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Neuropsychopharmacology : Official... Nov 2023Fetal alcohol exposure has deleterious consequences on the motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of...
Fetal alcohol exposure has deleterious consequences on the motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic interneurons (CINs) and dopamine function impair action learning and execution, yet the effects of GEE on acetylcholine (ACh) and striatal dopamine release remain unexplored. Here, we report that alcohol exposure during the first ten postnatal days (GEE), which mimics ethanol consumption during the last gestational trimester in humans, induces sex-specific anatomical and motor skill deficits in female mice during adulthood. Consistent with these behavioral impairments, we observed increased stimulus evoked-dopamine levels in the dorsolateral striatum (DLS) of GEE female, but not male, mice. Further experiments revealed sex-specific deficits in β2-containing nicotinic ACh receptor (nAChR)-modulation of electrically evoked dopamine release. Moreover, we found a reduced decay of ACh transients and a decreased excitability of striatal CINs in DLS of GEE females, indicating striatal CIN dysfunctions. Finally, the administration of varenicline, a β2-containing nAChR partial agonist, and chemogenetic-mediated increase in CIN activity improved motor performance in adult GEE females. Altogether, these data shed new light on GEE-induced striatal deficits and establish potential pharmacological and circuit-specific interventions to ameliorate motor symptoms of FASD.
Topics: Humans; Male; Pregnancy; Mice; Female; Animals; Adult; Dopamine; Acetylcholine; Motor Skills; Ethanol; Fetal Alcohol Spectrum Disorders; Corpus Striatum; Nicotinic Agonists
PubMed: 37188849
DOI: 10.1038/s41386-023-01594-4 -
JAMA Network Open Apr 2024Smoking is the leading preventable cause of death and illness in the US. Identifying cost-effective smoking cessation treatment may increase the likelihood that health... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Smoking is the leading preventable cause of death and illness in the US. Identifying cost-effective smoking cessation treatment may increase the likelihood that health systems deliver such treatment to their patients who smoke.
OBJECTIVE
To evaluate the cost-effectiveness of standard vs enhanced varenicline use (extended varenicline treatment or varenicline in combination with nicotine replacement therapy) among individuals trying to quit smoking.
DESIGN, SETTING, AND PARTICIPANTS
This economic evaluation assesses the Quitting Using Intensive Treatments Study (QUITS), which randomized 1251 study participants who smoked into 4 conditions: (1) 12-week varenicline monotherapy (n = 315); (2) 24-week varenicline monotherapy (n = 311); (3) 12-week varenicline combination treatment with nicotine replacement therapy patch (n = 314); or (4) 24-week varenicline combination treatment with nicotine replacement therapy patch (n = 311). Study enrollment occurred in Madison and Milwaukee, Wisconsin, between November 11, 2017, and July 2, 2020. Statistical analysis took place from May to October 2023.
MAIN OUTCOMES AND MEASURES
The primary outcome was 7-day point prevalence abstinence (biochemically confirmed with exhaled carbon monoxide level ≤5 ppm) at 52 weeks. The incremental cost-effectiveness ratio (ICER), or cost per additional person who quit smoking, was calculated using decision tree analysis based on abstinence and cost for each arm of the trial.
RESULTS
Of the 1251 participants, mean (SD) age was 49.1 (11.9) years, 675 (54.0%) were women, and 881 (70.4%) completed the 52-week follow-up. Tobacco cessation at 52 weeks was 25.1% (79 of 315) for 12-week monotherapy, 24.4% (76 of 311) for 24-week monotherapy, 23.6% (74 of 314) for 12-week combination therapy, and 25.1% (78 of 311) for 24-week combination therapy, respectively. The total mean (SD) cost was $1175 ($365) for 12-week monotherapy, $1374 ($412) for 12-week combination therapy, $2022 ($813) for 24-week monotherapy, and $2118 ($1058) for 24-week combination therapy. The ICER for 12-week varenicline monotherapy was $4681 per individual who quit smoking and $4579 per quality-adjusted life-year (QALY) added. The ICER for 24-week varenicline combination therapy relative to 12-week monotherapy was $92 000 000 per additional individual who quit smoking and $90 000 000 (95% CI, $15 703 to dominated or more costly and less efficacious) per additional QALY.
CONCLUSIONS AND RELEVANCE
This economic evaluation of standard vs enhanced varenicline treatment for smoking cessation suggests that 12-week varenicline monotherapy was the most cost-effective treatment option at the commonly cited threshold of $100 000/QALY. This study provides patients, health care professionals, and other stakeholders with increased understanding of the health and economic impact of more intensive varenicline treatment options.
Topics: Humans; Varenicline; Female; Male; Cost-Benefit Analysis; Middle Aged; Adult; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Tobacco Use Cessation
PubMed: 38683609
DOI: 10.1001/jamanetworkopen.2024.8727 -
Psychopharmacology Apr 2024Varenicline is considered one of the most effective treatment options for smoking cessation. Nonetheless, it is only modestly effective. A deeper comprehension of the... (Review)
Review
BACKGROUND
Varenicline is considered one of the most effective treatment options for smoking cessation. Nonetheless, it is only modestly effective. A deeper comprehension of the effects of varenicline by means of the in-depth review of relevant fMRI studies may assist in paving the development of more targeted and effective treatments.
METHODOLOGY
A search of PubMed and Google Scholar databases was conducted with the keywords "functional magnetic resonance imaging" or "fMRI", and "varenicline". All peer-reviewed articles regarding the assessment of smokers with fMRI while undergoing treatment with varenicline and meeting the predefined criteria were included.
RESULTS
Several studies utilizing different methodologies and targeting different aspects of brain function were identified. During nicotine withdrawal, decreased mesocorticolimbic activity and increased amygdala activity, as well as elevated amygdala-insula and insula-default-mode-network functional connectivity are alleviated by varenicline under specific testing conditions. However, other nicotine withdrawal-induced changes, including the decreased reward responsivity of the ventral striatum, the bilateral dorsal striatum and the anterior cingulate cortex are not influenced by varenicline suggesting a task-dependent divergence in neurocircuitry activation. Under satiety, varenicline treatment is associated with diminished cue-induced activation of the ventral striatum and medial orbitofrontal cortex concomitant with reduced cravings; during the resting state, varenicline induces activation of the lateral orbitofrontal cortex and suppression of the right amygdala.
CONCLUSIONS
The current review provides important clues with regard to the neurobiological mechanism of action of varenicline and highlights promising research opportunities regarding the development of more selective and effective treatments and predictive biomarkers for treatment efficacy.
Topics: Humans; Varenicline; Smoking Cessation; Nicotine; Magnetic Resonance Imaging; Nicotinic Agonists; Brain; Substance Withdrawal Syndrome
PubMed: 38430396
DOI: 10.1007/s00213-024-06556-2 -
BMC Public Health Sep 2023Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these...
Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial.
BACKGROUND
Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these medications or find them helpful. We aim to investigate the therapeutic potential of an analogous combination, by evaluating the effectiveness, safety, and acceptability of combining nicotine salt e-cigarettes with cytisine, compared to nicotine salt e-cigarettes or cytisine only, on smoking abstinence at six months.
METHODS
A pragmatic, community-based, investigator-blinded, randomised superiority trial design will be utilised. Eligible participants will be people who smoke daily (N = 800, 90% power) from throughout New Zealand, who are: aged ≥ 18 years, motivated to quit in the next two weeks, able to provide online consent, willing to use e-cigarettes and/or cytisine, and have daily access to a mobile phone. Recruitment will utilise multi-media advertising. Participants will be randomised (3:3:2 ratio) to 12 weeks of: 1) e-cigarettes (closed pod system, 3% nicotine salt, tobacco flavour) plus cytisine; 2) e-cigarettes alone, or 3) cytisine alone. All groups will receive a six-month, text-message-based behavioural support programme. The primary outcome is self-reported, biochemically verified, continuous abstinence at six months post-quit date. Secondary outcomes, measured at quit date, then one, three, six, and 12 months post-quit date, include self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes smoked per day, withdrawal and urge to smoke, time to (re)lapse, treatment use and compliance, treatment crossover, dual-use, use of other cessation products, change in e-cigarette products, continuation of product use, acceptability, change in health state, health-related quality of life, change in body mass index, adverse events, and cost per quitter.
DISCUSSION
Pragmatic trials are of particular value as they reflect the 'real world' impact of interventions. The trial will provide some of the first evidence on the effectiveness of combining nicotine salt e-cigarettes with cytisine for smoking cessation, in a country with strong tobacco control policy. Findings will be incorporated into relevant systematic reviews, informing practice and policy.
TRIAL REGISTRATION
NCT05311085 ClinicalTrials.gov. Registered 5th April, 2022.
Topics: Humans; Nicotine; Smoking Cessation; Electronic Nicotine Delivery Systems; Vaping; New Zealand; Quality of Life; Varenicline; Tobacco Use Cessation Devices; Sodium Chloride, Dietary; Randomized Controlled Trials as Topic
PubMed: 37697327
DOI: 10.1186/s12889-023-16665-w -
EClinicalMedicine Feb 2024Smoking cessation is challenging, despite making use of established smoking cessation therapies. Preclinical studies and one clinical pilot study suggest the...
Effect of dulaglutide in promoting abstinence during smoking cessation: 12-month follow-up of a single-centre, randomised, double-blind, placebo-controlled, parallel group trial.
BACKGROUND
Smoking cessation is challenging, despite making use of established smoking cessation therapies. Preclinical studies and one clinical pilot study suggest the antidiabetic drug glucagon-like peptide-1 (GLP-1) analogue to modulate addictive behaviours and nicotine craving. Previously, we reported the short-term results of a randomised, double-blind, placebo-controlled trial. Herein we report long-term abstinence rates and weight developments after 24 and 52 weeks.
METHODS
This single-centre, randomised, double-blind, placebo-controlled, parallel group trial was done at the University Hospital Basel in Switzerland. We randomly assigned (1:1) individuals with at least a moderate nicotine dependence willing to quit smoking to either a 12-week treatment with dulaglutide 1.5 mg or placebo subcutaneously once weekly in addition to standard of care smoking cessation therapy (varenicline 2 mg/day and behavioural counselling). After 12 weeks, dulaglutide or placebo injections were discontinued and the participants were followed up at week 24 and 52. The primary outcome of self-reported and biochemically confirmed point prevalence abstinence rate, and secondary outcome of secondary outcome of weight change were assessed at weeks 24 and 52. All participants who received one dose of the study drug were included in the intention to treat set and participants who received at least 10/12 doses of the study drug formed the per protocol set. The trial was registered at ClinicalTrials.gov, NCT03204396.
FINDINGS
Of the 255 participants who were randomly assigned between June 22, 2017 and December 3, 2020, 63% (80/127) (dulaglutide group) and 65% (83/128) (placebo group) were abstinent after 12 weeks. These abstinence rates declined to 43% (54/127) and 41% (52/128), respectively, after 24 weeks and to 32% (41/127) and 32% (41/128), respectively, after 52 weeks. Post-cessation weight gain was prevented in the dulaglutide group (-1.0 kg, standard deviation [SD] 2.7) as opposed to the placebo group (+1.9 kg, SD 2.4) after 12 weeks. However, at week 24, increases in weight from baseline were observed in both groups (median, interquartile range [IQR]: dulaglutide: +1.5 kg, [-0.4, 4.1], placebo: +3.0 kg, [0.6, 4.6], baseline-adjusted difference in weight change -1.0 kg (97.5% CI [-2.16, 0.16])), and at week 52 the groups showed similar weight gain (median, IQR: dulaglutide: +2.8 kg [-0.4, 4.7], placebo: +3.1 kg [-0.4, 6.0], baseline-adjusted difference in weight change: -0.35 kg (95% CI [-1.72, 1.01])). In the follow-up period (week 12 to week 52) 51 (51%) and 48 (48%) treatment-unrelated adverse events were recorded in the dulaglutide and the placebo group, respectively. No treatment-related serious adverse events or deaths occurred.
INTERPRETATION
Dulaglutide does not improve long-term smoking abstinence, but has potential to counteract weight gain after quitting. However, 3 months of treatment did not have a sustained beneficial effect on weight at 1 year. As post-cessation weight gain is highest in the first year after quitting smoking, future studies should consider a longer treatment duration with a GLP-1 analogue in abstinent individuals.
FUNDING
Swiss National Science Foundation, the Gottfried and Julia Bangerter-Rhyner Foundation, the Goldschmidt-Jacobson Foundation, the Hemmi-Foundation, the University of Basel, the Swiss Academy of Medical Sciences.
PubMed: 38371479
DOI: 10.1016/j.eclinm.2024.102429 -
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 -
Cureus Feb 2024The smoking epidemic is the greatest threat to global public health that has ever existed. Teenagers constantly perceive smoking as a way to communicate with friends and... (Review)
Review
The smoking epidemic is the greatest threat to global public health that has ever existed. Teenagers constantly perceive smoking as a way to communicate with friends and express their emotions. Adolescent smokers should be noticed immediately before the extended period of tobacco addiction and being resistant to the interventions. The aim of this study is to assess the effectiveness of healthcare interventions targeting smoking cessation in adolescents within low- and middle-income countries (LMICs) and to summarize the options, benefits, and affordability of interventions for quitting smoking that may be implemented in LMICs. The review highlights the effectiveness of various pharmacological interventions, such as nicotine replacement therapy (NRT), bupropion, nortriptyline, varenicline, and cytosine, shedding light on their respective success rates in aiding smoking cessation. Additionally, the study delves into the realm of behavioral interventions, emphasizing the significant impact of counseling, brief advice, and automated text messaging in promoting smoking cessation among adolescents. Furthermore, the review examines the influence of external factors, such as an increase in cigarette prices and changes in the smoking environment, on smoking habits. It underscores the importance of creating smoke-free areas and leveraging community involvement to enhance the effectiveness of interventions. The study also evaluates the affordability and sustainability of smoking cessation interventions, emphasizing the need for a balanced combination of pharmacotherapy and behavioral support. The advantages of quitting smoking will improve the nation's health and boost economic productivity.
PubMed: 38481929
DOI: 10.7759/cureus.54051 -
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 -
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 -
The Lancet Regional Health. Western... Apr 2024Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote...
BACKGROUND
Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease.
METHODS
This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4.
FINDINGS
In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred.
INTERPRETATION
OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population.
FUNDING
Jixing Pharmaceutical Co. Ltd.
PubMed: 38440130
DOI: 10.1016/j.lanwpc.2024.101032