Evaluating mediators of the effect of varenicline preloading on smoking abstinence in a randomized controlled trial
Bibliographic record
Abstract
BACKGROUND AND AIMS: Mechanisms of varenicline preloading in promoting smoking abstinence have not been evaluated. Based on an extinction of reinforcement framework, we tested the hypothesis that pre-quit reductions in smoking rate mediate the effect of extended preloading on abstinence. We also tested alternative indicators of change in smoking reinforcement, as well as smoking aversion, nausea and abstinence self-efficacy as candidate mediators. DESIGN, PARTICIPANTS AND INTERVENTION: Randomized, double-blind, placebo-controlled trial (NCT03262662) comparing extended (4-week varenicline) to standard (3 weeks of placebo, 1-week varenicline) preloading, preceding 11 weeks of open-label varenicline, in 320 adults (56% female). The primary outcome was self-reported continuous smoking abstinence during the last 4 weeks of treatment, with cotinine bio-verification at end of treatment (EOT). SETTING: University at Buffalo, State University of New York, USA (part of the trial was conducted at participants' homes due to the COVID-19 pandemic). MEASUREMENTS: Candidate mediators, including smoking rate and subjective effects of smoking (reward, satisfaction, aversion), self-reported craving, withdrawal, nausea and abstinence self-efficacy, were assessed daily during the pre-quit period with ecological momentary assessment. At two laboratory visits participants completed a choice task to assess smoking reinforcement. FINDINGS: There was a statistically significant indirect effect of extended preloading on greater EOT abstinence rates through pre-quit declines in smoking rate [a*b = 0.284, 95% confidence interval (0.072,0.616)] and percent reduction in smoking across the pre-quit period [a*b = 0.225, (0.080,0.437)]. There were also statistically significant indirect effects through reductions in pre-quit craving [a*b = 0.150, (0.01,0.420)] and increases in pre-quit self-efficacy [a*b = 0.157, (0.038,0.375)]. Sex-specific analyses suggested these mediated effects were consistently limited to females. No other candidate mediators yielded statistically significant indirect effects. CONCLUSIONS: Extended varenicline preloading mediated smoking abstinence through reduced pre-quit smoking and craving among female smokers seeking to quit; increased pre-quit abstinence self-efficacy was also a significant mediator.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.018 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".