Monday, June 30, 2014

Swedish Study: After a Heart Attack, Quitting Tobacco Better Than No Tobacco

A recent study by Gabriel Arefalk and colleagues at the University of Uppsala in Sweden, published in the American Heart Association flagship journal Circulation (abstract here), was purported by the authors, the AHA (here) and the media (here) to show that continuing snus use or smoking after a heart attack (myocardial infarction, MI) is twice as harmful as quitting.   

These conclusions are questionable.  Using the Arefalk numbers, Carl Phillips and I found that snus users, and perhaps even some smokers, are better off than non-users. 

We have submitted a letter to the editor of Circulation, and Carl has the full text of our letter in his CASAA blog post (here).    

The bottom line is that the authors tried to spin the results as suggesting that continuing snus use is dangerous after an MI.  In fact, continuing snus users actually had a lower death rate than people who used neither snus nor cigarettes. 

Whatever is happening in this population, it clearly does not support the simplistic “snus is bad” mantra.  There is a glaringly obvious explanation for why people who quit snus (or smoking) after an MI fare better than those who do not:  Those who are healthy (except for the recent MI, of course) and hope to recover are more likely to take steps to minimize their risks.  After being advised to give up snus, many also get physical therapy, exercise and maintain a healthier diet.  Meanwhile, those who are less healthy may not make changes in an attempt to regain long-term health.  The Arefalk analysis may not have adequately controlled for these confounding factors.

Of course, this would only partially explain the better outcomes of quitters compared to continuing users; it does nothing to explain why all of them (except those who continued to smoke) apparently fared better than non-users.  There are possible explanations for this in the form of statistical artifacts or real effects.  The key observation is that these unreported results do not support the authors’ main interpretation that snus use is dangerous after an MI.

With the publication of this article, peer review appears to have been woefully inadequate.   The prime statistical error we discovered is the key number reported in the first paragraph of the article’s results section.  Reviewers of this study failed to detect the glaring error.

Even without correcting that error or calculating the mortality rate for non-users, the (incorrect) number for the population as a whole the authors reported can still be compared to rates for people who used snus or cigarettes at the time of their MI.  This is enough to raise red flags about the analysis and conclusions, since it is still higher than the rate for those who kept using snus, and far higher than the rates for those who stopped using either product. 

In 2011 Arefalk was lead author on a study making dubious claims about snus use and heart failure.  I described that effort as “neither legitimate nor persuasive until the authors resolve the fundamental questions about the analysis.” (here).

The current article in Circulation is a classic example of anti-tobacco propaganda.  Credible epidemiologic studies do not report risks in exposed groups without reporting the comparable baseline risk among the unexposed.  The authors, and the journal editors and reviewers who enabled them, omitted this critical information.  Our letter to the editor gives them a chance to correct these deficiencies.

Thursday, June 26, 2014

Snus Nicotine Lowers Risk for Multiple Sclerosis, May be Therapeutic for Other Nerve Disorders

New research published in Multiple Sclerosis Journal (abstract here) and authored by Anna Hedström of Stockholm’s Karolinska Institute of Environmental Medicine confirms that snus users have a significantly lower risk for multiple sclerosis (MS) than nonusers of tobacco.  I discussed the researchers’ earlier findings on this subject five years ago in this blog (here).

Hedström’s study is based on some 7,900 Swedes with MS and 9,400 controls.  Compared with never users of tobacco, snus users had a lower risk for MS (odds ratio OR = 0.75, 95% confidence interval, CI= 0.63 – 0.90).  Hedström also showed an increased effect at higher duration-dose levels of snus.  For example, users with greater than ten packet-years (the number of snus doses per day and years of use) had an OR of 0.45 (CI= 028 – 0.68).  Smokers had modestly increased risk (OR= 1.49, CI= 1.40 – 1.59), a finding that is similar to that reported in Hedström’s previous study.

Scientific research is methodically unveiling the benefits of nicotine and smoke-free tobacco use with respect to degenerative brain diseases.  A finding that nicotine may improve performance in people with mild cognitive impairment (discussed here), has resulted in calls for more research on nicotine’s effect on dementia (reference here).

The impact of nicotine/tobacco use on Parkinson’s disease is well documented.  An American Cancer Society study (here) provides clear evidence that smokeless tobacco use may be protective for Parkinson’s disease (RR = 0.22, CI = 0.07 – 0.67).  In fact, nicotine is being discussed as therapy for this disorder (here, here  and here).

Alzheimer’s disease is the sixth leading cause of death in the United States, and Parkinson’s disease is the fourteenth.  The role of nicotine and smoke-free tobacco in reducing risk of or treating these disorders is of significant import.

Wednesday, June 18, 2014

Stroke Risk Same for Menthol and Nonmenthol Smokers

Dr. Nicholas Vozoris in 2012 reported that “…smokers of mentholated cigarettes, and in particular women and non–African Americans, have significantly increased odds of stroke compared with nonmentholated cigarette smokers.”  (reference here).  He used National Health and Nutrition Examination Surveys (NHANES) data to calculate odds ratios of 2.3 for all menthol smokers, 3.3 for women and 3.5 for non-African Americans.  Dr. Vozoris found no increased risk for hypertension, heart attack, congestive heart failure or emphysema among menthol smokers. 

If the Vozoris findings on menthol and stroke were independently confirmed, they could serve as a basis for a ban on menthol cigarettes.  Instead, an analysis of NHANES data by Dr. Brian Rostron (here) comes to an entirely different conclusion.

Dr. Rostron found that African-American menthol smokers had a significantly lower risk for stroke (OR = 0.52, 95% confidence interval= 0.28 – 0.99) than nonmenthol smokers.

“It is not clear to me,” Dr. Rostron writes, “how Vozoris obtained his findings, given that I cannot replicate his general results for stroke using the NHANES data and analyses that he specified.  Moreover, the absence of observed differences in stroke prevalence among NHANES menthol smokers would suggest that methodological or analytical issues may have affected his results.”

Dr. Rostron earlier showed that menthol smokers have lower lung cancer risks than nonmenthol smokers (here).

Promoted by the Archives of Internal Medicine (here), the Vozoris study was covered by major news media (here  and here).  The journal, which changed its name to JAMA Internal Medicine in January 2013, is not publicizing the study that corrects the deficient 2012 analysis.

Although medical journals cannot avoid publishing erroneous reports, editors should take all measures to correct the types of mistakes discovered by Rostron.

Tuesday, June 10, 2014

Swedish Match Files to Change Smokeless Tobacco Warnings

Swedish Match has filed a Modified Risk Tobacco Product (MRTP) application with the FDA Center for Tobacco Products (CTP).  The landmark event was announced in an AP story (here). 

The company wants to change three health warnings on ten of its snus products manufactured by the company in Gothenburg, Sweden and sold in the U.S.: 

1.  Remove the current warning, “This product can cause mouth cancer.”

2.  Remove the current warning, “This product can cause gum disease and tooth loss.”

3.  Replace the current warning, “This product is not a safe alternative to cigarettes,” with this text: “No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes.

4.  Retain the current warning, “Smokeless tobacco is addictive.”

Numerous studies document that the three targeted warnings have essentially no scientific basis (discussed here).  I previously noted the bogus nature of the mouth cancer warning, which was mandated in 1986, five years after Dr. Deborah Winn mischaracterized the magnitude and scope of smokeless tobacco’s mouth cancer risk (discussed previously in this blog here and here).  There is no foundation for an oral cancer warning for today’s American and Swedish smokeless products.

The gum disease/tooth loss warning is equally inappropriate.  Even in 1986, there was virtually no scientific evidence that smokeless tobacco was an independent risk factor for any dental problem.  The same is true today. 

The not-a-safe-alternative warning is particularly egregious.  The purpose of this 1986 warning was to deceive smokers into believing that smokeless tobacco was just as dangerous as smoking.  As I wrote in my book, “For Smokers Only” (here), this warning is simply ludicrous.

Swedish Match’s replacement warning is identical to a change requested by RJ Reynolds in a citizen petition filed with the FDA three years ago (discussed here).  The FDA ignored that petition, but it is obligated to consider the Swedish Match MRTP application.  After an administrative review for completeness, the agency must refer the application to the Tobacco Products Scientific Advisory Committee (TPSAC) and ask TPSAC to report its recommendations on the application to FDA within 60 days.  The FDA will also make the application public and request comments.  “FDA intends to act upon your MRTP application no later than 360 days after receipt…”

The misinformation in the current warnings has been shown to discourage smokers from switching (here). The welcome filing by Swedish Match could dramatically alter the landscape for tobacco harm reduction.

Thursday, June 5, 2014

E-Cigarette TV Ads: Adults’ Exposure Much Higher Than Kids’

The June 2nd edition of the journal Pediatrics features a study of e-cigarette advertising on television from 2011 to 2013 (here).  The research, led by Jennifer Duke of RTI International in North Carolina, found that exposure among youth (12-17 years old) to television ads for e-cigs increased about 2.5 fold, or 256% as reported by Dr. Duke. 

The author casts the industry as villain: “It appears that youth are being exposed to a sustained level of marketing about the benefits of e-cigarettes.” (here).  ABC TV was less subtle: “E-Cigarette TV Ads Target Kids.” (here).

In fact, the results in Figure 1 of the study (left), which were not fully described by the authors, show that the advertisements’ effects were mainly on adults.

The authors report exposure to e-cig ads in terms of target rating points (TRPs), a standard unit of measurement for the proportion of people exposed to an ad and its frequency. 

Duke and colleagues report that exposure of 12-17-year-olds to e-cig advertising peaked in 2nd quarter 2013 at 347 TRPs.  Young adults (18-24 years), for whom purchase of e-cigarettes is legal almost everywhere, had peak exposure of 611 TRPs in 2013, indicating much higher exposure than youth. 

The authors fail to note that older adults had far higher peak levels of exposure to e-cig ads.  My table contains the estimated peak TRPs for each age group in Figure 1.

Peak Exposure to E-cigarette Television Advertising (TRPs) By Age Groups in 2nd Quarter 2013
Age Group (years)Population (millions)Peak Exposure (TRPs)
18-24 30611

This data shows that 234 million adults 18 years or older were the primary recipients of e-cigarette advertising.