Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 1. Study design and methodology

Abstract

A randomized, multi-center study was conducted to assess potential improvement in health status measures, as well as changes in biomarkers of tobacco exposure and biomarkers of biological effect, in current adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) evaluated over 24 weeks. Study design, conduct and methodology are presented here along with subjects’ disposition, characteristics, compliance and safety results. This design and methodology, evaluating generally healthy adult smokers over a relatively short duration, proved feasible. Findings from this randomized study provide generalized knowledge of the risk continuum among various tobacco products.

Trial registration: ClinicalTrials.gov identifier: NCT02061917.     

Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 3. Biomarkers of biological effect

Abstract

A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) for 24 weeks was conducted. Evaluation of biomarkers of biological effect (e.g. inflammation, lipids, hypercoaguable state) indicated that the majority of consistent and statistically significant improvements over time within each group were observed in markers of inflammation. Consistent and statistically significant differences in pairwise comparisons between product groups were not observed. These findings are relevant to the understanding of biomarkers of biological effect related to cigarette smoking as well as the risk continuum across various tobacco products.

Trial registration: ClinicalTrials.gov identifier: NCT02061917.     

Global methylation profiles in buccal cells of long-term smokers and moist snuff consumers

Abstract

Purpose: Alternations in gene methylation and other epigenetic changes regulate normal development as well as drive disease progression. The aim of this study is to investigate global methylation changes in the buccal cells of smokers and smokeless tobacco users.

Materials and methods: Generally healthy adult male subjects were recruited into smoker (SMK), moist snuff consumer (MSC) and non-tobacco consumer (NTC) cohorts (40 subjects/cohort) (ClinicalTrials.gov Identifier: NCT01923402). Global methylation profiling was performed on Illumina 450?K methylation arrays using buccal cell DNAs.

Results: The SMK cohort exhibited larger qualitative and quantitative changes relative to MSC. Approximately half of the differentially methylated 1252 gene loci were grouped as combustible tobacco-related (CTR) signatures and a third of the changes, tobacco-related (TR) signatures, were associated with smoking. Very few (41) differentially methylated gene loci were exclusively associated with moist snuff use and were designated as moist snuff-related (MSR) signature. Pathway enrichment analyses revealed that developmental and immune response pathways, among others, were impacted due to tobacco use.

Conclusions: Chronic cigarette smoking causes hyper- and hypo-methylation of genes that could contribute to smoking-related diseases. These results help place combustible and non-combustible tobacco products along a risk continuum and provide additional insights into the effects of tobacco consumption.     

EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as Tobacco Cigarettes Substitute: A Prospective 12-Month Randomized Control Design Study

Background

Electronic cigarettes (e-cigarettes) are becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms, and to continue having a ‘smoking’ experience, but with reduced health risks. Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Methods ECLAT is a prospective 12-month randomized, controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model (‘Categoria’; Arbi Group Srl, Italy) compared to its non-nicotine choice. GroupA (n = 100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n = 100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n = 100) received no-nicotine cartridges for 12 weeks. The study consisted of nine visits during which cig/day use and exhaled carbon monoxide (eCO) levels were measured. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.

Results

Declines in cig/day use and eCO levels were observed at each study visits in all three study groups (p<0.001 vs baseline), with no consistent differences among study groups. Smoking reduction was documented in 22.3% and 10.3% at week-12 and week-52 respectively. Complete abstinence from tobacco smoking was documented in 10.7% and 8.7% at week-12 and week-52 respectively. A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study. Participants’ perception and acceptance of the product under investigation was satisfactory.

Conclusion

In smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01164072","term_id":"NCT01164072"}}NCT01164072 {"type":"clinical-trial","attrs":{"text":"NCT01164072","term_id":"NCT01164072"}}NCT01164072     

The effects of simvastatin treatment on plasma lipid-related biomarkers in men with dyslipidaemia

Background: Lipidomic biomarkers will facilitate the development of novel anti-atherosclerotic therapies.

Objective: To evaluate the responses of circulating biomarkers to simvastatin treatment.

Methods: A randomized, cross-over study in men with mixed dyslipidaemia was used to compare effects of simvastatin 40?mg/day with placebo.

Results: Plasma concentrations of nine fatty acids (FA; of 33 evaluated) were reduced significantly by simvastatin. No changes in the rates of FA synthesis or in hepatic lipase or lipoprotein lipase activities were apparent. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased.

Conclusion: We identified lipidomic biomarkers of simvastatin treatment effect that are consistent with statin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.

Trial registration: ClinicalTrials.gov identifier: NCT00935259.     

Neuroglobin and Nogo-a as biomarkers for the severity and prognosis of traumatic brain injury

Abstract

Objective: To identify the early changes of serum neuroglobin and Nogo-A concentrations and the relations to traumatic brain injury (TBI) severity and prognosis.

Methods: Serum samples were obtained and analyzed from 34 patients with TBI within the first 96?h after injury. Comparative analysis combined with Glasgow Coma Scale (GCS) scores and the 6-month prognosis of these patients was performed.

Results: Significant correlations were found between peak serum neuroglobin and Nogo-A concentrations and a patient’s GCS score on admission (p?<?0.001). The mean peak serum neuroglobin and Nogo-A concentrations were both significantly higher in patients with an unfavorable outcome at 6 months after injury (p?<?0.05).

Conclusions: Serum neuroglobin and Nogo-A levels could be suggested as biomarkers for predicting TBI severity and prognosis.

Trial registration: ClinicalTrials.gov identifier: NCT02229643.     

Circulating chemokines in relation to coronary plaque characteristics on radiofrequency intravascular ultrasound and cardiovascular outcome

Abstract

Objective: To investigate relations of several circulating chemokines with extent and phenotype of coronary atherosclerosis and with 1-year clinical outcome.

Methods: Intravascular ultrasound virtual histology (IVUS-VH) imaging of a coronary artery was performed in 581 patients. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β and regulated upon activation normal T cell expressed and secreted (RANTES) were measured in plasma.

Results: Higher MCP-1, MIP-1α and lower RANTES were associated with coronary plaque burden. Higher MCP-1, MIP-1α and lower RANTES were associated with the presence of IVUS-VH-derived thin-cap fibroatheroma lesions. RANTES was associated with major adverse cardiac events.

Conclusions: RANTES is a promising biomarker that is inversely associated with coronary plaque burden and vulnerability, as well as with death and acute coronary syndrome.

Trial registration: ClinicalTrials.gov identifier: NCT01789411.     

Effects of reduced exposure to cigarette smoking on changes in biomarkers of potential harm in adult smokers: results of combined analysis of two clinical studies

Purpose: Nonconventional vapor products (NVP), designed to reduce exposure to cigarette smoke toxicants (CSTs), could cause changes in biomarkers of potential harm (BoPH). Although, NVPs reduced CSTs exposure compared to conventional cigarettes (CC), the changes in the BoPH values varied among the studies. Hence, further information on BoPH using NVPs is needed.

Material and methods: The data of two similarly designed studies using a kind of NVP, a noncombustion and nonheating inhaler type of smokeless tobacco product (NCIT) used under 31-day confinement, were pooled, and the differences in 15 BoPH between smokers and nonsmokers at baseline and between the 1?mg tar CC (CC1) group and NCIT group at Day 28/29 were analyzed.

Results: At baseline, the levels of eight BoPH (red blood cells, white blood cells, 8-epi-prostaglandin F2α, 8-hydroxy-2′-deoxyguanosine, malondialdehyde, 11-dehydrothromboxane B2, total cholesterol and glucose) were significantly different between smokers and nonsmokers. At Day 28/29, the levels of six BoPH were significantly different between NCIT and CC1 (8-epi-prostaglandin F2α, malondialdehyde, 11-dehydrothromboxane B2: CC1?>?NCIT, total bilirubin, low-density lipoprotein cholesterol and total cholesterol: CC1?<?NCIT).

Conclusions: Reduced exposure to CSTs has favorable effects on BoPH associated with oxidative stress, antioxidant capacity and platelet activation/coagulation but not in lipid metabolism.     

Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study

Objective

To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes), directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both.

Design

Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up.

Data Sources

Direct contact and structured questionnaires by phone or via internet.

Methods

Adults (30–75 years) were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers), users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers), or smokers of both tobacco and e-cigarettes (dual smokers). Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence.

Main Outcome Measures

Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily.

Data Synthesis

We used linear and logistic regression, with region as cluster unit.

Results

Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%). All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35–8.02), whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall).

Conclusions

Adding e-cigarettes to tobacco smoking did not facilitate smoking cessation or reduction. If e-cigarette safety will be confirmed, however, the use of e-cigarettes alone may facilitate quitters remaining so.

Registration Number

NCT01785537.     

Clinical Profiling of BCL-2 Family Members in the Setting of BRAF Inhibition Offers a Rationale for Targeting De Novo Resistance Using BH3 Mimetics

While response rates to BRAF inhibitiors (BRAFi) are high, disease progression emerges quickly. One strategy to delay the onset of resistance is to target anti-apoptotic proteins such as BCL-2, known to be associated with a poor prognosis. We analyzed BCL-2 family member expression levels of 34 samples from 17 patients collected before and 10 to 14 days after treatment initiation with either vemurafenib or dabrafenib/trametinib combination. The observed changes in mRNA and protein levels with BRAFi treatment led us to hypothesize that combining BRAFi with a BCL-2 inhibitor (the BH3-mimetic navitoclax) would improve outcome. We tested this hypothesis in cell lines and in mice. Pretreatment mRNA levels of BCL-2 negatively correlated with maximal tumor regression. Early increases in mRNA levels were seen in BIM, BCL-XL, BID and BCL2-W, as were decreases in MCL-1 and BCL2A. No significant changes were observed with BCL-2. Using reverse phase protein array (RPPA), significant increases in protein levels were found in BIM and BID. No changes in mRNA or protein correlated with response. Concurrent BRAF (PLX4720) and BCL2 (navitoclax) inhibition synergistically reduced viability in BRAF mutant cell lines and correlated with down-modulation of MCL-1 and BIM induction after PLX4720 treatment. In xenograft models, navitoclax enhanced the efficacy of PLX4720. The combination of a selective BRAF inhibitor with a BH3-mimetic promises to be an important therapeutic strategy capable of enhancing the clinical efficacy of BRAF inhibition in many patients that might otherwise succumb quickly to de novo resistance. Trial Registrations: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01006980","term_id":"NCT01006980"}}NCT01006980;ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01107418","term_id":"NCT01107418"}}NCT01107418; ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01264380","term_id":"NCT01264380"}}NCT01264380; ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01248936","term_id":"NCT01248936"}}NCT01248936; ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00949702","term_id":"NCT00949702"}}NCT00949702; ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01072175","term_id":"NCT01072175"}}NCT01072175     

Comparison of Manual and Automated Preprocedural Segmentation Tools to Predict the Annulus Plane Angulation and C-Arm Positioning for Transcatheter Aortic Valve Replacement

BackgroundPreprocedural manual multi-slice-CT-segmentation tools (MSCT-ST) define the gold standard for planning transcatheter aortic valve replacement (TAVR). They are able to predict the perpendicular line of the aortic annulus (PPL) and to indicate the corresponding C-arm angulation (CAA). Fully automated planning-tools and their clinical relevance have not been systematically evaluated in a real world setting so far.ConclusionsA-MSCT-analysis provides precise preprocedural information on CAA for optimal visualization of the aortic annulus compared to the M-MSCT gold standard. Intraprocedural application of this information during TAVR significantly reduces the levels of contrast and radiation exposure.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01805739","term_id":"NCT01805739"}}NCT01805739     

Intention to Switch to Smokeless Tobacco Use among South African Smokers: Results from the 2007 South African Social Attitudes Survey

Background

Some smokeless tobacco products (SLT) have been shown to be associated with only a fraction of the risks of cigarettes. This study assessed South African smokers’ interest in switching to a hypothetical reduced harm SLT product.

Methods

The 2007 South African Social Attitudes Survey was analysed for 678 exclusive cigarette smokers. Respondents were asked about their perceptions about relative harm of snuff compared to cigarettes, and their interest in switching to snuff if informed it was 99% less harmful than cigarettes.

Results

About 49.7% of exclusive cigarette smokers believed that snuff was equally as harmful as cigarettes; 12.9% thought snuff was more harmful; 5.7% thought snuff was less harmful; while 31.8% did not know if there was a difference in harm between snuff and cigarettes. Approximately 24.2% of exclusive cigarette smokers indicated interest in switching to snuff, with significantly greater interest observed among those exposed to 100% smoke-free work environment. Interest in switching was highest (34.7%) among smokers who believed a priori that using snuff was more harmful than cigarettes, and lowest (14.5%) among those who did not know if there was a difference in harm. In a multi-variable adjusted logistic regression model, this latter group remained less likely to be interested in harm reduction switching (adjusted odds ratio = 0.42; 95% CI: 0.19–0.91).

Conclusion

About a quarter of smokers indicated interest in harm reduction switching to snuff. SLT products have a potential role in reducing the harm from smoking in South Africa, but only if they are not used to circumvent smoke-free laws that have been associated with reduced smoking.     

Does Smoke from Biomass Fuel Contribute to Anemia in Pregnant Women in Nagpur,India? A Cross-Sectional Study

BackgroundAnemia affects upwards of 50% of pregnant women in developing countries and is associated with adverse outcomes for mother and child. We hypothesized that exposure to smoke from biomass fuel – which is widely used for household energy needs in resource-limited settings – could exacerbate anemia in pregnancy, possibly as a result of systemic inflammation.ObjectiveTo evaluate whether exposure to smoke from biomass fuel (wood, straw, crop residues, or dung) as opposed to clean fuel (electricity, liquefied petroleum gas, natural gas, or biogas) is an independent risk factor for anemia in pregnancy, classified by severity.MethodsA secondary analysis was performed using data collected from a rural pregnancy cohort (N = 12,782) in Nagpur, India in 2011-2013 as part of the NIH-funded Maternal and Newborn Health Registry Study. Multinomial logistic regression was used to estimate the effect of biomass fuel vs. clean fuel use on anemia in pregnancy, controlling for maternal age, body mass index, education level, exposure to household tobacco smoke, parity, trimester when hemoglobin was measured, and receipt of prenatal iron and folate supplements.ResultsThe prevalence of any anemia (hemoglobin < 11 g/dl) was 93% in biomass fuel users and 88% in clean fuel users. Moderate-to-severe anemia (hemoglobin < 10 g/dl) occurred in 53% and 40% of the women, respectively. Multinomial logistic regression showed higher relative risks of mild anemia in pregnancy (hemoglobin 10-11 g/dl; RRR = 1.38, 95% CI = 1.19-1.61) and of moderate-to-severe anemia in pregnancy (RRR = 1.79, 95% CI = 1.53-2.09) in biomass fuel vs. clean fuel users, after adjusting for covariates.ConclusionIn our study population, exposure to biomass smoke was associated with higher risks of mild and moderate-to-severe anemia in pregnancy, independent of covariates.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT 01073475","term_id":"NCT01073475"}}NCT 01073475     

Effect of Test-Based versus Presumptive Treatment of Malaria in Under-Five Children in Rural Ghana – A Cluster-Randomised Trial

BackgroundMalaria-endemic countries in sub-Saharan Africa are shifting from the presumptive approach that is based on clinical judgement (CJ) to the test-based approach that is based on confirmation through test with rapid diagnostic tests (RDT). It has been suggested that the loss of the prophylactic effect of presumptive-administered ACT in children who do not have malaria will result in increase in their risk of malaria and anaemia.ConclusionThe test-based approach to the management of malaria did not increase the incidence of malaria or anaemia among under-five children in this setting.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00832754","term_id":"NCT00832754"}}NCT00832754     

Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption

BackgroundAs pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women.ConclusionIn this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure.

Trial Registration

ClinicalTrials.gov, Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02776748","term_id":"NCT02776748"}}NCT02776748     

Uptake and Population-Level Impact of Expedited Partner Therapy (EPT) on Chlamydia trachomatis and Neisseria gonorrhoeae: The Washington State Community-Level Randomized Trial of EPT

BackgroundExpedited partner therapy (EPT), the practice of treating the sex partners of persons with sexually transmitted infections without their medical evaluation, increases partner treatment and decreases gonorrhea and chlamydia reinfection rates. We conducted a stepped-wedge, community-level randomized trial to determine whether a public health intervention promoting EPT could increase its use and decrease chlamydia test positivity and gonorrhea incidence in women.ConclusionsA public health intervention promoting the use of free PDPT substantially increased its use and may have resulted in decreased chlamydial and gonococcal infections at the population level.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01665690","term_id":"NCT01665690"}}NCT01665690     

Graphic Warning Labels Elicit Affective and Thoughtful Responses from Smokers: Results of a Randomized Clinical Trial

Objective

Observational research suggests that placing graphic images on cigarette warning labels can reduce smoking rates, but field studies lack experimental control. Our primary objective was to determine the psychological processes set in motion by naturalistic exposure to graphic vs. text-only warnings in a randomized clinical trial involving exposure to modified cigarette packs over a 4-week period. Theories of graphic-warning impact were tested by examining affect toward smoking, credibility of warning information, risk perceptions, quit intentions, warning label memory, and smoking risk knowledge.

Methods

Adults who smoked between 5 and 40 cigarettes daily (N = 293; mean age = 33.7), did not have a contra-indicated medical condition, and did not intend to quit were recruited from Philadelphia, PA and Columbus, OH. Smokers were randomly assigned to receive their own brand of cigarettes for four weeks in one of three warning conditions: text only, graphic images plus text, or graphic images with elaborated text.

Results

Data from 244 participants who completed the trial were analyzed in structural-equation models. The presence of graphic images (compared to text-only) caused more negative affect toward smoking, a process that indirectly influenced risk perceptions and quit intentions (e.g., image->negative affect->risk perception->quit intention). Negative affect from graphic images also enhanced warning credibility including through increased scrutiny of the warnings, a process that also indirectly affected risk perceptions and quit intentions (e.g., image->negative affect->risk scrutiny->warning credibility->risk perception->quit intention). Unexpectedly, elaborated text reduced warning credibility. Finally, graphic warnings increased warning-information recall and indirectly increased smoking-risk knowledge at the end of the trial and one month later.

Conclusions

In the first naturalistic clinical trial conducted, graphic warning labels are more effective than text-only warnings in encouraging smokers to consider quitting and in educating them about smoking’s risks. Negative affective reactions to smoking, thinking about risks, and perceptions of credibility are mediators of their impact.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01782053","term_id":"NCT01782053"}}NCT01782053     

Does Effectiveness of Adolescent Smoking-Cessation Intervention Endure Into Young Adulthood? 7-Year Follow-Up Results from a Group-Randomized Trial

Background

The Hutchinson Study of High School Smoking was the first randomized trial to show effectiveness of a smoking cessation intervention on 6-months prolonged smoking abstinence at one year post-intervention in a large population-based sample of adolescent smokers. An important question remains: Do the positive effects from teen smoking cessation interventions seen at up to 12 months post-intervention endure into young adulthood? This study examines for the first time whether such positive early effects from teen smoking cessation intervention can endure into young adulthood in the absence of additional intervention.

Methods

High school smokers (n = 2,151) were proactively recruited into the trial from fifty randomly selected Washington State high schools randomized to the experimental (Motivational Interviewing + Cognitive Behavioral Skills Training telephone counseling intervention) or control (no intervention) condition. These smokers were followed to 7 years post high school to ascertain rates of six-year prolonged smoking abstinence in young adulthood. All statistical tests are two-sided.

Results

No evidence of intervention impact at seven years post high school was observed for the main endpoint of six-year prolonged abstinence, neither among all smokers (14.2% in the experimental condition vs. 13.1% in the control condition, difference = +1.1%, 95% confidence interval (CI) = -3.4 to 5.8, p = .61), nor among the subgroups of daily smokers and less-than-daily smokers, nor among other a priori subgroups. But, observed among males was some evidence of an intervention impact on two endpoints related to progress towards quitting: reduction in number of days smoked in the past month, and increase in the length of the longest quit attempt in the past year.

Conclusions

There was no evidence from this trial among adolescent smokers that positive effectiveness of the proactive telephone intervention for smoking abstinence, observed previously at one year post-intervention, was sustained for the long-term into young adulthood. In light of the positive short-term effectiveness consistently observed from this and other trials for teen smokers, together with the lack of evidence from this study that such short-term impact can endure into young adulthood, sustained interventions that continue into young adulthood should be developed and tested for long-term impact.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00115882","term_id":"NCT00115882"}}NCT00115882