***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: Background Cigarette smoking is a tough addiction to break . Therefore , improved approaches to smoking cessation are necessary . The electronic-cigarette ( e-Cigarette ) , a battery-powered electronic nicotine delivery device ( ENDD ) resembling a cigarette , may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated . Methods In this prospect i ve proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers ( unwilling to quit ) experimenting the ' Categoria ' e-Cigarette with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend a total of five study visits : at baseline , week-4 , week-8 , week-12 and week-24 . Product use , number of cigarettes smoked , and exhaled carbon monoxide ( eCO ) levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events and product preferences were also review ed . Results Sustained 50 % reduction in the number of cig/day at week-24 was shown in 13/40(32.5 % ) participants ; their median of 25 cigs/day decreasing to 6 cigs/day ( p < 0.001 ) . Sustained 80 % reduction was shown in 5/40(12.5 % ) participants ; their median of 30 cigs/day decreasing to 3 cigs/day ( p = 0.043 ) . Sustained smoking abstinence at week-24 was observed in 9/40(22.5 % ) participants , with 6/9 still using the e-Cigarette by the end of the study . Combined sustained 50 % reduction and smoking abstinence was shown in 22/40 ( 55 % ) participants , with an overall 88 % fall in cigs/day . Mouth ( 20.6 % ) and throat ( 32.4 % ) irritation , and dry cough ( 32.4 % ) were common , but diminished substantially by week-24 . Overall , 2 to 3 cartridges/day were used throughout the study . Participants ' perception and acceptance of the product was good . Conclusion The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit ( http:// Clinical Trials.gov number NCT01195597 ) Electronic cigarettes ( e-Cigarette ) are battery-operated devices design ed to vaporise nicotine that may aid smokers to quit or reduce their cigarette consumption . Research on e-Cigarettes is urgently needed to ensure that the decisions of regulators , healthcare providers and consumers are evidence based . Here we assessed long-term effectiveness and tolerability of e-Cigarette used in a ‘ naturalistic ’ setting . This prospect i ve observational study evaluated smoking reduction/abstinence in smokers not intending to quit using an e-Cigarette ( ‘ Categoria ’ ; Arbi Group , Italy ) . After an intervention phase of 6 months , during which e-Cigarette use was provided on a regular basis ,  cigarettes per day ( cig/day ) and  exhaled carbon monoxide ( eCO ) levels were followed up in an observation phase at 18 and 24 months . Efficacy measures included : ( a ) ≥50 % reduction in the number of cig/day from baseline , defined as self-reported reduction in the number of cig/day ( ≥50 % ) compared to baseline ; ( b ) ≥80 % reduction in the number of cig/day from baseline , defined as self-reported reduction in the number of cig/day ( ≥80 % ) compared to baseline ; ( c ) abstinence from smoking , defined as complete self-reported abstinence from tobacco smoking ( together with an eCO concentration of ≤10 ppm ) . Smoking reduction and abstinence rates were computed , and adverse events review ed . Of the 40 subjects , 17 were lost to follow-up at 24 months . A > 50 % reduction in the number of cig/day at 24 months was shown in 11/40 ( 27.5 % ) participants with a median of 24 cig/day use at baseline decreasing significantly to 4 cig/day ( p = 0.003 ) . Smoking abstinence was reported in 5/40 ( 12.5 % ) participants while combined > 50 % reduction and smoking abstinence was observed in 16/40 ( 40 % ) participants at 24 months . Five subjects stopped e-Cigarette use ( and stayed quit ) , three relapsed back to tobacco smoking and four up grade d to more performing products by 24 months . Only some mouth irritation , throat irritation , and dry cough were reported . Withdrawal symptoms were uncommon . Long-term e-Cigarette use can substantially decrease cigarette consumption in smokers not willing to quit and is well tolerated . ( http:// Clinical Trials.govnumberNCT01195597 ) Background Electronic cigarettes ( e-cigarettes or electronic nicotine delivery systems [ ENDS ] ) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and /or glycerol mist to the airway of users when drawing on the mouthpiece . Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device . People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids . However , to date there have been no adequately powered r and omised trials investigating their cessation efficacy or safety . This paper outlines the protocol for this study . Methods / design Design : Parallel group , 3-arm , r and omised controlled trial . Participants : People aged ≥18 years resident in Auckl and , New Zeal and ( NZ ) who want to quit smoking . Intervention : Stratified blocked r and omisation to allocate participants to either Elusion ™ e-cigarettes with nicotine cartridges ( 16 mg ) or with placebo cartridges ( i.e. no nicotine ) , or to nicotine patch ( 21 mg ) alone . Participants r and omised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day , while participants r and omised to patches will be told to use them daily for the same period . All participants will be offered behavioural support to quit from the NZ Quitline . Primary outcome : Biochemically verified ( exhaled carbon monoxide ) continuous abstinence at six months after quit day . Sample size : 657 people ( 292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarettes group ) will provide 80 % power at p = 0.05 to detect an absolute difference of 10 % in abstinence between the nicotine e-cigarette and nicotine patch groups , and 15 % between the nicotine and placebo e-cigarette groups . Discussion This trial will inform international debate and policy on the regulation and availability of e-cigarettes . If shown to be efficacious and safe , these devices could help many smokers as an alternative smoking cessation aid to st and ard nicotine products . Trial registration Australian NZ Clinical Trials Registry ( ACTRN12610000866000 ) Abstract Background Smoking is Australia ’s leading preventable cause of premature mortality and a major contributor to the national disease burden . If quit rates do not dramatically improve , then smoking will continue to be a major public health issue for decades to come . Harm-reduction approaches using novel nicotine products like e-cigarettes as long term replacements for smoking have the potential to improve quit rates . However , little research has assessed such approaches . Methods / Design Design : Three-arm parallel-group pragmatic r and omised controlled trial . Participants : People living in Australia who are at least 18 years old , smoke five or more cigarettes per day and are willing to try a sample of nicotine products . Intervention : Participants are r and omised to receive st and ard quit advice and medicinal nicotine ( Condition A ) ; quit or substitute advice and medicinal nicotine ( Condition B ) ; or quit or substitute advice and medicinal nicotine and e-cigarettes ( Condition C ) . Participants choose which ( if any ) nicotine products to receive to try in a free sample pack followed by a two to three week free supply of their favourite product(s ) and the option to purchase more at a discounted price . Follow-up surveys will assess nicotine product use and smoking . Primary outcome : Continuous abstinence for at least 6 months . Target sample size : 1600 people ( Condition A : 340 ; Condition B : 630 ; Condition C : 630 ) provides at least 80 % power at p = 0.05 to detect a 5 % difference in abstinence rates between each condition . Discussion This trial will provide data on tobacco harm-reduction approaches and in particular the use of e-cigarettes as a replacement for smoking . Trial registration Australian and New Zeal and Clinical Trials Registry : ACTRN12612001210864 . Date of registration : 15/11/2012 In a clinical study , changes in 14 biomarkers of exposures ( BOEs ) from 10 tobacco smoke constituents and mutagens detected by the urine mutagenicity test were investigated using a non-combustion inhaler type of tobacco product ( NCIT ) by switching from a conventional cigarette . This study was conducted in 80 Japanese healthy adult males with a 4-week residential , controlled , open-label , parallel group design . After r and omization , 40 smokers used  NCIT  with approximately 750 aspirations , other 20 smokers smoked approximately 20 pieces of an assigned 1-mg ISO tar conventional cigarette ( CC1 ) every day . Twenty non-smokers ( NS ) did not use any tobacco product . Under this study condition , switching from cigarette to NCIT showed significant reduction in all BOEs measured . On day 29 , the levels of these BOEs were almost the same as those in the NS group , except BOEs of nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ( NNK ) . This suggested that the exposure to 8 constituents and mutagens in the NCIT group was similar to that in the NS group , while the exposure to nicotine was higher . Although the precise exposure level to NNK was not estimated because of the long half-life of its BOE , it would be substantially lower in the NCIT group than in the CC1 group Background While electronic cigarettes are forbidden in several countries , their sales are exploding in many others . Although e-cigarettes have been proposed as long-term substitutes for traditional smoking or as a tool for smoking cessation , very scarce data are available on their efficacy and safety . We describe the protocol of a 5-year multicentric prospect i ve study aim ed to evaluate short- and long-term adherence to e-cigarette smoking and the efficacy of e-cigarettes in reducing and /or quitting traditional cigarette smoking . The study will also compare the health effects of electronic vs traditional vs mixed cigarette smoking . Methods / design From June to December 2013 , we will enroll adult smokers of : ( EC ) e-cigarettes ( self-reported inhaling ≥ 50 puffs per week since ≥ 6 months ) ; ( TC ) traditional cigarettes ( ≥ 1 per day since ≥ 6 m ) ; ( Mixed ) both electronic and traditional cigarettes ( ≥1 per day since ≥ 6 m ) . Eligible subjects will be requested participation through newspaper advertisements and direct contact at the shops . Each subject will have to compile a structured question naire at enrolment and after 6 , 12 , 24 , 36 and 60 months . The level of carbon monoxide in expired after breath will be evaluated in all subjects declaring no traditional cigarette smoking in any follow-up phase , using portable carbon monoxide analyzers . The primary outcomes are traditional smoking cessation rates and number of smoked cigarettes . Secondary outcomes include adherence to e-cigarettes , self-reported adverse events , quality of life , and time to hospital admission for one among cardiovascular diseases , chronic obstructive pulmonary diseases , cancer of the lung , esophagus , larynx , oral cavity , bladder , pancreas , kidney , stomach , cervix , and myeloid leukemia . Admissions will be checked using official discharge data of the Abruzzo Region . A minimum of 500 subjects in each group will be enrolled , for a total of 1500 participants .  Cox proportional hazards analysis will be used to calculate adjusted relative hazards of smoking cessation by each variable . Discussion Data on long-term efficacy and safety of e-cigarettes will be of utmost importance to form the basis for guidelines and regulatory decisions on e-cigarettes . Trial registration The protocol has been registered ( NCT01785537 ) and approved by the Ethics Committee of the University of Chieti ( Record n. 6 ; 25 - 03 - 2013 ) Background and Aims Electronic cigarettes ( e-cigarettes ) are rapidly increasing in popularity . Two r and omized controlled trials have suggested that e-cigarettes can aid smoking cessation , but there are many factors that could influence their real-world effectiveness . This study aim ed to assess , using an 
    Output:
    
The most frequently reported AEs were mouth and throat irritation , most commonly dissipating over time .
The most commonly reported adverse effects were irritation of the mouth and throat .