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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.

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INTRODUCTION: Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial. METHODS: 175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed. RESULTS: Treatment arm belief was significantly associated with actual arm assignment (χ2(2)=13.0, p=0.002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, vs. "not sure" (RR=3.05 [1.41-6.60], p=0.005). Participants in the placebo arm were just as likely to believe they were taking placebo vs. "not sure" (χ2[2]=0.75, p=0.69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR=5.91 [2.06-16.92], p=0.001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline B=0.077 [0.002-0.192], p <0.05). CONCLUSIONS: Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.

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Rationale: Not all individuals with tobacco dependence are ready to give up smoking. Research reveals behavioral differences between adults ready to discontinue tobacco use and those who are not. Thus, the interventions applied to these populations might differ. However, the evidence of using varenicline in individuals who are not ready to discontinue tobacco use is uncertain. Objectives: To determine if, in tobacco-dependent adults who report not being ready to discontinue tobacco use, clinicians should begin treatment with varenicline or wait until subjects are ready to discontinue tobacco use. Methods: We conducted a systematic review to assess the effectiveness and safety of treatment with varenicline in tobacco-dependent adults who are not ready to discontinue tobacco use. We systematically searched the Cumulative Index to Nursing and Allied Health Literature, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials comparing varenicline versus placebo for individuals who were not ready to discontinue tobacco use. Outcomes of interest include point prevalence abstinence during treatment or at six months or longer, smoking reduction, motivation to quit, adverse events, and withdrawal symptoms. Two authors independently extracted data and assessed eligibility and risk of bias using a standardized data collection form. We followed the Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of evidence. Results: Five trials met our inclusion criteria. All 2,616 participants were adults who were not ready to discontinue tobacco use at study entry. For 7-day point prevalence abstinence at six months or longer, high-certainty evidence suggested that varenicline increased abstinence compared with placebo (relative risk, 2.00 [95% confidence interval (CI), 1.70-2.35]; absolute risk reduction, 173 more per 1,000 [95% CI, 121 more to 234 more]). We identified moderate-certainty evidence suggesting that varenicline increased serious adverse events (relative risk, 1.75 [95% CI, 0.98-3.13]; absolute risk reduction, 12 more per 1,000 [95% CI, 0 fewer to 35 more]). For withdrawal, low-certainty evidence suggested that varenicline treatment was associated with a lower symptom score (mean difference, 1.54 points lower; 95% CI, 2.15-0.93 points lower; low certainty) assessed using the Brief Questionnaire of Smoking Urges. Conclusions: In tobacco-dependent adults who are not ready to discontinue tobacco use, initiating varenicline treatment results in a large increase in abstinence and likely results in a slight increase in serious adverse events.

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PURPOSE: Dry eye disease is characterized by loss of tear film stability. OC-01 (varenicline solution) is a small-molecule nicotinic acetylcholine receptor agonist administered as a nasal spray that stimulates tear production. METHODS: In MYSTIC (NCT03873246) patients aged ≥22 years with dry eye disease were randomized 1:1:1 to OC-01 0.03 mg, OC-01 0.06 mg, or vehicle (n = 41 per group), administered twice daily via intranasal spray, for 12 weeks (84 days). Primary efficacy endpoint was mean change from baseline in anesthetized Schirmer's test score (STS) in study eye at day (D) 84. RESULTS: Patients receiving OC-01 0.03 and 0.06 mg had statistically significantly increased tear production at D84 versus vehicle; least squares mean changes from baseline in STS were 10.8 mm and 11.0 mm for OC-01 0.03 and 0.06 mg, respectively. A trend toward a higher proportion of patients experiencing ≥10-mm improvement in STS from baseline was observed with OC-01 0.03 mg (36.6%; p > 0.05), and was significant for OC-01 0.06 mg (48.8%; p = 0.024), versus vehicle (24.4%). Non-ocular treatment-emergent adverse events (TEAEs) were reported by 21 patients; the most common was sneezing (OC-01 0.03 mg, 2 [4.9%]; OC-01 0.06 mg, 3 [7.3%]), with similar frequencies between treatment groups. No severe or serious TEAEs were reported. CONCLUSIONS: OC-01 (varenicline solution) nasal spray improved tear production in patients with dry eye disease over a long-term (12-week) period, and represents a receptor neuro-activator with a nasal route of administration that spares the ocular surface to stimulate tear production.

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OBJECTIVES: To assess the cost-effectiveness of varenicline in comparison to currently funded smoking cessation strategies in Brazil. METHODS: We modeled the lifetime direct costs and health-related quality of life of a hypothetical cohort of smokers with a single attempt to quit smoking using one of the following: (1) cognitive behavioral therapy (CBT) without any pharmacological intervention, (2) varenicline, (3) bupropion, (4) nicotine replacement therapy (NRT) with transdermal patch, (5) bupropion in combination with NRT transdermal patch, and (6) combined NRT (oral plus transdermal). All drug alternatives were considered with concomitant CBT. The analysis relied on a Markov model based on the Benefits of Smoking Cessation and Outcomes study and used different age and sex categories in the consideration of relative risks and incidence rates of the diseases included in the model. The analysis was conducted from the healthcare system perspective, and a 3% discounting rate for costs and outcomes was applied. Model parameter values were sourced from published literature. Probabilistic and deterministic sensitivity analyses assessed robustness. RESULTS: Among the smoking cessation alternatives available in Brazil, varenicline and combined NRT were estimated to have higher effectiveness; varenicline, however, was dominated due to its higher average cost. In the base-case analysis, combined NRT had an incremental gain of 0.25 quality-adjusted life-years (QALYs) in comparison to the second-best option (bupropion in combination with NRT transdermal patch) and an incremental cost-effectiveness ratio of R$2173.47/QALY ($595.45/QALY). CONCLUSIONS: Combination of oral and transdermal NRT (coupled with CBT) was the most effective smoking cessation option and was 100% cost-effective within a conservative willingness-to-pay threshold.

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Introduction and objectives: Although cardiologists frequently assist patients who suffer damage from smoking, the degree of training they receive to manage this problem during their residency is unknown. Because of this, we'd proposed to ­evaluate the preferences and practices of cardiology residents for smoking cessation of the attending patients. Materials and methods: Closed, prefixed, voluntary and anonymous survey among doctors who carried out the specialty of cardiology in 5 countries of Latin America and Spain. Results: 716 residents were surveyed; 62.4% from Argentina, 19% from Mexico, 6.8% from Spain, 6.7% from Chile, 3.2% from Uruguay, and 1.9% from Paraguay. When asked about the importance they assigned to this problem (using a scale of 1-10), 85.8% assigned this question a score of 8 or higher. While 80.5% of the participants expressed giving short anti-tobacco advice routinely, only 27.7% used pharmacological therapy for this purpose. Among those who did not use pharmacological therapy, 58.3% said that the reason was not being familiar with the treatments; 62.9% of the surveyed said they had not received any type of training in this problem. Those residents who received some type of training reported feeling more prepared for this (p < 0.0001). Conclusion: We found that cardiology residents have a low knowledge of pharmacological treatment and relatively low confidence to provide assistance in smoking cessation. This topic should be included in the training of future cardiologists in order to achieve a more comprehensive cardiovascular prevention.

Introducción y objetivos: Si bien los cardiólogos asisten cotidianamente a pacientes que sufren daño por el tabaquismo, no se conoce el grado de formación que reciben sobre esta problemática durante su residencia. Debido a ello nos propusimos evaluar las preferencias y prácticas de los residentes de cardiología para la cesación tabáquica de los pacientes que asisten. Materiales y métodos: Encuesta cerrada, prefijada, voluntaria y anónima entre médicos que realizaban la especialidad de cardiología en cinco países de Latinoamérica y España. Resultados: Se encuestaron 716 residentes: un 62.4% de Argentina, un 19% de México, un 6.8% de España, un 6.7% de Chile, un 3.2% de Uruguay y un 1.9% de Paraguay. Con respecto a la importancia que asignaban a esta problemática (empleando una escala de 1-10), el 85.8% le asignó a esta pregunta una puntuación de 8 o mayor. Mientras el 80.5% de los participantes expresó dar consejo breve antitabáquico sistemáticamente, solamente un 27.7% empleaban terapia farmacológica con este fin. Entre quienes no empleaban terapia farmacológica, el 58.3% manifestó que el motivo era no encontrarse familiarizados con los tratamientos. El 62.9% de los encuestados dijo no haber recibido ningún tipo de formación en esta problemática. Aquellos residentes que recibieron algún tipo de formación manifestaron sentirse más preparados (p < 0.0001). Conclusión: Encontramos un bajo conocimiento sobre el tratamiento farmacológico y relativamente poca seguridad por parte de los residentes de cardiología para brindar asistencia en cesación tabáquica. Consideramos esencial incluir este tópico en la formación de los futuros cardiólogos a fin de lograr una prevención cardiovascular más integral.

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INTRODUCTION: Varenicline effectively helps smokers quit by reducing withdrawal symptoms and blocking the reward of smoking. However, most quitters return to smoking within one year. 'Cue Restricted Smoking' is a behavioral technique designed to increase quit rates by asking smokers attempting to quit to restrict smoking to the standing position, while alone, in an isolated area facing a wall, with the cigarette as the only stimulus. METHODS: Using retrospective clinic records we compared quit rates in 281 smokers (50% males) instructed in the cue restricted smoking cessation method during 2016-2018 to quit rates in 324 smokers (46% males) advised to completely stop smoking on the target quit date which we previously used during 2011-2014. All were prescribed varenicline for 12 weeks alone, with the addition of bupropion if needed after 4 weeks. Follow-up consisted of behavioral support at 4-6 visits during active drug treatment and telephone counselling at 24 and 52 weeks. The smoking cessation rate was confirmed with exhaled carbon monoxide at the clinic visit at 12 weeks and only by telephone at 52 weeks. RESULTS: The mean age of smokers was 49 years in both groups and the number of cigarettes smoked daily was similar (18/day in the cue restricted vs 19/day in the target quit day group). The smoking cessation rate at 12 weeks was 75% in the cue restricted versus 45% in the target quit day group (relative risk, RR=1.8; 95% CI: 1.4-2.2, p<0.001). At 52 weeks the quit rate was 65% vs 34%, respectively (RR=1.9; 95% CI: 1.5-2.4, p<0.001). CONCLUSIONS: Cue restricted smoking was associated with a substantially increased chance of quitting compared with standard advice during treatment with varenicline. These results should be further studied in a randomized controlled trial.

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The beneficial effects of drugs that act via nicotinic acetylcholine receptors (nAChRs) on Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition. Varenicline, an α4β2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated varenicline effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to varenicline (2 mg/kg) by gavage. After that, MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate dopamine and DOPAC levels. To verify whether varenicline was protective during the MPTP insult, a separate group of MPTP animals received varenicline from PN90 to PN124. MPTP reduced cortical dopamine content and increased dopamine turnover. Those effects were not reversed by varenicline treatment. Interestingly, varenicline reversed the MPTP-induced hyperactivity in the open field. Both maintenance of varenicline treatment during MPTP exposure or its interruption before MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that varenicline treatment reduced the MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect, varenicline could exert neuroprotective effects on circuits that control motor activity in PD.

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Resumen Diferentes investigaciones han evidenciado que el tratamiento con vareniclina es efectivo para dejar de fumar cuando se combina con un tratamiento psicológico. Sin embargo, existe una carencia de estudios respecto a cuánta efectividad aporta la vareniclina al tratamiento psicológico. El objetivo del presente estudio piloto fue evaluar si la efectividad de una intervención psicológica cognitivo-conductual incrementa con la inclusión de la vareniclina. La muestra de este estudio la conformaron 22 fumadores (M edad = 30.5; de = 15.4 años), con un consumo diario promedio de 12.29 (de = 5.7) cigarrillos. Cada participante eligió una de dos intervenciones: 11 fumadores recibieron la Intervención Breve Motivacional para Dejar de Fumar (ibmdf) y 11 la misma intervención más vareniclina. Los resultados indican que no hay diferencias significativas entre las intervenciones. Así, la inclusión de la vareniclina no incrementó la efectividad de la intervención psicológica. Las conclusiones de este estudio deben ser tomadas con cautela debido al tamaño de la muestra, por lo tanto, es necesario aumentar las investigaciones al respecto.

Abstract Different studies have shown that treatment with varenicline is effective for smoking cessation when it is combined with psychological treatment. However, there are few studies on the effectiveness that varenicline adds to psychological treatment. The aim of this pilot study was to assess if the effectiveness of a cognitive behavioral intervention increases with the inclusion of varenicline. The sample of this study were 22 smokers (M age = 39.5, SD = 15.4 years), with an average daily consumption of 12.29 cigarettes (SD = 5.7). Each participant chose one of the two interventions: 11 smokers received the Motivational Smoking Cessation Brief Intervention (mscbm) and 11 the same intervention plus varenicline. The results showed no significant differences between interventions. Thus, the inclusion of varenicline did not increase the effectiveness of psychological intervention. The findings of this study should be taken with caution due to the sample size. More research is therefore needed.

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INTRODUCTION: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation with varenicline. METHODS: We included 74 smokers starting treatment with varenicline. Gene expression analysis was performed through the custom RT² Profiler qPCR array assay, including 17 genes. Times for sample collection were before the start of therapy (T0) and two weeks (T2) and four weeks (T4) after the start of treatment. RESULTS: For gene expression analysis, we selected 14 patients who had success and 13 patients resistant to varenicline treatment. Success was considered to be when a patient achieved tobacco abstinence until the fourth week of treatment and resistant was when a patient had not stopped smoking as of the fourth week of treatment. We observed a significant difference for CHRNA7 gene expression: in the resistant group, samples from T2 and T4 had lower expression compared with T0 (fold change: 0.38, P = 0.007; fold change: 0.67, P = 0.004; respectively). CONCLUSION: This exploratory clinical study, searching for a possible predictor of effectiveness for varenicline, reaffirmed the association of the α7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline.

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SUMMARY Varenicline is a useful pharmacological option for smoking cessation. Unfortunately, there is a lack of studies on its effectiveness, retention, and side effects in low- and middle-income countries. The present study aimed to investigate gender differences regarding these outcomes in a Brazilian clinical sample (n = 124). The 12-week treatment protocol included six consultations with a psychiatrist and six sessions of cognitive-behavioral therapy. All subjects received varenicline on the first evaluation, following the standard posology for 12 weeks and instructions to stop smoking after the second week of treatment. Both Mini-International Neuropsychiatric Interview (MINI) Plus and Fagerstrom Test for Nicotine Dependence were applied at baseline. The UKU-Side Effects Rating Scale was administered at weeks 3, 7, and 11, and the Questionnaire of Smoking Urges-Brief at weeks 1, 5, and 9 to ascertain the side effects of the medication and craving, respectively. At the end of the 12-week treatment, abstinence was biochemically assessed. At months 6 and 12 after the treatment, follow-up telephone interviews were conducted to access nicotine abstinence. Short- and long-term abstinence and retention rates did not differ between genders. However, women presented more side effects than men, especially in the second half of the treatment. Increased dream activity, reduced duration of sleep, constipation, and weight loss were the most notable side effects. Despite women reporting more side effects than men, this difference did not influence the treatment success rates.

RESUMO A vareniclina é uma opção farmacológica útil para a cessação do tabagismo. Infelizmente, há uma ausência de estudos sobre a eficácia, retenção e efeitos colaterais para este medicamento em países de baixa e média renda. O presente estudo teve como objetivo investigar diferenças entre gênero em relação a esses desfechos em uma amostra clínica brasileira (n = 124). O protocolo de tratamento de 12 semanas incluiu seis consultas com um psiquiatra e seis sessões de psicoterapia cognitivo-comportamental. Todos os indivíduos receberam vareniclina na primeira avaliação, seguindo a posologia padrão por 12 semanas e instrução para parar de fumar a partir da segunda semana de tratamento. Tanto o Mini-International Neuropsychiatric Interview (MINI) Plus quanto o Teste de Fagerstrom para Dependência de Nicotina foram aplicados no início do estudo. A escala de efeitos colaterais (UKU-Side Effects Rating Scale) foi aplicada nas semanas 3, 7 e 11, e o Questionário Breve de Fissura (Questionnaire of Smoking Urges-Brief) nas semanas 1, 5 e 9 para investigar os efeitos colaterais da medicação e fissura, respectivamente. No final do tratamento de 12 semanas, a abstinência foi avaliada bioquimicamente. Aos 6 e 12 meses após o tratamento, foram realizadas entrevistas telefônicas de acompanhamento para acessar a abstinência de nicotina. As taxas de abstinência e retenção de curto e longo prazo não diferiram entre gêneros. No entanto, as mulheres apresentaram mais efeitos colaterais do que os homens, principalmente na segunda metade do tratamento. Aumento da atividade dos sonhos, redução da duração do sono, constipação e perda de peso foram os efeitos colaterais mais notáveis. Apesar de as mulheres relatarem mais efeitos colaterais que os homens, essa diferença não influenciou as taxas de sucesso do tratamento.

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RESUMO Objetivo O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental. Métodos Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas. Resultados Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas. Conclusões Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar.

ABSTRACT Objective This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study. Methods A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out. Results Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations. Conclusion This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.

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Despite so many global efforts, smoking still remains to be one of the most common addictions worldwide. Even though most smokers wish to quit smoking, many of them fail. In this respect, genetic variants are thought to be remarkable factors in nicotine dependence and in treatment of smoking cessation. This is a paper investigating a single variant p-glycoprotein (P-gp) polymorphisms and its effect on Varenicline efficacy in the smoking cessation. 158 smokers and 52 non-smoker healthy volunteers were included. We determined the P-gp C3435T gene polymorphisms in all subjects. Face to face interviews with smokers were performed for smoking cessation and Varenicline was given for smoking cessation. Cessation success was evaluated in the 6th month and success rates were compared according to the P-gp genotype distributions. In our study, smoking cessation rate by Varenicline was 57.0%. This rate was 55.0% in females, and 57.2% in males (p=0.85). The P-gp C3435T gene distribution was similar in control, quitters and not-quitter groups. Cessation rate was at highest point in genotype CT (62.2%) and at the lowest in TT (47.6%). It was 53.8% in genotype CC and there was no statistically significant difference (p=0.27). Our results suggest that genetic variants of P-gp C3435T did not significantly affect Varenicline treatment for smoking cessation.

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Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors. Recent clinical trial data support use of varenicline for treatment of conditions/addictions that are not related to smoking cessation. Considering the importance of this issue and the need for new studies on its effects, especially on behavior, more studies using animal models are necessary. Thus, the aim of this study was to evaluate the effects of prolonged exposure to varenicline in anxiety-like behavior and memory, as well as in cerebral neurochemistry of rats. Male rats received three different doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3?mg/kg orally (gavage) for 30?days. Animal behavior was analyzed through open field, elevated plus maze, light/dark box, social interaction, Barnes maze and novel object recognition tests. Neurotransmitter levels and their metabolites in different brain structures (hippocampus, striatum and frontal cortex) were measured. Results showed that prolonged exposure of rats to varenicline: 1) did not interfere in motor activity, but caused an anxiogenic effect on elevated plus maze, light/dark box and social interaction testes; 2) did not alter memory; and 3) promoted alterations on serotoninergic system in the striatum and frontal cortex. In conclusion, compilation of the data indicates that prolonged exposure of rats to varenicline promoted anxiogenic effects and alteration in serotonergic system, which corroborated behavioral findings.

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Resumen: Considerando que la población chilena tiene una historia de alto consumo de tabaco, la Sociedad Chilena de Enfermedades Respiratorias en colaboración con las Sociedades Chilenas de Cardiología; Endocrinología y Diabetes formó un grupo interdisciplinario que emitió un conjunto de recomendaciones para el enfrentamiento del paciente fumador, asesorado metodológicamente por expertos. Estas intervenciones deben priorizarse en grupos de alto riesgo. Métodos: El panel elaboró y graduó las recomendaciones siguiendo la metodología GRADE. Para estimar el efecto de cada intervención, se identificó revisiones sistemáticas y estudios clínicos aleatorizados. Además, se realizó una búsqueda de estudios realizados con población chilena. Para cada una de las preguntas, el panel determinó la dirección y fuerza de la recomendación mediante una tabla de la Evidencia a la Decisión. Recomendaciones: Para todos los fumadores, el panel recomienda usar consejería breve sobre no intervención, consejería vía telefonía móvil sobre no intervención, y mensajes de texto sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos).Para los individuos motivados, con indicación de fármacos para dejar de fumar el panel recomienda terapia de reemplazo de nicotina sobre no intervención, bupropión sobre no intervención, vareniclina sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos).Discusión: Se emiten recomendaciones basadas en la evidencia para el tratamiento del tabaquismo.

Considering that the Chilean population has a high tobacco consumption history, the Chilean Association of Respiratory Diseases in collaboration with the Chilean Associations of Cardiology and Endocrinology and Diabetes, formed an interdisciplinary group, that issued a set of recommendations for the treatment of the smoker, methodologically advised by experts. These interventions should be prioritized in high-risk groups. Methods: The panel elaborated and graded the recommendations following the GRADE methodology. To assess the effect of each intervention, systematic reviews and randomized clinical trials were identified. In addition, a search of studies done in the Chilean population was carried out. For each of the questions, the panel determined the direction and strength of the recommendation through a decision evidence table.Recommendations: For all smokers, the panel recommends using brief counseling ABC over non-intervention, using mobile telephone counseling over non-intervention, using text messages over non-intervention, (strong recommendation; moderate certainty in the evidence of the effects) For motivated individuals, with indication for pharmacological interventions for quitting smoking, the panel recommends using nicotine replacement therapy over non-intervention, using bupropion over non-intervention, using varenicline over non-intervention. (strong recommendation; moderate certainty in the evidence of the effects) Discussion: This clinical practice guidelines provides recommendations based on the current evidence for smoking cessation.

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Considering that a high proportion of the Chilean general population smokes, the Chilean Society of Respiratory Diseases in collaboration with the Chilean Societies of Cardiology and, Endocrinology and Diabetes, formed an interdisciplinary group, who issued a set of recommendations for the treatment of the smoker, methodologically advised by experts. These interventions should be prioritized in high-risk groups. Methods The panel elaborated and graded the recommendations following the GRADE methodology. To assess the effect of each intervention, systematic reviews and randomized clinical trials were identified. In addition, a search of studies done with the Chilean population was carried out. For each of the questions, the panel determined the direction and strength of the recommendation through a decision evidence table. Recommendations For all smokers, the panel recommends using brief counseling ABC on non-intervention, using mobile telephone interventions on non-intervention, using text message on non-intervention, (strong recommendation; moderate certainty in the evidence of the effects). For motivated individuals, with indication for quitting drugs the panel recommends using nicotine replacement therapy on non-intervention, using bupropion on non-intervention, using varenicline on non-intervention. (strong recommendation; moderate certainty in the evidence of the effects). Discussion This clinical practice guide provides recommendations based on the evidence for smoking cessation.

El propósito de esta guía es presentar recomendaciones basadas en evidencia sobre las intervenciones disponibles para dejar de fumar. Su audiencia objetivo corresponde a todos los profesionales de la salud y su población objetivo corresponde a personas fumadoras atendidas en ambientes ambulatorios u hospitalarios, además de poblaciones especiales como embarazadas, adolescentes y pacientes con enfermedad psiquiátrica (compensada por al menos tres meses).

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RESUMEN Considerando que la población chilena tiene una historia de alto consumo de tabaco la Sociedad Chilena de Enfermedades Respiratorias en colaboración con las Sociedades Chilenas de Cardiología; Endocrinología y Diabetes formó un grupo interdisciplinario que emitió un conjunto de recomendaciones para el enfrentamiento del paciente fumador, asesorado metodológicamente por expertos. Estas intervenciones deben priorizarse en grupos de alto riesgo. Métodos: El panel elaboró y graduó las recomendaciones siguiendo la metodología GRADE. Para estimar el efecto de cada intervención, se identificó revisiones sistemáticas y estudios clínicos aleatorizados. Además, se realizó una búsqueda de estudios realizados con población chilena. Para cada una de las preguntas, el panel determinó la dirección y fuerza de la recomendación mediante una tabla de la Evidencia a la Decisión. Recomendaciones: Para todos los fumadores, el panel recomienda usar consejería breve sobre no intervención, consejería vía telefonía móvil sobre no intervención, y mensajes de texto sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos). Para los individuos motivados, con indicación de fármacos para dejar de fumar el panel recomienda terapia de reemplazo de nicotina sobre no intervención, bupropión sobre no intervención, vareniclina sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos). Discusión: Se emiten recomendaciones basadas en la evidencia para el tratamiento del tabaquismo.

Considering that Chilean population has a high tobacco consumption history, the Chilean Society of Respiratory Diseases in collaboration with the Chilean Societies of Cardiology and, Endocrinology and Diabetes, formed an interdisciplinary group, who issued a set of recommendations for the treatment of the smoker, methodologically advised by experts. These interventions should be prioritized in high-risk groups. Methods: The panel elaborated and graded the recommendations following the GRADE methodology. To assess the effect of each intervention, systematic reviews and randomized clinical trials were identified. In addition, a search of studies done with the Chilean population was carried out. For each of the questions, the panel determined the direction and strength of the recommendation through a decision evidence table. Recommendations: For all smokers, the panel recommends using brief counseling ABC on non-intervention, using mobile telephone interventions on non-intervention, using text message on non-intervention, (strong recommendation; moderate certainty in the evidence of the effects). For motivated individuals, with indication for quitting drugs the panel recommends using nicotine replacement therapy on non-intervention, using bupropion on non-intervention, using varenicline on non-intervention. (strong recommendation; moderate certainty in the evidence of the effects). Discussion: This clinical practice guide provides recommendations based on the evidence for smoking cessation.

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Resumen Vareniclina es terapia de primera línea para la cesación del tabaquismo, y presenta la mayor efectividad demostrada ampliamente en ensayos clínicos logrando cifras de abandono al año del orden de 25-35%. En la más reciente revisión de efectividad realizada por la Cochrane se evaluaron 39 ensayos que randomizaban vareniclina contra placebo y en comparación con sustitutos de nicotina (TRN) y bupropión. Con vareniclina se objetivó un RR de 2,24 para abstinencia a 6 meses o más prolongado a dosis standard (2 mg al día) contra placebo. El RR de vareniclina versus placebo comparando con bupropión o TRN fue de 1,3 y 1,25 respectivamente mostrando su superioridad una vez más. Cuando se evaluó el uso de vareniclina por un periodo más prolongado que 12 semanas, se observó que la droga fue bien tolerada sugiriendo que es factible su uso sin intensificar los efectos adversos.

Varenicline is a first-line therapy cessation of smoking, and has the highest effectiveness widely demonstrated in clinical trials with drop-out figures per year of the order of 25-35%. In the most recent effectiveness review conducted by the Cochrane, 39 trials were evaluated that randomized varenicline versus placebo and compared with nicotine substitutes (NRT) and bupropion. With varenicline, a RR of 2.24 was observed for abstinence at 6 months or longer at standard doses (2 mg daily) versus placebo. The RR of varenicline versus placebo compared with bupropion or NRT was 1.3 and 1.25 respectively showing its superiority once again. When the use of varenicline was evaluated for a period longer than 12 weeks, it was observed that the drug was well tolerated suggesting that its use is feasible without intensifying the adverse effects.

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Resumen La terapia combinada es la de mezcla de farmacos para al cesación del tabaquismo, tal como terapias de reemplazo nicotínico (TRN) en modalidad prolongada como es el parche junto a una modalidad de acción corta como puede ser chicle, goma, lozenge, pastillas o inhalador nasal), es decir dos o más fármacos aprobados y demostrados útlies para el cese del tabaco con o sin el apoyo de TRN. Es muy importante considerar la comorbilidad médica y psiquiatrica porque la población que persiste adicta es cada vez más compleja en términos de comorbilidades y elevado nivel adictivo. La mayor parte de las terapias combinadas usan TRN asociadas a bupropión o vareniclina. Existe evidencia sobre efectividad y seguridad de las TRN utilizadas entre ellas o en asociación a vareniclina o bupropión, sin embargo, la evidencia sobre seguridad en la modalidad combinada no es tan robusta como la que existe para cada fármaco en monoterapia, ya que los efectos adversos se suman de manera que se sugiere reservar las combinaciones para personas con alto nivel de adicción y/o con historia de fracaso en intentos previos con monoterapia. En suma, los fármacos de demostrada efectividad y seguridad como TRN, bupropión y vareniclina pueden usarse en combinación doble o triple, preferenciando el uso de TRN de corta acción cuando se adiciona a alguno de los fármacos orales para aliviar la ansiedad por fumar.

This therapy is a combination of medicines consisting of nicotine replacement therapy (NRT) using a prolonged modality such as the patch, along with a short-acting medicine such as chewing gum, lozenge, gum, or nasal inhaler). This means two or more drugs approved and demonstrated useful for cessation of smoking with or without the support of NRT. It is very important to consider medical and psychiatric comorbidity because the population that persists addicted is increasingly complex in terms of comorbidities and high addictive level. Most of the combination therapies use NRT associated with bupropion or varenicline. There is evidence on the effectiveness and safety of TRN used in both modalitres (long and short acting) in combination with varenicline or bupropion. However, safety evidence is not robust for the combination modality as it is for, each drug as monotherapy, since adverse effects are added so it is suggested to reserve the combinations for people with high level of addiction and / or history of failure in previous attempts with monotherapy. In summary, therapy with demonstrated effectiveness as NRT, bupropion and varenicline can be used in double or triple combination, prefering the use of short acting NRT added to one of the oral drugs to alleviate smoking anxiety.

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Background: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. Aim: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. Patients and Methods: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. Results: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). Conclusions: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

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