Mediators of a successful web-based smokeless tobacco cessation program

Aim To examine self‐efficacy and program exposure as possible mediators observed treatment effects for a web‐based tobacco cessation intervention. Design The ChewFree trial used a two‐arm design to compare tobacco abstinence at both the 3‐ and 6‐month follow‐up for participants randomized to either an enhanced intervention condition or a basic information‐only control condition. Setting Internet in US and Canada. Participants Our secondary analyses focused upon 402 participants who visited the web‐based program at least once, whose baseline self‐efficacy rating showed room for improvement, who reported that they were still using tobacco at the 6‐week assessment, and for whom both 3‐ and 6‐month follow‐up data were available. Intervention An enhanced web‐based behavioral smokeless tobacco cessation intervention delivered program content using text, interactive activities, testimonial videos and an ask‐an‐expert forum and a peer forum. The basic control condition delivered tobacco cessation content using static text only. Measurements Change in self‐efficacy and program exposure from baseline to 6 weeks were tested as simple and multiple mediators on the effect of treatment condition on point‐prevalence tobacco abstinence measured at 3‐ and 6‐month follow‐up. Findings While both participant self‐efficacy and program exposure satisfied the requirements for simple mediation, only self‐efficacy emerged as a mediator when we used the more robust test of multiple mediation. Conclusions Results confirm the importance of self‐efficacy change as a probable underlying mechanism in a successful web‐based behavioral intervention. While program exposure was found to be a simple mediator of tobacco abstinence, it failed to emerge as a mediator when tested with self‐efficacy change in a multiple mediator test suggesting that self‐efficacy and program exposure share a complex, possibly reciprocal relationship with the tobacco abstinence outcome. Our results underscore the utility of searching for mediators in research on web‐based interventions.     

The effectiveness of personalized smoking cessation strategies for callers to a Quitline service

Aim To assess the effectiveness of a program of computer‐generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation. Design Randomized controlled trial comparing: (1) untailored self‐help materials; (2) computer‐generated tailored advice only, and (3) computer‐generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months. Setting Victoria, Australia. Participants A total of 1578 smokers who called the Quitline service and agreed to participate. Measurements Smoking status at follow‐up; duration of cessation, if quit; use of nicotine replacement therapy; and extent of participation in the callback service. Findings At the 3‐month follow‐up, significantly more (χ²(2) = 16.9; P < 0.001) participants in the computer‐generated tailored advice plus telephone counselling condition were not smoking (21%) than in either the computer‐generated advice only (12%) or the control condition (12%). Proportions reporting not smoking at the 12‐month follow‐up were 26%, 23% and 22%, respectively (NS) for point prevalence, and for 9 months sustained abstinence; 8.2, 6.0, and 5.0 (NS). In the telephone counselling group, those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months (10.2 compared with 4.0, P < 0.05). Logistic regression on 3‐month data showed significant independent effects on cessation of telephone counselling and use of NRT, but not of computer‐generated tailored advice. Conclusion Computer‐generated tailored advice did not enhance telephone counselling, nor have any independent effect on cessation. This may be due to poor timing of the computer‐generated tailored advice and poor integration of the two modes of advice.     

Predictors and Patterns of Cigarette and Smokeless Tobacco Use Among Adolescents in 32 Countries, 2007–2011

PurposeThis study compared data from 32 countries to assess predictors and patterns of cigarette and smokeless tobacco (SLT) use among students aged 13–15 years old.MethodsData from the 2007–2008 Global Youth Tobacco Surveys were analyzed for students aged 13–15 years in 31 countries located in all six World Health Organization regions. In addition, the 2011 National Youth Tobacco Survey was analyzed for U.S. students aged 13–15 years. Country-specific prevalence of current smoking, current SLT use, and concurrent use patterns were assessed.ResultsThe national prevalence of current cigarette smoking among students aged 13–15 years ranged from 1.8% (Rwanda) to 32.9% (Latvia), whereas current SLT use ranged from 1.1% (Montenegro) to 14.4% (Lesotho). In the U.S. and most European countries surveyed, current smoking prevalence was significantly higher than SLT prevalence, in contrast to patterns observed in low- and middle-income countries. Also, in most of the surveyed countries outside of Europe and the United States, SLT use among girls was as common as their use of cigarettes, and not significantly different from use by boys. When compared with U.S. adolescents, the odds of SLT use were highest among African adolescents (adjusted odds ratio = 3.98; 95% CI: 2.19–7.24) followed by those in the Southeast Asian region (adjusted odds ratio = 2.76; 95% CI: 1.38–5.53).ConclusionsRegion-specific patterns of tobacco use were noticed. Furthermore, it is alarming that in several low- and middle-income countries, the prevalence of SLT use among females did not differ from that among males, suggesting the possibility of a future shared burden of disease between both males and females.     

成都市某区青年警察吸烟现状及健康教育调查

目的了解成都市某区青年警察的吸烟现状及健康教育方式,为决策部门制定相关控烟政策提供依据。方法2013-03-16/05-07,调查对象为成都市某区178位青年警察,调查内容主要包括调查对象的人口学特征、对吸烟危害的知晓情况、家庭、单位控烟状况等。运用χ2检验和秩和检验等方法进行统计分析。所有数据采用SPSS 13.0软件处理。结果吸烟人数113人,吸烟率为63.48%。吸烟和不吸烟人群在年龄（χ2=3.50,P〉0.05）、文化程度（χ2=4.74,P〉0.05）、婚姻状况（χ2=3.60,P〉0.05）等方面差异均无统计学意义。吸烟与不吸烟人群相比,关于用过滤嘴抽烟能否降低危害（z=-2.39,P〉0.05）、被动吸烟对健康有无危害（z=-8.68,P〈0.01）、世界卫生组织提倡的健康生活方式（z=-5.75,P〈0.01）回答正确率差异有统计学意义。吸烟和不吸烟人群家庭控烟（χ2=0.79,P〉0.05）、单位控烟（χ2=0.36,P〉0.05）差异均无统计学意义。结论成都市某区青年警察对吸烟危害的认识不足,建议从宏观和微观两个层面,对其开展烟草健康危害教育。     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Natural history-driven,plant-mediated RNAi-based study reveals CYP6B46’s role in a nicotine-mediated antipredator herbivore defense

Manduca sexta (Ms) larvae are known to efficiently excrete ingested nicotine when feeding on their nicotine-producing native hostplant, Nicotiana attenuata. Here we describe how ingested nicotine is co-opted for larval defense by a unique mechanism. Plant-mediated RNAi was used to silence a midgut-expressed, nicotine-induced cytochrome P450 6B46 (CYP6B46) in larvae consuming transgenic N. attenuata plants producing MsCYP6B46 dsRNA. These and transgenic nicotine-deficient plants were planted into native habitats to study the phenotypes of larvae feeding on these plants and the behavior of their predators. The attack-behavior of a native wolf spider (Camptocosa parallela), a major nocturnal predator, provided the key to understanding MsCYP6B46’s function: spiders clearly preferred CYP6B46-silenced larvae, just as they had preferred larvae fed nicotine-deficient plants. MsCYP6B46 redirects a small amount (0.65%) of ingested nicotine from the midgut into hemolymph, from which nicotine is exhaled through the spiracles as an antispider signal. CYP6B46-silenced larvae were more susceptible to spider-attack because they exhaled less nicotine because of lower hemolymph nicotine concentrations. CYP6B46-silenced larvae were impaired in distributing ingested nicotine from midgut to hemolymph, but not in the clearing of hemolymph nicotine or in the exhalation of nicotine from hemolymph. MsCYP6B46 could be a component of a previously hypothesized pump that converts nicotine to a short-lived, transportable, metabolite. Other predators, big-eyed bugs, and antlion larvae were insensitive to this defense. Thus, chemical defenses, too toxic to sequester, can be repurposed for defensive functions through respiration as a form of defensive halitosis, and predators can assist the functional elucidation of herbivore genes.Plants produce a pharmacopeia of potent chemical defenses that prevent the attack of unadapted herbivores and thwart the growth of adapted ones. Frequently, lepidopteran herbivores co-opt these diet-acquired toxins for their own defensive purposes. The eastern tent caterpillar (Malacosoma americanum) regurgitates hydrogen cyanide and benzaldehyde ingested from their cyanogenic hostplants when attacked by ants (1). The Atala butterfly (Eumaeus atala) acquires a toxic azoxyglycoside from its cycad hosts and becomes unpalatable to bird and ant predators (2). Similarly, rattlebox moths (Utetheisa ornatrix) co-opt pyrrolizidine alkaloids that their larvae sequester while feeding on rattlebox legume hostplants (Crotalaria spp.) to deter predatory spiders (3). Prey frequently advertise their toxic status with warning colorations, odors, and behaviors, and predators readily learn these aposematic signals to avoid consuming toxic prey (4). The molecular mechanisms of how herbivores co-opt plant defenses for their own defense remain largely unexplored.The pyridine alkaloid nicotine is a defense metabolite of several Nicotiana spp. Nicotine is extremely effective against herbivores because of its ability to poison the essential neuromuscular junction common to all animals that use muscles to move: the acetylcholine receptor (5, 6). Nicotiana spp. hostplants respond to the herbivore attack with large increases in nicotine accumulation (7). However, the tobacco hornworm (Manduca sexta, Ms), a specialist lepidopteran herbivore that feeds on nicotine-producing Nicotiana plants, tolerates doses of nicotine that are lethal for unadapted herbivores (8). More endoparasitoid wasps (Cotesia congregata) emerged as adults from parasitized M. sexta larvae fed on low nicotine varieties of cultivated tobacco than from larvae fed on nicotine-rich varieties (9). The generalist predatory argentine ant (Iridomyrmex humilis) also preferred M. sexta larvae reared on artificial diets (AD) without nicotine over those reared on high nicotine diets, and were deterred by topical nicotine treatments (10). These results suggest that M. sexta larvae might be able to use this diet-derived toxin for their own protection. How this happens remains a mystery, as the larvae’s resistance of ingested nicotine does not appear to include sequestration and storage of this toxin.The exact mechanisms responsible for M. sexta’s nicotine resistance remain unclear, but both efficient excretion and metabolism appear to be involved. Some researchers have focused on the polar metabolites of nicotine, such as cotinine and the N-oxides of both nicotine and cotinine, which are commonly found in the urine and blood of human smokers (8, 11, 12); cytochrome P450s (CYPs) are thought to mediate nicotine’s oxidation to these metabolites (8, 11, 13–15), but other researchers have been unable to find the oxides in M. sexta’s excretions and propose that nicotine is rapidly excreted without modification (16–18). Although this theory is widely accepted, most studies have not been able to recover all of the ingested nicotine in the frass and nicotine can be found in the hemolymph of larvae feeding on nicotine-containing diets. Hence, within these physiological limits of M. sexta’s excretory-based tolerance lie opportunities for the defensive use of nicotine. Whether nicotine-resistance and co-option are regulated by a common mechanism remains unknown.Here we examine how M. sexta larvae co-opt diet-ingested nicotine for their own defense. In a previous unbiased microarray study, we found that a midgut-expressed cytochrome P450 (CYP6B46) was strongly down-regulated in larvae that were fed genetically modified hostplants with suppressed nicotine production (19, 20). To evaluate if this CYP6B46 is involved in nicotine resistance and co-option, we used a reverse genetics approach, plant-mediated RNA interference (PMRi) (20, 21), to silence this gene in larvae feeding on nicotine-containing, native coyote tobacco (Nicotiana attenuata) hostplants transformed to harbor the silencing construct. Lepidopteran herbivores appear to lack the RNA-dependent RNA polymerase required to sustain gene silencing by RNAi; however, a continuous supply of double-stranded (ds)RNA administered via the hostplant (or diet) effectively silences genes in these herbivores (21, 22).N. attenuata plants were transformed with an expression vector containing a 300-bp fragment of CYP6B46 in an inverted repeat (ir) orientation. Continuous dsRNA ingestion efficiently silenced CYP6B46 in the midguts of larvae feeding on these plants in a highly target-sequence–specific manner, as the most similar CYP expressed in larval midguts, CYP6B45, was not cosilenced (20). These PMRi plants were planted into the native habitat of both hostplant and larvae, the Great Basin Desert, Utah, which teems with larval predators—such as bugs, mantids, ants, antlions, spiders, and lizards—but lacks the Argentine ants and C. congregata endoparasitoids previously reported to be nicotine-sensitive. One of these predators, a wolf spider [Camptocosa parallela (Lycosidae)], selectively attacked CYP6B46-silenced larvae just as it did larvae feeding on nicotine-free hostplants. The particular predatory behavior of these spiders revealed the function of MsCYP6B46 in externalizing ingested nicotine for defensive use. The combination of natural history studies and the plant- and herbivore-reverse genetic procedures can fruitfully dissect the molecular mechanisms governing the tritrophic interactions.