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Monaldi Archives For Chest Disease =... Dec 2023Given the increased health dangers of tobacco use, particularly in developing countries, smoking cessation intervention is crucially important. The aim of this study is...
Given the increased health dangers of tobacco use, particularly in developing countries, smoking cessation intervention is crucially important. The aim of this study is to determine and assess the effectiveness of a comprehensive smoking cessation intervention program, incorporating behavior modification, counseling, and pharmacologic treatments, in the context of the Indian scenario. The process of initiating smoking or tobacco cessation begins with the evaluation of the distinct stages that smokers undergo as part of their journey toward behavioral change. There are five different levels of preparation for quitting smoking, i.e., i) not prepared (pre-contemplation); ii) unsure (contemplation); iii) prepared (preparation); iv) action; and v) maintenance. Behavior modification and counseling are essential. The "5 A's"-based intervention uses ask, advise, assess, assist, and arrange as part of its strategy. First-line treatments such as nicotine replacement therapy, bupropion, and varenicline, as well as second-line treatments such as clonidine, cytisine, and nortriptyline, are the foundation of pharmacologic care. Every healthcare professional has a duty to help smokers stop using tobacco, and the intervention should be both therapeutic and diagnostic. Combining behavioral and social support yields the best results, along with pharmacotherapy whenever needed.
PubMed: 38050469
DOI: 10.4081/monaldi.2023.2814 -
BMJ Open Respiratory Research Nov 2023Smoking remains the single largest cause of preventable death, disability and health inequality. Smoking tobacco directly contributes to over 500 000 hospital admissions...
Smoking remains the single largest cause of preventable death, disability and health inequality. Smoking tobacco directly contributes to over 500 000 hospital admissions each year, making hospitals an important location to optimise treatment for tobacco dependency. The third British Thoracic Society Tobacco Dependency Audit was undertaken to determine how effectively national standards for treating tobacco-dependent smokers have been implemented and assess if any progress has been made from previous audits. Data on 14579 patients from 119 hospitals revealed 21% of patients were current smokers, 45% were offered very brief advice and 5% prescribed combination nicotine replacement therapy or varenicline. Only 9% completed a consultation with a specialist tobacco dependency practitioner during their inpatient stay and fewer than 1% of smokers were abstinent at 4 weeks following discharge. Clinical leadership of tobacco dependency services was deficient, and staff were ill equipped in supporting current smokers in their efforts to quit with only 50% of trusts offering regular smoking cessation training. There has been little meaningful improvement from previous audits and there remains woefully inadequate provision of tobacco dependency treatment for patients who smoke. The National Health Service (NHS) Long Term Plan has committed substantial, new funding to the NHS to ensure every patient that smokes admitted to hospital will be offered evidence-based support and treatment for tobacco dependency. The findings of this audit highlight the urgency with which this programme must be implemented to tackle the greatest cause of premature death in the UK and to achieve the wider well-recognised benefits for the healthcare system.
Topics: Humans; Health Status Disparities; Smoking; Smoking Cessation; State Medicine; Tobacco Use Cessation Devices; Tobacco Use Disorder
PubMed: 38030263
DOI: 10.1136/bmjresp-2022-001532 -
International Journal of Molecular... Oct 2023Positron emission tomography (PET) radioligands that bind with high-affinity to α4β2-type nicotinic receptors (α4β2Rs) allow for in vivo investigations of the...
Positron emission tomography (PET) radioligands that bind with high-affinity to α4β2-type nicotinic receptors (α4β2Rs) allow for in vivo investigations of the mechanisms underlying nicotine addiction and smoking cessation. Here, we investigate the use of an image-derived arterial input function and the cerebellum for kinetic analysis of radioligand binding in mice. Two radioligands were explored: 2-[F]FA85380 (2-FA), displaying similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [F]Nifene, displaying similar pKa and binding affinity to nicotine. Time-activity curves of the left ventricle of the heart displayed similar distribution across wild type mice, mice lacking the β2-subunit for ligand binding, and acute nicotine-treated mice, whereas reference tissue binding displayed high variation between groups. Binding potential estimated from a two-tissue compartment model fit of the data with the image-derived input function were higher than estimates from reference tissue-based estimations. Rate constants of radioligand dissociation were very slow for 2-FA and very fast for Nifene. We conclude that using an image-derived input function for kinetic modeling of nicotinic PET ligands provides suitable results compared to reference tissue-based methods and that the chemical properties of 2-FA and Nifene are suitable to study receptor response to nicotine addiction and smoking cessation therapies.
Topics: Mice; Animals; Nicotine; Brain; Tobacco Use Disorder; Kinetics; Ligands; Positron-Emission Tomography; Receptors, Nicotinic
PubMed: 37958495
DOI: 10.3390/ijms242115510 -
The Lancet Regional Health. Western... Oct 2023Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death....
BACKGROUND
Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation.
METHODS
This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers.
FINDINGS
A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome.
INTERPRETATION
The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China.
FUNDING
Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).
PubMed: 37927997
DOI: 10.1016/j.lanwpc.2023.100826 -
Tobacco Induced Diseases 2023During the pandemic, smokers who wished to access support to quit faced additional barriers. A smoking cessation service which utilized pharmacist independent...
INTRODUCTION
During the pandemic, smokers who wished to access support to quit faced additional barriers. A smoking cessation service which utilized pharmacist independent prescribers working within community pharmacy was implemented. Clients received behavioral advice via a consultation with an advisor and then three consultations with a pharmacist, who prescribed varenicline, where appropriate. Consultations were by phone or video. This evaluation assessed the self-reported outcomes and experiences of clients and pharmacists.
METHODS
A mixed-methods approach was used involving both on-line questionnaires to clients and interviews with a sample of questionnaire respondents and participating prescribing pharmacists.
RESULTS
The questionnaire was completed by 85 clients with 59% reporting they had quit. Eleven clients and seven out of eight pharmacists were interviewed. Varenicline had been received by 96% of clients. The best aspects of the service reported by clients in the questionnaire and at interview were support received from the pharmacist and ease of access to varenicline. Clients regarded the service as being 'safe' to access during the pandemic. Nearly three-quarters of client respondents (72%) stated no service improvements were required. However, national supply challenges made collection of varenicline from the nominated pharmacy an issue. Some clients experienced a long wait-time before accessing the service. For pharmacists, the service offered flexibility including the opportunity to contact clients 'out of office' hours without distractions. However, not being physically in the pharmacy could result in them not being able to access the client's medicine history. Pharmacists identified that remote consultations were not ideal for all clients.
CONCLUSIONS
Pharmacist prescribers can deliver effective smoking cessation services through remote consultations. Greater flexibility would allow the service to be tailored to the client's need.
PubMed: 37901881
DOI: 10.18332/tid/170580 -
Biomedicines Oct 2023Dengue virus (DENV) poses a significant global health challenge, with millions of cases each year. Developing effective antiviral drugs against DENV remains a major...
Dengue virus (DENV) poses a significant global health challenge, with millions of cases each year. Developing effective antiviral drugs against DENV remains a major hurdle. Varenicline is a medication used to aid smoking cessation, with anti-inflammatory and antioxidant effects. In this study, varenicline was investigated for its antiviral potential against DENV. This study provides evidence of the antiviral activity of varenicline against DENV, regardless of the virus serotype or cell type used. Varenicline demonstrated dose-dependent effects in reducing viral protein expression, infectivity, and virus yield in Vero and A549 cells infected with DENV-1 and DENV-2, with EC50 values ranging from 0.44 to 1.66 μM. Time-of-addition and removal experiments demonstrated that varenicline had a stronger inhibitory effect on the post-entry stage of DENV-2 replication than on the entry stage, as well as the preinfection and virus attachment stages. Furthermore, cell-based trans-cleavage assays indicated that varenicline dose-dependently inhibited the proteolytic activity of DENV-2 NS2B-NS3 protease. Docking models revealed the formation of hydrogen bonds and van der Waals forces between varenicline and specific residues in the DENV-1 and DENV-2 NS2B-NS3 proteases. These results highlight the antiviral activity and potential mechanism of varenicline against DENV, offering valuable insights for further research and development in the treatment of DENV infection.
PubMed: 37893127
DOI: 10.3390/biomedicines11102754 -
JMIR Formative Research Oct 2023Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied....
BACKGROUND
Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied. In addition, smoking cessation medication adherence is often poor, thus, challenging the ability to evaluate medication efficacy.
OBJECTIVE
This study examined the effects of combined varenicline and oral NRT and smartphone medication reminders on pharmacotherapy adherence and smoking abstinence among adults enrolled in smoking cessation treatment.
METHODS
A 2×2 factorial design was used. Participants (N=34) were randomized to (1) varenicline + oral NRT (VAR+NRT) or varenicline alone (VAR) and (2) smartphone medication reminder messages (REM) or no reminder messages (NREM) over 13 weeks. Participants assigned to VAR+REM received varenicline reminder prompts, and those assigned to VAR+NRT+REM also received reminders to use oral NRT. The other 2 groups (VAR+NREM and VAR+NRT+NREM) did not receive medication reminders. Participants were not blinded to intervention groups. All participants received tobacco cessation counseling. Smartphone assessments of smoking as well as varenicline and NRT use (if applicable) were prompted daily through the first 12 weeks after a scheduled quit date. Descriptive statistics were generated to characterize the relations between medication and reminder group assignments with daily smoking, daily varenicline adherence, and daily quantity of oral NRT used. Participants completed follow-up assessments for 26 weeks after the quit date.
RESULTS
Participants were predominantly White (71%), and half were female (50%). On average, participants were 54.2 (SD 9.4) years of age, they smoked an average of 19.0 (SD 9.0) cigarettes per day and had smoked for 34.6 (SD 12.7) years. Descriptively, participants assigned to VAR+NRT reported more days of smoking abstinence compared to VAR (29.3 vs 26.3 days). Participants assigned to REM reported more days of smoking abstinence than those assigned to NREM (40.5 vs 21.8 days). Participants assigned to REM were adherent to varenicline on more days compared to those assigned to NREM (58.6 vs 40.5 days), and participants assigned to VAR were adherent to varenicline on more days than those assigned to VAR + NRT (50.7 vs 43.3 days). In the subsample of participants assigned to VAR+NRT, participants assigned to REM reported more days where ≥5 pieces of NRT were used than NREM (14.0 vs 7.4 days). Average overall medication adherence (assessed via the Medication Adherence Questionnaire) showed the same pattern as the daily smartphone-based adherence assessments.
CONCLUSIONS
Preliminary findings indicated that smoking cessation interventions may benefit from incorporating medication reminders and combining varenicline with oral NRT, though combining medications may be associated with poorer adherence. Further study is warranted.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03722966; https://classic.clinicaltrials.gov/ct2/show/NCT03722966.
PubMed: 37889541
DOI: 10.2196/48857 -
Brain Stimulation 2023Current smoking cessation treatments are limited in terms of efficacy, particularly with regards to long term abstinence. There is a large amount of evidence implicating... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Current smoking cessation treatments are limited in terms of efficacy, particularly with regards to long term abstinence. There is a large amount of evidence implicating the insula in nicotine addiction.
OBJECTIVE
To examine the efficacy of bilateral repetitive transcranial magnetic stimulation (rTMS) directed to the insular cortex with the H11 coil, relative to sham stimulation, on smoking abstinence and smoking outcomes in smokers who are receiving standard varenicline treatment.
METHODS
This randomized, double-blind, sham controlled trial recruited 42 participants who were randomized to receive either active (n = 24) or sham (n = 18) high frequency rTMS directed to the insula (4 weeks), while receiving varenicline treatment (12 weeks). The primary outcome was 7-day point prevalence abstinence at the end of 12 weeks.
RESULTS
Smokers in the active group had significantly higher abstinence rates than those in the sham group (82.4% vs. 30.7%, p = 0.013) at the end of treatment (Week 12). Secondary outcome measures of abstinence rate at the end of rTMS treatment (Week 4), abstinence rate at 6 months, and smoking outcomes (e.g., craving, withdrawal) showed no significant differences between groups. No differences were found in adverse events reported between the groups.
CONCLUSION
This study provides evidence of the potential benefit of having a combined treatment for smoking cessation using insula rTMS with the H11 coil and varenicline. Maintenance rTMS sessions and continuation of varenicline for those in abstinence may induce longer-term effects and should be considered in future studies.
Topics: Humans; Varenicline; Smoking Cessation; Transcranial Magnetic Stimulation; Insular Cortex; Tobacco Use Disorder; Double-Blind Method; Treatment Outcome
PubMed: 37806524
DOI: 10.1016/j.brs.2023.10.002 -
Science Translational Medicine Oct 2023Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with persistent pain. Chemogenetics has shown promise as a means to...
Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with persistent pain. Chemogenetics has shown promise as a means to suppress such excitability, yet chemogenetic approaches suitable for human applications are needed. PSAM-GlyR is a modular system based on the human α7 nicotinic acetylcholine and glycine receptors, which responds to inert chemical ligands and the clinically approved drug varenicline. Here, we demonstrated the efficacy of this channel in silencing both mouse and human sensory neurons by the activation of large shunting conductances after agonist administration. Virally mediated expression of PSAM-GlyR in mouse sensory neurons produced behavioral hyposensitivity upon agonist administration, which was recovered upon agonist washout. Stable expression of the channel led to similar reversible suppression of pain-related behavior even after 10 months of viral delivery. Mechanical and spontaneous pain readouts were also ameliorated by PSAM-GlyR activation in acute and joint pain inflammation mouse models. Furthermore, suppression of mechanical hypersensitivity generated by a spared nerve injury model of neuropathic pain was also observed upon activation of the channel. Effective silencing of behavioral hypersensitivity was reproduced in a human model of hyperexcitability and clinical pain: PSAM-GlyR activation decreased the excitability of human-induced pluripotent stem cell-derived sensory neurons and spontaneous activity due to a gain-of-function Na1.7 mutation causing inherited erythromelalgia. Our results demonstrate the contribution of sensory neuron hyperexcitability to neuropathic pain and the translational potential of an effective, stable, and reversible humanized chemogenetic system for the treatment of pain.
Topics: Humans; Mice; Animals; Neuralgia; Sensory Receptor Cells; Mutation; Ganglia, Spinal
PubMed: 37792955
DOI: 10.1126/scitranslmed.adh3839 -
Journal of Neural Transmission (Vienna,... Jan 2024Alcohol Use Disorder (AUD) is a relapsing brain disorder that involves perturbations of brain dopamine (DA) systems, and combined treatment with...
Alcohol Use Disorder (AUD) is a relapsing brain disorder that involves perturbations of brain dopamine (DA) systems, and combined treatment with varenicline + bupropion produces additive effects on accumbal DA output and abolishes the alcohol deprivation effect (ADE) in rats. Also, direct and indirect glycine receptor (GlyR) agonists raise basal DA, attenuate alcohol-induced DA release in the nucleus Accumbens (nAc) and reduce alcohol consumption in rats. This study in rats examines whether the GlyT1-inhibitor Org 24598, an indirect GlyR agonist, enhances the ADE-reducing and DA elevating action of the combined administration of varenicline + bupropion in lower doses than previously applied. Effects on voluntary alcohol consumption, the ADE and extracellular levels of glycine and DA in nAc were examined following treatment with Org 24598 6 and 9 mg/kg i.p., bupropion 3.75 mg/kg i.p. and varenicline 1.5 mg/kg s.c., in monotherapy or combined, using a two-bottle, free-choice alcohol consumption paradigm with an ADE paradigm, and in vivo microdialysis in male Wistar rats. Notably, all treatment regimens appeared to abolish the ADE but only the effect produced by the triple combination (Org24598 + varenicline + bupropion) was significant compared to vehicle. Hence, addition of Org 24598 may enhance the ADE-reducing action of varenicline + bupropion and appears to allow for a dose reduction of bupropion. Treatment with Org 24598 raised accumbal glycine levels but did not significantly alter DA output in monotherapy. Varenicline + bupropion produced a substantial elevation in accumbal DA output that was slightly enhanced following addition of Org 24598. Conceivably, the blockade of the ADE is achieved by the triple combination enhancing accumbal DA transmission in complementary ways, thereby alleviating a hypothesized hypodopaminergia and negative reinforcement to drink. Ultimately, combining an indirect or direct GlyR agonist with varenicline + bupropion may constitute a new pharmacological treatment principle for AUD, although further refinement in dosing and evaluation of other glycinergic compounds are warranted.
Topics: Rats; Male; Animals; Rats, Wistar; Varenicline; Dopamine; Bupropion; Glycine; Ethanol; Receptors, Glycine; Alcoholism
PubMed: 37773223
DOI: 10.1007/s00702-023-02701-x