Characterising the nicotine metabolite ratio and its association with treatment choice: A cross sectional analysis of Stop Smoking Services in England.
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ABSTRACT:
SUBMITTER: Shahab L
PROVIDER: S-EPMC5730579 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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Characterising the nicotine metabolite ratio and its association with treatment choice: A cross sectional analysis of Stop Smoking Services in England.
Shahab Lion L Mortimer Emily E Bauld Linda L McGowan Jennifer A JA McNeill Ann A Tyndale Rachel F RF
Scientific reports 20171214 1
Pharmacotherapy provision based on Nicotine Metabolite Ratio (NMR) status (slow/normal metabolism) may improve smoking cessation rates. However, it is unclear whether NMR status is consistent across patient characteristics and current treatment choice. Data come from 1,826 participants attending Stop Smoking Services (SSS) across England in 2012/13. Sociodemographic, mental/physical health, smoking and treatment characteristics (nicotine replacement therapy vs. other pharmacotherapy; group vs. o ...[more]
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Project description:INTRODUCTION:The decrease in smoking rates in North America has plateaued, underscoring the need for new approaches to treat nicotine dependence. Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism. A phenotypic measure of CYP2A6 activity is the nicotine metabolite ratio (NMR), the ratio of 3'hydroxycotinine/cotinine. The NMR is associated with smoking cessation. However, the NMR is also associated with genetic (eg, CYP2A6 genotype) and other (eg, sex and ethnicity) factors. Here we aimed to determine if previously identified non-CYP2A6 sources of variation in the NMR mitigated the association between the NMR and short-term abstinence. METHODS:The NMR was determined from blood samples collected at intake from daily smokers aged 18-65. Biochemically-verified point prevalence abstinence (exhaled carbon monoxide level ? 8 ppm) was measured at 1 week following the target quit date in participants from a smoking cessation clinical trial (NCT01314001). Analyses were restricted to N = 462 blacks and N = 693 whites in the intent-to-treat sample. RESULTS:Lower NMR (<0.31) was associated with a higher likelihood of 1-week abstinence (OR = 1.43; 95% CI = 1.12, 1.84). NMR was associated with abstinence even after controlling for treatment arm (nicotine patch or varenicline) and factors previously associated with NMR variation including sex, ethnicity, estrogen-containing hormonal therapy, body mass index, alcohol, and cigarette consumption. CONCLUSIONS:NMR was associated with 1-week smoking abstinence; NMR may be a useful addition to medication screening approaches evaluating treatments for nicotine dependence.
| S-EPMC6220835 | biostudies-literature
Project description:AimTo evaluate the cost-effectiveness of e-cigarettes as a smoking cessation aid used in routine stop smoking services in England.DesignCost-effectiveness analysis was performed from the National Health Service (NHS) and Personal Social Services (PSS) perspective for 12-month periods and life-time. Costs, including that of both treatments, other smoking cessation help and health-care services, and health benefits, estimated from EQ-5D-5L and measured in quality-adjusted life-years (QALYs), for the 12-month analysis, came from a randomized controlled trial. Life-time analysis was model-based with input from both trial data and published secondary data sources. Cost-effectiveness was measured by an incremental cost-effectiveness ratio (ICER).SettingThree stop-smoking service sites in England.ParticipantsAdult smokers (n = 886) who sought help to quit in the participating sites.Intervention and comparatorAn e-cigarette (EC) starter kit versus provision of nicotine replacement therapy (NRT) for up to 3 months, both with standard behavioural support. A total of 886 participants were randomized (439 in the EC arm, 447 in the NRT arm). Excluding one death in each arm, the 1-year quit rate was 18.0 and 9.9%, respectively.MeasurementsCost of treatments was estimated from the treatment log. Costs of other smoking cessation help and health-care services and EQ-5D-5 L were collected at baseline, 6- and 12-month follow-ups. Incremental costs and incremental QALYs were estimated using regression adjusting for baseline covariates and their respective baseline values.FindingsThe ICER was £1100 per QALY gained at the 12 months after quit date (87% probability below £20 000/QALY). Markov model estimated the life-time ICER of EC to be £65 per QALY (85% probability below £20 000/QALY).ConclusionUsing e-cigarettes as a smoking cessation aid with standard behavioural support in stop-smoking services in England is likely to be more cost-effective than using nicotine replacement therapy in the same setting.
| S-EPMC7318206 | biostudies-literature
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| S-EPMC9610903 | biostudies-literature
Project description:Background: Smoking is the leading cause of preventable death worldwide. It is responsible for several types of cancer, cardiovascular diseases, and diseases of the reproductive system, among others. Therefore, advances in research are increasingly necessary in order to make smoking cessation treatment more effective. Some studies have investigated the association of the nicotine metabolite ratio (NMR) with general characteristics and treatment outcomes. In the present study, the main aim was to evaluate the NMR in smoking patients from an Assistance Program of a tertiary cardiology hospital. Methodology: Serum samples were collected from 185 patients at T0 (while patients were still smoking and before starting pharmacological treatment). Cotinine and hydroxycotinine analytes were measured using liquid-chromatography tandem mass-spectrometry (LC-MS/MS). By looking at the relationship between hydroxycotinine and cotinine, we can obtain the NMR, with which it is possible to classify patients into slow metabolizers (NMR < 0.31), as well as normal or fast metabolizers (NMR ≥ 0.31). Results: From 185 patients, 55 were considered slow metabolizers and 130 as normal/fast. The metabolite averages were associated with the number of cigarettes smoked per day (p < 0.001 for cotinine and 0.023 hydroxycotinine). However, we were unable to analyze the association of the NMR with general and clinical characteristics of patients under smoking cessation treatment. Conclusion: We were able to evaluate the NMR, and to observe categories of metabolizers in Brazilian patients under pharmacological treatments. Thus, this study can contribute to the indication of a form of analysis, which might form part of the customization of smoking cessation treatments and, consequently, improve the success rates.
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Project description:The UK National Health Service provides Stop Smoking Services for pregnant women (SSSP) but there is a lack of evidence concerning how these are best organised. This study investigates influences on services' effectiveness and also on their propensity to engage pregnant smokers with support in stopping smoking.Survey data collected from 121/141 (86%) of SSSP were augmented with data from Hospital Episode Statistics and the 2011 UK National Census. 'Reach' or propensity to engage smokers with support was defined as the percentage of pregnant smokers setting a quit date with SSSP support, and 'Effectiveness' as the percentage of women who set a quit date who also reported abstinence at four weeks later. A bivariate (i.e. two outcome variable) response Markov Chain Monte Carlo model was used to identify service-level factors associated with the Reach and Effectiveness of SSSP.Beta coefficients represent a percentage change in Reach and Effectiveness by the covariate. Providing the majority of one-to-one contacts in a clinic rather than at home increased both Reach (%) (β: 6.97, 95% CI: 3.34, 10.60) and Effectiveness (%) (β: 7.37, 95% CI: 3.03, 11.70). Reach of SSSP was also increased when the population served was more deprived (β for increase in Reach with a one unit increase in IMD score: 0.55, 95% CI: 0.25, 0.85), had a lower proportion of people with dependent children (β: -2.52, 95% CI: -3.82, -1.22), and a lower proportion of people in managerial or professional occupations (β: -0.31, 95% CI: -0.59, -0.03). The Effectiveness of SSSP was decreased in those areas that had a greater percentage of people >16 years with no educational qualifications (β: -0.51, 95% CI: -0.95, -0.07).To engage pregnant smokers and to encourage them to quit, it may be more efficient for SSSP support to be focussed around clinics, rather than women's homes. Reach of SSSP is inversely associated with disadvantage and efforts should be made to contact these women as they are less likely to achieve abstinence in the short and longer term.
| S-EPMC5549362 | biostudies-other
Project description:This study examined the prevalence of non-smoking norms in England and their associations with motivation to stop smoking, quit attempts, and cessation. Data were from a representative cross-sectional survey of 1,521 adults (301 combustible tobacco smokers). Descriptive non-smoking norms were endorsed, with just 16% of adults (12% of smokers) believing smoking was uncommon. Injunctive non-smoking norms were more prevalent, with 60-77% of adults (17-48% of smokers) viewing smoking as something of which others disapproved. Personal non-smoking norms were also prevalent among all adults (73% indicated they would prefer to live with a non-smoker) but not smokers (69% had no preference). Smokers who endorsed stronger descriptive non-smoking norms had increased odds of reporting high motivation to stop smoking (ORadj?=?1.63, 95%CI 1.06-2.52). Female (but not male) past-year smokers who endorsed stronger injunctive (ORadj?=?2.19, 95%CI 1.41-3.42) and personal (ORadj?=?1.90, 95%CI 1.29-2.82) non-smoking norms had increased odds of having made a past-year quit attempt. In conclusion, perceived descriptive non-smoking norms are not held by the majority of adults in England. Injunctive and personal non-smoking norms are prevalent among all adults but lower among smokers. There is some evidence that smokers - in particular, women - who endorse stronger non-smoking norms are more likely to be motivated to stop smoking and to make a quit attempt.
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Project description:IntroductionThe ratio of trans 3'-hydroxycotinine (3HC) to cotinine (nicotine metabolite ratio [NMR]) is a biomarker of the rate of nicotine metabolism, with higher NMR indicating faster metabolism. Higher NMR has been found to be associated with higher daily cigarette consumption and less success stopping smoking in cessation trials. This study examines differences in NMR among population-based samples of smokers in the five countries and explores the relationship between NMR and smoking abstinence.MethodsParticipants (N = 874) provided saliva samples during International Tobacco Control (ITC) surveys in the United States, United Kingdom, Mauritius, Mexico, and Thailand conducted in 2010/2011 with follow-up surveys in 2012/2013. When all samples were received, they were sent to a common laboratory for analysis using liquid chromatography and tandem mass spectroscopy.ResultsThere was significant variation in NMR across countries (F = 15.49, p < .001). Those who reported smoking at follow-up had a mean NMR of 0.32, compared to a mean NMR of 0.42 in participants who reported that they had stopped (F = 8.93; p = .003). Higher mean NMR values were also associated with longer quit duration (p = .007). There was no substantial difference in NMR between current smokers who made a failed quit attempt and those who made no attempt-both had significantly lower NMR compared to those who quit and remained abstinent. Smokers with a higher NMR were more likely to report that they stopped smoking compared to those with a lower NMR (odds ratio = 2.67; 95% confidence interval: 1.25 to 5.68).ConclusionsThese results suggest faster nicotine metabolizers may be less likely to relapse following a quit attempt. This finding differs from results of clinical trials testing stop smoking medications, where slower metabolizers have been found to be more likely to maintain abstinence from smoking.ImplicationsResults of this study suggest faster nicotine metabolizers may be less likely to relapse following a quit attempt. This finding differs from results of clinical trials testing stop smoking medications, where slower metabolizers have been found to be more likely to maintain abstinence from smoking.
| S-EPMC5896535 | biostudies-literature
Project description:Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. We investigated the relationships between CYP2A6 genotype, baseline plasma trans- 3'-hydroxycotinine/cotinine (3HC/COT) (a phenotypic marker of CYP2A6 activity), and smoking behavior in African-American light smokers. Cigarette consumption, age of initiation, and dependence scores did not differ among 3HC/COT quartiles or CYP2A6 genotype groups. Slow metabolizers (SMs; both genetic and phenotypic) had significantly higher plasma NIC levels, suggesting that cigarette consumption was not reduced to adjust for slower rates of NIC metabolism. Individuals in the slowest 3HC/COT quartile had higher quitting rates with both placebo and NIC gum treatments (odds ratio 1.85, 95% confidence interval (CI) 1.08-3.16, P = 0.03). Similarly, the slowest CYP2A6 genotype group had higher quitting rates, although this trend did not reach significance (odds ratio 1.61, 95% CI 0.95-2.72, P = 0.08). The determination of the 3HC/COT ratio, and possibly CYP2A6 genotype, may be useful in the future for personalizing the choice of smoking cessation treatment in African-American light smokers.
| S-EPMC3698861 | biostudies-literature
Project description:Genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in the CHRNA5/A3/B4 gene cluster with heaviness of smoking. The nicotine metabolite ratio (NMR), a measure of the rate of nicotine metabolism, is associated with the number of cigarettes per day (CPD) and likelihood of cessation. We tested the potential interacting effects of these two risk factors on CPD.Pretreatment data from three prior clinical trials were pooled for analysis. One thousand and thirty treatment seekers of European ancestry with genotype data for the CHRNA5/A3/B4 SNPs rs578776 and rs1051730 and complete data for NMR and CPD at pretreatment were included. Data for the third SNP, rs16969968, were available for 677 individuals. Linear regression models estimated the main and interacting effects of genotype and NMR on CPD.We confirmed independent associations between the NMR and CPD as well as between the SNPs rs16969968 and rs1051730 and CPD. We did not detect a significant interaction between NMR and any of the SNPs examined.This study demonstrates the additive and independent association of the NMR and SNPs in the CHRNA5/A3/B4 gene cluster with smoking rate in treatment-seeking smokers.
| S-EPMC3103715 | biostudies-literature
Project description:Background and aimsIn smoking treatment trials comparing varenicline with transdermal nicotine replacement therapy (NRT), stratified by nicotine metabolite (3-hydroxycotinine/cotinine) ratio (NMR), the relative benefit of varenicline is greater among normal rather than slow metabolizers. This study tested if the relative effectiveness of varenicline and NRT is associated with NMR status in a natural treatment setting. A secondary aim was to test if this relationship is moderated by behavioural support.DesignProspective observational multi-centre study with 4-week and 52-week follow-up.SettingNine English Stop Smoking Services (SSS).ParticipantsData came from 1556 smokers (aged ≥ 16 years) attending SSS between March 2012 and March 2013.InterventionsParticipants received pharmacotherapy together with behavioural support.MeasurementsThe primary outcome was carbon monoxide-verified continuous abstinence at both follow-up times. Main explanatory variables were (1) NMR status [slow (NMR < 0.31, n = 451) versus normal (NMR ≥ 0.31, n = 1105) metabolizers]; (2) pharmacotherapy (varenicline versus NRT) and (3) behavioural support (individual versus group-based treatment). Analyses adjusted for baseline socio-demographic, SSS, mental/physical health and smoking characteristics.FindingsOf participants, 44.2% [95% confidence interval (CI) = 41.7-46.6%] and 8.0% (95% CI = 6.8-9.5%) were continuously abstinent at 4 and 52 weeks. Varenicline was more effective than NRT at 4 weeks (P < 0.001) but only marginally so at 52 weeks (P = 0.061). There was no or inclusive evidence that NMR status moderated relative efficacy of varenicline and NRT at 4- [P = 0.60, Bayes factor (BF) = 0.25] or 52-week follow-ups (P = 0.74, BF = 0.73). However, this relationship was moderated by behavioural support (p = 0.012): the relative benefit of varenicline over NRT at 52-week follow-up was greater in slow, not normal, metabolizers receiving group rather than individual support (P = 0.012).ConclusionsIn a real-world setting, the nicotine metabolite ratio status of treatment-seeking smokers does not appear to contribute substantially to the differential effectiveness of varenicline and nicotine replacement therapy in Stop Smoking Services, when both pharmacotherapy and behavioural support are self-selected.
| S-EPMC6492100 | biostudies-literature