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Primary Care Corner with Geoffrey Modest MD: lung cancer screening results at the VA

28 Feb, 17 | by EBM

By Dr. Geoffrey Modest

A recent real-world study reported on the results of the implementation of the low-dose CT (LDCT) lung cancer screening in smokers at 8 VA hospitals (see doi:10.1001/jamainternmed.2016.9022​).


  • 93,033 primary care patients assessed: 4246 met criteria for screening, 2452 [57.7%, a pretty low number…] agreed to be screened: 96% men, mean age 65,
  • Of note, there was a large variation in the number of positive LDCT screens by site, varying from 31% to 85%. [This raises the issue of lack of consistency in radiologist interpretation of LDCTs, which is also found in mammography evaluation and for several other x-rays]


  • 1257 (60%) had lung nodules, of whom 1184 (56%) required tracking (solid nodules <8mm without suspicious features (irregular or speculated borders) and not known to be new or growing based on prior imaging, ground glass nodules >5mm, or mixed solid and round glass nodules of any size)
  • 42 (2%) required further evaluation but did not have cancer
  • 31 (1.5%) had lung cancer within 330 days of follow-up
  • False-positive rate of 97.5% !!!
  • 857 (41%) had incidental findings (e.g. emphysema, other pulmonary abnormalities, coronary artery calcification)
  • They calculated that 880,899 patients in the VA system would meet criteria for lung cancer screening


  • The recommendation for LDCT screening of smokers was largely based on the National Lung Screening Trial (NLST), but
    • There were significant differences in the demographics of these VA patients’ vs the NLST participants: more men, older group (53% were 65 or older), more current smokers (57% vs 48%)
    • The rate of positive screens was more than twice as high in this study (60%, vs 27% in NLST)
    • I have sent out many blogs on LDCT screening in the past (see below), but my concerns are several: the large number of false positives, the amount of radiation, the fact that one good trial (NLST) which lasted only 3 years generated a massive screening initiative (which can last up to 22 years, or 25 years if you go by the USPSTF guidelines!!), had very few lung cancers actually detected (despite their extrapolation which projected saving 3 deaths/1000 high-risk individuals screened), did not include some high risk patients and did include some low risk ones, and reinforced the false perception that the main problem with smoking is lung cancer.
  • The editorialists wrote a very powerful response (see doi:10.1001/jamainternmed.2016.9446), noting:
    • For every 1000 people screened:
      • 10 would be diagnosed with early-stage lung cancer (potentially curable)
      • 5 diagnosed with incurable advanced-stage lung cancer
      • 20 would undergo unnecessary invasive procedures (bronchoscopy and thoracotomy) because of the screening
      • 550 will have unnecessary alarm and repeated CT scanning, with its attendant radiation [which, as noted in my prior blogs, actually increases the average radiation exposure from the low-dose from the initial screen by 4-fold to that of a regular chest CT, given the follow-up requisite high-dose regular CTs, PET scans etc.]
    • They also point out that many of the anticipated problems from LDCT screening were articulated by the CMS advisory body MEDCAC (Medicare Evidence Development and Coverage Advisory Committee), noting that they had “low confidence” that LDCT benefits would exceed the risks, and “high confidence” that evidence gaps remained after the initial studies (NLST did find benefit, though 3 European trials found no benefit)

So, to me, this VA study suggested several things:

  • I think it reinforces that there really should be multiple studies done in different patient populations (include some “real-world” sites, where the recommendations will actually be implemented)
  • That it is a bit crazy to generalize from a 3-year study to guidelines which could potentially expose millions of people to 22+ years of radiation.
  • That all of this is especially true before we embark on a screening test which is so resource-intensive. Not just the cost (which is a lot, and could be used for many other social or medical issues which are underfunded), but also the intensity of resources (developing systems to track these patients, carving out time from the already time-limited primary care encounter to deal with shared decision-making, being sure that the patient qualifies for the study, doing the referral for the screenings over the years, devoting the time and resources of other office staff to dealing with all of this as well, and then doing all of the above for following up on the very common incidental findings (41% in this study), false positives (97.5%) etc….
  • And, by the way, another article in the same journal (see doi:10.1001/jamainternmed.2016.9016 ) found that from 2010 to 2015 (NSLT was published in 2011), there were large % increases in LDCT done in never-smokers and low-risk smokers, such that many more of these who actually do not qualify per the guidelines are getting LDCTs than those who do qualify, suggesting that this very low-risk group is pretty undoubtedly getting risk with almost no benefit, and that there is some collateral damage to having guidelines: either confusion on the part of the clinicians, or insistence on the part of patients who do not want to be denied this (???) potentially life-saving intervention……
  • And, speaking of collateral damage, one of the big concerns in primary care is that we are working in a quite litigious society, and we may be medico-legally responsible if a smoker who meets criteria for LDCT does not get one, even if logic is on our side…

Prior related blogs:


Primary Care Corner with Geoffrey Modest MD: Light smoking and mortality

8 Dec, 16 | by EBM

By Dr. Geoffrey Modest

One increasingly common issue in primary care is what to say to patients who smoke only a few cigarettes a day. A recent observational study suggests that even smoking <1 cigarette per day as a consistent, long-term habit is associated with significantly increased mortality (see doi:10.1001/jamainternmed.2016.7511).


  • The National Institutes of Health – AARP Diet and Health Study is a huge database of 168,140 men and women aged 59 to 82 from 2004-2005 that has very specific information on cigarette smoking, including patient recall of their average number of cigarettes per day (CPD) during nine periods of time, starting with <15 yo to >70 yo (most of the time intervals were every 5 years until age 30 then every 10 years after that) along with number of CPD broken down into six categories (0, <1, then intervals of 10 CPD until 30, then >30 CPD). This database includes people from six states (California, Florida, Pennsylvania, New Jersey, North Carolina, Louisiana) and two metropolitan areas (Atlanta Georgia, and Detroit Michigan).
  • Mean age 71, 58% men. At the 2004-5 baseline, there were 22,333 current smokers/156,405 former smokers/111,473 never smokers. Mean follow-up 6.6 years, during which 37331 people died.
  • Of 19,853 current smokers with complete information, 1341 (6.8%) reported smoking <1 CPD and 6036 (30.4%) smoked 1-10 CPD at baseline.


  • Most people who smoked <1 CPD or 1-10 CPD at the 2004-5 baseline did smoke more CPD earlier in their lives. But, 159 (9.1%) and 1493 (22.5%) of these individuals reported consistently smoking those small amounts throughout their lives.
  • Lifelong consistent smokers with <1 CPD or 1-10 CPD tended to start smoking at a later age, were more likely to be non-Hispanic black or Hispanic, and have lower educational levels, less alcohol use, and less history of MI or emphysema.
  • As compared to never smokers,
    • Current consistent smokers at the baseline exam who smoked <1 CPD had a 64% increased all-cause mortality [HR, 1.64 (1.07-2.51)]
    • Current consistent smokers at the baseline exam who smoked 1-10 CPD had an 87% increased all-cause mortality [HR 1.87 (1.64-2.13)]
    • These associations were similar in men and women, and were found in an array of smoking-related causes of death, but especially strong for:
      • Lung cancer: HR 9.12 (2.92-28.47) for those who smoked <1 CPD; and HR 11.61 (8.25-16.35) for those who smoked 1-10 CPD.
      • Respiratory disease deaths: HR 6.00 (4.05-8.89) for those who smoked 1-10 CPD, but there were too few respiratory deaths in those smoking <1 CPD for statistical power.
      • Cardiovascular deaths: HR 2.78 (1.49-5.18) for those who smoked <1CPD; HR 1.50 (1.13-1.99) for those who smoked 1-10 CPD
    • The former smokers who had consistently smoke <1 CPD or 1-10 CPD, and those who quit at a younger age, had progressively lower mortality risks; those who quit after age 50 had a higher mortality, about 43% for each of these “light” CPD groups


  • Smoking is one of the biggest public health challenges, associated with 5 million deaths per year globally. It has also been found in several analyses to be the single most powerful risk factor for cardiovascular disease.
  • The issue of exposure to small amounts of cigarette smoke is increasingly common in the US. The percent of daily smokers who smoke <10 CPD has increased from 16 to 27% from 2005 to 2014. And, the percent of people who do not smoke every day has increased from 19 to 23%. However, there are studies finding that, especially in young people, they believe that low levels of smoking is safe.
  • In this study, as others, former smokers have a significantly decreased mortality as compared to current smokers. From other studies, these data are particularly robust for cardiovascular disease, where there is a dramatic decrease after about six months of smoking cessation. This may be in part because of the rapid decrease in the prothrombotic fibrinogen levels, which are really elevated in current smokers.
  • The authors make a strong point that smoking duration is associated with much more adverse health effects than smoking intensity. However, on my review of their references (including Flanders WD. Cancer Res. 2003:63(19): 6556), these studies did not look at those who had stopped smoking, where the cardiovascular effects (quickly, as above) and lung cancer affects (over about 15 years) revert to levels close to those of non-smokers. Also, in these old studies, people were smoking many more cigarettes than currently. However, it does make sense to impress upon current “light” smokers that duration of smoking is likely to be more important than the fact that they are only smoking a few cigarettes, and using this to reinforce the importance to quit.

So, my general approach previously had been to assume that even light smoking led to lung cancer, based on data from secondhand smoking studies, and that there is likely increased cardiovascular mortality, based on the fact that smoking even small amounts seems to rapidly increase fibrinogen levels (I have not seen robust data on this last point). The above observational study, however, gives pretty good support to the conclusion that even smoking fewer than one cigarette per day over the long-term is associated with increased all-cause as well as cardiovascular mortality. And, my experience in doing motivational interviewing even in these “light” smokers has been pretty effective.

Primary Care Corner with Geoffrey Modest MD: E-Cigarettes Help Smoking Cessation??

24 Oct, 16 | by EBM

By Dr. Geoffrey Modest

There has been a lot of controversy about the potential benefits of using e-cigarettes to help current smokers quit vs the potential harms of e-cigs in normalizing and promoting nicotine use for nonsmokers, possibly leading to smoking the much more toxic regular cigarettes. A recent large data analysis from the UK did suggest that e-cigs may be a helpful aid for smoking cessation (see


  • England has a “liberal regulatory framework for e-cigarettes and has seen a considerable growth in their use”
  • This study looked a 2 sources of information over time: the Smoking Toolkit Study (monthly household, face-to-face scripted surveys of a representative UK population >16 yo, with data from 2006 on 170,490 individuals, of whom 41K were past smokers, 38K were current smokers, with about 1200 smokers being surveyed quarterly); and statistics on the use of the  English National Health Service (NHS) stop smoking services (8,029,012 people had set quit dates)


  • The prevalence of self-reported quit attempts decreased over time (45.4% in 2006 to 31.2% in 2014), but the percent of successful quit rate rose from 10.6% to 15.2%
  • There as a striking increased use of e-cigs, beginning in 2012 and increasing to 35% by 2014
  • E-cig use by smokers was positively associated with successful attempts to quit, by 0.098% [0.064 to 0.132); P<0.001] for every 1% increase in the prevalence of e-cigarette use by smokers
  • E-cig use in quit attempts was also positively associated with quit success, by058% [0.038 to 0.078; P<0.001] for every 1% increase in e-cigarette use during a recent quit attempt
  • Data were inconclusive about the association between current e-cigarette use and the overall rate of quit attempts, use of NRT (nicotine replacement therapy) bought over the counter, use of prescription treatment, or use of behavioral support. [Note: “inconclusive” does not mean “ineffective”]
  • There was evidence that expenditure on mass media was positively associated with use of stop smoking services
  • A negative association was found between e-cigarette use during a recent quit attempt and use of NRT obtained through prescription by 0.098% for every 1% increase in e-cig use in a quit attempt (P=0.04), and there was a pretty remarkable but apparently nonsignificant decrease in over-the-counter (OTC) NRT purchases from 40.0% to 20.6% of smokers [e., it appeared that the more e-cigs were used, the less NRT used. Substitution by the patients??)


  • The above numbers were adjusted for changes in differences in stop smoking services over time, introduction of a smoking ban in 2007, change in minimum age of sale of cigarettes from 16 to 18 yo in 2007, and changes in price of cigarettes
  • The overall decrease in smoking prevalence in England dropped 1 percentage point between 2014-5.
  • From their mathematical modeling: in 2015, quit attempts was 32.5% (of 8 million smokers) and the prevalence of e-cig use in quit attempts was 36%, so 54,288 more quitters stopped at least short to medium term. And if 2/3 relapse (the usual %), then e-cigs would have contributed to 18,000 additional long-term quitters.
  • And, a 40yo who quits smoking is likely to gain about 9 years of life
  • The generalizability to other areas may be limited by their differences to UK policies on e-cigs as well as smoking cessation supports, media campaigns, etc
  • Other studies do find a rise in e-cig experimentation in nonsmokers, though the rate of regular use is <1%
  • As mentioned in prior blogs (e.g., see ), I have had some impressive success with e-cigs (either initiated by the patient or by me) in getting some really long-term smokers to quit. I do regularly try the other motivational and medical therapies first, so the group who do finally quit with e-cigs is a pretty resistant one. So, my bottom line is that if e-cigs are legal and available, I do consider it part of my smoking cessation options, even as a means for harm reduction (i.e., using e-cigs to decrease cigarettes, which have 3000 additives and some known to be carcinogenic). And I do counsel adolescents in particular about the potential harm of initiating e-cig use and nicotine’s profound addiction potential.

Primary Care Corner with Geoffrey Modest MD: Lung Cancer Screening for Smokers, an Individual Risk-Based Approach

20 Jul, 16 | by EBM

By Dr. Geoffrey Modest

The USPSTF strongly recommends low-dose chest CT (LDCT) annual screening for ever-smokers with >30 pack-year smoking history aged 55-80 or until they are 15 years after stopping smoking, based on the 3-year National Lung Screening Trial (NLST). JAMA just published an article evaluating the use of risk models/individual risk-based strategies to help focus the LDCT intervention (see  doi:10.1001/jama.2016.6255). By looking at individual lung cancer risk beyond the criteria of NLST, they actually found relatively higher risk in some patients with a low risk by NLST (and therefore no screening done in NLST or offered by USPSTF) but a low risk for many included in the USPSTF guidelines. Of note, there is no currently accepted validated risk tool for lung cancer for population screening.


  • They looked at 3 databases: the CXR-only wing of the NLST (2002-2009), the ever-smokers control group of the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (PLCO, 1993-2009), and the National Health Interview Survey (NHIS, 1997-2001)
    • PLCO: 155K US men and women 55-74 yo had 4 annual CXRs and found no benefit from screening CXR in smokers
    • NLST randomized 53.5K smokers aged 55-74 with at least 30 pack-years smoking to LDCT vs CXR and found 20% decrease in lung cancer mortality by LDCT
    • NHIS: 87.5K people followed in annual cross-sectional US group from 2004, with linkage to the National Death Index. This database from 1997-2001 was used to validate the lung cancer death model. Then the model was applied to a more contemporary US population (NHIS 2010-2012) looking at all ever-smokers aged 50-80, which included 18,643 people, 52% male, 72% white/15% black/9% Hispanic, 55% post-high school education, 32% with BMI>30, 36% current smoker and 26% <10 pack-yrs, 21% 10-20, 15% 20-30, 14% 30-40, 24% >40; 67% had quit >15 years; 98% no family history, 7% had emphysema.
  • They assessed an array of characteristics from these databases (including age; education; sex; race; smoking intensity, duration, and quit-years; BMI; family history of lung cancer; self-reported symptoms of emphysema) to develop risk-based models for lung cancer incidence and deaths, then applied that to the later NHIS database.


  • Hazard Ratios for lung cancer incidence (will only mention the really significant ones)
    • Age, very highly correlated with lung cancer incidence (HR 80) and lung cancer death (HR 432)
    • Pack-years smoking:
      • 30-40: HR 1.63 for lung cancer incidence; 1.74 for lung cancer death
    • 90% of the CT-preventable lung cancer deaths are likely preventable by screening only 49% of US ever-smokers aged 50-80
    • One remarkable finding: in the risk-based model to USPSTF, 36% of the USPSTF-eligible smokers would not be screened (5-year lung cancer risk, 1.3%; NNS, 647), and would be replaced by 36% high-risk smokers (5-year lung cancer risk, 3.2%; NNS, 226) who did not meet the USPSTF criteria (mostly because they were African-American, lower BMI, less educated; 22% smoked <30 pack-years but tended to be longer-term smokers (>45 years, but 61% smoked <1/2  pack-per-day), and 14% quit > 15 years ago but were high intensity smokers, almost all having >30 pack-years and 53% >45 pack-years ).e., following the USPSTF recommendations, instead of an individual risk-based approach (incorporating more than just the smoking history), would both over-screen many low-risk people and not screen some of the high risk ones.
  • The lung cancer incidence model was validated by the chest x-ray groups of the NLS and PLCO of ever-smokers; the lung cancer death model was validated in the 1997-2001 NHIS and in the PLCO x-ray group of ever-smokers
  • Lung cancer mortality, by this model, was 24% lower than expected in the NLST x-ray group
  • Based on the NHIS 2010-2012 data, there was an estimated 43.4 million ever-smokers aged 50-80 in the US.
  • Screening the 9 million ever-smokers eligible by the USPSTF criteria for LDCT: the estimate was to prevent 46,488 deaths over 5 years
  • But screening 9 million of the highest risk group by the risk-based population would prevent 55,717 deaths (9229 more)
    • So, in this risk-based model NNS (number-needed-to-screen to prevent a death) was 162 vs 194 with USPSTF, with fewer false-positives (116 vs 133), all with p<0.001
    • And if one used the USPSTF NNS of 194 and applied that to the highest risk of the risk-based group (with risk >1.9%) [i.e., increasing the screening by the risk-based analysis to equal the NNS from USPSTF], then 3.1 million more people would be screened and then 62,382 deaths would be prevented. This increase to 12.1 million would also not have an increase in numbers of false positives.


  • So, this study did a good job developing risk models and validating them through several US cohorts, thereby suggesting that they are pretty robust and transportable. The models seemed to be more efficient than the USPSTF recommendations in terms of identifying higher risk individuals, decreasing lung cancer incidence and mortality, and decreasing the false-positive rates from LDCTs.
  • In the NLST itself, 88% of CT-prevented lung cancer deaths occurred in the 60% of those at highest risk and there were 64% with false positive results; only 1% of the lung cancer deaths occurred in the 20% at the lowest risk (see Kovalchik SA. N Engl J Med 2013; 369: 245). In fact, if one looks at those with normal LDCT in the initial NSLT, there was a dramatically lower risk of lung cancer development or death (see blog at end), to the point that I am strongly considering stopping LDCT after a couple of negative scans.
  • A few limitations of the risk-based study:
    • There is the assumption that the 20% decreased mortality in NSLT-eligible would apply to the NSLT-ineligible that would be included in the risk-based strategy.
    • The NHIS cohort only has data on lung cancer mortality not incidence, so the above risk-based model for mortality was validated only by the 2 research studies (PLCO and NLST x-ray only groups)
    • Confining the LDCTs to the high risk only, by using the risk-model, may be associated with more complications from procedures and surgery (these people are generally at higher surgical risk), so might distort the risk:benefit calculations from NLST
  • The risk-based approach does have some improvement in decreasing lung cancer deaths from 46488/9 million screened to 55717/9 million, which is increasing absolute numbers from 5.2 to 6.1/1000 screened. Still pretty small numbers.
  • So, as per my prior blogs on the USPSTF recommendations, I think they way-over interpreted NLST by extending a 3 year study (with decreasing pickup of incident lung cancers by the 3rd year), to the potential for 25 years of annual screening and the attendant high radiation exposure, to extending the upper age limit from 74 in NLST to 80, and then to codifying a single but good study into routine practice though the absolute risk reduction was relatively small (62 deaths per 100,000 person-years). The current individual risk-based approach suggests that there are many high risk patients who would not be screened by the USPSTF criteria, and many on the USPSTF list who are actually quite low risk and likely do not benefit much from the screening. I hope (and sort of expect) that the current USPSTF guidelines will be reviewed and reconsidered at some point in the next couple of years… And, it is important to remember that, as pointed out in the other blogs, lung cancer is not even close to being the primary killer associated with smoking (heart disease from smoking being much more prevalent, and COPD, etc. rating pretty high as well). And focusing on lung cancer screening may dilute the bigger message (i.e., it would be pretty awful if patients who had a normal LDCT felt that smoking was not really so bad for them, and it was okay to continue smoking…) see older blogs below for more on this.

See: which analyzes a retrospective study from NLST finding that those with an initial normal LDCT had about 35% lower rates of lung cancer incidence and mortality is a critique of NLST, especially its perhaps overenthusiastic acceptance and extensions by USPSTF

Primary Care Corner with Geoffrey Modest MD: E-Cigarettes as a Tool to Quitting Smoking/Harm Reduction

10 May, 16 | by EBM

By Dr. Geoffrey Modest

This is the second of the smoking-related emails, a provocative perspective appeared in the journal Addiction arguing for easier access to vaporized nicotine products (VNPs) as a means of harm reduction for smoking (see doi:10.1111/add.13394 ). Their lines of argument (which does include some mathematical modeling to assess the potential long-term outcomes of these pretty new devices):

  • A multi-criteria decision analysis estimated that exclusive VNP use would be associated with about 5% of smoking’s mortality risk (and is similar to low-nitrosamine smokeless tobacco).
  • Studies looking at cancer biomarkers suggest an even lower risk for cancer, 9-450 times lower than cigarette smoking
  • So, the crux of the decision analysis of benefits of VNPsreally relies on whether VNPs do lead to cigarette smoking in those not having smoked before, whether their use is helpful in smoking cessation, and if their use as least leads to a reduction of the much more toxic cigarettes.
  • Here are the fragments of evidence so far:
    • Transitions of never smokers to cigarette smokers
      • Studies have shown in general that adolescents/young adults are far more likely to have smoked cigarettes before using VNPs than to start with VNPs
        • 2014 study in UK: past month use of VNPs was 0.2% among never smokers but 13.5% among current smokers; 8.2% of those who ever used a VNP subsequently smoked a cigarette vs 68.2% who smoked a cigarette before a VNP
        • Several studies in the US and other countries (they cite 7) in youths/young adults find current smokers >15 times more likely to use VNPs than never smokers
        • As a perspective quantifying the VNP use, though 13.4% of US high school kids reported using a VNP in the prior 30 days, only 15.5% had used them >=20 days (i.e., 2% of high school students)
      • It is important to remember that those who try VNPs are at higher risk group to smoke than those who never did: more likely to engage in other high risk behaviors or have executive function deficits as found in smokers. (This suggests that the model may be one of common liabilities as opposed to VNPs being a  “gateway” drug)
      • Studies looking at transition from current smoking to VNPs
        • 2 RCTs found that VNPs lead to smoking cessation, at a rate roughly equivalent to nicotine replacement therapy. Uncontrolled prospective studies have repeatedly found higher rates of smoking abstinence with VNPs; a 2015 UK public health review suggested using VNPs to help stop smoking when other methods fail.
      • Of note, of those who are long-term ex-smokers, very few (0.8%) used VNPs (in contrast to recent quitter, where 13% have)
      • And, there is concern that ex-smokers might relapse more often if they use VNPs. at this point long-term data suggest that about 6% of former smokers who used daily VNPs relapsed to cigarettes after 1 month and 6% at 1 year (similar to rates in non VNPs users)
    • Decreases in amount of cigarette smoking if also using VNPs
    • One background issue is that though these VNPshave some reasonable arguments to decrease the only-too-well-known harms of cigarettes, 55 of 123 countries surveyed have bans or laws that prohibit or restrict their sales, and 71 have laws to regulate the minimum purchase age, marketing or taxation (increased cost leading to decreased use). The FDA may well get a law passed to regulate them (though the really huge available carcinogens, tobacco and alcohol, are not regulated…). More restrictive VNP regulations may ironically result in more people smoking cigarettes and perhaps making it longer/harder for them to quit or cut down
    • Concerns include the ever-ingenious companies increasing the likability of VNPs (newer, more seductive flavors), their targeted advertising (perhaps including comments about how safe they are compared to cigarettes). And with this, not only alluring young people into using VNPs but making it increasingly attractive to continue to do so for a really long time (so, this is different from nicotine replacement therapy, where most of my patients are disgusted by the taste of the gum/lozenges and do not like the patches so much, leading to pretty short-term usage). And, I think a real issue (somewhat downplayed in this article) is that encouraging VNPs does undercut the pretty successful public health message that “tobacco is bad for you” (witness the 50% drop in smoking in the past 50 years), in effect “normalizing” or at least de-demonizing tobacco use.
    • Over the past couple of years I personally have encouraged many patients to try VNPs if they have not been successful with the usual meds to quit smoking, with the following results: a few have been able to quit entirely with VNPs, and more have been able to cut down significantly in their cigarette usage for a sustained period. And, though they use VNPs, they really don’t like them and they wean themselves off them within a few months. Also, interestingly, even the pretty heavy smokers using VNPs often just use a few puffs a day (and get much less nicotine than if they had smoked many full cigarettes), though they may have 1-2 cigarettes as well (and I continue to work with them on that)
    • One positive issue is that the VNPs industry is pretty separate from the traditional tobacco companies. So, there is no profit in this industry promoting simultaneous cigarette smoking (those tobacco companies producing smokeless tobacco do encourage dual use with cigarettes)
    • The mathematical assumptions in terms of long-term risk are likely to be reasonable, since VNPs have many fewer toxic chemicals added (see , which analyzes a pretty deeply flawed article suggesting that VNPs do not help with smoking cessations, but I argue that VNPs are much less toxic than cigarettes, which have on the order of 3000 chemical additives. There are certainly additives in e-cigarettes, including propylene glycol, as an emulsifier; several flavors such as vanilla, menthol; several chemicals to improve the smell such as 2-acetylpyridine and others; and none of these are regulated by the FDA since e-cigarettes are not a “drug”, but are likely less toxic than the multitude of chemicals in cigarettes, including known carcinogens).
    • So, the real issue is that about 40% of smokers make a quit attempt every year (i.e., a large % really do want to quit!!). Perhaps availability of VNPs could help some of these actually quit. Clearly it is in the public health interest to help them, but also to discourage never smokers from using VNPs, since their use is not benign. But my experience has really been consistent with the conclusions of this paper: VNPs seem to have a role in helping people quit or cut back on cigarettes, and I think should be on the list of harm reduction tools we have for cigarette smokers. But there should be a vigorous public health campaign to try to limit their use in kids who have not smoked (even perhaps limiting the array of fanciful flavors???)
    • And, by coincidence, this am the NY Times had a report that the Royal College of Physicians in UK came out with an endorsement of using VNPs to help people quit smoking. See

Primary Care Corner with Geoffrey Modest MD: Smoking Cessation Meds in Pts with Psych Disorders

9 May, 16 | by EBM

By Dr. Geoffrey Modest

A couple of recent articles dealt with issues of smoking cessation:

  1. The lancet had a study finding no significant increase in psychiatric risk with any of the smoking cessation medications (see ). The FDA had issued an early warning on neuropsych concerns with varenicline, later extended to bupropion, based on case reports, and issued a post-marketing requirement for makers of both drugs to do RCTs to assess these risks. Hence this drug-company sponsored study.


  • 8144 smokers smoking at least 10 cigarettes/d in the past year, 4116 having underlying psych disorders/4028 in the non-psych cohort. In terms of the cohorts:
  • Nonpsych cohort: mean age 46, 50% female, 83% white/13% black, wt 80 kg, 47% US/33% Western Europe/11% Eastern Europe/10% Central/South America, Fagertstrom Test for Cigarette Dependence (FTCD) score 5.5 [a score signifying moderate dependence], 13 years duration of smoking, 21 cigs/day in past month, 3.3 prior quit attempts
  • Psych cohort: mean age 47, 62% female, 80% white/16% black, wt 80 kg, 58% US/29% Western Europe/9% Eastern Europe/4% Central/South America, Fagertstrom Test for Cigarette Dependence (FTCD) score 6.0, 12 years duration of smoking, 21 cigs/day in past month, 3.5 prior quit attempts. 70% with unipolar or bipolar depression, 20% anxiety disorder, 9% psychotic. 33% on antidepressants, 15% anxiolytics, 16% antipsychotics [of note: all had to be stable for the prior 6 months and not at risk for self-injury]
  • Randomized to nicotine patch 21 mg/d with taper, varenicline 1mg bid, or bupropion SR 150mg bid for 12 weeks with 12 week non-treatment follow-up. Done in 14 centers in 16 countries between 2011-2015 (this was a double-blind, triple dummy, placebo controlled trial – i.e. everyone took pills from 2 different unmarked bottles and used a patch)
  • All had brief smoking cessation counseling (no more than 10 minutes, at each clinic visit)
  • Quit date was 1 week after randomization, coinciding with end of uptitration of bupropion and varenicline and initiation of patch
  • Main outcomes: composite measure of moderate and severe neuropsych events; and biochemically confirmed continuous abstinence from smoking for weeks 9-12.


  • The same percent (78%) of each group completed the study
  • In the non-psychiatric cohort: moderate-to-severe neuropsych adverse events occurred in
    • Varenicline: 13 of 990 people (1.3%)
    • Bupropion: 22 of 989 (2.2%)
    • Patch: 25 of 1006 (2.5%)
    • Placebo: 24 of 999 (2.4%)
    • The only significant difference between active drug and placebo: varenicline-placebo risk difference was 1.28. Of note, there were essentially zero patients with psychosis, panic, mania, suicidal ideation or behavior, anxiety, or depression.
  • In the psychiatric cohort:
    • Varenicline: 67 of 1026 people (6.5%)
    • Bupropion 68 of 1017 (6.7%)
    • Patch: 53 of 1016 (5.2%)
    • Placebo: 50 of 1015 (4.9%)
    • No significant risk differences between active drug and placebo, though there were 14 of patients (2%) in the psych group who developed suicidal ideation
  • Quit rates at 9-12 weeks, vs placebo (documented by exhaled carbon monoxide measurements):
    • Varenicline (statistically significantly better than the other 2 active treatments), with OR 3.61 (3.07-4.24); most frequent adverse effect: 25% nausea
    • Bupropion: OR 2.07 (1.75-2.45); most frequent adverse effect: insomnia 12%
    • Patch: OR 2.15 (1.82-2.54); most frequent adverse effect: abnormal dreams 12%
    • Placebo: headache in 10%
    • Quit rates looking at weeks 9-24 showed some deterioration over those from weeks 9-12, but the order and significance of efficacy remained as above

So, this study adds a few things to the literature:

  • As a large study, it showed that neither varenicline nor bupropion posed a significant risk to smokers with or without a psych history.
  • The odds ratios for efficacy in smoking cessation did not vary by initial psych status: those with underlying psych issues had similar abstinence rates to those without
  • And, this is pretty important since the likelihood of smoking is 2-3x higher in those with underlying psych disorders (perhaps as self-medication with nicotine, a pretty potent psychoactive drug/anxiolytic: evidence shows improved vigilance, attention and cognition; decreased perceived stress, embarrassment, irritability, or depression; nicotine can be both a stimulant and relaxant, with initial epinephrine release causing stimulation but increasing dosages causing sedation)
  • A few caveats:
    • As per prior blog ( there might have been more success if the patch had been started earlier than 1 week before the quit date
    • I would still be concerned about using varenicline in those with psychotic disorders, since these were pretty underrepresented in the psych cohort (as were those with personality disorders, <1% of the cohort). But importantly, a large % (34%) had a history of suicidal ideation and 13% had a history of suicidal behavior. Also of importance, this study did not include patients with underlying with substance use disorders, including alcohol, in the past 12 months.
    • Although varenicline outshined the others, this trial only looked at monotherapy, and there are many studies showing the superior efficacy of multi-therapies
    • The evaluation of smoking cessation at 12 weeks should be viewed with some caution, since this may not reflect long-term abstinence
  • So, bottom line, varenicline, as a single agent, seemed to be the most effective in smoking cessation and did not seem to have any real increased neuropsych risk, even in those with underlying psych disorders (i.e.: assessing the confidence intervals above, it did not appear that there could be more than a 1.5 percentage point increase in neuropsych events by either varenicline or bupropion in those without psych disorders, or more than 4 percentage points in those with psych disorder). For patients with underlying psych disorders who meet the above criteria (including being stable psychiatrically and non-other-substance using), any of these methods seemed to work well and be well-tolerated, though I would really follow them more closely.

Primary Care Corner with Geoffrey Modest MD: Need Annual Low-Dose Chest CTs?

5 Apr, 16 | by EBM

By Dr. Geoffrey Modest

A retrospective cohort analysis of participants in the National Lung Screening Trial (NSLT), the trial that propelled forward low-dose lung CT (LDCT)​ screening in smokers, found that those with a negative initial LDCT actually had a much lower subsequent incidence of lung cancer and that annual screening may not be necessary (see S1470-2045(15)00621-X​). See blogs at the end for details and my analysis of the NSLT study, and the perhaps overenthusiastic guidelines than ensued.


  • 26,231 people were screened, according to the criteria: aged 55-74, with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years. They had 3 annual LDCT screens and were followed for 5 years after the last screen.
  • 19,066 (73%) had a negative initial screen


  • Those with a negative initial screen had a lower incidence of:
    • Lung cancer than the group as a whole (371.88/100K person-yrs, vs 661.23)
    • Lung cancer-related mortality than the group as a whole (185.82/100K person-yrs, vs 277.20)
  • ​The finding of lung cancer at the first annual LDCT screen in those with initially negative initial screen was:
    • 34% (62 screen-detected cancers out of 18,121 screens), which was much lower than on the initial screen of all participants, 1.0% (267 of 26,231)
  • The mathematical estimate was that if those with negative initial LDCT screens had skipped the first annual screen, at most 28 additional participants would have died from lung cancer (i.e., a rise in mortality from 185.82 to 212.14/100K person-yrs over the course of the trial).

So, this brings up a few points:

  • Not so shockingly, if you cull out those with lung cancer on the initial screen from those with normal screens, the pick-up of lung cancer the next year would be lower
  • Why might this be true?? Perhaps those smokers with normal looking lungs at the initial screen are actually different from the group who develop lung cancer. Perhaps there are factors beside the quantity of cigarettes smoked which matter… well, it turns out that an old study from 30 years ago, based on the Johns Hopkins Lung Project participants (one of the 3 early clinical trials looking at sputum cytology and CXR as a means to pickup early lung cancer in smokers), found that “among cigarette smokers, the presence of airways obstruction was more of an indicator for the subsequent development of lung cancer than was age or the level of smoking. The risk for lung cancer also increased in proportion to the degree of airways obstruction. These data suggest that smokers with ventilatory obstruction are at greater risk for lung cancer than are smokers without obstruction. ” (see Ann Intern Med 1987; 106: 512). And, in fact, emphysema in NSLT conferred a 96% increase in lung cancer risk in those with an initially negative LDCT
  • So, maybe there should be more risk stratification in doing LDCT screening. My real concern here is that radiation is bad for you. There is a potential creation of cancers by excessive radiation (and given the high false-positivity rate of LDCT, 39% in NSLT as mentioned in blogs below, the actual dose of radiation is on average about 4x higher, equivalent to a regular high-dose CT). And, I would imagine, it might well be that lungs that are adversely affected by smoking, perhaps those with COPD from tissue destruction and maybe with important changes in local defenses, may be even more susceptible to radiation-induced lung cancer (i.e., even more than the estimated one cancer death in 2500 screened). Perhaps assessing airway obstruction, as in the old Annals study above, would be useful (and spare lots of people from the potentially harmful effects of radiation)
  • And, besides, there is no biological reason to think that annual screening is the correct interval anyway, even if long-term screening were appropriate. It’s just that annual screening was arbitrarily chosen by NSLT (which, again from the perspective of this study, only did 3 screens, yet this was generalized in the recommendations to a whopping potential of 22 screens). And, by the way, as mentioned in prior blogs, though not statistically significant (perhaps from low numbers of cases and short-term followup), the NSLT pick-up rate for positive LDCT screens went from 27.3% in year 1 to 27.9% in year 2, then dropped to 16.8% in year 3. Would that continue to decrease? Are there subgroups where the decrease was more profound?​ These are really essential questions to answer in order to optimize screening in terms of the risk/benefit ratio.
  • But, the wholesale acceptance of annual LDCT by the USPSTF and by Medicare does put us at very significant medico-legal risk if someone develops lung cancer and were not screened (and it is hard to prove on an individual basis that one prevented a cancer by not screening). Just makes things harder for us to figure out what to do for our patients…. is a critical review of the NSLT and the US Preventative Services Task Force ​ recommendations, including that NSLT actually had decreasing pick-up of lung cancers on year 3 vs year 1 of the 3-year study which reviews Medicare recommendations and highlights several points, including that screening for just 3 years is projected to create one cancer death per 2500 screened from radiation. And, per Medicare, patients could be subjected to 22 annual screens if they continue to smoke and we follow the letter of the guidelines.​

Primary Care Corner with Geoffrey Modest MD: Abrupt vs. Gradual Smoking Cessation

28 Mar, 16 | by EBM

By Dr. Geoffrey Modest

An English study tested two strategies to achieve smoking cessation: a gradual vs abrupt approach (see doi:10.7326/M14-2805). The background is that most guidelines recommend abrupt cessation (“setting a quit date and then stopping cold turkey”), though many smokers report stopping more gradually.

Details of the study:

  • 697 adult smokers (at least 15 cigarettes/d), recruited to quit smoking, choosing a quit date 2 weeks after starting the program. These patients were randomized to either an abrupt cessation program, smoking normally then stopping at the quit date, or a more gradual reduction program, reducing their smoking by daily increments to achieve a 50% reduction by the end of the first week, and a 75% reduction by the end of the second week and then stopping.
  • Both groups received behavioral support from nurses and used nicotine replacement therapy (NRT) before and after the quit date (it is not quite explicit, but I think they all used 21-mg patches in the 2 weeks before the quit date, and those in the gradual group also used short acting NRT such as gum or lozenges. They all used both patches and short-acting NRT after the quit date).
  • Median age 49, 50% male, 94% white, 50% with postsecondary school education, 55% working, 39% lived with a smoker, median prior quit attempts = 2, 20 cigarettes/d, expired CO=24 ppm, median Fagerstrom Test for Cigarette Dependence score = 6 (i.e., highly dependent), 51% preferred gradual cessation and 32% abrupt.
  • Behavioral therapy focused on the commitment to abstain, with early support when withdrawal symptoms are worst/relapse more likely.
  • Nurses saw the patient initially, 1 day before the quit date, weekly for 4 weeks, and finally 8 weeks after the quit date
  • Results, comparing the gradual vs abrupt quit rates:
    • At 4 weeks, 39.2% (34.0-44.4%) vs 49.0% (43.8-54.2%); RR 0.80 (0.66-0.93)
    • At 6 months, 15.5% (12.0-19.7%) vs 22.0% (18.0-26.6%); RR 0.71 (0.446-0.91)
    • Fewer people made a quit attempt (>24 hours of self-reported abstinence) in the gradual cessation group (61.4% vs 71% in the abrupt group; though in the gradual group, they had reduced their cigarette consumption by 48% by the end of the first pre-cessation week (target 50%) and by 68% by the end of the second week (target 75%)
    • ​And, participants who preferred gradual vs abrupt cessation prior to randomization were less likely to be abstinent at 4 weeks (38.3% vs 52.2%)
    • No significant study-related adverse events

So, a few points:

  • This study was done in 31 primary care practices in London. Their explanation for the lack of racial diversity was that the minorities in London tend to smoke much less than the majority white population. But this difference may limit the generalizability of the results to other populations.
  • Those who preferred the gradual cessation method did worse, independent of which group they were assigned to [this is consistent with my practice: very few people who try to cut back gradually do actually achieve abstinence, though very few of them do such a severe reduction program as above, with 75% reduction in 2 weeks]
  • This study raises the issue of starting patches prior to the quit date. In looking at their reference for this (Addiction 2008; 103: 557), this meta-analysis of 4 studies actually showed that patches given 2-4 weeks prior to smoking cessation led to a 2-fold increased long-term quit rate, at both 6 weeks and 6 months. This is not something I have prescribed, though now will do so, 2 weeks prior to the quit date.
  • The people in this study were really nicotine-dependent, and to me their 49% cessation rate at 4 weeks in the abrupt group is very impressive, as is their 22% at 6 months. Especially since smoking an average of a pack a day is not only very addicting physiologically, but involves a pretty extensive amount of time smoking each day, with many more smoking-related associations than those who smoke just a few cigarettes/d (i.e., those who smoke throughout the day may well associate smoking with many different things: waking up, after meals, hanging out with friends, having a beer….), much more so than those who smoke a cigarette on awakening and then after dinner. So, psychologically, heavy smokers also have more cigarette-related associations to deal with in order to quit.
  • I know some clinicians are trying to get patients to cut back to 1/2 ppd (10 cigarettes) prior to setting a quit date, thinking that the overall chances of success would be higher. I am not aware of data looking at this, but this study suggests otherwise.
  • So, I think this data and that of other studies (some but not all) suggest that we push for a more abrupt quit date, ideally with pre-cessation patches (if that is the method chosen). However, as with all of these substance dependencies, there will be many people who are unable to adhere to such a program, and our goal continues to be harm reduction and allowing the patient to determine their own approach to nicotine reduction. And it is important to remember that most smokers take 3-4 quit attempts to finally succeed.

Primary Care Corner with Geoffrey Modest MD: E-Cigarettes and Smoking Cessation, Are They Useful?

11 Feb, 16 | by EBM


By Dr. Geoffrey Modest

So, it turns out that there was a systematic review/meta-analysis last month in Lancet Respiratory Medicine on the use of e-cigarettes and smoking cessation (see Thanks, again, to Karen Henley for bringing this up to me, after I had mentioned in a blog earlier this week that I had a few patients who were able to quit smoking by using e-cigarettes after they had failed with the traditional medical therapies. As a review of this article:

  • 38 studies were included, including 20 with control groups.
  • Results:
    • Odds of quitting cigarettes was 28% LOWER with e-cigarettes [OR 0.72 (0.57-0.91)]
    • The studies are a mixed bag and fraught with confounders (e.g. several just compared patients who were not interested in quitting but who used e-cigarettes vs those who did not, finding mixed results as to who quit later). Looking at studies which included only smokers interested in quitting found a nonsignificant 16% lower likelihood of smoking cessation in e-cig users. One study found that the heavier users of e-cigarettes were more likely to quit than occasional users.
    • In fact, the only randomized controlled trial which compared e-cigarettes to nicotine patches (see Lancet 2013; 382: 1629) randomized 657 heavy smokers with mean of 18 cigarettes/d who wanted to quit smoking into 289 on nicotine e-cigs, 295 to nicotine patches, and 73 to placebo e-cigs. Their results at 6 months was verified nicotine abstinence in 7.3% with nicotine e-cigarettes, 5.8% with patches, and 4.1% with placebo e-cigarettes. These numbers were well under the expected quit rate, and there was no statistical difference between the interventions. This trial was criticized because the e-cigarettes were provided to the patients, but those on patches only got a voucher for them. The only other clinical trial was nonrandomized (differentiated patients who were willing vs not willing to accept e-cigarettes), also finding a non-significant increase in smoking cessation with e-cigarettes.

So, a few points:

  • This systematic review and meta-analysis brings out an interesting and not-so-uncommon issue: in the abstract of the article the authors present this study as pretty unequivocally showing “the odds of quitting cigarettes were 28% lower in those who used e-cigarettes”, and that this was true pretty much regardless of the study design or subgroup analyses. A pretty strong statement given that the largest group of studies involved patients who were not even trying to quit cigarettes (and those smoking e-cigarettes may have wanted even more nicotine) and their later comment (buried in the article), that if you evaluate only the studies of people wanting to quit, there was only a nonsignificant trend towards less quitting with e-cigs. They commented extensively at the end of the paper that there was no standard definition of smoking cessation, these were almost all observational studies (and the two cited above, closest to actual controlled studies, found NO difference and a trend to more smoking cessation with e-cigs), there were large differences in the quality of the studies or even the extent of e-cigarette use, most studies just had patient reports without confirmation of smoking cessation, and there was no assessment of the types or quality of the e-cigarette use reported. And, given the preponderance of potentially useful medical articles in huge numbers of journals (e.g. Lancet itself now has an array of more specialized journals, such as the one for this article), it is really important for the abstract to reflect the real and clinically-important conclusions of the study, and not rely on meticulous reading of the methodology and actually reviewing the content of several of the articles included in the systematic review, to get at the real issues. We just do not have enough time to try to keep up in the medical literature without having clear and accurate summaries.
  • As noted in the article “no clinical trials have done a true head-to-head comparisons of e-cigarettes with standard therapies (i.e., nicotine patch, gum, or inhaler) approved by the US FDA for smoking cessation”. And this type of trial in the US is unlikely, since it would only be done if the e-cigarette makes requested approval by the FDA as an Investigational New Drug. Again, no mention of this rather compelling deficiency in the abstract, or on brief scan of the article.
  • Why might e-cigarettes not help? After all, they do emulate the actual process of smoking, which may be a very long term behavioral response to stress, nicotine withdrawal, other social cues such as meeting with certain friends/drinking a beer etc. And therefore it seems to me that using e-cigs could be part of the gradual process of getting off cigarettes, and, as a good thing, they are less satisfying than cigarettes, per my patients, so getting off them may be easier later. One observation by the authors is e-cigs are not prescribed by clinicians. Nicotine replacement therapy, when prescribed, seems to work (see prior blogs at ), but this is not clearly the case when they are bought over-the-counter (see JAMA 2002; 288: 1260).
  • Is there a role for e-cigarettes in harm reduction? I would think so. Much less toxic than cigarettes, which have on the order of 3000 chemical additives (there are certainly additives in e-cigarettes, including propylene glycol, as an emulsifier; several flavors such as vanilla, menthol; several chemicals to improve the smell such as 2-acetylpyridine and others; and none of these are regulated by the FDA since e-cigarettes are not a “drug”, but are likely less toxic than the multitude of chemicals in cigarettes). And, when my patients have used them, they usually take only 1-2 puffs and stop. So, I would guess, they often get much less inhaled nicotine.

Primary Care Corner with Geoffrey Modest MD: Smoking Cessation Comparison of Therapies

10 Feb, 16 | by EBM

By Dr. Geoffrey Modest

A randomized controlled trial was compared different therapies to aid in smoking cessation (see JAMA. 2016;315(4):371).


  • 1086 smokers (mean age 48, 52% women, 67% white/28% black/3% latino, mean income >$35K in 46%) who had been smoking a mean of 17 cigarettes/d​ over mean of 29 years. Fagerstrom Test of Nicotine Dependence (FTND) score of 4.8, reflecting low-to-moderate dependence, with 77% smoking within 30 minutes of awakening
  • Randomized to open-label varenicline, titrating up to 1mg bid as tolerated; nicotine replacement patch (NRT), starting with 8 weeks of 21-mg patch, then 2 weeks of 14-mg patch, then 2 weeks of 7-mg patch (but in those smoking 5-10 cigarettes/d, 10 weeks of 14-mg patch then 2 of 7-mg patch); or patch plus nicotine lozenges (C-NRT group), with patches as in other group plus 2 or 4mg lozenges and asked to use at least 5/day. All interventions were for 12 weeks.
  • All received 5 counseling sessions at the times of visits, and 1 telephone call.
  • Smoking assessment was at 26 and 52 weeks post quit date by telephone interview; quit rates confirmed by exhaled carbon monoxide <= 5 ppm, which “optimally distinguishes smokers from nonsmokers”.
  • Results (none of these showed any significant difference for one method over another):
    • Medication adherence rates were similar: at week 8 — 45.2% for patch; 49.3% for varenicline; and 49.6% (patch) and 43.0% (lozenges) for C-NRT
    • 7-day point-prevalence abstinence at 26 weeks post-quit date were:
      • 8% for nicotine patch alone
      • 6% for varenicline
      • 6% for C-NRT (patch plus lozenges)
    • 7-day point-prevalence abstinence at 52 weeks post-quit date were:
      • 8% for nicotine patch alone
      • 1% for varenicline
      • 2% for C-NRT (patch plus lozenges)
    • Prolonged abstinence at 26 weeks (no smoking from day 7 to day 181 after quit date):
      • 9% for nicotine patch alone
      • 5% for varenicline
      • 4% for C-NRT (patch plus lozenges)
    • ​Adverse events: more rash (11%) and itching/hives (20%)with patch. More vivid dreams (23%), insomnia (22.2%)/sleepiness (16%), and nausea (28.5%) with varenicline

So, a few points:

  • Though there were some minor differences early in the study (varenicline and C-NRT were better than patch alone in reducing withdrawal and craving symptoms; C-NRT had higher initial abstinence rates), there was no difference at the 26 and 52-week marks
  • This study does call into question the model of basal nicotine and rapid-acting lozenges for “break-through” urges, since there really was no difference in terms of clinically-relevant outcomes. Also, this study, unlike some others, did not show clinical superiority for varenicline over other treatments, with pretty clearly increased significant adverse events.
  • And, putting this in perspective, in terms of preventing cardiovascular disease, the single most effective intervention is smoking cessation for those who are smokers, more efficacious than lowering blood pressure, improving diabetic control, or using a statin or aspirin. This study confirms the efficacy of differing modalities in helping patients stop smoking. I would add that for some patients combination therapies work better (NRT plus bupropion, or even NRT plus varenicline), though I usually try a single intervention first to minimize adverse events. Also, I would stress that motivational interviewing is really helpful both in helping patients get ready for smoking cessation as well as helping them through the process. And, at risk of my devolving (?again) to be a pariah, I have had some reasonable success with some patients by encouraging e-cigarettes as a crutch to stopping smoking (though I usually suggest the more traditional medical therapies, as above, first).

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