Electronic Nicotine-Delivery Systems for Smoking Cessation.

BACKGROUND: Electronic nicotine-delivery systems - also called e-cigarettes - are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed. METHODS: In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy. The primary outcome was biochemically validated, continuous abstinence from smoking at 6 months. Secondary outcomes included participant-reported abstinence from tobacco and from any nicotine (including smoking, e-cigarettes, and nicotine-replacement therapy) at 6 months, respiratory symptoms, and serious adverse events. RESULTS: A total of 1246 participants underwent randomization; 622 participants were assigned to the intervention group, and 624 to the control group. The percentage of participants with validated continuous abstinence from tobacco smoking was 28.9% in the intervention group and 16.3% in the control group (relative risk, 1.77; 95% confidence interval, 1.43 to 2.20). The percentage of participants who abstained from smoking in the 7 days before the 6-month visit was 59.6% in the intervention group and 38.5% in the control group, but the percentage who abstained from any nicotine use was 20.1% in the intervention group and 33.7% in the control group. Serious adverse events occurred in 25 participants (4.0%) in the intervention group and in 31 (5.0%) in the control group; adverse events occurred in 272 participants (43.7%) and 229 participants (36.7%), respectively. CONCLUSIONS: The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking-cessation counseling alone. (Funded by the Swiss National Science Foundation and others; ESTxENDS ClinicalTrials.gov number, NCT03589989.).

Smoking Cessation Pharmacotherapy Efficacy in Comorbid Medical Populations: Secondary Analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) Randomized Clinical Trial.

INTRODUCTION: This study sought to compare medication efficacy in participants with medical comorbidities who smoke in the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) trial, a double-blind, triple-dummy, placebo- and active-controlled randomized controlled trial. AIMS AND METHODS: Participants were from the U.S. cohort of the main trial and randomized (1:1:1:1) to varenicline, bupropion, nicotine replacement therapy (NRT) patch, or placebo for 12 weeks with follow-up through week 24. Medical comorbidity data were derived from the baseline medical screening questionnaire and categorized into four subgroups (cardiac, respiratory, vascular, and diabetes). Within each comorbidity, generalized linear mixed models were used to assess the association between treatment and continuous abstinence rates from weeks 9-12 to 9-24. Similar models were used to test the effect of number of comorbidities on abstinence. RESULTS: Varenicline resulted in the highest week 12 abstinence rates across all pharmacotherapies and compared to placebo in all comorbidity subgroups: Cardiac (40.0% vs. 3.6%; odds ratios [OR] = 23.3 [5.1-107.1]), respiratory (24.7% vs. 12.8%; OR = 2.2 [1.3-3.8]), vascular (29.1% vs. 10.4%; OR = 3.6 [2.3-5.7]), and diabetes (30.9% vs. 8.3%; OR = 6.5 [2.3-19.0]). This was maintained at week 24 for those with cardiac (23.3% vs. 1.8%; OR = 21.7 [2.7-178.2]), vascular (18.9% vs. 7.1%; OR = 3.1 [1.8-5.3]), and diabetes (20.6% vs. 4.2%; OR = 8.4 [2.1-33.7]) comorbidities. Treatment contrasts within some comorbidity subgroups revealed superior efficacy of varenicline over other pharmacotherapies. All pharmacotherapies increased the odds of abstinence regardless of number of comorbidities. CONCLUSIONS: Varenicline is the most efficacious option for patients with manageable cardiac, respiratory, vascular, and diabetes conditions to quit smoking, supporting recent clinical practice guidelines that recommend varenicline as first-line pharmacotherapy. Bupropion and NRT demonstrated efficacy for some comorbidity subgroups. IMPLICATIONS: This secondary analysis of the EAGLES trial demonstrated that varenicline is the most efficacious option for patients with cardiac, respiratory, vascular, and diabetes diagnoses to quit smoking. This demonstration of varenicline efficacy among individuals with comorbid medical conditions supports recent clinical practice guidelines that recommend varenicline as a first-line pharmacotherapy for smoking cessation.

What is the impact of nicotine pouches on oral health: a systematic review.

BACKGROUND: Increase in nicotine pouch (NP) users, particularly among the young, is a matter of concern requiring a comprehensive understanding of its short- and long-term oral health implications. The objective of this research was to systematically review potential oral side-effects associated with NP usage. METHODS: This systematic review was conducted following the PRISMA guidelines. Databases (Medline via PubMed, Scopus, Cochrane Trial, and Google Scholar) were searched for relevant studies up to February 2024. Modified Newcastle-Ottawa Scale (NOS) and the Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool were used to assess the quality and bias of the included studies. RESULTS: Three studies were included for this review, two from Europe and one from USA, and considered of a total of 190 participants. All studies were deemed to have a high risk of bias. Participants used NP for periods ranging from 1 month to 10 years. Among these studies, only one study provided information on the usage pattern between 1 and 5 units for an average of 11 ± 7 min per session. Oral mucosal changes at the site of placement were common among NP users. Oral lesions varied from slight wrinkling to various white lesions, seemingly related to the NP units consumed per day and their duration of usage. Other oral side effects included dry mouth, soreness, gingival blisters, and a strange jaw sensation. CONCLUSIONS: Research on the use of NP and its effect on oral health are currently limited. The use of NP should take into consideration the short-and-long-term effects, especially on oral health. Further studies are crucial to understand oral health implications associated with NP usage. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration number CRD 42,024,500,711.

Vaporized nicotine use among patients in HIV care who smoke tobacco: perceived health effects and effectiveness as a smoking cessation tool.

Evidence suggests adverse health effects from vaporized nicotine (VN) use, such as electronic "e" cigarettes, and limited efficacy to aid tobacco cessation. People with HIV (PWH) smoke tobacco at higher rates than the general population, with greater morbidity, highlighting the necessity of effective tobacco cessation tools. PWH may be more vulnerable to adverse effects of VN. Using semi-structured 1:1 interviews, we examined health beliefs regarding VN, patterns of use, and perceived effectiveness for tobacco cessation among PWH in HIV care at three geographically diverse U.S. sites. PWH (n = 24) had limited understanding of VN product content or health effects, presuming VN less harmful than tobacco cigarettes (TC). VN failed to adequately replicate the psychoactive effects or desired ritual of smoking TC. Concurrent TC use, and continuous VN use throughout the day, was common. Satiety using VN was elusive, and consumption quantity was difficult to track. VN had limited desirability and durability as a TC cessation tool among the interviewed PWH.

Development and Content Validation of a Questionnaire for Measuring Beliefs About Using Nicotine Replacement Therapy for Smoking Cessation in Pregnancy.

INTRODUCTION: Improving adherence to nicotine replacement therapy (NRT) in pregnancy may result in higher smoking cessation rates. Informed by the Necessities and Concerns Framework, we developed an intervention targeting pregnancy NRT adherence. To evaluate this, we derived the NRT in pregnancy necessities and concerns questionnaire (NiP-NCQ), which measures perceived need for NRT and concerns about potential consequences. AIMS AND METHODS: Here we describe the development and content validation of NiP-NCQ. From qualitative work, we identified potentially modifiable determinants of pregnancy NRT adherence and classed these as necessity beliefs or concerns. We translated these into draft self-report items and piloted items on 39 pregnant women offered NRT and a prototype NRT adherence intervention, assessing distributions and sensitivity to change. After removing poorly performing items, smoking cessation experts (N = 16) completed an online discriminant content validation (DCV) task to determine whether retained items measure a necessity belief, concern, both, or neither construct. RESULTS: Draft NRT concern items encompassed safety for the baby, side effects, too much or insufficient nicotine, and addictiveness. Draft necessity belief items included perceived need for NRT for short- and longer-term abstinence, and desire to minimize or cope without NRT. Of 22 out of 29 items retained after piloting, four were removed following the DCV task: three were judged to measure neither construct and one possibly both. The final NiP-NCQ comprised nine items per construct (18 total). CONCLUSIONS: The NiP-NCQ measures potentially modifiable determinants of pregnancy NRT adherence within two distinct constructs and may have research and clinical utility for evaluating interventions targeting these. IMPLICATIONS: Poor adherence to NRT in pregnancy may result from low perceived need and concerns about consequences; interventions challenging these beliefs may yield higher smoking cessation rates. To evaluate an NRT adherence intervention informed by the Necessities and Concerns Framework, we developed the NiP-NCQ. Through the content development and refinement processes described in this paper, we derived an evidence-based, 18-item questionnaire measuring two distinct constructs within two nine-item subscales. Higher concerns and lower necessity beliefs indicate more negative NRT beliefs; NiP-NCQ may have research and clinical utility for interventions targeting these.

Oral side effects of locally delivered nicotine replacement therapy: A meta-analysis of randomized controlled trials.

BACKGROUND: Nicotine replacement therapy is the first choice pharmacotherapy for smoking cessation. Oral side effects caused due to NRT lead to discontinuation of treatment. The objective of this meta-analysis was to look for the certainty of evidence on the number of patients that reported oral side effects due to the use of NRT. METHOD: Eligible studies were selected and data extraction was carried out independently into a pre-tested data extraction form. Risk of bias was assessed using Cochrane Tool. The heterogeneity between the studies was assessed using Chi-square and I2 tests. Mean difference and Odds ratio at 95% confidence interval were the effect estimates. GRADE working group approach was used to assess the quality of evidence. RESULTS: Twenty-eight studies were included with moderate to low risk of bias. The pooled estimates revealed a statistically significant number of patients developed mouth or throat irritation (2.54 [1.23, 5.25]), or oral soreness (2.22 [1.40, 3.55]) or gastric reflux or vomiting (1.97 [1.34, 2.90]) due to NRT. CONCLUSION: It is important to understand that significant implications are caused due to NRT, on oral health. All patients on NRT must adhere to their regular dentist visits and must check their oral mucosa before initiating NRT.

Maternal nicotine exposure induces congenital heart defects in the offspring of mice.

Maternal cigarette smoking is a risk factor for congenital heart defects (CHDs). Nicotine replacement therapies are often offered to pregnant women following failed attempts of smoking cessation. However, the impact of nicotine on embryonic heart development is not well understood. In the present study, the effects of maternal nicotine exposure (MNE) during pregnancy on foetal heart morphogenesis were studied. Adult female mice were treated with nicotine using subcutaneous osmotic pumps at 0.75 or 1.5 mg/kg/day and subsequently bred with male mice. Our results show that MNE dose-dependently increased CHDs in foetal mice. CHDs included atrial and ventricular septal defects, double outlet right ventricle, unguarded tricuspid orifice, hypoplastic left ventricle, thickened aortic and pulmonary valves, and ventricular hypertrophy. MNE also significantly reduced coronary artery size and vessel abundance in foetal hearts. Moreover, MNE resulted in higher levels of oxidative stress and altered the expression of key cardiogenic regulators in the developing heart. Nicotine exposure reduced epicardial-to-mesenchymal transition in foetal hearts. In conclusion, MNE induces CHDs and coronary artery malformation in mice. These findings provide insight into the adverse outcomes of foetuses by MNE during pregnancy.

A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy.

BACKGROUND: E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments. METHODS: We randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. Participants who were lost to follow-up or did not provide biochemical validation were considered to not be abstinent. Secondary outcomes included participant-reported treatment usage and respiratory symptoms. RESULTS: A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath. CONCLUSIONS: E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. (Funded by the National Institute for Health Research and Cancer Research UK; Current Controlled Trials number, ISRCTN60477608 .).

The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial.

IMPORTANCE: Improving treatment outcomes for smokers with major depressive disorder (MDD) can have significant public health implications. OBJECTIVE: To evaluate the safety and efficacy of smoking cessation pharmacotherapy among smokers with MDD. DESIGN: Secondary analysis of a randomized, double-blind, active- (nicotine patch) and placebo-controlled trial of 12 weeks of either varenicline or bupropion with a 12-week follow-up. PARTICIPANTS: Community volunteers 18-75 years of age; smoke 10+ cigarettes/day; with clinically stable MDD (N = 2635) or no psychiatric disorder (N = 4028), from 140 sites in 16 countries. INTERVENTION: Twelve weeks of pharmacotherapy (placebo [PLA], nicotine replacement therapy [NRT], bupropion [BUP], varenicline [VAR]) plus brief cessation counseling. MEASURE(S): Primary safety outcome: the occurrence of ≥1 treatment-emergent, moderate to severe neuropsychiatric adverse event (NPSAE). Primary efficacy outcome: biochemically confirmed continuous abstinence (CA) during the final 4 weeks of treatment (Weeks 9-12). RESULTS: A total of 6653 participants (56% female; 39% MDD) ~47 years old. Risk of NPSAEs did not differ by medication for MDD. MDD had higher risk (p < .0001) for NPSAEs than the NPC. Efficacy (6653; intent-to-treat): CA rates for MDD versus NPC respectively were 31.2% versus 38.0% VAR; 23.0% versus 26.1% BUP; 22.6% versus 26.4% NRT; and 13.4% versus 13.7% PLA but no differential treatment effect was noted within the cohorts. All active treatments differed from PLA but VAR showed the largest effect. CONCLUSIONS: Results suggest that for MDD smokers, inclusive of those with recurrent episode, varenicline plus counseling may be the best pharmacological option for the treatment of smoking given its greater efficacy effect size and similar risk of NPSAEs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01456936. https://clinicaltrials.gov/ct2/show/NCT01456936.

Bupropion XL and SR have similar effectiveness and adverse event profiles when used to treat smoking among patients at a comprehensive cancer center.

BACKGROUND AND OBJECTIVES: Bupropion extended-release (XL; once-daily dosing) has equal efficacy with the sustained-release (SR) formulation (twice-daily dosing) for treating depression, but no studies have compared the two formulations for the treatment of smoking. In a naturalistic open-label study, we compared the effectiveness and the adverse event profiles of XL and SR in treating cancer patients for smoking. METHODS: Cancer patients (N = 648) were prescribed bupropion XL (n = 454) or SR (n = 194) alone or in combination with nicotine replacement therapy (NRT) for treating smoking from September 2006 to December 2017. We analyzed 7-day point prevalence abstinence at end-of-treatment (EOT; 3 months postmedication initiation) and evaluated for noninferiority. We also analyzed the adverse event profile differences between the medications. RESULTS: There were no significant differences in abstinent rates at EOT between bupropion XL and SR when using intent-to-treat models, regardless of concomitant NRT. XL demonstrated noninferiority in treatment efficacy compared to SR when excluding those on combined treatment with NRT. Further, there were no significant differences in spontaneously reported adverse events between XL and SR. CONCLUSIONS: Our data did not reveal a difference between bupropion XL and SR formulations in terms of effectiveness or adverse event profiles among cancer patients prescribed bupropion alone or in combination with NRTs to quit smoking. SCIENTIFIC SIGNIFICANCE: In this first published direct comparison of their effectiveness and adverse event profiles, we found that bupropion XL is likely therapeutically equivalent to bupropion SR when treating smoking among cancer patients, and produces similar side effects.

Is There a Smoking Gun for Nicotine? A Review of the Role of Nicotine in Dermatologic Surgery.

BACKGROUND: Dermatologic surgeons are faced with a dilemma when counseling actively smoking patients who require dermatologic surgery: recommend total cessation of all nicotine that is associated with extremely high rates of cessation failure or recommend nicotine replacement therapy (NRT). OBJECTIVE: To determine the safety of NRT in dermatologic surgery. MATERIALS AND METHODS: PubMed was queried: [(nicotine OR electronic cigarettes) AND (flap OR wound healing)]. RESULTS: Smoking tobacco is detrimental to wound healing, supported by ample evidence (1A). Perioperative smoking cessation reduces risk (1B). Basic science demonstrates both a benefit and detriment of nicotine depending on the factor studied (2A). Human studies suggest no detrimental effect of nicotine on perioperative complications (1B). Nicotine may be detrimental to flaps, but evidence is limited to basic science (2A). CONCLUSION: Dermatologists should consider recommending nicotine replacement for smokers in the perioperative period. Evidence is lacking to determine safety in flaps. It is presumed based on animal studies that nicotine has a negative effect on flaps; however, it is likely less than tobacco. Weighing the risk of cessation failure without nicotine replacement versus nicotine replacement after flap is challenging. Electronic cigarettes should be discouraged as a means of NRT.

Smoking cessation by combined medication and counselling: a feasibility study in lung cancer patients.

PURPOSE: Smoking cessation in patients with diagnosed lung cancer has positive effects on cancer therapy and overall prognosis. Despite this, knowledge on smoking cessation in lung cancer patients is sparse. METHODS: This is an observational single centre, 12-week, prospective, single-arm trial at a tertiary lung cancer centre. Responsive patients were enrolled following confirmed lung cancer diagnosis. Smoking cessation intervention included counselling as well as pharmacotherapy. The primary endpoint was the point prevalence abstinence rate at week 12 based on biochemical verification. Secondary endpoints were the abstinence rate at week 26, quality of life and side effects. RESULTS: 80 patients were enrolled. Mean age was 62.6 ± 7.9 years. Most patients (63%) were treated with chemotherapy or radiochemotherapy. 39 patients used nicotine replacement therapy, 35 varenicline whereas six patients did not use pharmacotherapy. During the study period 13 patients died. Data were available in 72 patients after 12 weeks and 57 patients at week 24. Point prevalence abstinence rates were 37.5% (95% CI 26.4-49.7%) at week 12 and 32.8% (95% CI 21.8-45.4%) at week 26, respectively. Quality of life and side effects were not significantly affected by pharmacotherapy. CONCLUSION: In conclusion, our results suggest that smoking cessation is feasible in patients with newly diagnosed lung cancer. The observed abstinence rate is comparable to other patient cohorts. Furthermore, pharmacotherapy in addition to cancer therapy was safe and did not show novel side effects in these seriously ill patients. Thus, smoking cessation should be an integral part of lung cancer treatment. Trial registration The study was conducted in accordance with good clinical practice standards (GCP) and approved by the local ethics committee (16/3/14), the European PAS registry (EUPAS8748) and the German BfArM (NIS-Studien-Nr. 5508). All patients provided written informed consent before study enrollment.

Chemical characterization of tobacco-free "modern" oral nicotine pouches and their position on the toxicant and risk continuums.

As compared with cigarette smoking, use of Swedish snus is associated with significantly fewer health risks. Nicotine pouches (NPs), a new form of oral nicotine product, are smokeless and tobacco-free, comprising a nicotine-containing cellulose matrix inside a fiber pouch. NPs are similar in appearance/use to snus, but without tobacco, have the potential to further reduce tobacco-related harm. This study aimed to evaluate toxicant levels of NPs to estimate their position on the tobacco/nicotine product continuums of toxicant delivery and risk. NPs, snus and nicotine replacement therapy products (NRTs) were analyzed for 24-26 compounds applicable to oral tobacco, and their levels were compared. Twenty of these compounds were further used to compare the toxicant profile of NPs, as well as estimated daily toxicant exposure from NP use, with that of tobacco/nicotine products spanning the risk continuum. Of the compounds measured, 22 (NPs), 22 (lozenge NRT), 20 (gum NRT), and 11 (snus) were not quantifiable. Compared with snus, NPs had lower levels of 10 HPHCs and comparable/undetectable levels of a further 13. Across the product categories, NPs and NRTs had the lowest toxicant profiles and estimations of relative toxicant exposure. Based on the present chemical analysis and estimated exposure, use of NPs appears likely to expose users to lower levels of toxic compounds than Swedish snus, which is recognized to offer reduced levels of harm than associated with tobacco smoking. We conclude that NPs should be placed close to NRTs on the tobacco/nicotine product toxicant delivery continuum, although further studies will be needed to confirm this.

Pathophysiology of nicotine, place of nicotine substitutes and electronic cigarettes in plastic surgery: A review of the literature.

OBJECTIVE: Smokers are more likely to undergo postoperative complications after plastic surgeries. Our main purpose was to update nicotine's effects after plastic surgeries and assess whether nicotine-replacement therapy and vaping are safe enough to be recommended in peri-operatory circumstances. METHODS: We set up a literature review including 40 documents from 1986 to 2020 available on Pubmed. RESULTS: Nicotine has undeniable detrimental effects on patients undergoing plastic surgeries like cutaneous necrosis, skin flap failure and surgical site infection. Nevertheless, this toxicity seems to depend on the plasma concentration of nicotine and thus on the way of administration. While smoking is definitely harmful, nicotine replacement therapies (NRT) like patches and gums do not appear to increase postoperative risks based on available studies. The situation is different with the electronic cigarette since the pharmacokinetic parameters are close to those of the traditional cigarette. Even if powerful studies are lacking because the device is recent, preliminary in vitro studies and case reports suggest non-zero surgical risks for e-cigarette users. CONCLUSION: It seems more appropriate to suggest stopping all nicotine intake before and after plastic surgery. However, if strict cessation is not achievable, it appears preferable to use nicotine replacement therapies rather than e-cigarettes and most of all tobacco.

Comparative efficacy and safety of pharmacological interventions for smoking cessation in healthy adults: A network meta-analysis.

Smoking is the leading cause of morbidity and mortality in different non-communicable diseases, and cessation leads to immense health benefits. The present network meta-analysis has been conducted to evaluate and compare the effects of available pharmacological interventions for smoking cessation in adults. A standard meta-analysis protocol was developed and after performing a comprehensive literature search on MEDLINE/PubMed, Cochrane databases, and International Clinical Trials Registry Platform, reviewers extracted data from 97 randomized controlled trials. PRISMA guidelines were followed in data extraction, analysis and reporting of findings. Random effects Bayesian network meta-analysis was done to pool the effects across the interventions. Network graph was built, and for closed triangles in the network graph, node splitting analysis was performed. The primary outcome measure was self-reported biochemically verified smoking abstinence at six months. The number of participants achieving continuous abstinence was reported. Data for the number of participants reporting at least one adverse event was also extracted, if available. Combination of nicotine receptor agonist and nicotine replacement therapy had a significant odd of 4.4 (95%CrI:2.2-8.7), bupropion and nicotine receptor agonist 4.0 (95%CrI:2.1-7.7), bupropion and nicotine replacement therapy 3.8 (95%CrI:2.3-6.2), combination nicotine replacement therapy has an odd of 2.6 (95%CrI:1.8-3.8), and nicotine receptor agonist had a significant odd of 2.7 (95%CrI:2.3-3.2) when compared to placebo (moderate quality of evidence) for continuous abstinence at 6 months. When compared with behavioural therapy, the odds ratio of interventions was not statistically significant. Combination of nicotine receptor agonist and nicotine replacement therapy has the highest probability of being the best treatment for abstinence from smoking.

Cost-Effectiveness Analysis of Smoking Cessation Interventions in the United Kingdom Accounting for Major Neuropsychiatric Adverse Events.

OBJECTIVES: Smoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom. METHODS: An established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information. RESULTS: When limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose. CONCLUSION: Although found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators.