***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Considerable research , ranging from survey to clinical to genetic , has utilized traditional measures of tobacco dependence , such as the Fagerstrom Test of Nicotine Dependence ( FTND ) and the Diagnostic and Statistical Manual ( 4th ed . ) ( DSM-IV ) criteria , that focus on endpoint definitions of tobacco dependence such as heavy smoking , time to first cigarette in the morning , and smoking despite consequences . In an effort to better underst and possible theories and mechanisms underlying tobacco dependence , which could be used to improve treatment and research , two multidimensional measures of tobacco dependence have been developed : the  Nicotine Dependence Syndrome Scale ( NDSS ) and the  Wisconsin Inventory of Smoking Dependence Motives ( WISDM ) . This research used data from three r and omized smoking cessation trials to examine the internal consistency and validity ( convergent , concurrent and predictive ) of these scales , relative to each other and the traditional measures . Results reveal that NDSS and WISDM subscales are related to important dependence criteria , but in a heterogeneous fashion . The data suggest that there are important underlying mechanisms or motives that are significantly related to different important outcomes , such as withdrawal and cessation . The FTND was most strongly related to abstinence at 1 week and 6 months post-quit , whereas the WISDM Tolerance subscale was most strongly related to abstinence at the end of treatment . The NDSS Priority subscale was consistently predictive of outcome at all three follow-up time points . There is also evidence that WISDM subscales are related to a biomarker of the rate of nicotine metabolism Objectives The ratio of trans-3′hydroxycotinine/cotinine ( 3HC/COT ) is a marker of CYP2A6 activity , an important determinant of nicotine metabolism . This analysis sought to conduct a combined genetic epidemiologic and pharmacogenetic investigation of the 3HC/COT ratio in plasma and urine . Methods One hundred and thirty-nine twin pairs [ 110 monozygotic and 29 dizygotic ] underwent a 30-min infusion of stable isotope-labelled nicotine and its major metabolite , cotinine , followed by an 8-h in-hospital stay .  Blood and urine sample s were taken at regular intervals for analysis of nicotine , cotinine , and metabolites . DNA was genotyped to confirm zygosity and for variation in the gene for the primary nicotine metabolic enzyme , CYP2A6 ( variants genotyped : * 1B , * 1 × 2 , * 2 , * 4 , * 9 , * 12 ) . Univariate biometric analyses quantified genetic and environmental influences on each measure in the presence and absence of covariates , including measured CYP2A6 genotype . Results There was a substantial amount of variation in the free 3HC/COT ratio in plasma ( 6 h postinfusion ) attributable to additive genetic influences ( 67.4 % , 95 % confidence interval=55.9–76.2 % ) . The heritability estimate was reduced to 61.0 and 49.4 % , respectively , after taking into account the effect of covariates and CYP2A6 genotype . In urine ( collected over 8 h ) , the estimated amount of variation in the 3HC/COT ratio attributable to additive genetic influences was smaller ( 47.2 % , 95 % confidence interval=0–67.2 % ) and decreased to 44.6 and 42.0 % after accounting for covariates and genotype . Conclusion Additive genetic factors are prominent in determining variation in plasma 3HC/COT but less so in determining variation in urine 3HC/COT OBJECTIVES --(a ) To evaluate the efficacy of transdermal nicotine patches as an aid to stopping smoking when used as an adjunct to brief advice and support in a general practice setting ; ( b ) to see whether an increase in nicotine patch dosage enhances the rate of initial cessation . DESIGN --R and omised double blind placebo controlled parallel group study with one year of follow up . SETTING --30 general practice s in 15 English counties . SUBJECTS--600 dependent heavy smokers ( > or = 15 cigarettes daily ) who were well motivated to give up . INTERVENTIONS --Brief general practitioner advice , booklet , and 16 hours per day patch treatment for 18 weeks with brief support and follow up at one , three , six , 12 , 26 , and 52 weeks . MAIN OUTCOME MEASURES --Self reported complete abstinence for up to one year with biochemical validation at all follow up points . RESULTS --Nicotine patches reduced the severity of craving and adverse mood changes in the first weeks of withdrawal and doubled the rate of initial cessation at week 3 ( nicotine group 36 % of patients ( 144/400 ) , placebo group 16.5 % of patients ( 33/200 ) ) and of continuous abstinence throughout one year ( nicotine group 9.3 % ( 37 ) , placebo group 5.0 % ( 10 ) ) . A dose increase at week 1 among patients experiencing difficulty in quitting increased the proportion who achieved abstinence at week 3 . There were no adverse systemic effects attributable to nicotine , but the incidence of moderate or severe local irritation or itching at the patch site was 16.4 % ( 63 patients ) , compared with 3.8 % ( seven ) with placebo . CONCLUSION --Transdermal nicotine patches used as an adjunct to brief advice and support in a general practice setting are an effective aid to long term cessation of smoking in highly dependent smokers We examined whether a pretreatment phenotypic marker of nicotine metabolism rate ( NMR ) predicts successful smoking cessation with bupropion .  Smokers ( N = 414 ) were tested for pretreatment NMR , based on the ratio of 3′‐hydroxycotinine/cotinine derived during smoking , before entering a placebo‐controlled r and omized trial of bupropion plus counseling . At the end of the 10‐week treatment phase , slow metabolizers ( 1st NMR quartile ) had equivalent quit rates  with placebo or bupropion ( 32 % ) . Fast metabolizers ( 4th NMR quartile ) had low quit rates  with placebo ( 10 % ) , and these were enhanced significantly by bupropion ( 34 % ) . Smokers in the 2nd quartile ( placebo : 25 % , bupropion : 30 % ) and the 3rd quartile ( placebo : 20 % , bupropion : 30 % ) did not benefit significantly from bupropion . At the 6‐month follow‐up , the relationship between the NMR and quitting remained similar , but was no longer statistically significant . A pretreatment assessment of NMR may identify smokers who are most and least likely to benefit from treatment with bupropion for smoking cessation 
    Output:
    
The ratio is a reasonably accurate proxy for RNM .
There is little evidence that the ratio is related to question naire measures of dependence , though the existing data are limited and the ratio has been linked to smoking at night and to some aspects of smoking topography .
The ratio is also only weakly associated with cigarette consumption .
Importantly , the ratio seems to predict responses both to NRT and bupropion , and thus could guide pharmacotherapy .
Conclusions The evidence that the ratio is related to smoking behaviours and to cigarette dependence is limited , but the ratio seems to influence treatment response to two stop smoking medications .