Varenicline Solution Nasal Spray 0.03 Mg for the Treatment of Dry Eye Disease Following Photorefractive Keratectomy.

Purpose: To evaluate the use of varenicline solution nasal spray 0.03 mg (VNS) as a treatment option for the signs and symptoms of dry eye disease following photorefractive keratectomy (PRK). Patients and methods: Subjects electing to undergo PRK were randomized to VNS (study group) or vehicle (control group) twice daily and started treatment with VNS 28 days prior to surgery with continued use of the treatment for 84 days after PRK. After starting treatment, subjects were seen on the day of the procedure and postoperatively at days 2, 3, 4, 7, 28 and 84. The primary outcome measure was the mean change in NEI-VFQ-25, a dry eye item questionnaire, from baseline to day 84. The second primary outcome measure was the rate of corneal epithelial healing following PRK. Secondary outcome measures included eye dryness score (EDS), tear break up time and visual outcomes. The use of rescue therapy was also evaluated. Results: Twenty-one subjects were enrolled in the study group, and twenty subjects were enrolled in the control group. Results from the NEI-VFQ-25 questionnaire revealed positive results in both groups and the between-group difference was not statistically significant (P > 0.05). There was a trend towards faster re-epithelialization in patients treated with VNS vs placebo, where 100% epithelial closure was observed by Day 3 in the VNS group versus Day 4 in the control group; however, the between-group difference was not statistically significant (P > 0.05). Three subjects had rescue therapy in the control group while a single subject was rescued in the study group. A higher rate of eyes achieved vision of 20/16 or better in the study group (82.5%) versus the control group (72.5%) at 3 months. Conclusion: VNS is a favorable dry eye treatment option for patients following PRK, particularly in patients hoping to avoid additional topical medications or punctal occlusion. The higher percentage of eyes with UCDVA of 20/16 or better in the treatment group may suggest optimization of epithelial recovery after PRK.

Smoking cessation pharmacotherapy; varenicline or bupropion?

OBJECTIVES: Tobacco smoking is a worldwide health problem and one of the leading causes of premature deaths in last years. As there are lots of researches focusing on cessation strategies with attention to pharmacotherapy and behavioral counseling, the aim of this study was to compare two of the first-line FDA-approved pharmacotherapies for smoking cessation; varenicline and bupropion. EVIDENCE ACQUSITION: This writing is an overview of researches published in Pubmed database from 2012 to 2022 with "Varenicline" and "Bupropion" as key words. Among the researches that were found, 24 articles were selected which mainly focused on comparison of these two medicines. RESULTS: Varenicline and bupropion are known as non-nicotinic pharmacotherapy and have been used in addition to nicotine replacement therapy for smoking cessation. Varenicline is partial agonist for α4ß2 nicotinic acetyl choline receptors while bupropion, classified as an atypical antidepressant, is actually a norepinephrine and dopamine reuptake inhibitor. Although these treatments can result in some adverse effects including nausea, insomnia, anxiety, irritability, fatigue and abnormal dreams, their efficacy in reduction of craving and also maintenance of abstinence is well been studied and approved by FDA. Moreover, adverse effects are usually mild to moderate clinical symptoms which can be tolerated and also easily managed and prevented in cases. CONCLUSION: The efficacy and tolerability of varenicline and bupropion as treatments for smoking cessation is well understood. However, studies have shown that varenicline seems to be more effective in maintaining of abstinence and also reducing craving than bupropion and NRT.

Sex-specific predictive factors of smoking cessation in subjects at high cardiovascular risk.

Smoking is a major risk factor for cardiovascular diseases (CVD), in particular in women, but smoking cessation (SC) reduces or even cancels the risk for both sexes. Using a nationwide SC services database, we aimed to determine the predictive factors of SC in men and women smokers with CV risk factors (CVRF) or CVD. A retrospective study from the French CDTnet database was conducted. Inclusion criteria were age ≥18years, and≥1 CVRF (Body Mass Index ≥25kg/m2, hypertension, diabetes, hypercholesterolemia) or CVD (myocardial infarction (MI) or angina pectoris, stroke, peripheral arterial disease [PAD]). Self-reported smoking abstinence (≥28 consecutive days) was confirmed by exhaled carbon monoxide<10ppm. Logistic regression analysis assessed the association between SC and sociodemographic, medical characteristics, and smoking profile. Among the 36,864 smokers at high CV risk, abstinence rate was slightly lower in women than in men, (52.6% [n=8,102] vs 55.0% [n=11,848], P<0.001). For both sexes, factors associated with the lowest abstinence rates were diabetes, respiratory and psychiatric diseases, anxiolytic/antidepressant use, and cannabis consumption. In women, the factors associated with smoking abstinence were suffering from MI or angina and taking contraceptive pill and the factors associated with persistent smoking were alcohol disorder and high cigarette consumption. In men, there was a positive relationship between overweight and abstinence while being dual users of cigarettes and electronic cigarettes at first visit, having tobacco-related diseases (cancer and PAD) and taking opioid substitution treatment were associated with persistent smoking. Finally, in both sexes, the factors associated with abstinence were: age≥65years, having a diploma, being employed, self-referred or encouraged by entourage, ≥1 previous quit attempt, ≤20 cigarettes per day consumption, benefiting from SC medication prescription and ≥4 follow-up visits. In conclusion, our results suggest the relevance of SC intensive management in smokers at high CV risk, based on sociodemographic, medical, and smoking behaviour characteristics, as well as a gender-specific SC approach.

Metabolic Changes Following Smoking Cessation in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Smoking cessation is crucial for reducing complications of type 2 diabetes mellitus (T2DM), but associated weight gain can worsen glycemic control, discouraging quitting attempts. Varenicline, a partial agonist of α4ß2 nicotinic receptors, aids smoking cessation. This study examines the effects of varenicline on body weight and metabolic parameters in patients with T2DM and prediabetes. METHODS: Fifty-three patients were enrolled, of which 32 successfully quit smoking after a three-month course of varenicline and were examined after an additional month with no medication. Measurements taken at baseline, 2.5 months, and 4 months included body weight, blood pressure, resting metabolic rate (RMR), glycated hemoglobin (HbA1c), fasting glucose, blood lipids, C-reactive protein (CRP), appetite-related hormones, and physical activity. RESULTS: Post-treatment, there were no significant changes in body weight, blood pressure, RMR, or glycemic control. Total (CHOL) and low-density lipoprotein (LDL-C) cholesterol decreased significantly at 4 months of the study (from 168 to 156 mg/dL, p = 0.013, and from 96 to 83 mg/dL, p = 0.013, respectively). Leptin levels increased (from 11 to 13.8 ng/dL, p = 0.004), as did glucagon-like peptide-1 (GLP-1) levels (from 39.6 to 45.8 pM, p = 0.016) at 4 months of follow-up. The percentage of participants who reported moderate-intensity activity increased from 28% to 56%, while those reporting high-intensity activity increased from 19% to 22%, respectively (p = 0.039). CONCLUSIONS: Our study showed that smoking cessation with varenicline in smokers with T2DM and prediabetes led to significant improvements in lipid profile, significant increase in plasma leptin and GLP-1 levels, and increased physical activity, without significant weight gain. Thus, smoking cessation without weight gain or deteriorated glycemic control is feasible for these smokers, with added benefits to lipid profiles, GLP-1 regulation, and physical activity.

[Systematic review on the efficacy and safety of cytisine against nicotine dependence]. / Revisión sistemática sobre la eficacia y seguridad de la citisina contra la dependencia de nicotina.

Introduction: Tobacco is one of the main causes of preventable mortality in our environment, in addition to having been correlated with numerous diseases. Smoking cessation improves health status and life expectancy. Pharmacological treatment of smoking cessation increases the likelihood that patient will successfully quit smoking. Method and design: A search was carried out in the PubMed and UpToDate databases, obtaining a total of 11 systematic reviews or meta-analyses published in the last five years. After applying inclusion criteria and reading summaries, 5 total articles were obtained for the final review. Results and discussion: Cytisine is a safe and effective treatment for smoking cessation. The most effective treatment in the clinical trials reviewed is varenicline associated with nicotine replacement therapy.There is less evidence collected on cytisine treatment, but it shows that it is also an effective therapy in smoking cessation, also demonstrating its usefulness in the long term. In addition, therapy with cytisine seems to entail fewer adverse effects than treatment with varenicline.

Characterizing reward and relief/habit drinking profiles in a study of naltrexone, varenicline, and placebo.

INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.

The Effect of Varenicline on Smoking Cessation in Hospitalized Patients: A Systematic Review and Meta-Analysis.

Background: Varenicline tartrate is a new and selective agonist of the nicotinic acetylcholine receptor (nAChR). This systematic review and meta-analysis aimed to determine varenicline efficacy in smoking cessation among hospitalized patients. Methods: We looked through worldwide databases such as Web of Science, Embase, PubMed, Cochrane, and Scopus. Relevant pieces of research published on varenicline efficacy on smoking cessation among hospitalized patients were discovered using proper keywords. The data were analyzed using Stata software version 14 and a random-effects model meta-analysis. Findings: Nine studies were eligible to be included in this study, with a total sample size of 2131. Generally, the point abstinence rate was significantly greater in the varenicline group than in the placebo group at weeks 12 (odds ratio [OR]=0.59; 95% CI: 053-0.65; P<0.001), 24 (OR=0.78; 95% CI: 0.72-0.84; P<0.001), and 52 (OR=0.86; 95% CI: 0.80-0.92; P<0.001). Furthermore, the continuous abstinence rate for weeks 4 (OR=0.70; 95% CI: 019-0.54; P=0.000), 12 (OR=0.26; 95% CI: 019-0.54; P<0.001), 24 (OR=0.32; 95% CI: 019-0.53; P<0.001), and 52 (OR=0.32; 95% CI: 019-0.54; P<0.001) was significantly greater in the varenicline group than in the placebo group. Conclusion: According to the high efficacy of varenicline in both short- and long-term smoking settings and considering the importance of smoking cessation in high-risk hospitalized patients, varenicline consumption could be considered as a main smoking cessation strategy in these patients.

Varenicline OTC Trial on Efficacy and Safety.

INTRODUCTION: Varenicline helps people who smoke quit at rates 2-3 times greater than placebo. Currently in the U.S., varenicline is not available over the counter (OTC). In this study, we assessed the safety and efficacy of 1mg and 0.5mg varenicline as an OTC medication for smoking cessation in comparison to placebo. METHODS: This randomized, double-blind, placebo-controlled study was performed at two clinical sites in the United States of n=313 people. The treatment period was 12 weeks. During the COVID pandemic, the protocol was modified to allow remote participation; verification of smoking status was via breath carbon monoxide levels for in-person visits and mailed urine cotinine kits for the remote participants. RESULTS: There was no difference in biologically confirmed continuous abstinence by condition between Weeks 8-12; however, the odds of biologically confirmed point prevalence abstinence were higher for those in the 1mg b.i.d. condition than for those in the placebo condition at Week 12 (OR 3.39; 95% CI 1.49, 7.71), and were higher for those assigned to the 1.0mg b.i.d. condition than the 0.5mg b.i.d. condition at Week 12 (OR 2.37; 95% CI 1.11, 5.05). Adverse events were modest, and as expected (vivid dreams and nausea in the medication conditions). CONCLUSIONS: The results are suggestive that varenicline is safe and effective as an OTC medication.

The efficacy and acceptability of pharmacological monotherapies and e-cigarette on smoking cessation: a systemic review and network meta-analysis.

Background and aims: Several pharmacological interventions, such as nicotine replacement therapy (NRT), varenicline, and bupropion, have been approved for clinical use of smoking cessation. E-cigarettes (EC) are increasingly explored by many RCTs for their potentiality in smoking cessation. In addition, some RCTs are attempting to explore new drugs for smoking cessation, such as cytisine. This network meta-analysis (NMA) aims to investigate how these drugs and e-cigarettes compare regarding their efficacy and acceptability. Materials and methods: This systematic review and NMA searched all clinical studies on smoking cessation using pharmacological monotherapies or e-cigarettes published from January 2011 to May 2022 using MEDLINE, COCHRANE Library, and PsychINFO databases. NRTs were divided into transdermal (TDN) and oronasal nicotine (ONN) by administrative routes, thus 7 network nodes were set up for direct and indirect comparison. Two different indicators measured the efficacy: prevalent and continuous smoking abstinence. The drop-out rates measured the acceptability. Results: The final 40 clinical studies included in this study comprised 77 study cohorts and 25,889 participants. Varenicline is more effective intervention to assist in smoking cessation during 16-32 weeks follow-up, and is very likely to prompt dropout. Cytisine shows more effectiveness in continuous smoking cessation but may also lead to dropout. E-cigarettes and oronasal nicotine are more effective than no treatment in encouraging prevalent abstinence, but least likely to prompt dropout. Finally, transdermal nicotine delivery is more effective than no treatment in continuous abstinence, with neither significant effect on prevalent abstinence nor dropout rate. Conclusion: This review suggested and agreed that Varenicline, Cytisine and transdermal nicotine delivery, as smoking cessation intervention, have advantages and disadvantages. However, we had to have reservations about e-cigarettes as a way to quit smoking in adolescents.

Nicotinic acetylcholine receptor-mediated effects of varenicline on LPS-elevated prostaglandin and cyclooxygenase levels in RAW 264.7 macrophages.

Introduction: 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 in vitro model. Materials and Methods: 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 fluorometric intracellular ROS assay kit. 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. Results: 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. Discussion: 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.

Cytisine for smoking cessation: A 40-day treatment with an induction period.

INTRODUCTION: Cytisine is a smoking cessation drug now used worldwide. Most of the data available in the literature predict a 25-day treatment, accepted on the basis of previous clinical experience in Eastern Europe. There are few studies on dosing, and only recently some researchers have tried a longer treatment period. METHODS: This real-world retrospective cross-sectional study analyzed data collected consecutively from 2015 to 2021, in seven smoking cessation centers in north-central Italy. The aim of this study is to evaluate the effectiveness and tolerability of a 40-day cytisine treatment with an induction phase and a slower reduction schedule. Data were collected from a group of 871 patients treated with cysteine, varenicline, and nicotine replacement therapy (NRT). The sample was not randomized. Behavioral support (4-6 sessions, each lasting 20-30 min, plus the evaluation session) was delivered to all patients. RESULTS: Subgroups taking cytisine (n=543 for 40 days), varenicline (n=281 for 12 weeks), and NRT (n=47 for eight weeks) showed biochemically confirmed smoking abstinence at 6 months of 50.5%, 55.9%, and 51.0%, respectively, with a statistically significant difference between cytisine versus varenicline (p<0.01) but not between cytisine versus NRT (p=0.5597). Adverse events were 4.4% with cytisine and 33.3% with varenicline. Behavioral support was an important factor in effectiveness. CONCLUSIONS: This study produced preliminary evidence that the 40-day regimen of cytisine, appears to have less effectiveness in comparison to varenicline but the magnitude of the effect is comparable. The results and tolerability seem to be better than in most other studies.

Clinical factors associated with smoking cessation among smokers with Chronic Obstructive Pulmonary Disease by sex: Longitudinal analyses from French smoking cessation services.

Background: Smoking is responsible for 80 % of cases of Chronic Obstructive Pulmonary Disease (COPD), while the prognosis is improved by smoking cessation (SC). We examined clinical factors associated with SC among smokers with COPD comparing women and men. Methods: The study comprised a cohort of 1470 smokers who visited a SC service and completed at least 28-day of follow-up visits. The outcome was smoking status at follow-up (abstinence, reduction, no change). Abstinence was defined as continuous abstinence for at least 28 days, validated by the measurement of expired Carbon Monoxide. Reduction was defined as a halving of the baseline tobacco consumption. Results: The average age of the population was 53 (±11) years and 58.2 % were women. Men were 2 years younger than women and consulted more likely after a hospital contact, whereas women consulted on their own initiative. Women more often had a depression history, whereas men had medical comorbidities and co-addictions. There was no significant difference by sex regarding the abstinence rate (41.0 % in women vs 40.7 in men, p > 0.9). The factors significantly associated with higher abstinence rates in both sexes were: at least one previous quit attempt and number of follow-up visits ≥4. The factors negatively associated with quitting in women were diabetes, intake of mood stabilizers and consuming more than 10 cigarettes per day while having a chronic bronchitis, taking antidepressants and having consumed cannabis in the last 30 days hampered SC in men. Conclusions: Concerning factors associated with SC, few differences were found between female and male smokers suffering from COPD. However, due to the different medical and smoking behavior characteristics according to sex, it might be important to take these differences into account in order to provide tailored SC management.

Functions and pharmacology of α2ß2 nicotinic acetylcholine receptors; in and out of the shadow of α4ß2 nicotinic acetylcholine receptors.

Although α2 was the first neuronal nicotinic acetylcholine receptor (nAChR) receptor subunit to be cloned, due to its low level of expression in rodent brain, its study has largely been neglected. This study provides a comparison of the α2 and α4 structures and their functional similarities, especially in regard to the existence of low and high sensitivity forms based on subunit stoichiometry. We show that the pharmacological profiles of the low and high sensitivity forms of α2ß2 and α4ß2 receptors are very similar in their responses to nicotine, with high sensitivity receptors showing protracted responses. Sazetidine A, an agonist that is selective for the high sensitivity α4 receptors also selectively activates high sensitivity α2 receptors. Likewise, α2 receptors have similar responses as α4 receptors to the positive allosteric modulators (PAMs) desformylflustrabromine (dFBr) and NS9283. We show that the partial agonists for α4ß2 receptors, cytisine and varenicline are also partial agonists for α2ß2 receptors. Studies have shown that levels of α2 expression may be much higher in the brains of primates than those of rodents, suggesting a potential importance for human therapeutics. High-affinity nAChR have been studied in humans with PET ligands such as flubatine. We show that flubatine has similar activity with α2ß2 and α4ß2 receptors so that α2 receptors will also be detected in PET studies that have previously presumed to selectively detect α4ß2 receptors. Therefore, α2 receptors need more consideration in the development of therapeutics to manage nicotine addiction and declining cholinergic function in age and disease.

Design and rationale of the Botswana Smoking Abstinence Reinforcement Trial: a protocol for a stepped-wedge cluster randomized trial.

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.

Varenicline Solution Nasal Spray for the Treatment of Dry Eye Disease Following LASIK.

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.

Laser in situ keratomileusis (LASIK) is a very successful refractive surgery option for patients hoping to reduce or eliminate their need for spectacles. Signs and symptoms of dry eye disease are very common after LASIK owing to the transection of corneal nerves that occurs during the procedure, and many patients are advised to manage it with frequent instillation of artificial tears. This study evaluated the use of a varenicline solution nasal spray, a recently introduced pharmacologic option that stimulates natural tear production through activation of the trigeminal nerve pathway. This is the first study to evaluate the use of the varenicline solution nasal spray in patients after refractive surgery and demonstrates that it could represent a favorable, ocular surface-sparing option for patients to minimize the signs and symptoms of dry eye following LASIK, a procedure known to trigger symptoms of dry eye disease.

Efficacy of bupropion and varenicline genetic markers in choosing pharmacological treatment for smoking cessation, and implications for combining drugs: A randomized controlled trial - GENTSMOKING.

INTRODUCTION: Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed. METHODS: This partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8-12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy. RESULTS: Abstinence rates were 42.9% (95% CI: 36-64) in the control group versus 30.4% (95% CI: 23-37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67-80) versus 52% (95% CI: 49-64) at Week 12 (p<0.001), respectively. The strategy of combining drugs after Week 4 increased abstinence rates in both groups and the significant difference between genetic and control groups was maintained. CONCLUSIONS: Results show that using these selected genetic markers was inferior to starting treatment with varenicline (control group), which is currently the most effective smoking cessation drug; moreover, the addition of bupropion in cases of varenicline monotherapy failure improves the efficacy rate until the end of treatment. CLINICAL TRIAL IDENTIFIER: NCT03362099.

Impact of the disruption in supply of varenicline since 2021 on smoking cessation in England: A population study.

BACKGROUND AND AIMS: Varenicline is one of the most effective smoking cessation treatments. Its supply in England was disrupted in July 2021 due to nitrosamine impurities found by its supplier, Pfizer. This study measured the impact of this disruption on smoking cessation in England. DESIGN, SETTING AND PARTICIPANTS: The study used repeated cross-sectional surveys conducted monthly, from June 2018 to December 2022. Set in England, it comprised a total of 3024 adults who reported smoking during the past year and had made at least one serious attempt to quit in the past 6 months. MEASUREMENTS: Generalized additive models analyzed the association of the varenicline supply disruption with the trend in self-reported varenicline use in the most recent quit attempt. We used these results to estimate the population-level impact of the disruption on smoking cessation. FINDINGS: Before July 2021, the proportion of past 6-month quit attempts using varenicline was stable at approximately 3.9% [risk ratio (RR)trend = 1.034, 95% confidence interval (CI) = 0.823-1.298]. The trend in varenicline use has changed sharply since the supply disruption (RRΔtrend = 0.297, 95% CI = 0.120-0.738), with prevalence falling by 69.3% per year since; from 4.1% in June 2021 to 0.8% in December 2022. Convergently, National Health Service general practitioner prescribing data reported that just 0.1% of prescriptions for smoking cessation treatments in December 2022 were for varenicline. Assuming that varenicline does not return to the market, we estimate that this could result in ~8400 fewer people stopping smoking for at least 6 months, ~4200 fewer long-term ex-smokers and ~1890 more avoidable deaths each year. CONCLUSIONS: In England, the disruption in supply of varenicline since 2021 has coincided with a substantial fall in the use of varenicline in attempts to quit smoking.

Changes in distinct brain systems identified with fMRI during smoking cessation treatment with varenicline: a 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.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

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.