***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: INTRODUCTION Tobacco smoking leads to changes in hemodynamic parameters such as heart rate and systolic or diastolic blood pressure . It has a direct influence on the elasticity of blood vessels and increases arterial stiffness , which can result in development of atherosclerosis . Data show that the nicotine in tobacco smoke probably is responsible for these changes . Electronic cigarettes ( e-cigarettes ) were supposedly a healthier alternative to combustible cigarettes because they imitate a process of cigarettes smoking but generate nicotine aerosol without the toxic substances from tobacco combustion . However , the use of e-cigarettes is still controversial because their toxicity , safety and long term use health impact have not been sufficiently studied . AIM The aim of this study was to evaluate changes in arterial stiffness parameters after smoking a cigarette or e-cigarette use . METHODS Fifteen healthy women , aged 19 - 25 years old , smoking ≥5 cigarettes per day for at least two years participated in the study . A non-invasive measurement of arterial stiffness parameters - Stiffness Index ( SI ) and Reflection Index ( RI ) - was conducted and systolic and diastolic blood pressure and heart rate were measured before and after smoking a conventional cigarette as well as use of an e-cigarette . RESULTS Statistically significant changes in the SI and RI were observed before and after smoking of a conventional cigarette [ SI : 6.75 m/s ( 6.66 - 6.85 , 95 % CI ) vs 6.56 m/s ( 6.46 - 6.65 . 95 % CI ) , p=0.0056 ; RI : 54.0 % ( 51.5 - 56.7 , 95 % CI ) vs 49.6 % ( 47.5 - 51.8 , 95 % CI ) , p=0.010 ] . The use of e-cigarettes result ed in no statistically significant changes in the SI and RI . After both product use systolic and diastolic blood pressure and heart rate increased but the changes were not statistically significant . CONCLUSIONS In contrast to conventional cigarette use , the use of electronic cigarettes causes no changes in arterial stiffness . This may indicate lower bioavailability of nicotine from the e-cigarette or an additional effect of other substances present in cigarette smoke but absent in an e-cigarette aerosol Importance Quitting smoking is enhanced by the use of pharmacotherapies , but concerns have been raised regarding the cardiovascular safety of such medications . Objective To compare the relative cardiovascular safety risk of smoking cessation treatments . Design , Setting , and Participants A double-blind , r and omized , triple-dummy , placebo- and active-controlled trial ( Evaluating Adverse Events in a Global Smoking Cessation Study [ EAGLES ] ) and its nontreatment extension trial was conducted at 140 multinational centers . Smokers , with or without established psychiatric diagnoses , who received at least 1 dose of study medication ( n = 8058 ) , as well as a subset of those who completed 12 weeks of treatment plus 12 weeks of follow up and agreed to be followed up for an additional 28 weeks ( n = 4595 ) , were included . Interventions Varenicline , 1 mg twice daily ; bupropion hydrochloride , 150 mg twice daily ; and nicotine replacement therapy , 21-mg/d patch with tapering . Main Outcomes and Measures The primary end point was the time to development of a major adverse cardiovascular event ( MACE : cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) during treatment ; secondary end points were the occurrence of MACE and other pertinent cardiovascular events ( MACE+ : MACE or new-onset or worsening peripheral vascular disease requiring intervention , coronary revascularization , or hospitalization for unstable angina ) . Results Of the 8058 participants , 3553 ( 44.1 % ) were male ( mean [ SD ] age , 46.5 [ 12.3 ] years ) . The incidence of cardiovascular events during treatment and follow-up was low ( < 0.5 % for MACE ; < 0.8 % for MACE+ ) and did not differ significantly by treatment . No significant treatment differences were observed in time to cardiovascular events , blood pressure , or heart rate . There was no significant difference in time to onset of MACE for either varenicline or bupropion treatment vs placebo ( varenicline : hazard ratio , 0.29 ; 95 % CI , 0.05 - 1.68 and bupropion : hazard ratio , 0.50 ; 95 % CI , 0.10 - 2.50 ) . Conclusions and Relevance No evidence that the use of smoking cessation pharmacotherapies increased the risk of serious cardiovascular adverse events during or after treatment was observed . The findings of EAGLES and its extension trial provide further evidence that smoking cessation medications do not increase the risk of serious cardiovascular events in the general population of smokers . Trial Registration clinical trials.gov Identifier : ABSTRACT Acute changes in select physiological parameters associated with cardiovascular physiology ( systolic and diastolic blood pressure ( BP ) and heart rate ( HR ) ) , pulmonary function ( FVC , FEV1 , and exhaled CO and NO ) and adverse events were measured in 105 clinical ly confined subjects who were r and omized into groups that either completely or partially switched from  conventional cigarettes to e‐cigarettes  or completely discontinued using tobacco and nicotine products altogether . Use of the e‐cigarettes for five days under the various study conditions did not lead to higher BP or HR values , negative respiratory health outcomes or serious adverse health events . Reductions in BP and HR vital signs were observed in most of the participants that either ceased tobacco and nicotine products use altogether or switched completely to using e‐cigarettes . Pulmonary function tests showed small but non‐statistically significant improvements in FVC and FEV1 measurements in most use groups . Statistically significant ( p < 0.05 ) benefits associated with smoking reduction were also noted in exhaled CO and NO levels . All study products were well tolerated . The study findings suggest that there are potential cardiovascular and pulmonary function benefits when smokers switch to using e‐cigarette products . This further reinforces the potential that e‐cigarettes offer smokers seeking an alternative to conventional tobacco products . HIGHLIGHTSSwitching to e‐cigarettes led to small improvements in cardiovascular and pulmonary function . Reductions in vital signs were observed in most subjects that switched to using e‐cigarettes . Use of e‐cigarettes for 5 days did not lead to negative respiratory health outcomes .Physiological changes associated with smoking reduction were noted in exhaled breath . Short‐term use of e‐cigarettes did not result in any serious adverse effects Background Electronic cigarettes ( e-cigarettes ) are becoming increasingly popular with smokers worldwide . Users report buying them to help quit smoking , to reduce cigarette consumption , to relieve tobacco withdrawal symptoms , and to continue having a ‘ smoking ’ experience , but with reduced health risks . Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators , healthcare providers and consumers are based on science . Methods ECLAT is a prospect i ve 12-month r and omized , controlled trial that evaluates  smoking reduction/abstinence  in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model ( ‘ Categoria ’ ; Arbi Group Srl , Italy ) compared to its non-nicotine choice . GroupA ( n = 100 ) received 7.2 mg nicotine cartridges for 12 weeks ; GroupB ( n = 100 ) , a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges ; GroupC ( n = 100 ) received no-nicotine cartridges for 12 weeks . The study consisted of nine visits during which cig/day use and exhaled carbon monoxide ( eCO ) levels were measured . Smoking reduction and abstinence rates were calculated . Adverse events and product preferences were also review ed . Results Declines in cig/day use and eCO levels were observed at each study visits in all three study groups ( p<0.001 vs baseline ) , with no consistent differences among study groups . Smoking reduction was documented in 22.3 % and 10.3 % at week-12 and week-52 respectively . Complete abstinence from tobacco smoking was documented in 10.7 % and 8.7 % at week-12 and week-52 respectively . A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study . Participants ’ perception and acceptance of the product under investigation was satisfactory . Conclusion In smokers not intending to quit , the use of e-cigarettes , with or without nicotine , decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects . Trial Registration Clinical Trials.gov NCT01164072 Abstract We present prospect i ve blood pressure ( BP ) and hear rate ( HR ) changes in smokers invited to switch to e-cigarettes in the ECLAT study . BP and HR changes were compared among ( 1 ) different study groups ( users of high , low , and zero nicotine products ) and ( 2 ) pooled continuous smoking phenotype classification ( same phenotype from week 12 to -52 ) , with participants classified as quitters ( completely quit smoking ) , reducers ( ≥50 % reduction in smoking consumption ) and failures ( < 50 % or no reduction in smoking consumption ) . Additionally , the latter comparison was repeated in a subgroup of participants with elevated BP at baseline . No significant changes were observed among study groups for systolic BP , diastolic BP , and HR . In 145 subjects with a continuous smoking phenotype , we observed lower systolic BP at week 52 compared to baseline but no effect of smoking phenotype classification . When the same analysis was repeated in 66 subjects with elevated BP at baseline , a substantial reduction in systolic BP was observed at week 52 compared to baseline ( 132.4 ± 12.0 vs. 141.2 ± 10.5 mmHg , p < 0.001 ) , with a significant effect found for smoking phenotype classification . After adjusting for weight change , gender and age , reduction in systolic BP from baseline at week 52 remains associated significantly with both smoking reduction and smoking abstinence . In conclusion , smokers who reduce or quit smoking by switching to e-cigarettes  may lower their systolic BP in the long term , and this reduction is apparent in smokers with elevated BP . The current study adds to the evidence that quitting smoking with the use of e-cigarettes does not lead to higher BP values , and this is independently observed whether e-cigarettes are regularly used or not Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background Electronic cigarettes have been developed and marketed in recent years as smoking substitutes . However , no studies have evaluated their effects on the cardiovascular system . The purpose of this study was to examine the immediate effects of electronic cigarette use on left ventricular ( LV ) function , compared to the well-documented acute adverse effects of smoking . Methods Echocardiographic examinations were performed in 36 healthy heavy smokers ( SM , age 36 ± 5 years ) before and after smoking 1 cigarette and in 40 electronic cigarette users ( ECIG , age 35 ± 5 years ) before and after using the device with “ medium-strength ” nicotine concentration ( 11 mg/ml ) for 7 minutes . Mitral flow diastolic velocities ( E , A ) , their ratio ( E/A ) , deceleration time ( DT ) , isovolumetric relaxation time ( IVRT ) and corrected-to-heart rate IVRT ( IVRTc ) were measured . Mitral annulus systolic ( Sm ) , and diastolic ( Em , Am ) velocities were estimated . Myocardial performance index was calculated from Doppler flow ( MPI ) and tissue Doppler ( MPIt ) . Longitudinal deformation measurements of global strain ( GS ) , systolic ( SRs ) and diastolic ( SRe , SRa ) strain rate were also performed . Results Baseline measurements were similar in both groups . In SM , IVRT and IVRTc were prolonged , Em and SRe were decreased , and both MPI and MPIt were elevated after smoking . In ECIG , no differences were observed after device use . Comparing after-use measurements , ECIG had higher Em ( P = 0.032 ) and SRe ( P = 0.022 ) , and lower IVRTc ( P = 0.011 ) , MPI ( P = 0.001 ) and MPIt ( P = 0.019 ) . The observed 
    Output:
    
Unless supported by stronger evidence , the electronic cigarette should not be labelled as a cardiovascular safe product .