18B.7Potential positive impacts

Material under review: December 2018     

Suggested citation: Greenhalgh, EM, & Scollo, MM. InDepth 18B: Electronic cigarettes (e-cigarettes). In Scollo, MM and Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2018. Available from: http://www.tobaccoinaustralia.org.au/chapter-18-harm-reduction/indepth-18b-e-cigarettes

Consumers of e-cigarettes report mixed reasons for their use. Some use them as a substitute for cigarettes, either in an attempt to reduce consumption, or to enable nicotine use in situations where use of traditional cigarettes would not be allowed or acceptable. As indicated in Section 18B5, risks associated with smoking are unlikely to be reduced by e-cigarettes if users continue to smoke tobacco cigarettes in the long term. Crucial to assessing the potential benefits of increasing use of e-cigarettes, then,  is whether such use will increase or decrease the likelihood of a smoker eventually quitting tobacco.1 That is, whether use of e-cigarettes increases or decreases

  • the likelihood of smokers making quit attempts
  • the likelihood of a given quit-attempt being successful
  • the likelihood of reducing use of cigarettes eventually leading to quitting.

18B.7.1 Increasing quit attempts

Many smokers report using e-cigarettes as a cessation aid.2, 3  A large study in England found no clear association between e-cigarette use and prevalence of quit attempts, although such use was associated with a decrease in the use of prescription NRT.4 A number of other studies have found smokers who use e-cigarettes are more likely to attempt to quit conventional cigarettes.5-12 However, this may be due to motivation (i.e. smokers who use e-cigarettes are already interested in quitting smoking).13 Some studies showed that such attempts did not appear to translate to increased long-term quitting success,5, 6, 10 while others found an increased rate of sustained cessation among e-cigarette users.8, 11, 12  

18B.7.2 Increasing success in quitting

Several major reviews of the effectiveness of e-cigarettes as a cessation aid were published in 2018. Overall, they conclude that there is limited evidence that e-cigarettes may be effective cessation aids in the short-term, particularly when the products contain nicotine; however, it is unclear whether use of e-cigarettes leads to long-term cessation, or whether they are as effective as other forms of cessation support (such as NRT).13-15 Along with using e-cigarettes that contain nicotine,16 sustained8 and frequent17-22 e-cigarette users appear to be more likely to successfully quit than those who use the products short-term or intermittently. Infrequent e-cigarette users—who comprise the majority of users—may be less likely to quit, with research showing an association between non-daily use and both lower motivation to quit17 and lower rates of successful cessation.20   

Each of the reviews to date note the limited/low quality nature of the evidence,16, 23-34 and call for long-term randomised controlled trials. 

18B.7.3 Cutting down as a step towards quitting

Large declines in daily consumption of conventional cigarettes in users of e-cigarettes have been noted in several studies,35, 36 and reviews;26, 27 however, this may not lead to meaningful changes in consumption at a population level.37 Further, evidence suggests that the health benefits of reducing consumption of conventional tobacco products are minimal.  Several large cohort studies have found that smokers who reduce their consumption do not significantly reduce their risk of premature death.38, 39 Smoking just 1–4 cigarettes per day significantly increases a person’s risk of dying from smoking-related disease.40 This lack of health benefits is often attributed to compensatory smoking: those who cut down tend to inhale each cigarette more deeply, and smoke more of it.41 (See Section 18.3 for further detail).

A number of studies have shown that dual use of NRT and cigarettes can help alleviate the issue of compensation,42-44 leading some to advocate long-term use of NRT in combination with cutting down as a harm reduction strategy.45, 46 Researchers have suggested that it may be possible that the use of e-cigarettes while smoking could similarly reduce intake of nicotine and toxins from each cigarette. However, data on the long-term safety of e-cigarettes is lacking, and they may be less safe than existing, licenced NRT products.6  

The main benefit of cutting down seems to be its role as a step toward quitting.38, 47 While cutting down cigarettes may be a less effective strategy than going ‘cold turkey’,48 a 2015 review exploring the usefulness of cutting down determined that smokers who reduce the number of daily cigarettes smoked are more likely than smokers who do not cut down to attempt to quit and actually achieve smoking cessation. This is particularly the case when the quit attempt is combined with NRT.49 NRT-assisted reduction appears to be an effective intervention for achieving sustained smoking abstinence, particularly for smokers not currently intending to quit (or quit abruptly),50, 51 and is effective and cost effective compared to no quit attempt.47  E-cigarettes may similarly prove to be a useful form of NRT in combination with smoking reduction as part of ‘cutting down to quit’, but further research is needed on the efficacy of the products in this context.49  

18B.7.4 Modelling of net impact of use of e-cigarettes on smoking prevalence and tobacco-related disease

Given the uncertainty of the rapid increase in e-cigarette use on smoking behaviours and public health, researchers have attempted to model hypothetical scenarios and estimate possible outcomes. Such modelling is limited by a lack of understanding of long-term health effects, effects on smoking uptake, and effectiveness for cessation, and conclusions subsequently vary substantially depending on the assumptions and parameters used by researchers. 

One study modelled the potential future effects of e-cigarette use on smoking behaviour and concluded that, based on current usage patterns, smoking prevalence appears to be far more sensitive to e-cigarette effects on smoking cessation than initiation. Results from the model suggested that if e-cigarettes increase both uptake and quitting of conventional cigarettes, the effects on uptake would have to be extremely large (i.e., increase over 200%) to offset even small cessation effects on population smoking prevalence.52  

Another study similarly concluded that a substantial gateway effect (of vaping to smoking by never smokers) or an increase in the magnitude of harms from e-cigarettes relative to cigarettes (or both) would be required before the harms to public health outweigh the benefits of e-cigarette uptake. The authors estimate a net public health benefit associated with e-cigarettes resulting in 21% fewer smoking-attributable deaths and a 20% reduction in life years lost.53 A more recent modelling study by some of the same researchers concluded that, under an ‘optimistic scenario’, replacement of cigarette by e-cigarette use over a 10-year period would yield 6.6 million fewer premature deaths with 86.7 million fewer life years lost. Even under pessimistic assumptions regarding cessation, initiation and relative harm, they argue that replacing cigarette smoking with vaping would yield substantial life year gains, particularly among younger cohorts.54

On the other hand, other researchers have estimated that, based on the most up-to-date evidence, e-cigarette use in 2014 represents a population-level harm in the US of about 1.6 million years of life lost over the lifetime of all adolescent and young adult never-cigarette smokers and adult current cigarette smokers. If e-cigarette use confers long-term health risks, the model estimated even greater population-level harm. They argue that previous models—which reached more favourable conclusions about the public health impact of e-cigarettes—are based on faulty assumptions about uptake and smoking initiation among young people.55

Another study that modelled the potential health effects of increasing e-cigarette use concluded that—in order for there to be any benefits to public health—most e-cigarette users need to be current smokers interested in quitting or people who would have otherwise gone on to be smokers.  Other scenarios, such as e-cigarette use renormalising smoking, dual use, or significant uptake by young people (those young people who would otherwise never have smoked tobacco cigarettes) have the potential to increase population-level harm. The authors suggest that the likelihood of negative scenarios eventuating will ultimately depend on the regulatory environment, with benefits to public health being more probable with strict regulations on the sale, promotion, and use of the products; i.e., regulations that encourage use only by smokers,56 and only without simultaneous use of tobacco products.

Overall, any population-level effects may include some groups incurring harm (e.g., young people who start smoking), and some incurring benefits (e.g., smokers who quit). Changing cessation rates are seen earlier than the effects of changing initiation rates, due to the health effects of smoking taking many years to manifest. Conclusions of various models will therefore vary based on whether the projections are short- or long-term, with potential harms from increased initiation by youth occurring decades after the benefits of increased cessation are seen.15  


Relevant news and research

For recent news items and research on this topic, click here (Last updated January 2019)    



1. Rahman MA, Hann N, Wilson A, and Worrall-Carter L. Electronic cigarettes: Patterns of use, health effects, use in smoking cessation and regulatory issues. Tobacco Induced Diseases, 2014; 12(1):21. Available from: http://www.biomedcentral.com/content/pdf/1617-9625-12-21.pdf

2. Filippidis FT, Laverty AA, and Vardavas CI. Experimentation with e-cigarettes as a smoking cessation aid: A cross-sectional study in 28 European Union member states. BMJ Open, 2016; 6(10):e012084. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27855092

3. Gorini G, Ferrante G, Quarchioni E, Minardi V, Masocco M, et al. Electronic cigarette use as an aid to quit smoking in the representative Italian population PASSI survey. Preventive Medicine, 2017; 102:1–5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28652088

4. Beard E, West R, Michie S, and Brown J. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: Time series analysis of population trends. British Medical Journal, 2016; 354:i4645. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27624188

5. Pasquereau A, Guignard R, Andler R, and Nguyen-Thanh V. Electronic cigarettes, quit attempts and smoking cessation: A 6-month follow-up. Addiction, 2017; 112(9):1620–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28504457

6. Brose LS, Hitchman SC, Brown J, West R, and McNeill A. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction, 2015; 110(7):1160–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25900312

7. Nayak P, Pechacek TF, Weaver SR, and Eriksen MP. Electronic nicotine delivery system dual use and intention to quit smoking: Will the socioeconomic gap in smoking get greater? Addictive Behaviors, 2016; 61:112–6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27268063

8. Zhuang YL, Cummins SE, Sun JY, and Zhu SH. Long-term e-cigarette use and smoking cessation: A longitudinal study with US population. Tobacco Control, 2016; 25(Suppl 1):i90–i5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27697953

9. Brown-Johnson CG and Popova L. Exploring smoking stigma, alternative tobacco product use, & quit attempts. Health Behavior and Policy Review, 2016; 3(1):13–20. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27088103

10. Christensen T, Welsh E, and Faseru B. Profile of e-cigarette use and its relationship with cigarette quit attempts and abstinence in Kansas adults. Preventive Medicine, 2014; 69:90–4. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25230365

11. Zhu SH, Zhuang YL, Wong S, Cummins SE, and Tedeschi GJ. E-cigarette use and associated changes in population smoking cessation: Evidence from US current population surveys. British Medical Journal, 2017; 358:j3262. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28747333

12. Johnson L, Ma Y, Fisher SL, Ramsey AT, Chen LS, et al. E-cigarette usage is associated with increased past-12-month quit attempts and successful smoking cessation in two US population-based surveys. Nicotine & Tobacco Research, 2018. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30304476

13. Byrne S, Brindal E, Williams G, Anastasiou K, Tonkin A, et al. E-cigarettes, smoking and health. A literature review update. CSIRO, Australia,  2018. Available from: https://www.csiro.au/en/Research/BF/Areas/Nutrition-and-health/E-cigarettes-report.

14. McNeill A, Brose LS, Calder R, Bauld L, and Robson D. Evidence review of e-cigarettes and heated tobacco products 2018: A report commissioned by public health England. Public Health England, London: Public Health England, 2018. Available from: https://www.gov.uk/government/publications/e-cigarettes-and-heated-tobacco-products-evidence-review.

15. National Academies of Sciences Engineering and Medicine. Public health consequences of e-cigarettes. The National Academies Press, Washington, DC 2018. Available from: http://nationalacademies.org/hmd/Reports/2018/public-health-consequences-of-e-cigarettes.aspx.

16. Hartmann-Boyce J, McRobbie H, Bullen C, Begh R, Stead LF, et al. Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews, 2016; 9:CD010216. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27622384

17. Biener L and Hargraves JL. A longitudinal study of electronic cigarette use in a population-based sample of adult smokers: Association with smoking cessation and motivation to quit. Nicotine & Tobacco Research, 2014; 17(2):127–33. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375383/pdf/ntu200.pdf

18. Delnevo CD, Giovenco DP, Steinberg MB, Villanti AC, Pearson JL, et al. Patterns of electronic cigarette use among adults in the United States. Nicotine & Tobacco Research, 2016; 18(5):715–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896829/pdf/ntv237.pdf

19. Hitchman SC, Brose LS, Brown J, Robson D, and McNeill A. Associations between e-cigarette type, frequency of use, and quitting smoking: Findings from a longitudinal online panel survey in Great Britain. Nicotine & Tobacco Research, 2015; 17(10):1187–94. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580313/pdf/ntv078.pdf

20. Giovenco DP and Delnevo CD. Prevalence of population smoking cessation by electronic cigarette use status in a national sample of recent smokers. Addictive Behaviors, 2018; 76:129–34. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28802179

21. Berry KM, Reynolds LM, Collins JM, Siegel MB, Fetterman JL, et al. E-cigarette initiation and associated changes in smoking cessation and reduction: The population assessment of tobacco and health study, 2013-2015. Tobacco Control, 2018. Available from: https://tobaccocontrol.bmj.com/content/tobaccocontrol/early/2018/08/17/tobaccocontrol-2017-054108.full.pdf

22. Coleman B, Rostron B, Johnson SE, Persoskie A, Pearson J, et al. Transitions in electronic cigarette use among adults in the population assessment of tobacco and health (path) study, waves 1 and 2 (2013-2015). Tobacco Control, 2018. Available from: https://tobaccocontrol.bmj.com/content/tobaccocontrol/early/2018/04/25/tobaccocontrol-2017-054174.full.pdf

23. Grana R, Benowitz N, and Glantz SA. E-cigarettes: A scientific review. Circulation, 2014; 129(19):1972–86. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018182/pdf/cir-129-1972.pdf

24. Kalkhoran S and Glantz S. E-cigarettes and smoking cessation in real-world and clinical settings: A systematic review and meta-analysis. The Lancet, 2016; 4(2):116–28. Available from: http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2815%2900521-4/abstract

25. Lam C and West A. Are electronic nicotine delivery systems an effective smoking cessation tool? Canadian Journal of Respiratory Therapy, 2015; 51(4):93–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631136/pdf/cjrt-51-93.pdf

26. Rahman MA, Hann N, Wilson A, Mnatzaganian G, and Worrall-Carter L. E-cigarettes and smoking cessation: Evidence from a systematic review and meta-analysis. PLoS ONE, 2015; 10(3):e0122544. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378973/pdf/pone.0122544.pdf

27. McRobbie H, Bullen C, Hartmann-Boyce J, and Hajek P. Electronic cigarettes for smoking cessation and reduction. Cochrane Database of Systematic Reviews, 2014; 12(12):CD010216. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25515689

28. Malas M, van der Tempel J, Schwartz R, Minichiello A, Lightfoot C, et al. Electronic cigarettes for smoking cessation: A systematic review. Nicotine & Tobacco Research, 2016; 18(10):1926–36. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27113014

29. El Dib R, Suzumura E, Akl E, Gomaa H, Agarwal A, et al. Electronic nicotine delivery systems and/or electronic non-nicotine delivery systems for tobacco smoking cessation or reduction: A systematic review and meta-analysis. BMJ Open, 2017; 7(2):e012680. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337697/pdf/bmjopen-2016-012680.pdf

30. Knight-West O and Bullen C. E-cigarettes for the management of nicotine addiction. Subst Abuse Rehabil, 2016; 7:111–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27574480

31. Khoudigian S, Devji T, Lytvyn L, Campbell K, Hopkins R, et al. The efficacy and short-term effects of electronic cigarettes as a method for smoking cessation: A systematic review and a meta-analysis. International Journal of Public Health, 2016; 61(2):257–67. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26825455

32. Orellana-Barrios MA, Payne D, Medrano-Juarez RM, Yang S, and Nugent K. Electronic cigarettes for smoking cessation. Am J Med Sci, 2016; 352(4):420–6. Available from: https://www.amjmedsci.org/article/S0002-9629(16)30387-1/fulltext

33. Vanderkam P, Boussageon R, Underner M, Langbourg N, Brabant Y, et al. [efficacy and security of electronic cigarette for tobacco harm reduction: Systematic review and meta-analysis]. Presse Med, 2016; 45(11):971–85. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27597300

34. Glasser A, Collins L, Pearson J, Abudayyeh H, Niaura R, et al. Overview of electronic nicotine delivery systems: A systematic review. American Journal of Preventive Medicine, 2017; 52(2):e33–e66. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253272/pdf/nihms827983.pdf

35. Bullen C, Howe C, Laugesen M, McRobbie H, Parag V, et al. Electronic cigarettes for smoking cessation: A randomised controlled trial. The Lancet, 2013; 382(9905):1629–37. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61842-5/fulltext

36. Adkison S, O'Connor R, Bansal-Travers M, Hyland A, Borland R, et al. Electronic nicotine delivery systems: International tobacco control four-country survey. American Journal of Preventive Medicine, 2013; 44(3):207–15. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627474/pdf/nihms437547.pdf

37. Beard E, Brown J, Michie S, and West R. Is prevalence of e-cigarette and nicotine replacement therapy use among smokers associated with average cigarette consumption in England? A time-series analysis. BMJ Open, 2018; 8(6):e016046. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020958/pdf/bmjopen-2017-016046.pdf

38. Hart C, Gruer L, and Bauld L. Does smoking reduction in midlife reduce mortality risk? Results of 2 long-term prospective cohort studies of men and women in scotland. American Journal of Epidemiology, 2013; 178(5):770–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755643/pdf/kwt038.pdf

39. Tverdal A and Bjartveit K. Health consequences of reduced daily cigarette consumption. Tobacco Control, 2006; 15(6):472–80. Available from: http://tobaccocontrol.bmj.com/content/15/6/472.full

40. Bjartveit K and Tverdal A. Health consequences of smoking 1–4 cigarettes per day. Tobacco Control, 2005; 14(5):315–20. Available from: http://tobaccocontrol.bmj.com/content/14/5/315.full.html

41. McNeill A. Harm reduction. Review. British Medical Journal, 2004; 328(7444):885–7. Available from: http://www.bmj.com/cgi/content/full/328/7444/885

42. Dalack GW and Meador-Woodruff JH. Acute feasibility and safety of a smoking reduction strategy for smokers with schizophrenia. Nicotine & Tobacco Research, 1999; 1(1):53–7. Available from: http://ntr.oxfordjournals.org/content/1/1/53.abstract

43. Bolliger CT, Zellweger J-P, Danielsson T, van Biljon X, Robidou A, et al. Smoking reduction with oral nicotine inhalers: Double blind, randomised clinical trial of efficacy and safety. British Medical Journal, 2000; 321(7257):329–33. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27447/pdf/329.pdf

44. Fagerström KO, Tejding R, Westin A, and Lunell E. Aiding reduction of smoking with nicotine replacement medications: Hope for the recalcitrant smoker? Tobacco Control, 1997; 6(4):311–6. Available from: http://tobaccocontrol.bmj.com/content/6/4/311.abstract

45. Bittoun R, Barone M, Mendelsohn CP, Elcombe EL, and Glozier N. Promoting positive attitudes of tobacco-dependent mental health patients towards NRT-supported harm reduction and smoking cessation. Australian and New Zealand Journal of Psychiatry, 2014; 48(10):0004867414535673. Available from: http://anp.sagepub.com/content/early/2014/06/05/0004867414535673

46. Cohen B, Harm reduction in substance use: Smoking cessation for marginalised populations. Bayside Medicare Local; 2014. Available from: http://bml.org.au/BML%20Smoking%20Cessation%20in%20Marginalised%20Populations.pdf.

47. Wang D, Connock M, Barton P, Fry-Smith A, Aveyard P, et al. 'Cut down to quit' with nicotine replacement therapies in smoking cessation: A systematic review of effectiveness and economic analysis. Health Technology Assessment, 2008; 12(2):1–135. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18093448

48. Lindson-Hawley N, Banting M, West R, Michie S, Shinkins B, et al. Gradual versus abrupt smoking cessation: A randomized, controlled noninferiority trial. Annals of Internal Medicine, 2016; 164(9):585–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26975007

49. Begh R, Lindson-Hawley N, and Aveyard P. Does reduced smoking if you can't stop make any difference? BMC Medicine, 2015; 13:257. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601132/pdf/12916_2015_Article_505.pdf

50. Moore D, Aveyard P, Connock M, Wang D, Fry-Smith A, et al. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: Systematic review and meta-analysis. British Medical Journal, 2009; 338(b1024):b1024. Available from: http://www.bmj.com/cgi/doi/10.1136/bmj.b1024

51. Stead L and Lancaster T. Interventions to reduce harm from continued tobacco use. The Cochrane Database of Systematic Reviews, 2007; (3):CD005231. Available from: http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD005231/frame.html

52. Cherng S, Tam J, Christine P, and Meza R. Modeling the effects of e-cigarettes on smoking behavior: Implications for future adult smoking prevalence. Epidemiology, 2016; 27(6):819–26. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039081/pdf/nihms802712.pdf

53. Levy DT, Borland R, Villanti AC, and Abrams DB. The application of a decision-theoretic model to estimate the public health impact of vaporized nicotine product initiation in the United States. Nicotine & Tobacco Research, 2016; 19(2):149–59. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27613952

54. Levy DT, Borland R, Lindblom EN, Goniewicz ML, Meza R, et al. Potential deaths averted in USA by replacing cigarettes with e-cigarettes. Tobacco Control, 2018; 27(1):18–25. Available from: https://tobaccocontrol.bmj.com/content/tobaccocontrol/27/1/18.full.pdf

55. Soneji SS, Sung HY, Primack BA, Pierce JP, and Sargent JD. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLoS ONE, 2018; 13(3):e0193328. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29538396

56. Kalkhoran S and Glantz SA. Modeling the health effects of expanding e-cigarette sales in the United States and United Kingdom: A monte carlo analysis. JAMA Internal Medicine, 2015; 175(10):1671–80. Available from: http://dx.doi.org/10.1001/jamainternmed.2015.4209


      Previous Chapter Next Chapter