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Frontiers in Molecular Biosciences 2024The purpose of this study is to delineate anti-inflammatory and antioxidant potential of varenicline, a cigarette smoking cessation aid, on decreasing...
The purpose of this study is to delineate anti-inflammatory and antioxidant potential of varenicline, a cigarette smoking cessation aid, on decreasing lipopolysaccharide (LPS)-elevated proinflammatory cytokines in RAW 264.7 murine macrophage cultures which we showed earlier to occur via cholinergic anti-inflammatory pathway (CAP) activation. To this end, we investigated the possible suppressive capacity of varenicline on LPS-regulated cyclooxygenase (COX-1 and COX-2) via α7 nicotinic acetylcholine receptor (α7nAChR) activation using the same model. In order to test anti-inflammatory effectiveness of varenicline, the levels of COX isoforms and products (PGE2, 6-keto PGF1α, a stable analog of PGI2, and TXA2) altered after LPS administration were determined by Enzyme Linked Immunosorbent Assay (ELISA). The antioxidant effects of varenicline were assessed by measuring reductions in reactive oxygen species (ROS) using a f intracellular a. We further investigated the contribution of nAChR subtypes by using non-selective and/or selective α7nAChR antagonists. The results were compared with that of conventional anti-inflammatory medications, such as ibuprofen, celecoxib and dexamethasone. Varenicline significantly reduced LPS-induced COX-1, COX-2 and prostaglandin levels and ROS to an extent similar to that observed with anti-inflammatory agents used. Significant downregulation in LPS-induced COX isoforms and associated decreases in PGE2, 6-keto PGF1α, and TXA2 levels along with reduction in ROS may be partly mediated via varenicline-activated α7nAChRs.
PubMed: 38859932
DOI: 10.3389/fmolb.2024.1392689 -
Public Health in Practice (Oxford,... Dec 2023Compare financial barriers to the most effective smoking cessation medications - varenicline and combination nicotine replacement therapy (CNRT) across major insurance...
OBJECTIVES
Compare financial barriers to the most effective smoking cessation medications - varenicline and combination nicotine replacement therapy (CNRT) across major insurance categories and determine whether these financial barriers impact smoking cessation outcomes.
STUDY DESIGN
Longitudinal retrospective observational cohort study.
METHODS
Patients seen at Duke Smoking Cessation Program 05/2016 through 07/2021 were studied. Those prescribed varenicline or CNRT were determined to have financial barriers to access if they could not purchase the medication using insurance or their own funds. Outcomes were compared between Medicare, Medicaid, and private insurers. Abstinence was defined as self-reported 7-day smoking abstinence.
RESULTS
Patients with Medicare were 5.08 times more likely to face a financial barrier to highly effective smoking cessation medications compared to patients with private insurance (p<0.00001) and 2.81 times more likely compared to Medicaid (p<0.00001). Patients able to access these highly effective medications achieved a smoking abstinence rate that was 1.58 times higher than those who could not (p = 0.01).
CONCLUSIONS
Findings suggest Medicare coverage of the most effective smoking cessation medications is considerably worse than Medicaid or private insurance; inability to access these medications may lead to lower rates of smoking abstinence.
PubMed: 37766740
DOI: 10.1016/j.puhip.2023.100427 -
Health Promotion Journal of Australia :... Oct 2023Adherence to smoking cessation medications is low and predicts the success of quit attempts. Health care providers (HCPs) role in delivering smoking cessation support is...
ISSUE ADDRESSED
Adherence to smoking cessation medications is low and predicts the success of quit attempts. Health care providers (HCPs) role in delivering smoking cessation support is crucial. HCPs support to improve adherence to smoking cessation medication has not been evaluated in Australia. This study describes the attitudes and practices of HCPs in Australia towards adherence to smoking cessation medications (nicotine replacement therapies, varenicline and bupropion) and intervention options.
METHODS
A descriptive cross-sectional study was conducted using a convenience sample of 70 HCPs in Australia. Participants were recruited through the social media platforms of professional societies in Australia. Data was collected in the periods between November 2020 and September 2021. Descriptive statistics were performed using SPSS statistical software version 27.0 and data was presented using proportions and percentages.
RESULTS
The majority of participants were doctors, nurses and midwives (82.8%). Almost two-thirds of the participants (68.6%) self-reported that they provided adequate adherence support to individuals taking smoking cessation medications. The majority of participants (87.1%) identified adherence support service as part of their professional role. Only 11.1% of the participants who did not believe supporting medication adherence to be their role reported providing adherence support. The main perceived barriers to adherence support are lack of skill, knowledge, time and resources. HCPs believed that providing additional counselling and monitoring of adherence can improve adherence rates.
CONCLUSIONS
In an online survey conducted in Australia, HCPs indicated multiple barriers to providing adherence support and intervention strategies that should be considered for smoking cessation programs. A higher proportion of participants who perceived adherence support as their professional role reported supporting adherence to smoking cessation medications. SO WHAT?: Considerations should be given to improve HCPs attitudes and practices towards smoking cessation medications adherence support. Smoking cessation programs should consider the issue of adherence support. Further studies with a larger sample size across a broader range of HCPs are needed to extensively understand adherence service provision among HCPs in Australia.
Topics: Humans; Smoking Cessation; Smoking; Cross-Sectional Studies; Tobacco Use Cessation Devices; Australia; Health Personnel
PubMed: 36284364
DOI: 10.1002/hpja.674 -
Implementation Science Communications May 2024With expanded and sustained availability of HIV treatment resulting in substantial improvements in life expectancy, the need to address modifiable risk factors...
BACKGROUND
With expanded and sustained availability of HIV treatment resulting in substantial improvements in life expectancy, the need to address modifiable risk factors associated with leading causes of death among people living with HIV/AIDS (PLWH), such as tobacco smoking, has increased. Tobacco use is highly prevalent among PLWH, especially in southern Africa, where HIV is heavily concentrated, and many people who smoke would like to quit but are unable to do so without assistance. SBIRT (Screening, Brief Intervention and Referral to Treatment) is a well-established evidence-based approach successful at supporting smoking cessation in a variety of settings. Varenicline is efficacious in supporting smoking cessation. We intend to assess the effectiveness of SBIRT and varenicline on smoking cessation among PLWH in Botswana and the effectiveness of our implementation.
METHODS
BSMART (Botswana Smoking Abstinence Reinforcement Trial) is a stepped-wedge, cluster randomized, hybrid Type 2 effectiveness-implementation study guided by the RE-AIM framework, to evaluate the effectiveness and implementation of an SBIRT intervention consisting of the 5As compared to an enhanced standard of care. SBIRT will be delivered by trained lay health workers (LHWs), followed by referral to treatment with varenicline prescribed and monitored by trained nurse prescribers in a network of outpatient HIV care facilities. Seven hundred and fifty people living with HIV who smoke daily and have been receiving HIV care and treatment at one of 15 health facilities will be recruited if they are up to 18 years of age and willing to provide informed consent to participate in the study.
DISCUSSION
BSMART tests a scalable approach to achieve and sustain smoking abstinence implemented in a sustainable way. Integrating an evidence-based approach such as SBIRT, into an HIV care system presents an important opportunity to establish and evaluate a modifiable cancer prevention strategy in a middle-income country (MIC) setting where both LHW and non-physician clinicians are widely used. The findings, including the preliminary cost-effectiveness, will provide evidence to guide the Botswanan government and similar countries as they strive to provide affordable smoking cessation support at scale.
CLINICAL TRIAL REGISTRATION
NCT05694637 Registered on 7 December 2022 on clinicaltrials.gov, https://clinicaltrials.gov/search?locStr=Botswana&country=Botswana&cond=Smoking%20Cessation&intr=SBIRT.
PubMed: 38720363
DOI: 10.1186/s43058-024-00588-7 -
CMAJ : Canadian Medical Association... Feb 2024
Topics: Humans; Smoking Cessation; Transcranial Magnetic Stimulation; Smoking; Prefrontal Cortex; Treatment Outcome
PubMed: 38378215
DOI: 10.1503/cmaj.230806 -
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 -
Neuropsychopharmacology Reports Dec 2023Cigarette smoking is a preventable risk factor for various diseases such as cancer, ischemic stroke, cardiac stroke, and chronic obstructive pulmonary disease. Smoking...
AIMS
Cigarette smoking is a preventable risk factor for various diseases such as cancer, ischemic stroke, cardiac stroke, and chronic obstructive pulmonary disease. Smoking cessation is of great importance not only for individual smokers but also for social health. Regarding current cessation therapies, the effectiveness of nicotine replacement is limited, and the cost of varenicline medication is considerable. Thus, a method for screening smokers who are responsive to cessation therapy based on the therapeutic effectiveness is required. Peripheral biomarkers reflecting smoking dependence status are necessary to establish a method for achieving effective cessation therapy.
METHODS
Methylation status of smokers' blood DNA was evaluated focusing on SHATI/NAT8L, an addiction-related gene. Eight CpG sites in SHATI/NAT8L were quantified by pyrosequencing.
RESULTS
There was no difference in the methylation status of this gene between smokers (n = 129) and non-smokers (n = 129) at all CpG sites. No correlations between the methylation status of SHATI/NAT8L and indicators of smoking dependence were found.
CONCLUSIONS
Although the present study found no significance in the DNA methylation of SHATI/NAT8L among smokers, the exploration of predictable peripheral biomarkers for the effectiveness of smoking cessation therapy is required.
Topics: Humans; DNA Methylation; Smokers; Smoking Cessation; Tobacco Use Cessation Devices; Biomarkers; Tobacco Products; Acetyltransferases
PubMed: 37668111
DOI: 10.1002/npr2.12373 -
Ophthalmology and Therapy Jun 2024The purpose of this study is to evaluate the use of a varenicline solution nasal spray (VNS) for reducing the signs and symptoms of dry eye following laser in situ...
INTRODUCTION
The purpose of this study is to evaluate the use of a varenicline solution nasal spray (VNS) for reducing the signs and symptoms of dry eye following laser in situ keratomileusis (LASIK).
METHODS
Subjects electing to undergo LASIK were randomized to VNS (study group) or placebo/vehicle (control group) and initiated treatment with the nasal spray twice daily 28 days prior to surgery with continued treatment for 84 days following LASIK. After initiation of treatment, subjects were seen on the day of surgery and postoperatively on Days 1, 7, 28, 84 (3 months) and 168 (6 months). The primary outcome measure was the mean change in NEI-VFQ-25, a 25-item dry eye questionnaire, from baseline to 3 months. The second primary outcome measure was the mean change in corneal fluorescein staining. Secondary outcome measures included evaluation of tear break-up time, Schirmer testing, tear osmolarity and eye dryness score (EDS).
RESULTS
Twenty subjects were enrolled in each group and successfully underwent LASIK. Both groups demonstrated an improvement in the National Eye Institute Visual Function Questionnaire (NEI-VFQ) at 3 months. The study group demonstrated improved corneal staining scores at months 1 and 3. Similarly, the study group demonstrated improvement in tear osmolarity scores versus the placebo group at the same time points. Although the study group was numerically greater than placebo for each time point for both corneal staining and tear osmolarity, the differences were not statistically significant for any primary or secondary outcome measures.
CONCLUSION
VNS is a dry eye treatment option for patients following LASIK and may have potential benefit for patients hoping to avoid additional topical medications. The results were not statistically significant compared to placebo in this trial, and further investigation of the use of VNS following LASIK in a larger trial would be beneficial.
PubMed: 38662191
DOI: 10.1007/s40123-024-00949-4 -
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 -
Drug and Alcohol Dependence Reports Sep 2023Significance There are sex effects in abstinence outcomes across all smoking cessation medications, but there is limited information regarding sex effects on...
UNLABELLED
Significance There are sex effects in abstinence outcomes across all smoking cessation medications, but there is limited information regarding sex effects on cessation-related neuropsychiatric adverse events (NPSAEs) or interactions with psychiatric status.
METHODS
Secondary analysis of data from EAGLES of 8144 adults who smoke cigarettes randomized to varenicline, bupropion, nicotine patch or placebo. Design characteristics included region (within/outside US), psychiatric cohort (absent/present), and treatment. Baseline variables included demographics, smoking history, prior use of study treatments, lifetime suicide-related history, and prior psychiatric co-morbidities and medication use. Design characteristics were forced into logistic regressions models, and then interactions among sex, design elements, and baseline characteristics were evaluated for NPSAEs and 6-month cessation outcomes.
RESULTS
Findings demonstrated a significant interaction of sex and race ( < 0.02); Black women were more likely to report NPSAEs than Black men. For cessation outcomes, there were no significant interactions with psychiatric cohort and sex. Women vs men with higher baseline levels of smoking had lower odds of continuous abstinence. Women vs men who used varenicline previously had lower odds of continuous abstinence. For 6-month point prevalence, sex interacted with baseline cigarettes per day ( < 0.01) similar to the interaction for continuous abstinence. Sex interacted with medication ( < 0.03), such that women vs men had relatively greater success at achieving point prevalence abstinence on varenicline.
CONCLUSIONS
Overall, results demonstrated important sex and racial differences in the incidence of NPSAEs, but psychiatric status did not interact with sex on cessation outcomes. Findings did support prior work demonstrating relative increased efficacy of varenicline for women.
PubMed: 37520849
DOI: 10.1016/j.dadr.2023.100177