nicotine

INTRODUCTION:

E-cigarettes deliver an aerosol of nicotine by heating a liquid and are promoted as an alternative to combustible tobacco. This study determines the longitudinal associations between e-cigarette use and respiratory disease controlling for combustible tobacco use.

METHODS:

This was a longitudinal analysis of the adult Population Assessment of Tobacco and Health Waves 1, 2, and 3. Multivariable logistic regression was performed to determine the associations between e-cigarette use and respiratory disease, controlling for combustible tobacco smoking, demographic, and clinical variables. Data were collected in 2013-2016 and analyzed in 2018-2019.

RESULTS:

Among people who did not report respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or asthma) at Wave 1, the longitudinal analysis revealed statistically significant associations between former e-cigarette use (AOR=1.31, 95% CI=1.07, 1.60) and current e-cigarette use (AOR=1.29, 95% CI=1.03, 1.61) at Wave 1 and having incident respiratory disease at Waves 2 or 3, controlling for combustible tobacco smoking, demographic, and clinical variables. Current combustible tobacco smoking (AOR=2.56, 95% CI=1.92, 3.41) was also significantly associated with having respiratory disease at Waves 2 or 3. Odds of developing respiratory disease for a current dual user (e-cigarette and all combustible tobacco) were 3.30 compared with a never smoker who never used e-cigarettes. Analysis controlling for cigarette smoking alone yielded similar results.

CONCLUSIONS:

Use of e-cigarettes is an independent risk factor for respiratory disease in addition to combustible tobacco smoking. Dual use, the most common use pattern, is riskier than using either product alone.

Some pharmaceuticals are regulated as hazardous waste under the Resource Conservation and Recovery Act (RCRA) when discarded. This final rule adds regulations for the management of hazardous waste pharmaceuticals by healthcare facilities and reverse distributors. Healthcare facilities (for both humans and animals) and reverse distributors will manage their hazardous waste pharmaceuticals under this new set of sector-specific standards in lieu of the existing hazardous waste generator regulations. Among other things, these new regulations prohibit the disposal of hazardous waste pharmaceuticals down the drain and eliminates the dual regulation of RCRA hazardous waste pharmaceuticals that are also Drug Enforcement Administration (DEA) controlled substances. The new rules also maintain the household hazardous waste exemption for pharmaceuticals collected during pharmaceutical take-back programs and events, while ensuring their proper disposal. The new rules codify Environmental Protection Agency (EPA)'s prior policy on the regulatory status of nonprescription pharmaceuticals going through reverse logistics. Additionally, EPA is excluding certain U.S. Food and Drug Administration (FDA) approved over-the-counter (OTC) nicotine replacement therapies (NRTs) from regulation as hazardous waste and is establishing a policy on the regulatory status of unsold retail items that are not pharmaceuticals and are managed via reverse logistics, fulfilling the commitment we made in the Retail Strategy of September 2016.

BACKGROUND:

Nicotine replacement therapy (NRT) aims to replace nicotine from cigarettes to ease the transition from cigarette smoking to abstinence. It works by reducing the intensity of craving and withdrawal symptoms. Although there is clear evidence that NRT used after smoking cessation is effective, it is unclear whether higher doses, longer durations of treatment, or using NRT before cessation add to its effectiveness.

OBJECTIVES:

To determine the effectiveness and safety of different forms, deliveries, doses, durations and schedules of NRT, for achieving long-term smoking cessation, compared to one another.

SEARCH METHODS:

We searched the Cochrane Tobacco Addiction Group trials register, and trial registries for papers mentioning NRT in the title, abstract or keywords. Date of most recent search: April 2018.

SELECTION CRITERIA:

Randomized trials in people motivated to quit, comparing one type of NRT use with another. We excluded trials that did not assess cessation as an outcome, with follow-up less than six months, and with additional intervention components not matched between arms. Trials comparing NRT to control, and trials comparing NRT to other pharmacotherapies, are covered elsewhere.

DATA COLLECTION AND ANALYSIS:

We followed standard Cochrane methods. Smokingabstinence was measured after at least six months, using the most rigorous definition available. We extracted data on cardiac adverse events (AEs), serious adverse events (SAEs), and study withdrawals due to treatment. We calculated the risk ratio (RR) and the 95% confidence interval (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate, using a Mantel-Haenszel fixed-effect model.

MAIN RESULTS:

We identified 63 trials with 41,509 participants. Most recruited adults either from the community or from healthcare clinics. People enrolled in the studies typically smoked at least 15 cigarettes a day. We judged 24 of the 63 studies to be at high risk of bias, but restricting the analysis only to those studies at low or unclear risk of bias did not significantly alter results, apart from in the case of the preloading comparison. There is high-certainty evidence that combination NRT (fast-acting form + patch) results in higher long-term quit rates than single form (RR 1.25, 95% CI 1.15 to 1.36, 14 studies, 11,356 participants; I2 = 4%). Moderate-certainty evidence, limited by imprecision, indicates that 42/44 mg are as effective as 21/22 mg (24-hour) patches (RR 1.09, 95% CI 0.93 to 1.29, 5 studies, 1655 participants; I2 = 38%), and that 21 mg are more effective than 14 mg (24-hour) patches (RR 1.48, 95% CI 1.06 to 2.08, 1 study, 537 participants). Moderate-certainty evidence (again limited by imprecision) also suggests a benefit of 25 mg over 15 mg (16-hour) patches, but the lower limit of the CI encompassed no difference (RR 1.19, 95% CI 1.00 to 1.41, 3 studies, 3446 participants; I2 = 0%). Five studies comparing 4 mg gum to 2 mg gum found a benefit of the higher dose (RR 1.43, 95% CI 1.12 to 1.83, 5 studies, 856 participants; I2 = 63%); however, results of a subgroup analysis suggest that only smokers who are highly dependent may benefit. Nine studies tested the effect of using NRT prior to quit day (preloading) in comparison to using it from quit day onward; there was moderate-certainty evidence, limited by risk of bias, of a favourable effect of preloading on abstinence (RR 1.25, 95% CI 1.08 to 1.44, 9 studies, 4395 participants; I2 = 0%). High-certainty evidence from eight studies suggests that using either a form of fast-acting NRT or a nicotine patch results in similar long-term quit rates (RR 0.90, 95% CI 0.77 to 1.05, 8 studies, 3319 participants; I2 = 0%). We found no evidence of an effect of duration of nicotine patch use (low-certainty evidence); 16-hour versus 24-hour daily patch use; duration of combination NRT use (low- and very low-certainty evidence); tapering of patch dose versus abrupt patch cessation; fast-acting NRT type (very low-certainty evidence); duration of nicotine gum use; ad lib versus fixed dosing of fast-acting NRT; free versus purchased NRT; length of provision of free NRT; ceasing versus continuing patch use on lapse; and participant- versus clinician-selected NRT. However, in most cases these findings are based on very low- or low-certainty evidence, and are the findings from single studies.AEs, SAEs and withdrawals due to treatment were all measured variably and infrequently across studies, resulting in low- or very low-certainty evidence for all comparisons. Most comparisons found no evidence of an effect on cardiac AEs, SAEs or withdrawals. Rates of these were low overall. Significantly more withdrawals due to treatment were reported in participants using nasal spray in comparison to patch in one trial (RR 3.47, 95% CI 1.15 to 10.46, 922 participants; very low certainty) and in participants using 42/44 mg patches in comparison to 21/22 mg patches across two trials (RR 4.99, 95% CI 1.60 to 15.50, 2 studies, 544 participants; I2 = 0%; low certainty).

AUTHORS' CONCLUSIONS:

There is high-certainty evidence that using combination NRT versus single-form NRT, and 4 mg versus 2 mg nicotine gum, can increase the chances of successfully stopping smoking. For patch dose comparisons, evidence was of moderate certainty, due to imprecision. Twenty-one mg patches resulted in higher quit rates than 14 mg (24-hour) patches, and using 25 mg patches resulted in higher quit rates than using 15 mg (16-hour) patches, although in the latter case the CI included one. There was no clear evidence of superiority for 42/44 mg over 21/22 mg (24-hour) patches. Using a fast-acting form of NRT, such as gum or lozenge, resulted in similar quit rates to nicotine patches. There is moderate-certainty evidence that using NRT prior to quitting may improve quit rates versus using it from quit date only; however, further research is needed to ensure the robustness of this finding. Evidence for the comparative safety and tolerability of different types of NRT use is of low and very low certainty. New studies should ensure that AEs, SAEs and withdrawals due to treatment are both measured and reported.