.0001). Conclusions Addition of very low nicotine content cigarettes to standard Quitline smoking cessation support may help some smokers to become abstinent.     

Nicotine patch therapy prior to quitting smoking: a meta-analysis

AIM: To evaluate the incremental efficacy of starting nicotine patch treatment prior to quitting compared to the current regimen of starting patch treatment on the target quit day. DESIGN AND MEASUREMENTS: Meta-analysis of four eligible studies using pre-cessation patch treatment, located by database search and contacts with cessation researchers. The studies all compared starting treatment with nicotine patch prior to the target quit date to starting active treatment at the quit date, some in the context of concurrent mecamylamine treatment. The primary end-point for the analysis was continuous abstinence for at least 28 days assessed at 6 weeks following quit day; 6-month outcomes were also examined. FINDINGS: Compared to starting active patch treatment on quit day, pre-cessation treatment with nicotine patches was found to double the odds of quitting. This was true both at 6 weeks [pooled odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.31-2.93] and 6 months (pooled OR = 2.17, 95% CI: 1.46-3.22) treatment outcomes. Mecamylamine co-treatment did not modify these effects. CONCLUSIONS: Across the four studies analyzed, pre-cessation patch treatment was found to produce a robust increase in quit rates compared to current regimens starting patch at quit day. Pre-cessation patch use represents a promising innovation in smoking cessation therapy with potential beneficial implications for improved public health by further increasing quitting success.     

Nicotine replacement therapy during pregnancy

In spite of the fact that smoking is the main cause of obstetric morbidity and mortality, 20% of North American women smoke during pregnancy. In Spain, this figure is as high as 30% to 35%. Treating smoking addiction in these patients should be the first and most important therapeutic measure undertaken by health professionals responsible for the care of pregnant women. All experts recommend the use of nicotine replacement therapy when more conservative treatments have failed. This article reviews the indications and contraindications for nicotine replacement therapy during pregnancy as well as other issues relating to the safety of this type of treatment.     

Diagnosis and treatment of nicotine dependence with emphasis on nicotine replacement therapy. A status report.

Tobacco use is a global health care problem. Repetitive exposure to nicotine produces neuroadaptation resulting in nicotine dependence. Cigarette smoking is particularly addictive due to the repeated delivery of bolus doses of nicotine to the bloodstream. Although compulsive tobacco use is sustained by nicotine addiction, it is the toxic combustion products in tobacco smoke such as carbon monoxide and oxidant gases that adversely affect the cardiovascular system. Smoking cessation produces significant health benefits and is a very cost-effective intervention. Evidence that nicotine is the addictive component of tobacco provides the rationale for using nicotine replacement therapy to aid cessation. Nicotine replacement therapy doubles successful smoking cessation rates and evidence-based guidelines for the treatment of tobacco addiction recommend routine use of nicotine replacement therapy, particularly in heavily dependent smokers. Success rates of up to 40% can be achieved in specialist clinics. Despite early concerns regarding the safety of nicotine replacement therapy in smokers with heart disease, it is now clear that the health risks of using nicotine replacement therapy to assist such patients to stop, or significantly reduce, smoking far outweigh any treatment-related risks.     

Residential smoking therapy

OBJECTIVE: To evaluate a pilot 4-day residential smoking treatment program for smokers who had relapsed after participation in an outpatient smoking program. DESIGN: A single-arm clinical trial. Participants stayed in a supportive, smoke-free environment for 4 days during which they attended educational sessions on nutrition, exercise, and psychology. Nicotine withdrawal was treated with nicotine inhalers and patches. After discharge, participants attended monthly outpatient group sessions for 6 months. SETTING: The Durham, NC Veterans Affairs Medical Center residential unit. PARTICIPANTS: Twenty-three medical outpatient smokers. MEASUREMENTS: Seven-day point prevalence smoking abstinence was determined by self-report of zero cigarettes smoked and verified by exhaled carbon monoxide <8 parts per million. MAIN RESULTS: Participants’ mean age was 57.4 years; 100% were male; 61% were Caucasian; and 39% were African American. The mean score on the Fagerström Test for Nicotine Dependence was 7.1 (SD 2.3). Daily nicotine doses ranged from the nicotine inhaler alone to 56 mg of transdermal nicotine plus nicotine inhaler. Verified smoking abstinence on discharge (after 4 days) was 21/23 or 91.3% (95% confidence interval [95% CI], 73 to 100). At 6 months, the 7-day point abstinence rate was 6/23 or 26.1% (95% CI, 15 to 36). CONCLUSIONS: This pilot residential smoking treatment program was designed to assist smokers who relapsed after outpatient treatment. Four days of residential smoking therapy successfully relieved smoking withdrawal. At 6 months after discharge, participants maintained an abstinence rate comparable to other medical therapies for smoking.     

A randomized clinical trial of methadone maintenance for prisoners: findings at 6 months post-release

AIMS: This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release. DESIGN: A three-group randomized controlled trial was conducted between September 2003 and June 2005. SETTING: A Baltimore pre-release prison. PARTICIPANTS: Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration. INTERVENTION: Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71). MEASUREMENTS: Addiction Severity Index at study entry and follow-up. Additional assessments at 6 months post-release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs. FINDINGS: Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid-positive urine specimen compared to counseling only (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants. CONCLUSIONS: Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.     

Smoking cessation in primary care clinics

OBJECTIVES: To document smoking cessation rates achieved by applying the 1996 Agency for Health Care Policy and Research (AHCPR) smoking cessation guidelines for primary care clinics, compare these quit rates with historical results, and determine if quit rates improve with an additional motivational intervention that includes education as well as spirometry and carbon monoxide measurements. DESIGN: Randomized clinical trial. SETTING: Two university-affiliated community primary care clinics. PATIENTS: Two hundred five smokers with routinely scheduled appointments. INTERVENTION: All smokers were given advice and support according to AHCPR guidelines. Half of the subjects received additional education with spirometry and carbon monoxide measurements. MEASUREMENTS AND MAIN RESULTS: Quit rate was evaluated at 9-month follow-up. Eleven percent of smokers were sustained quitters at follow-up. Sustained quit rate was no different for intervention and control groups (9% vs 14%; [OR] 0.6; 95% [CI] 0.2, 1.4). Nicotine replacement therapy was strongly associated with sustained cessation (OR 6.7; 95% CI 2.3, 19.6). Subjects without insurance were the least likely to use nicotine replacement therapy ( p =.05). Historical data from previously published studies showed that 2% of smokers quit following physician advice, and additional support similar to AHCPR guidelines increased the quit rate to 5%. CONCLUSIONS: The sustained smoking cessation rate achieved by following AHCPR guidelines was 11% at 9 months, which compares favorably with historical results. Additional education with spirometry did not improve the quit rate. Nicotine replacement therapy was the strongest predictor of cessation, yet was used infrequently owing to cost. These findings support the use of AHCPR guidelines in primary care clinics, but do not support routine spirometry for motivating patients similar to those studied here.     

Hormone replacement therapy and acquired resistance to activated protein C: results of a randomized, double-blind, placebo-controlled trial

Recent studies suggest that low-dose oral contraceptives may cause acquired resistance to activated protein C (APC). The aims of this study were to determine whether hormone replacement therapy (HRT) may also induce acquired APC resistance and to study the effects of APC resistance on the risk of recurrent thrombosis. The patients comprised 140 females with at least one previous venous thromboembolism (VTE), who were randomized to receive continuous treatment with 2 mg 17-beta-oestradiol and 1 mg norethisterone acetate (n = 71) or placebo (n = 69). Normalized APC sensitivity ratios (nAPCsr) were calculated by measurement of the effect of APC on thrombin generation in plasma collected at baseline and after 3 months of treatment. Of the 140 women, 121 had plasma samples collected both at baseline and after 3 months. The nAPCsr increased significantly (P < 0.001) on HRT (n = 62), both in females not carrying the factor V(Leiden) mutation [mean change 0.57 (95% CI 0.45-0.70), n = 50] and in females heterozygous for the factor V(Leiden) mutation [mean change 1.10 (0.71-1.49), n = 12], but remained unchanged on placebo (n = 59). The baseline nAPCsr as well as the increase in nAPCsr associated with HRT use was not higher in the five women who subsequently developed recurrent VTE. Free protein S and free TFPI were both important parameters for the acquired APC resistant phenotype. We conclude that HRT diminishes the efficacy by which APC downregulates in-vitro thrombin formation in a similar fashion to that observed with low-dose oral contraceptives, but the increase in nAPCsr alone is not sufficient to explain the increased risk of VTE associated with use of HRT.     

Does improved access and greater choice of nicotine replacement therapy affect smoking cessation success? Findings from a randomized controlled trial

Aims To determine the effect of offering smokers who want to quit easy access to nicotine replacement therapy (NRT), a period of familiarization and choice of product on smoking abstinence at 6 months. Design Single‐blind, randomized controlled trial. Setting New Zealand. Participants A total of 1410 adult smokers who called the national Quitline for quitting support were randomized to usual Quitline care or a box containing different NRT products (patch, gum, inhaler, sublingual tablet, oral pouch) to try for a week prior to quitting, and then to choose one or two of these products for 8 weeks' use. Measurements The primary outcome was 7‐day point prevalence smoking abstinence 6 months after quit day. Secondary outcomes included continuous abstinence, cigarette consumption, withdrawal, NRT choice and serious adverse events at 1 and 3 weeks and 3 and 6 months. Findings No differences in 6‐month quit rates (7‐day point prevalence or continuous abstinence) were observed between the groups. However, smokers allocated to the intervention group were more likely to have quit smoking at 3 months [self‐reported point prevalence, relative risk (RR) = 1.17, 95% confidence interval (CI): 1.02, 1.35, P = 0.03], had a longer time to relapse (median 70 days versus 28 days, P < 0.01) and used significantly more NRT. The selection box concept was highly acceptable to users, with the patch and inhaler combination the most popular choice (34%). Conclusions In terms of smoking abstinence at 6 months, offering smokers who want to quit free access to a wide range of nicotine replacement therapy, including a 1‐week period of familiarization and choice of up to two products, appears no different to offering reduced cost and choice of nicotine replacement therapy, with no familiarization period.