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Systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of emergency department–initiated tobacco control (ETC).Literature search in 7 databases and gray literature sources. Point prevalence tobacco abstinence at 1-, 3-, 6-, and/or 12-month follow-up was abstracted from each study. The proportionate effect (relative risk) of ETC on tobacco abstinence was calculated separately for each study and follow-up time and pooled, at different follow-up times, by Mantel-Haenszel relative risks. The effects of ETC on combined point prevalence tobacco abstinence across all follow-up times were calculated using generalized linear mixed models.Seven studies with overall 1,986 participants were included. The strongest effect of ETC on point prevalence tobacco abstinence was found at 1 month: Relative risk (RR) = 1.47 (3 studies) (95% confidence interval [CI]: 1.06–2.06), while the effect at 3, 6, and 12 months was RR = 1.24 (6 studies) (95% CI: 0.93–1.65); 1.13 (5 studies) (95% CI: 0.86–1.49); and 1.25 (1 study) (95% CI: 0.91–1.72). The benefit on combined point prevalence tobacco abstinence was RR = 1.33 (7 studies) (95% CI: 0.96–1.83), p = .08; with RR = 1.33 (95% CI: 0.92–1.92), p = .10, for the 5 studies combining motivational interviewing and booster phone calls.ETC combining motivational interviewing and booster phone calls showed a trend toward increased episodically measured tobacco abstinence up to 12 months. More methodologically rigorous trials are needed to effectively evaluate the impact of ETC.