What to do after smoking relapse? A sequential multiple assignment randomized trial of chronic care smoking treatments.

AIM: To compare effects of three post-relapse interventions on smoking abstinence. DESIGN: Sequential three-phase multiple assignment randomized trial (SMART). SETTING: Eighteen Wisconsin, USA, primary care clinics. PARTICIPANTS: A total of 1154 primary care patients (53.6% women, 81.2% White) interested in quitting smoking enrolled from 2015 to 2019; 582 relapsed and were randomized to relapse recovery treatment. INTERVENTIONS: In phase 1, patients received cessation counseling and 8 weeks nicotine patch. Those who relapsed and agreed were randomized to a phase 2 relapse recovery group: (1) reduction counseling + nicotine mini-lozenges + encouragement to quit starting 1 month post-randomization (preparation); (2) repeated encouragement to quit starting immediately post-randomization (recycling); or (3) advice to call the tobacco quitline (control). The first two groups could opt into phase 3 new quit treatment [8 weeks nicotine patch + mini-lozenges plus randomization to two treatment factors (skill training and supportive counseling) in a 2 × 2 design]. Phase 2 and 3 interventions lasted ≤ 15 months. MEASUREMENTS: The study was powered to compare each active phase 2 treatment with the control on the primary outcome: biochemically confirmed 7-day point-prevalence abstinence 14 months post initiating phase 2 relapse recovery treatment. Exploratory analyses tested for phase 3 counseling factor effects. FINDINGS: Neither skill training nor supportive counseling (each on versus off) increased 14-month abstinence rates; skills on versus off 9.3% (14/151) versus 5.2% (8/153), P = 0.19; support on versus off 6.6% (10/152) versus 7.9% (12/152), P = 0.73. Phase 2 preparation did not produce higher 14-month abstinence rates than quitline referral; 3.6% (8/220) versus 2.1% [3/145; risk difference = 1.5%, 95% confidence interval (CI) = -1.8-5.0%, odds ratio (OR) = 1.8, 95% CI = 0.5-6.9]. Recycling, however, produced higher abstinence rates than quitline referral; 6.9% (15/217) versus 2.1% (three of 145; risk difference, 4.8%, 95% CI = 0.7-8.9%, OR = 3.5, 95% CI = 1.0-12.4). Recycling produced greater entry into new quit treatment than preparation: 83.4% (181/217) versus 55.9% (123/220), P < 0.0001. CONCLUSIONS: Among people interested in quitting smoking, immediate encouragement post-relapse to enter a new round of smoking cessation treatment ('recycling') produced higher probability of abstinence than tobacco quitline referral. Recycling produced higher rates of cessation treatment re-engagement than did preparation/cutting down using more intensive counseling and pharmacotherapy.

[The e-cigarette - means of smoking cessation?] / Die E-Zigarette ­ Mittel zur Tabakentwöhnung?

After several years of declining tobacco consumption, the number of smokers in Germany is currently stagnating or rising again. The reasons seem to be manifold, e. g. stress caused by the pandemic with social isolation, rising cost of living and war in Europe.With tobacco use still widespread in the German population, evidence-based tobacco cessation is rarely implemented.According to recent studies, e-cigarettes are involved in the pathogenesis of lung disease, cardiac and vascular damage. In addition, their ingredients also have carcinogenic effects. However, clinical studies on long-term use are not yet available.E-cigarettes as a consumer product are not superior to nicotine replacement products and addiction-reducing medications recommended in guidelines. In the therapeutic setting, they are slightly more effective than nicotine replacement products. However, they are usually consumed continuously and thus perpetuate nicotine dependence. Their use increases the risk of relapse to tobacco smoking.Despite the various new approaches, such as Internet-based offerings, app, etc., talks and pharmacotherapy are the gold standard and more effective than any therapy on its own.

Identification of Sociodemographic, Clinical, and Genetic Factors to Aid Alaska Native and American Indian People to Successfully Quit Smoking.

INTRODUCTION: Alaska Native and American Indian (ANAI) people have a smoking prevalence of 23%. Nicotine metabolite ratio (NMR) and genetic testing may enable tailored selection of tobacco cessation medication. AIMS AND METHODS: The purpose of this study was to evaluate the relative contributions of NMR, cessation medication, demographics, and tobacco use history to cessation. Participants were recruited into an observational cohort study consisting of a baseline visit prior to their quit date and 6-week follow-up. Demographic and tobacco use surveys and blood, urine, and breath samples were collected at each visit. Electronic health records were queried for cessation medications. NMR was categorized into slow or normal nicotine metabolism phenotypes (<0.31 and ≥ 0.31, respectively). The main outcome was cessation at 6 weeks. Analyses consisted of descriptive statistics, medication and phenotype concordance, and estimates of relative risk (RR) of quitting. RESULTS: We enrolled 151 ANAI adults who smoked cigarettes daily. Two-thirds had normal nicotine metabolism phenotype. Retrospective medication and phenotype concordance was 39%. The overall quit rate was 25%. No demographic factors or tobacco use history were associated with quit success. Varenicline and bupropion increased the likelihood of quitting (RR = 2.93 [1.42, 6.03] and RR = 2.52 [1.12, 5.64], respectively) compared to nicotine replacement therapy. Non-optimal medication and phenotype concordance decreased likelihood of quit success (RR = 0.44 [0.22, 0.91]) compared to optimal concordance. CONCLUSIONS: This exploratory study found associations between quit success and tobacco cessation medication as well as medication and phenotype concordance. Additional research is needed to assess use of NMR for treatment selection among ANAI people. IMPLICATIONS: These results broadly support additional community-engaged research to improve medication and phenotype concordance in tribal health settings. Such future research on implementing meditcation and phenotype concordance holds promise to improve expectations, quit success, and health outcomes amongst individuals attempting to quit smoking.

Competitive inhibition of nicotine acetylcholine receptors using microneedles of nicotine and varenicline for smoking withdrawal therapy.

Current strategies for smoking withdrawal conditions involve monotherapy of nicotine and combinational therapy of nicotine with varenicline or bupropion as per the CDC and FDA. The available dosage forms for nicotine are patches, gums, inhalers and nasal sprays, bupropion and varenicline are available in tablet form. This research work focused on developing a microneedle delivery system to deliver combination drug for overcoming the obstacles encountered by oral route of administration of varenicline such as severe side effects (mood swings, agitation, depressed behaviour, seizures, etc), and nicotine therapy challenges such as short half-life, repeated dosing, nausea, and vomiting. The nanoparticles of nicotine prepared by nanoprecipitation method showed particle size PTZ (356.6 ± 65.98), percentage entrapment efficiency (35.55 % ± 0.007), in-vitro drug release (47.89 % ± 0.7) for 72 h. Microneedles showed height (600 µm), width (350 µm), and tip diameter (10 µm). The nanoparticles encapsulated in microneedles showed in-vitro sustained delivery of nicotine (67.00 % ± 4.92) and varenicline (79.78 % ± 1.09) in 48 h. Nicotine released in a sustained manner attaches to the nicotine acetylcholine receptors (nAchR) to release dopamine for controlling the withdrawal challenges such as anxiety, irritability, cravings, disturbed sleep pattern, etc. The varenicline released from microneedles binds to the nAchR and inhibits dopamine release responsible for the euphoric effect induced by nicotine, and thus assists in curbing the nicotine withdrawal symptoms. This combination microneedle system offers prolonged treatment in a single application for smoking withdrawal conditions wherein patients are not in stage of oral dosing because of repeated dosing resulting in adverse effects like seizures, hypertension, sleep disturbances, insomnia, and nausea.

Multiple Pharmacotherapy Adaptations for Smoking Cessation Based on Treatment Response in Black Adults Who Smoke: A Randomized Clinical Trial.

Importance: Adapting to different smoking cessation medications when an individual has not stopped smoking has shown promise, but efficacy has not been tested in racial and ethnic minority individuals who smoke and tend to have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality. Objective: To evaluate efficacy of multiple smoking cessation pharmacotherapy adaptations based on treatment response in Black adults who smoke daily. Design, Setting, and Participants: This randomized clinical trial of adapted therapy (ADT) or enhanced usual care (UC) included non-Hispanic Black adults who smoke and was conducted from May 2019 to January 2022 at a federally qualified health center in Kansas City, Missouri. Data analysis took place from March 2022 to January 2023. Interventions: Both groups received 18 weeks of pharmacotherapy with long-term follow-up through week 26. The ADT group consisted of 196 individuals who received a nicotine patch (NP) and up to 2 pharmacotherapy adaptations, with a first switch to varenicline at week 2 and, if needed, a second switch to bupropion plus NP (bupropion + NP) based on carbon monoxide (CO)-verified smoking status (CO ≥6 ppm) at week 6. The UC group consisted of 196 individuals who received NP throughout the duration of treatment. Main Outcomes and Measures: Anabasine-verified and anatabine-verified point-prevalence abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points). The χ2 test was used to compare verified abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points) between ADT and UC. A post hoc sensitivity analysis of smoking abstinence at week 12 was performed with multiple imputation using a monotone logistic regression with treatment and gender as covariates to impute the missing data. Results: Among 392 participants who were enrolled (mean [SD] age, 53 [11.6] years; 224 [57%] female; 186 [47%] ≤ 100% federal poverty level; mean [SD] 13 [12.4] cigarettes per day), 324 (83%) completed the trial. Overall, 196 individuals were randomized to each study group. Using intent-to-treat and imputing missing data as participants who smoke, verified 7-day abstinence was not significantly different by treatment group at 12 weeks (ADT: 34 of 196 [17.4%]; UC: 23 of 196 [11.7%]; odds ratio [OR], 1.58; 95% CI, 0.89-2.80; P = .12), 18 weeks (ADT: 32 of 196 [16.3%]; UC: 31 of 196 [15.8%]; OR, 1.04; 95% CI, 0.61-1.78; P = .89), and 26 weeks (ADT: 24 of 196 [12.2%]; UC: 26 of 196 [13.3%]; OR, 0.91; 95% CI, 0.50-1.65; P = .76). Of the ADT participants who received pharmacotherapy adaptations (135/188 [71.8%]), 11 of 135 (8.1%) were abstinent at week 12. Controlling for treatment, individuals who responded to treatment and had CO-verified abstinence at week 2 had 4.6 times greater odds of being abstinent at week 12 (37 of 129 [28.7%] abstinence) than those who did not respond to treatment (19 of 245 [7.8%] abstinence; OR; 4.6; 95% CI, 2.5-8.6; P < .001). Conclusions and Relevance: In this randomized clinical trial of adapted vs standard of care pharmacotherapy, adaptation to varenicline and/or bupropion + NP after failure of NP monotherapy did not significantly improve abstinence rates for Black adults who smoke relative to those who continued treatment with NP. Those who achieved abstinence in the first 2 weeks of the study were significantly more likely to achieve later abstinence, highlighting early treatment response as an important area for preemptive intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03897439.

How do patients and staff in an opioid agonist treatment service view smoking cessation medications and e-cigarettes?

INTRODUCTION: Tobacco use and related mortality is common in people receiving opioid agonist treatment (OAT). Smoking cessation medications are available and e-cigarettes are increasingly recommended for high risk populations. This study explores experience, knowledge and attitudes around smoking cessation medications (nicotine replacement therapy [NRT], bupropion and varenicline) and e-cigarettes in patients and clinicians in two public Australian OAT clinics. METHODS: Cross-sectional surveys of patients and clinicians and a randomly sampled retrospective medical record review. Patients were recruited through an advertisement in the clinic, and clinicians through advertisement at an educational session. RESULTS: Ninety-one patients and 10 clinicians completed the surveys. Most patients had at least one quit attempt and 43% were currently trying to quit. There were high levels of exposure to NRT, lower levels with varenicline and very limited exposure to bupropion. Patients considered e-cigarettes most helpful, but were more likely to consider using NRT. Few patients reported smoking cessation interventions from their clinicians. Most clinicians identified high tobacco use prevalence, considered this problematic, but reported low rates of smoking cessation intervention. NRT was the preferred medication. E-cigarettes were not considered helpful. Sixty-six percent of the 140 records reviewed documented patients as smokers. Tobacco cessation medication was rarely discussed or provided. DISCUSSION AND CONCLUSIONS: Patients report high rates of tobacco cessation planning, but low rates of intervention. Experience of varenicline and bupropion is limited. E-cigarettes were preferred over varenicline and bupropion. Improving patient's and clinician's knowledge of tobacco cessation medications could improve smoking cessation interventions and uptake of approved medications.

Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report.

BACKGROUND: Creating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders. CASE PRESENTATION: In this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors. CONCLUSION: The occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.

The 2022 Ferno Award Address: CrEATE, an Efficient Crossover Evaluation of Addiction Treatment Efficacy.

Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA terminology), with the vast majority failing to show efficacy. Even small randomized clinical trials (RCTs), the most common early Phase 2 tests, are costly undertakings, made more unappealing by their high likelihood of failure. At the same time, another early Phase 2 approach, acute tests of drug effects on surrogate endpoints such as withdrawal or craving severity, are more practical but have little predictive clinical validity. Described here is an innovative procedure that optimally combines the validity of clinical trials with the practical advantages of surrogate endpoint studies to more efficiently determine whether or not a novel drug warrants continued clinical development. This CrEATE procedure, or Crossover Evaluation of Addiction Treatment Efficacy, does so by assessing short-term quit success in smokers highly motivated to quit when briefly treated with active drug versus placebo in a crossover design, so that quit efficacy from both conditions is compared within participants. The program to develop and evaluate CrEATE demonstrates its sensitivity to efficacy from all three FDA-approved first-line cessation medications (NRT, varenicline, bupropion), tested here as model drugs, as well as specificity in identifying lack of efficacy with a drug known to be ineffective for cessation (modafinil). CrEATE has subsequently been used to evaluate a few novel interventions, concluding they lack efficacy in increasing quit success. Future directions for the potential utility of CrEATE are provided. Implications: The ability of CrEATE to reach a Go/No Go decision more quickly and with far less cost lowers the risk of failure, meaning widespread use of the procedure should encourage the evaluation of more novel candidate drugs. With its greater efficiency, failed tests, unfortunately the most likely outcome in early Phase 2 studies, will cause less waste of resources. At the same time, CrEATE tests that indicate a novel treatment has efficacy will justify the substantial time and expense of moving forward to evaluate the drug in late Phase 2 RCTs.

A Pragmatic Cluster-Randomized Trial of Provider Education and Community Health Worker Support for Tobacco Cessation.

OBJECTIVE: Individuals with serious mental illness have a high prevalence of tobacco use disorder and related early mortality but underutilize smoking cessation medication. The authors determined whether clinician-delivered education to primary care providers regarding safety, efficacy, and importance of cessation medication (provider education [PE]) alone or combined with community health worker (CHW) support would increase tobacco abstinence in this population, compared with usual care. METHODS: All adult current tobacco smokers receiving psychiatric rehabilitation for serious mental illness through two community agencies in Greater Boston were eligible, regardless of readiness to quit smoking. Primary care clinics were cluster randomized to PE or usual care, with a nested, participant-level randomization to CHW or no CHW in PE-assigned clinics. The primary outcome was blindly assessed, biochemically verified tobacco abstinence at year 2. RESULTS: Overall, 1,010 eligible participants were enrolled. PE was delivered to providers in 53 of 55 assigned clinics; 220 of 336 CHW-assigned participants consented to CHW support. Year 2 abstinence rates were significantly higher among participants assigned to PE+CHW versus usual care (12% vs. 5%; adjusted odds ratio [AOR]=2.40, 95% confidence interval [CI]=1.20-4.79) or PE alone (12% vs. 7%; AOR=1.84, 95% CI=1.04-3.24). No effect of PE alone on abstinence was detected. Compared with participants assigned to usual care, those assigned to PE+CHW had greater odds of varenicline use (OR=2.77, 95% CI=1.61-4.75), which was associated with higher year 2 abstinence (OR=1.97, 95% CI=1.16-3.33). CONCLUSIONS: Combined PE and CHW tobacco cessation support increased tobacco abstinence rates among adults with serious mental illness.

Psychopharmacology of smoking cessation medications: focus on patients with mental health disorders.

The adverse effects of smoking cessation in individuals with mental health disorders have been a point of concern, and progress in the development of treatment has been slow. The primary first-line treatments for smoking cessation are Nicotine Replacement Therapy, Bupropion, Varenicline, and behavioural support. Nortriptyline and Clonidine are second-line treatments used when the first-line treatments are not effective or are contraindicated. Smoking cessation medications have been shown to be effective in reducing nicotine cravings and withdrawal symptoms and promoting smoking cessation among patients living with mental disorders. However, these medications may have implications for patients' mental health and need to be monitored closely. The efficacy and side effects of these medications may vary depending on the patient's psychiatric condition, medication regimen, substance use, or medical comorbidities. The purpose of this review is to synthesise the pharmacokinetics, pharmacodynamics, therapeutic effects, adverse effects, and pharmacological interactions of first- and second-line smoking cessation drugs, with an emphasis on patients suffering from mental illnesses. Careful consideration of the risks and benefits of using smoking cessation medications is necessary, and treatment plans must be tailored to individual patients' needs. Monitoring symptoms and medication regimens is essential to ensure optimal treatment outcomes.

Smoking quit rates among patients receiving pharmacotherapy who received general practitioner counselling versus intensive counselling: a retrospective cohort study.

BACKGROUND: Behavioral treatments can augment the success of pharmacotherapy in smoking cessation. The aim of this study was to compare smoking quit rates between patients receiving individual counseling with their general practitioner during office visits or intensive counselling with behavioral support, both augmented by varenicline. METHODS: A nationwide retrospective cohort study conducted in a large Healthcare Maintenance Organization in Israel. We selected randomly patients who filled a prescription for varenicline and received either individual consulting by their general practitioner or intensive counselling with behavioural support, and asked them to answer a questionnaire. The outcome variables were smoking cessation 26-52 weeks following the beginning of treatment and satisfaction with the process. RESULTS: 870 patients were contacted and 604 agreed to participate (a response rate of 69%); 301 patients in the general practitioner group, 300 in the intensive counselling group and 3 were excluded due to missing date. The quit rate was 36.5% in the general practitioner group and 42.3% in the intensive counselling group (P = 0.147). In a logistic regression analysis, controlling for age, gender, socioeconomic status, ischemic heart disease, chronic obstructive pulmonary disease, pack years and duration of varenicline consumption, the adjusted OR for quitting in the general practitioner group was 0.79 (95% CI 0.56,1.13). The adjusted OR was higher in the group with the highest socioeconomic status at 2.06 (1.39,3.07) and a longer period of varenicline consumption at 1.30 (1.15,1.47). Age, gender and cigarette pack-years were not associated with quit rate. In the general practitioner group 68% were satisfied with the process, while 19% were not. In the intensive counselling group 64% were satisfied and 14% were not (P = 0.007). CONCLUSION: We did not detect a statistically significant difference in smoking quit rates, though there was a trend towards higher quit rates with intensive counselling.

A systematic review with meta-analysis of the effects of smoking cessation strategies in patients with rheumatoid arthritis.

OBJECTIVE: Smoking rates among patients with rheumatoid arthritis (RA) exceed those in the general population. This study identified smoking cessation strategies used in patients with RA and synthesized data on their effects. METHODS: We conducted a systematic review of studies that reported effects of interventions for smoking cessation in patients with RA. We searched 5 electronic databases until March 2022. Screening, quality appraisal, and data collection were done independently by 2 reviewers. RESULTS: We included 18 studies reporting interventions for patients or providers: 14 evaluated strategies for patients (5 education on cardiovascular risk factors including smoking, 3 educational interventions on smoking cessation alone, 3 education with nicotine replacement and counseling, and 1 study each: education with nicotine replacement, counseling sessions alone, and a social marketing campaign). Smoking cessation rates ranged from 4% (95% CI: 2%-6%, 24 to 48 weeks) for cardiovascular risk education to 43% (95% CI: 21%-67%, 104 weeks) for counseling sessions alone. The pooled cessation rate for all interventions was 22% (95% CI: 8%-41%, 4 weeks to 104 weeks; 9 studies). Four interventions trained providers to ascertain smoking status and provide referrals for smoking cessation. The pooled rates of referrals to quit services increased from 5% in pre-implementation populations to 70% in post-implementation populations. CONCLUSION: Studies varied in patient characteristics, the interventions used, and their implementation structure. Only 3 studies were controlled clinical trials. Additional controlled studies are needed to determine best practices for smoking cessation for patients with RA.

Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence: A Randomized Clinical Trial.

Importance: Even with varenicline, the leading monotherapy for tobacco dependence, smoking abstinence rates remain low. Preliminary evidence suggests that extending the duration of varenicline treatment before quitting may increase abstinence. Objective: To test the hypotheses that, compared with standard run-in varenicline treatment (1 week before quitting), extended run-in varenicline treatment (4 weeks before quitting) reduces smoking exposure before the target quit date (TQD) and enhances abstinence, particularly among women. Design, Setting, and Participants: This double-blind, randomized, placebo-controlled clinical trial enrolled participants from October 2, 2017, to December 9, 2020, at a single-site research clinic in Buffalo, New York. Of 1385 people screened, 320 adults reporting smoking 5 or more cigarettes per day (CPD) were randomized and followed up for 28 weeks. Data were analyzed from August 2021 to June 2022. Interventions: In the pre-TQD period (weeks 1-4), the extended run-in group received 4 weeks of varenicline; the standard run-in group received 3 weeks of placebo followed by 1 week of varenicline. Both groups received open-label varenicline during weeks 5 to 15 and brief quit counseling at 6 clinic visits. Main Outcomes and Measures: The primary outcome consisted of cotinine-verified (at end of treatment [EOT]) self-reported continuous abstinence from smoking (in CPD) during the last 4 weeks of treatment. Secondary outcomes included bioverified self-report of continuous abstinence at the 6-month follow-up and percentage of reduction in self-reported smoking rate during the prequit period (week 1 vs week 4). Results: A total of 320 participants were randomized, including 179 women (55.9%) and 141 men (44.1%), with a mean (SD) age of 53.7 (10.1) years. Continuous abstinence during the final 4 weeks of treatment (weeks 12-15; EOT) was not greater in the extended run-in group (64 of 163 [39.3%]) compared with the standard run-in group (57 of 157 [36.3%]; odds ratio [OR], 1.13 [95% CI, 0.72-1.78]), nor was the hypothesized group × sex interaction significant (OR, 0.52 [95% CI, 0.21-1.28]). Similar nonsignificant results were obtained for continuous abstinence at the 6-month follow-up. The mean (SE) decrease in self-reported smoking rate during the prequit period was greater in the extended run-in group (-38.8% [2.8%]) compared with the standard run-in group (-17.5% [2.7%]). Conclusions and Relevance: Among adult daily smokers, extending the duration of prequit varenicline treatment beyond the standard 1-week run-in period reduced prequit smoking exposure but, more importantly, did not significantly improve continuous abstinence rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03262662.

The Impact of Smoking on the Development and Severity of Chronic Pain.

PURPOSE OF REVIEW: The purpose of this review is to examine the impact of smoking and its role on the development of chronic pain and provide a critical review of recent literature. RECENT FINDINGS: Recent studies demonstrate the bidirectional and dependent relationship between smoking and chronic pain. Those who are in pain have a more difficult time in the cessation of smoking as well as an increased sensitivity to pain during abstinence, lower confidence, and higher relapse rates. The fear of pain and the anxiety and depression that abstinence causes results in a grim outcome for long-term cessation. The dependent nature between chronic pain and smoking is affected by numerous variables. Providers should consider a multiprong approach to treating chronic pain and targeting smoking cessation treatment by providing motivational therapy, nicotine replacement, and medication therapies to prevent relapse, and providing those who are more likely to relapse with a higher level of care.

Characterising the use of varenicline: an analysis of the Australian dispensing claims data.

BACKGROUND AND AIMS: In Australia, patterns of use of smoking cessation medications and factors associated with their dispensing are currently not known. This study aimed to measure the demographic and clinical factors associated with varenicline dispensing compared with nicotine replacement therapy (NRT) and bupropion among first-time users of Pharmaceutical Benefits Scheme (PBS) subsidised smoking cessation medicines in Australia and to characterise those who discontinued varenicline treatment prematurely. DESIGN: Retrospective, population-based study. Logistic regression was used to identify factors associated with varenicline dispensing compared with NRT and bupropion. Sensitivity analyses estimated the proportion of individuals who completed the recommended 12 weeks of varenicline treatment. SETTING AND PARTICIPANTS: First-time users of PBS subsidised smoking cessation medicines in Australia. Individuals first dispensed a smoking cessation medicine between 2011 and 2019 were identified from a 10% random sample of the national dispensing claims data. MEASUREMENTS: The outcome for the regression analysis was the dispensing of varenicline compared with NRT and bupropion. The dispensing of a smoking cessation medicine was identified using the World Health Organization Anatomical Therapeutic Chemical Classification System and PBS item codes. Independent variables included demographic and clinical characteristics such as sex, age, concessional status, year of treatment initiation and comorbidities identified using the Rx-Risk index. The proportion of people who discontinued varenicline treatment after the initiation pack was determined using prescription refill data. FINDINGS: A total of 94 532 people had their first PBS subsidised smoking cessation medicine. Of these, 62 367 (66.0%) were dispensed varenicline, 29 949 (31.7%) NRT and 2216 (2.3%) bupropion. The odds of varenicline dispensing were higher in males (OR, 1.18; 95% CI, 1.14-1.21), but lower in older adults (0.86 [0.82-0.90] in above 30 years to 0.49 [0.47-0.52] in 61 years and above), among concession beneficiaries (0.44; 0.43-0.46), and those with congestive heart failure (0.60; 0.53-0.68), depression (0.61; 0.54-0.69), anxiety (0.70; 0.66-0.73), psychotic illness (0.39; 0.37-0.42), and chronic obstructive pulmonary disease (0.87; 0.82-0.92). The majority (37 670; 60.4%) of those dispensed varenicline discontinued treatment after the initiation pack. Anxiety and psychotic illnesses were significantly more prevalent in those who discontinued treatment. Only 2804 (4.5%) of those dispensed varenicline completed 12 weeks of treatment. CONCLUSION: Individuals dispensed varenicline in Australia appear to be healthier compared with those who are dispensed nicotine replacement therapy or bupropion.

Assisted versus referred pharmacy smoking interventions for patients with thoracic malignancies or pulmonary nodules.

BACKGROUND: Tobacco use is the foremost preventable cause of death, disease, and disability in the United States. Continued tobacco use in malignant disease contributes to treatment failure and disease progression. Pharmacists are pivotal to tobacco cessation counseling, management, and follow up. METHODS: This retrospective, observational, single-center, cohort study of ambulatory cancer patients was designed to assess the impact of assisted versus "Ask, Advise, Refer" (AAR) pharmacy-driven smoking cessation interventions on patient-reported quit rates at 30- and 90-days. Those included were currently smoking or recently quit adults with a thoracic malignancy or nodule. Those in the assisted intervention were offered nicotine replacement therapy (NRT) for free according to a personalized quit plan. After July 1, 2020, patients were enrolled in the AAR intervention, whereby participants were referred to obtain NRT through insurance or external resources. Both clinical interventions were provided as standard of care. RESULTS: 129 participants were included (assisted n = 83; AAR n = 46) with baseline characteristics evenly matched. After excluding those unable to be reached at 30-days, 30 (44.8%) in the assisted intervention quit smoking versus 11 (27.5%) in the AAR intervention, p = 0.08. Lung cancer patients were more likely to report quitting at 30-days in the assisted intervention, 16 (64.0%) versus 5 (29.4%) in the AAR intervention, p = 0.03. After excluding those unable to be reached at 90-days, 30 (45.5%) in the assisted intervention quit versus 11 (35.5%) in the AAR intervention, p = 0.35. CONCLUSIONS: Pharmacy-led smoking cessation initiatives that include providing NRT are especially impactful on smoking cessation in lung cancer patients.

Smoking cessation and risk of type 2 diabetes.

Risk of type 2 diabetes mellitus (T2DM) is higher in tobacco smokers compared to non-smokers. The risk declines after smoking cessation. However, ex-smokers are also more prone to the metabolic syndrome. The question thus is, whether ex-smokers could temporarily have a higher risk of T2DM than current smokers. The available studies on this topic are not in agreement in their conclusions, as most of them also primarily do not compare ex-smokers to current smokers, but to non-smokers. However, based on the available studies, it rather seems the risk of T2DM is temporarily higher after smoking cessation. The higher risk of T2DM seems to be enhanced by weight gain that typically occurs first years after smoking cessation without intervention. Therefore, smoking cessation in patients who are in an increased risk of T2DM should be accompanied by T2DM preventative measures (lifestyle modification, weight monitoring and recommendation of pharmacotherapy of tobacco addiction to lower the risk of weight gain) and more frequent checks of blood glucose level to ensure early T2DM detection.

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.

Extended Duration Treatment of Tobacco Dependence: A Systematic Review and Meta-Analysis.

Rationale: The American Thoracic Society (ATS) developed a clinical practice guideline on initiating pharmacologic treatment in tobacco-dependent adults. Controller pharmacotherapies treat tobacco dependence effectively when taken as prescribed, but relapse after pharmacologic discontinuation is common. Objectives: To evaluate the effectiveness and safety of initiating controller for an extended (>12 wk) versus a standard duration (6-12 wk) in tobacco-dependent adults. Methods: We systematically searched PubMed, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to December 2021 to identify randomized controlled trials comparing extended versus standard duration of controllers for tobacco-dependent adults. We conducted meta-analyses using the Mantel-Haenszel method with random effects model. Outcomes of interest include point-prevalent abstinence at 1-year follow-up or longer, relapse, adverse events, quality of life, and withdrawal symptoms. Subgroup analyses were conducted according to types of treatment and duration of extended therapy when feasible. We assessed the certainty of the estimate following the grading of recommendations, assessment, development and evaluation methodology. Results: We included 13 randomized controlled trials including 8,695 participants that directly compared extended- (>12 wk) versus standard-duration controller therapy with varenicline, bupropion, or nicotine replacement therapy. Compared with standard-duration controller therapy, extended-duration controller therapy probably increased abstinence at 1-year follow-up, measured as 7-day point-prevalence abstinence (relative risk, 1.18; 95% confidence interval [CI], 1.05-1.33; moderate certainty). Extended-duration controller therapy probably reduced relapse compared with standard-duration controller therapy, assessed at 12-18 months after initiation of therapy (hazard ratio, 0.43; 95% CI, 0.29-0.64; moderate certainty). Moderate certainty evidence also suggested that extended-duration controller therapy probably did not increase risk of serious adverse events (relative risk, 1.37; 95% CI, 0.79-2.36). Conclusions: This systematic review supported the recommendation for extended-duration therapy with controllers. Further studies on optimal extended duration are warranted.

High-throughput cell-based assays for identifying antagonists of multiple smoking-associated human nicotinic acetylcholine receptor subtypes.

There is substantial evidence that in addition to nicotine, other compounds found in tobacco smoke significantly influence smoking behavior. Further, recent years have seen an explosion in the availability of non-combusted products that deliver nicotine, such as e-cigarettes and "home-brew" vaping devices that are essentially unregulated. There are many thousands of compounds in tobacco smoke alone, and new products are constantly introducing new compounds. Uncovering which of these compounds are active, across multiple smoking-relevant subtypes of the nicotinic acetylcholine receptor (nAChR) that influence tobacco/nicotine addiction, requires a high-throughput screening (HTS) approach. Accordingly, we developed a panel of HTS-friendly cell-based assays, all performed in the same cellular background and using the same membrane potential dye readout, to measure the function of the α3ß4-, α4ß2-, and α6ß2-nAChR subtypes. These subtypes have each been prominently and consistently associated with human smoking behavior. We validated our assays by performing pilot screening of an expanded set of the Prestwick FDA-approved drug library. The screens displayed excellent performance parameters, and moderate hit rates (mean of 1.2% across all three assays) were achieved when identifying antagonists (chosen since effects of endogenous antagonists on consumption of nicotine/tobacco products are under-studied). Validation rates using an orthogonal assay (86Rb+ efflux) averaged 73% across the three assays. The resulting panel of assays represents a valuable new platform with which to screen and identify nAChR subtype-selective compounds. This provides a resource for identifying smoking-related compounds in both combusted and non-combusted tobacco products, with potential relevance in the search for additional smoking-cessation therapies.