Smoker and ex-smoker reactions to cigarettes claiming reduced risk.

CONTEXT: The tobacco industry is introducing modified tobacco products claiming to reduce the risk of smoking (potential reduced exposure products, PREPs). If PREPs are perceived as safe, they may deter smokers from quitting and encourage re-initiation by smokers who have quit. OBJECTIVE: To assess smokers' and ex-smokers' perceptions of PREPs and the impact of PREP claims on interest in quitting (among smokers) or in resuming smoking (ex-smokers). DESIGN: A random-digit-dialled survey of US smokers and ex-smokers. We used Eclipse, a modified PREP cigarette, as an exemplar PREP. During the survey, the interviewer read risk reduction claims made for Eclipse by its manufacturer, assessing smokers' interest in quitting before and after the exposure. PARTICIPANTS: 1000 current cigarette smokers and 499 ex-smokers (300 quit within the last two years), over 18 years old. MAIN OUTCOME MEASURES: Perception of risk reduction from Eclipse; interest in using Eclipse; smokers' interest in quitting was assessed using a stage of change approach (pre- and post-exposure to claims). RESULTS: 91% of smokers thought Eclipse was safer than regular cigarettes. 24% believed Eclipse was completely safe. 57.4% of smokers were interested in using Eclipse; interest was greatest among smokers who were contemplating quitting. Exposure to Eclipse's claims was followed by reduced interest in quitting. Among all ex-smokers, interest in Eclipse was 6.2%, but interest was 15.2% among young adults (18-25 years) who had stopped smoking within two years. CONCLUSIONS: There is substantial risk that smokers will overinterpret reduced risk claims made for modified tobacco products. PREPs appeal to smokers who are contemplating quitting and exposure to reduced risk product claims appears to reduce smokers' readiness to quit. PREPs also appealed to young adults who had recently stopped smoking. Thus, reduced risk tobacco product claims can undermine adult cessation and youth prevention, possibly resulting in increased harm even if the products are less toxic.

Persistent use of nicotine replacement therapy: an analysis of actual purchase patterns in a population based sample.

BACKGROUND: In 1996, the US Food and Drug Administration (FDA) approved switching nicotine gum and patch from prescription to over-the-counter (OTC) status. Some expressed concerns that broader availability and lack of physician control might increase persistent use of nicotine replacement therapy (NRT)-that is, use beyond the period specified by the FDA approved label. OBJECTIVE: To estimate the incidence of persistent use of OTC nicotine gum and patch for periods of > 3 months, > or = 6 months, > or = 12 months, and > or 24 months. DESIGN: Analysis of NRT purchase patterns in data from a population based panel of US households that electronically scanned all household purchases between January 1997 and March 2000. SUBJECTS: In a national panel of 40,000 US households, 2690 recorded NRT purchases. RESULTS: Among 805 households that purchased nicotine gum, 2.3% of new purchase incidents led to continuous monthly purchase of gum for > or = 6 months. For nicotine patches (2050 households) the percentage was 0.9%. For both gum and patch, the incidence of persistent purchase dropped below 0.4% by 24 months. Allowing one month gaps within a "continuous" purchase run resulted in increased estimates (for gum: 6.7% for > or = 6 months and 1.0% for > or = 24 months; for patch: 1.7% for > or = 6 months and 0.05% for > or = 24 months). CONCLUSION: Persistent use of nicotine gum and patch is very rare and has not increased with the transition to OTC use, despite removal of physician oversight.

Smokers' beliefs about "Light" and "Ultra Light" cigarettes.

OBJECTIVE: To assess beliefs about the tar and nicotine delivery characteristics and health benefits of Light and Ultra Light cigarettes among cigarette smokers. DESIGN: Random digit dialed telephone survey conducted in September 1999. SUBJECTS: Daily smokers (n = 2120) of Regular (46%), Light (39%), and Ultra Light (15%) cigarettes in the USA. The sample was weighted to match the US smoker population on age, sex, and ethnicity. MAIN OUTCOME MEASURES: Beliefs about Light and Ultra Light cigarettes were summarised on three dimensions: Safety (reduced health risk), Delivery (lowered tar and nicotine delivery), and Sensation (less harsh). RESULTS: Most smokers believed Lights and Ultra Lights were less harsh and delivered less tar and nicotine. On average, smokers believed that Lights afforded a 25% reduction in risk, and Ultra Lights a 33% reduction in risk. Light and Ultra Light cigarette smokers evaluated the risks of their own cigarette types more favourably. Light smokers had greater interest in quitting than Ultra Light smokers. Quitting intention was modestly related to beliefs about these cigarettes. Believing that Lights and Ultra Lights delivered less tar and nicotine and that they were less harsh each independently contributed to the belief that these cigarettes were safer. CONCLUSIONS: Many Light and Ultra Light smokers believe that smoking these cigarettes impart a substantial health benefit, due in part to their experience that these cigarettes are less harsh and the belief that these cigarettes deliver less tar.

Effect of health messages about "Light" and "Ultra Light" cigarettes on beliefs and quitting intent.

OBJECTIVE: To test the impact of three health messages focusing on vent holes, sensory effects of Light and Ultra Light cigarettes, or health consequences of smoking, respectively, on beliefs and quitting intentions. DESIGN: In the course of a random digit dialed telephone survey, subjects were randomised to hear one of three messages. To test the effects of the messages, beliefs and quitting intentions were assessed both pre- and post-message. PARTICIPANTS: Daily smokers (n = 2120) of Regular (46%), Light (39%), and Ultra Light (15%) cigarettes in the USA. The sample was weighted to match the US smoker population on age, sex, and ethnicity. MAIN OUTCOME MEASURES: Beliefs were summarised on three dimensions: Safety (reduced health risk), Delivery (lower tar and nicotine delivery), and Sensation (less harsh). Quitting interest was captured by the "quit index", an aggregate measure of quitting interest and intent. RESULTS: The message focusing on smokers' sensory perceptions of Light and Ultra Light cigarettes resulted in the most positive change in beliefs about safety, delivery, and intent to quit, and was particularly effective among those who believed that these cigarettes were less harsh. The effect was most pronounced among young adults, and among smokers of Light and Ultra Light brands who most endorsed their sensory benefits. CONCLUSIONS: Addressing smokers' sensory experience that Light and Ultra Light cigarettes feel less harsh may be a promising strategy for changing their misconceptions about these cigarettes and enhancing their interest in quitting. Media counter-advertising on Lights and Ultra Lights, focusing on sensory aspects of these cigarettes, may be an important part of tobacco control efforts.

Test of "Light" cigarette counter-advertising using a standard test of advertising effectiveness.

OBJECTIVE: To evaluate systematically the effectiveness of six advertising strategies (two message strategies presented in three different contexts) designed to promote smoking cessation by addressing smokers' misperceptions about Light cigarettes. DESIGN: Smokers viewed one of six, 30 second test television concept advertisements, which varied by message (one emphasising how the sensory effects of Lights can be deceptive, the other describing the effects of vent blocking) and by ad context (non-commercial public service announcement (PSA), promotion of unbranded nicotine replacement therapy (NRT), or promotion of branded NRT). The effectiveness of each advertisement was determined using a validated advertising testing system in which ads were viewed in the context of reviewing a pilot television programme. Response to ads is assessed through shifts in subject choices of products offered as prizes before and after viewing the test advertisements. Included among the possible prizes were cigarettes and various pharmacotherapies for smoking cessation. SUBJECTS: Daily smokers (n = 1890) of Regular (34%), Light (47%), and Ultra Light (19%) cigarettes recruited from eight US cities. MAIN OUTCOMES MEASURES: The primary outcome of interest was the shift away from cigarettes as the selected prize following exposure to the test advertisements. Secondary outcomes of interest included movement away from Light cigarettes and movement towards assisted quitting products. RESULTS: Smokers who saw the advertisement emphasising the sensory characteristics of Light cigarettes were more likely than subjects who saw the advertisement emphasising the effect of vent blocking to move away from cigarettes (OR = 1.97, 95% confidence interval CI 1.25 to 3.09; chi(2)(1) = 8.69, p = 0.003). Similarly, subjects who saw the advertisement framed as a PSA, rather than as a promotion for either a branded or unbranded NRT product, were also somewhat more likely to move away from cigarettes (OR = 1.51, 95% CI 0.94 to 2.40; chi(2)(1) = 2.97, p = 0.085). The effect was observed regardless of sex, age, or type of cigarette smoked. CONCLUSIONS: Addressing smokers' sensory perceptions of Light cigarettes and presenting this information in an impartial way is likely to be an effective communication strategy for counter-marketing Light cigarettes.

The ethics of Pharmaceutical benefit management.

Efforts to limit pharmacy costs raise both ethical and economic considerations. Six values should inform pharmacy benefit management: (1) accepting resource constraints; (2) helping the sick; (3) protecting the worst off; (4) respecting autonomy; (5) sustaining trust; and (6) promoting inclusive decision making. Direct controls, such as formularies, step therapy, and prior authorization, can focus limited resources on the sick and worst off. However, direct controls limit autonomy and are administratively burdensome. Indirect controls, such as physician capitation, tiered copayments, and drug benefit caps, align physicians' and patients' interests with resource constraints, respect autonomy, and are administratively efficient. Unfortunately, they deter use based on cost, not medical need; they do not focus cuts on unnecessary or marginal drug use or focus resources on the sick. Budget caps are the least defensible, while tiered copays and physician capitation can be justified if implemented with safeguards. Formularies and step therapy are ethically justifiable if they can be efficiently instituted.

N-acetylgalactosamine on the putative insect receptor aminopeptidase N is recognised by a site on the domain III lectin-like fold of a Bacillus thuringiensis insecticidal toxin.

Binding of the insecticidal Bacillus thuringiensis Cry1Ac toxin to the putative receptor aminopeptidase N is specifically inhibited by N-acetylgalactosamine (GalNAc), suggesting that this toxin recognises GalNAc on the receptor. A possible structural basis for involvement of domain III of the toxin in carbohydrate-mediated receptor recognition was noted in the similarity between the domain III fold of the related toxin Cry3A and a carbohydrate-binding domain in the 1,4-beta-glucanase from Cellulomonas fimi. This possibility was investigated by making selected mutations in domain III of the Cry1Ac delta-endotoxin. Mutagenesis of residues Asn506, Gln509 or Tyr513 resulted in toxins with reduced binding and a slower rate of pore formation in Manduca sexta midgut membrane vesicles compared to the wild-type Cry1Ac. These mutants also showed reduced binding to the 120 kDa Cry1Ac putative receptor aminopeptidase N. Unlike the wild-type toxin, binding of the triple mutant N506D,Q509E,Y513A (Tmut) to M. sexta midgut membrane vesicles could not be inhibited by GalNAc. These data indicate that GalNAc binding is located on domain III of Cry1Ac and therefore support a lectin-like role for this domain. A preliminary analysis of the Cry1Ac crystal structure locates Asn506, Gln509 and Tyr513 in a region on and adjacent to beta-16 in domain III, which has a unique conformation compared to the other known Cry structures. These residues are in a favourable position to interact with either soluble or protein-bound carbohydrate.

Public health benefit of over-the-counter nicotine medications.

OBJECTIVE: To estimate the impact of allowing non-prescription sales of nicotine medications in the United States on increasing the numbers of smokers quitting. DESIGN: Sales and marketing data were used to compare the use of nicotine medications before and after non-prescription sales, and to estimate the impact of non-prescription sales on quit rates. SETTING: United States. MAIN OUTCOME MEASURES: Number of quit attempts using nicotine replacement therapy (NRT) products, number of smokers who quit smoking with over-the-counter (OTC) NRT or with NRT still sold by prescription, and incremental quits attributable to OTC NRT. RESULTS: Since the US Food and Drug Administration approved nicotine medications for OTC sale in 1996, use of the medications has increased by 152% compared with prior prescription use. With increased use of an efficacious treatment, OTC nicotine medications are estimated to yield from 114,000-304,000 new former smokers annually in the United States. CONCLUSIONS: The broader availability and promotion of effective treatments for tobacco dependence, specifically nicotine gum and patch, increase the number of smokers availing themselves of the medications. This increased use is estimated to contribute substantially to the number of former smokers in the United States.

Projections of the dorsal lateral geniculate and lateral posterior nuclei to visual cortex in the rabbit.

The origin and terminations of thalamic inputs to the striate cortex and the occipital cortex of the rabbit were studied using both anterograde autoradiographic techniques and retrograde transport of horseradish peroxidase (HRP). After injections of [3H]-leucine into the dorsal lateral geniculate nucleus (DLGN) the transport of radiolabeled material was demonstrated in separate loci in both the striate and the occipital cortex. In both these cortical areas, the principal site of geniculocortical termination was in lamina IV with some diminished input spreading into laminae II-III and a light termination in layer I overlying the lamina IV termination. Layer VI of striate cortex received a substantial projection from DLGN while infragranular laminae of occipital cortex received a similar although lighter and more diffuse projection. The lateral posterior nucleus (LPN) was similarly demonstrated to project to both striate and occipital cortices, the projection terminating principally in lamina IV of occipital cortex, lamina V of striate cortex, and layer I over a large, continuous area of the posterior pole of the cortex. Moreover, a projection from LPN to the retrosplenial cortex medial to the striate area was consistently seen. The autoradiographic demonstration of a projection from DLGN and LPN to both striate cortex and occipital cortex was corroborated by the retrograde studies. Following the injection of HRP into either the striate or occipital cortex, columns of retrogradely filled somata were identified in both the DLGN and LPN. The location of the column of labeled neurons within each nucleus varied predictably with the location of the injection in either the striate or the occipital cortex.