Recent eLetters

Why was Dr. Eissenberg so surprised to find very low levels of nicotine in the blood of subjects who had taken 10 puffs from an electronic cigarette? He implies that he expected to find equal nicotine levels when compared to 10 puffs from a tobacco cigarette. However, he cited as one of his references M. Laugesen's Poster presented to the joint conference of the Society for Research on Nicotine and Tobacco, Europe; April 30, 2009. In that poster, Dr. Laugesen reports on a clinical trial involving 40 subjects who were studied during a full day's ad libitum use of one of four products: An electronic cigarette containing nicotine, an electronic cigarette containing placebo, a Nicorette inhalator, or their own brand of cigarette. The poster states, "The 16mg EC delivered nicotine more rapidly (mean tmax 19.4 minutes) than Nicorette inhalator (30 minutes) but not as rapidly as cigarettes (14.3 min)." The highest cmax of nicotine from a tobacco cigarette was almost ten-fold that of the 16 mg. electronic cigarette. Given this background information about the slower absorption of nicotine from an electronic cigarette, if Dr. Eissenberg insisted on limiting his electornic cigarette subjects to 10 puffs, he should have limited his tobacco cigarette smokers to one puff.

This study does not prove that electronic cigarettes do not deliver nicotine effectively. All it proves is that 10 puffs from an electronic cigarette is an inadequate level of usage.

Conflict of Interest:

None declared

We have read with interest the paper by Williams et al.(1) assessing the prevalence of smoke-free hospital campuses' policies in the United States. In addition to the data and wise comments in the paper, we want to share some reflections from Europe. There is general consensus that health organizations should be an example in developing and implementing tobacco control policies(2,3). Many hospitals have become tobacco free by implementing indoor smoking bans. However, research conducted to evaluate the impact of smoke-free indoor policies in hospitals shows that the benefits obtained are lower and slower than in other organizations(4-6). Thus, when smoking restriction bans are implemented in hospitals, there is a small decrease in tobacco cessation rates, poor implementation and support by the employees, and low satisfaction among patients and visitors(4,7). There are two main hypotheses that could explain this problem. First, hospitals have provided outside areas where people go to smoke and this continues in the absence of out-of-doors bans(8,9). In addition, due to the lack of systematic smoking cessation interventions, smokers still use those areas to satisfy their nicotine cravings(6,10,11). Consequently, there is an intense debate over what a hospital should provide in terms of being considered a comprehensive tobacco-free organization.

In the 1990s, the paradigm of tobacco-free hospitals was limited to implementing indoor policies with or without offering tobacco cessation programs. In this millennium, a new paradigm has emerged: the Tobacco-free Hospital Campus. The rationale is that tobacco-free outdoor spaces set a clear example of good health practices, providing clear messages to patients, visitors, and employees that tobacco consumption is dangerous to health and therefore not allowed in all the grounds of the institution; encouraging them to quit tobacco; and maintaining a clean and neat environment.

Almost half of the American hospitals surveyed by Williams et al(1) have adopted a smoke-free campus policy (n= 865). In Europe, approximately 1,400 hospitals have joined the European Network of Tobacco-free Health Care services (ENSH- Global Network for Tobacco-free Healthcare Services), but only a few of them have extended the tobacco-free policies to outdoor places. This extension is vital since healthcare services have an important role to play in reducing tobacco consumption generally within society. A professional understanding of addictive diseases treatment and clinical practice indicates that healthcare services must offer, in addition to a ban on tobacco use, a systematically integrated tobacco cessation program that includes motivation and counseling. These are core elements within the ENSH Code and standards which support the implementation of Tobacco Free Healthcare Services (http://www.ensh.eu).

Since its creation in 1999, the ENSH has developed a practice based and continuously evaluated focus on establishing comprehensive tobacco free policies in hospitals and healthcare facilities. The concept is based on a 10 point European Code which includes tobacco free campuses. Through a consensus driven procedure, ENSH experts have developed various implementation tools including an implementation guide for tobacco free standards in health services, a self-audit questionnaire, and an accreditation process (www.ensh.eu)

The ENSH is taking valuable steps towards encouraging the implementation of tobacco free campuses. In May 2009, the German 'Reha -Zentrum Todtmoos' Hospital was honored with the first Gold Level Award for having implementing all the ENSH standards, on the basis of a tobacco- free outdoors. Five other hospitals from Ireland, Spain, and Belgium were also nominated for the Award.(12) Encouragement of hospital managers to adopt these policies is a necessity. However, strong support from national governments, quality agencies, and national and international networks is required. As organizations that foster tobacco control policies, we need to find new incentives to stimulate and consolidate this shift, such as rewards, training, reimbursements and appreciation. In addition, implementation of tobacco-free hospital campuses needs a careful monitoring and evaluation of its impact in terms of treatment quality, training standards, acceptability, observance, and tobacco consumption reduction among hospital workers and users.

Fortunately, we have two similar overseas strategies that are working on the same direction. The comparison between these two initiatives could enrich the knowledge of the effectiveness and efficacy of policies in different health systems. The opportunity to exchange, collaborate and learn from this new policy change process in tobacco control is in our hands.

Cristina Martinez, Esteve Fernandez, Begona Alonso, David Chalom, Jacques Dumont, Miriam Gunning, Florian Mihaltan, Ann O'Riordan, and Christa Rustler.

ENSH-Global Network for Tobacco-free Healthcare Services

Corresponding author: E. Fernandez (e-mail: efernandez@iconcologia.net)

References 1. Williams SC, Hafner JM, Morton DJ, Holm AL, Milberger SM, Koss RG, Loeb JM. The adoption of smoke-free hospital campuses in the united states. Tob Control. 2009; 18:451-458. 2. McKee M, Gilmore A, Novotny TE. Smoke-free hospitals and the role of smoking cessation services. BMJ. 2003;326:941-2. 3. West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: An update. health education authority. Thorax. 2000;55:987- 99. 4. Longo DR, Brownson RC, Johnson JC, Hewett JE, Kruse RL, Novotny TE, et al. Hospital smoking bans and employee smoking behavior: Results of a national survey. JAMA. 1996;275:1252-7. 5. Longo DR, Johnson JC, Kruse RL, Brownson RC, Hewett JE. A prospective investigation of the impact of smoking bans on tobacco cessation and relapse. Tob Control. 200;10:267-72. 6. Rigotti NA, Arnsten JH, McKool KM, Wood-Reid KM, Pasternak RC, Singer DE. Smoking by patients in a smoke-free hospital: Prevalence, predictors, and implications. Prev Med. 2000;31(2 Pt 1):159-66. 7. Martinez C, Garcia M, Mendez E, Peris M, Fernandez E. Barriers and challenges for tobacco control in a smoke-free hospital. Cancer Nurs. 2008;3188-94. 8. Ratschen E, Britton J, McNeill A. Smoke-free hospitals - the english experience: Results from a survey, interviews, and site visits. BMC Health Serv Res. 2008;8:41. 9. Parks T, Wilson CV, Turner K, Chin JW. Failure of hospital employees to comply with smoke-free policy is associated with nicotine dependence and motives for smoking: A descriptive cross-sectional study at a teaching hospital in the United Kingdom. BMC Public Health. 2009;9:238. 10. Freund M, Campbell E, Paul C, McElduff P, Walsh RA, Sakrouge R, et al. Smoking care provision in hospitals: A review of prevalence. Nicotine Tob Res. 2008;10:757-74. 11. Rigotti NA, Quinn VP, Stevens VJ, Solberg LI, Hollis JF, Rosenthal AC, et al. Tobacco-control policies in 11 leading managed care organizations: Progress and challenges. Eff Clin Pract. 2002;5:130-6. 12. European Network for Smoke-free Hospitals. Award gold level 2009. Available from: http://www.ensh.eu/ensh/racine/default.asp?id=985#=5258#. (accessed Nov 13, 2009)

Conflict of Interest:

None declared

We read the recent paper on the effects of the school-based smoking prevention program "Mission TNT.06" in Canada with interest [1]. The authors address an often neglected but nonetheless very important subject: The question of potential negative side effects of interventions that try to denormalize smoking in the classroom. To our knowledge, it is the first study outside Europe evaluating a school-based smoking prevention program based on contract management in which classes decide to be smokefree for a given period of time and successful classes are awarded with prizes in a lottery.

Kairouz and colleagues come to a very strong summarizing conclusion: "Mission TNT.06 may encourage young smokers to misreport their smoking status and to marginalize classmates who smoke." After reading the complete paper we were, however, not convinced that this strong conclusion really represents an appropriate interpretation of the data.

As we followed our Canadian colleagues they measured marginalization of classmates who smoke with the following two items: "If you knew that someone in your class smoked cigarettes, would you think that ... (i) people should not hang out with him/her; and (ii) you should not be friends with him/her".

First, this does not feel to us like a real measure of marginalization, but a measure of general attitudes towards smoking peers. Showing that endorsement to these statements decreases less over time in the intervention than in the control group seems to be chiefly an indicator that the intervention has changed students' attitudes towards smoking people. Is this in any way a surprising (or unwanted) result? If you - as a young student - learn that smoking is a dangerous and risky behavior, isn't it very likely that this will change the way you see and judge smoking people? Would we really assume (or want) the students to answer the two questions independent of intervention status? Anyway, no other attitudes towards smoking were assessed, so it is impossible to further validate the assumption of the authors.

Second, even if you interpret the statements literally, for really judging potential adverse effects of an intervention we need observations of adverse behaviors (or at least proxys of these like behavioral self- reports). A recently conducted study that assessed negative behaviors in class (i.e., bullying) did not find iatrogenic effects of a contract management intervention. In fact, if bullying was actually reported in classes: It was more often the smokers that bullied [2]!

Kairouz et al. [1] report another observation. They found a considerable number of students who reported lifetime smoking at baseline - at least just a puff - but indicated that they have never smoked at follow-up. The percentage of such reporting was higher in the intervention compared to the control group. What could be possible explanations for this difference? Kairouz et al. offer the interpretation that this difference is due to a higher tendency for cheating and concealing smoking in the intervention classes since these pupils' wish to increase the chance of their class to win a prize. At first sight, this seems to be a very plausible explanation: There is a motive for cheating. However, looking at it in more detail, this interpretation loses ground: Why should the kids cheat six to 11 months after the end of the competition - when all prizes have been awarded months ago? Furthermore, lifetime smoking (before the competition) is not a relevant variable for staying in the competition or for winning prizes.

Overall we think that Kairouz and colleagues raised important questions that could stimulate an ethical debate on how far tobacco control advocates should go in promoting social denormalization of smoking. However, we have considerable concerns about their way of data interpretation. As a side note: We guess, at least from the European perspective, that the overwhelming majority of parents would be very happy if their kids would say that they aren't hanging around with classmates who smoke.

References

[1] Kairouz S, O'Loughlin J, Lague J. Adverse effects of a social contract smoking prevention program for children in Quebec, Canada. Tob Control 2009; 18: 474-478.

[2] Hanewinkel R, Isensee B, Maruska K, Sargent JD, Morgenstern M. Denormalising smoking in the classroom: does it cause bullying? J Epidemiol Community Health 2009; doi:10.1136/jech.2009.089185.

Conflict of Interest:

The authors are involved in the European Smokefree Class Competition since many years.

Innovative opportunities and strategies should be considered for reducing the harm of tobacco in the 21st century. Since the mid 20th century, governmental approaches have evolved from a laissez-faire attitude to active NIH funding for tobacco research, aggressive promotion of nonsmoking environments and, now, congressionally mandated regulation of the tobacco industry. The tobacco industry itself has also evolved from the mid 20th century position denying tobacco-induced harm, to the current disclosure of health risks and a remarkable amount of support from some segments of the industry for both smoking prevention and cessation efforts.

Responding to these developments, over the last several years a growing community of scientists has been working with progressive elements within the tobacco industry to encourage efforts at cessation and harm reduction. With appropriate safeguards, the use of tobacco industry funding, like the use of tobacco taxes and tobacco settlement proceeds, can substantially add to the magnitude of research and outreach efforts intended to reduce tobacco-induced death and disease. However, in accepting tobacco industry funding, some of us have been exposed to unwarranted attacks from colleagues in tobacco control, who refuse to accept the possibility of appropriate relationships between these progressive elements and members of the scientific community.

While working toward a world without cigarettes, these colleagues appear to be more comfortable if tobacco companies put all of their resources into selling cigarettes, and do nothing positive to counteract the adverse health effects of smoking through the funding of smoking cessation research. In this black-or-white, good-or-evil, worldview, staunch anti-tobacco company campaigners could see themselves as champions of goodness. However, the real world, which allows tobacco companies to support valid research efforts, offers more true hope of saving countless lives lost to diseases caused by smoking.

A recent editorial by Malone and Smith (1) presents an attack on a study that we conducted at Duke University. This study aimed to evaluate the efficacy of the Philip Morris USA QuitAssist website, and was part of an overall project that also included a randomized controlled trial of the efficacy of the QuitAssist website relative to other smoking cessation support interventions. The straightforward question being asked by this survey of researchers in the tobacco control field was "Do you think the approach of the QuitAssist website is useful for helping people quit smoking or not?” A copy of the invitation to potential participants and the study protocol are available on our website (http://www.cnscr.org). The reader is particularly encouraged to read the invitation. Our institutional review board approved this research study, and required the normal confidentiality stipulation, as in all human subjects research, that the participants’ anonymity should be assured (cf. Declaration of Helsinki, http://www.wma.net/e/policy/pdf/17c.pdf). If we had denied our participants confidentiality, and they were subsequently subjected to abusive attacks in editorials such as the recent one by Malone and Smith, we would have failed to protect the rights of these volunteers. However, Malone and Smith take this requirement of confidentiality and twist it, to label it as “unethical.” Further, Malone and Smith distort the disclosure of and transparency about the funding for this project, coining the term “deceptive transparency,” which is obviously a contradiction in terms.

We believe that many tobacco control researchers should welcome the opportunity to provide their candid comments concerning the Philip Morris USA QuitAssist website. These comments could run the full gamut from positive to negative or disapproving. Indeed, any reasoned answers will be useful in determining how best to proceed to help smokers quit. Our field should take care not to stifle free scientific inquiry as was done for many years by elements of the tobacco industry.

Malone and Smith assert that participation in this effort will cause tobacco control advocates to “wonder about one another,” and question each other’s loyalty, thus “driving a wedge into the tobacco control community.” However, by maligning the integrity of ethical researchers, such as by depicting legitimate participant recruitment efforts as “phishing,” they themselves drive a wedge into the broader 21st century tobacco control community. Although the historical origins of their suspicions of tobacco industry sponsored research are quite understandable, Malone and Smith should also consider the history of our research program, and the progress it has made in tobacco addiction treatment.

Indeed, our center has a long and accomplished track record of progress in this area. In addition to having contributed significantly to the inception of the nicotine patch (2), which has been an important tool to aid smoking cessation, our research (3) has also contributed to the development of Chantix, another potent smoking cessation treatment (4).

Our center is currently supported from a variety of sources, including a grant from Philip Morris USA unequivocally dedicated to advancing smoking cessation treatment. The provisions of the funding agreement with Philip Morris USA (as with funding for the QuitAssist evaluation) explicitly deny the company any control over the design or execution of the research, and allow us complete publication freedom (see http://www.cnscr.org). Recent accomplishments emerging from our research program, aided by this support, include the following significant strides toward improving smoking cessation treatment effectiveness:

1) Developing a new dosing regimen for NRT that doubles smoking abstinence rates (5);

2) Inventing a novel form of NRT that promises to be more effective than current forms (6), and proceeding through the FDA review process;

3) Conducting preclinical studies to screen and identify promising new smoking cessation treatments (7);

4) Identifying genetic variants that predict smoking cessation outcome (8), which may ultimately be used to tailor treatment, providing the most effective treatment approach for a given smoker;

5) Initiating studies of adaptive treatment strategies (9), which modify treatment if early indicators of therapeutic response indicate an initial treatment is not likely to succeed.

In conclusion, we believe that if Malone and Smith had done their homework more carefully, they might have learned about the actual results of our research efforts, their implications for tobacco cessation and harm reduction, and the careful ways in which we have tried to integrate support from progressive aspects of tobacco companies, including assisting cessation and harm reduction efforts of the companies themselves. We, and like-minded 21st century thinkers, strive to continue to promote public health, utilizing government as well as industry support to accomplish this mission.

Sincerely,

Jed E. Rose, Ph.D. Director, Center for Nicotine and Smoking Cessation Research, Duke University Medical Center

Funding: The study described was funded by a grant from Philip Morris USA, with explicit provisions allowing free publication of any results, favorable or unfavorable.

Competing interest: The author is PI on grants funded by Philip Morris USA, with provisions protecting independent design, conduct and publication of studies. He is also named as an inventor on patent applications dealing with agonist-antagonist treatments, novel nicotine delivery systems and genetic predictors of smoking cessation treatment outcome.

References

1. Malone RE, Smith EA. Contact me soon!! Confidential, risk-free opportunity! Tob Control 2009; 18:249.

2. Rose JE, Herskovic JE, Trilling Y and Jarvik ME. Transdermal nicotine reduces cigarette craving and nicotine preference. Clin Pharm Ther 1985; 38:450-456.

3. Rose JE, Levin ED. Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence. Pharmacol Biochem Behav 1991; 41: 219-226.

4. Coe JW, et al. Varenicline: An alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 2005; 48: 3474–3477.

5. Rose JE, Herskovic JE, Behm FM,Westman EC. Pre-cessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment. Nicotine & Tobacco Research 2009; 11:1067-1075.

6. Rose JE, Rose SD, Turner JE, Murugesan T. Device and method for delivery of a medicament. International Patent application No. PCT/US2008/058122.

7. Levin ED, Slade S, Johnson M, Petro A, Horton K, Williams P, Rezvani AH, Rose JE. Ketanserin, a 5-HT2 antagonist, decreases nicotine self-administration in rats. Eur J Pharmacol 2008; doi: 10.1016/j.ejphar.2008.10.016.

8. Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE. Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs. BMC Genetics 2007; 8:10-20.

9. Murphy SA, Collins LM, and Rush AJ. Customizing Treatment to the Patient: Adaptive Treatment Strategies. Drug Alcohol Depend 2007; 88(Suppl 2): S1–S3.

The authors’ response to my comments fails to disqualify my criticism. A large part of their response consists of a misinterpretation of some of my points. This appears to be due to confusion about terminology. Unfortunately, terminology practices are not as perfectly unequivocal as would be desirable. If the authors had been well enough familiar with the international scientific literature in this field, they should have noticed that the phrase “quit rate” is used with different meaning in different settings. An instructive note on the terminology situation is found in the pertinent WHO guidelines [1]. After defining “prevalence of cessation”, the guidelines say (I quote from page 80): <<Other terms, such as the “quit rate”, the “quit index”, or the “quit ratio”, have also been used to describe this or a similar measure.>>

I had questioned the validity of the authors’ indication of rate of quitting during one year in their study, since the possibility of remaining relapses was not considered. This can have inflated the registered rate of quitting, and the likelihood of such a risk appears to be strengthened by my observation that in the same period the nationwide decrease in smoking prevalence (mainly due to cessation of smoking) was quite a bit lower.

I had also questioned an entirely different part of the original article, the comparison between cessation practices in the US and in Sweden. While the authors had no real basis at all for such a comparison, I just presented easily understandable evidence in terms of figures for “prevalence of cessation” in these two countries. When I thereby used the denominator phrase “quit rate” (cf above), I started with a perfectly clear, explicit definition of the meaning that I attached to that phrase (ratio between ex-smokers and ever-smokers), so there is no justification for the kind of misinterpretation brought forward in the authors’ response.

In their response the authors say: “The way that Ramstrom placed all his confidence in a single factor explanation without making an effort to rule out other strong alternative explanations strikes us as rather unscientific.” But there is no ground whatsoever for this statement, neither in my comments, nor in any other publication of mine. I have always been very careful to point out that the effect snus use in Sweden is just one of several factors contributing to the Swedish success in reducing smoking and smoking-related diseases. The authors’ procedure to groundlessly attribute a blameworthy opinion/behaviour to a counterpart in a scientific discussion, that is indeed ‘unscientific’.

As I said in the introduction to my original comments, the Zhu et al article did raise a number of interesting questions. And, beside the weaknesses that I have looked at, it did contain good points as well. But, I still find the final conclusion too pessimistic as far as the possibly positive role of low-toxicity smokeless tobacco is concerned.

Reference:

World Health Organization. Guidelines for controlling and monitoring the tobacco epidemic. World Health Organization. Geneva, 1998. ISBN 92 4 154508 9.