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Objective: Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. Approximately 30% of autosomal dominant sleep-related hypermotor epilepsy patients are medically intractable. In preclinical models, pathogenic nAChR variants cause a gain of function mutation with sensitivity to acetylcholine antagonists and agonists. Nicotine modifies the activity of nAChRs and can be used as targeted therapy., Methods: We reviewed next-generation sequencing epilepsy panels from a single laboratory (GeneDx) from patients at Children's Medical Center Dallas between 2011 and 2015 and identified patients with nAChR variants. Retrospective review of records included variant details, medical history, neuroimaging findings, and treatment history., Results: Twenty-one patients were identified. Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction., Conclusions: Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants. We propose consideration of transdermal nicotine treatment in intractable epilepsy with known nAChR variants as an experimental therapy. Further clinical trials are needed to fully define therapeutic effects.

Activation of the cholinergic anti-inflammatory pathway through direct activation of nicotinic acetylcholine receptors on immune cells can inhibit pro-inflammatory chemokine and cytokine release and thereby protect in a variety of inflammatory diseases. The aim of this study was to investigate whether nicotine treatment protected against acute lung inflammation. Mice challenged with intratracheal lipopolysaccharide (LPS, 50 μg) were treated with nicotine (0.2 or 0.4 mg/kg, sc). After 24 h, bronchoalveolar lavage fluid (BALF) was obtained to measure leukocyte infiltration, lung edema, and pro-inflammatory chemokine (MIP-1α, MIP-2, and eotaxin) and cytokine (IL-1, IL-6, and TNF-α) levels. Nicotine treatment reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by decreased BALF inflammatory cells, myeloperoxidase, and protein. Nicotine also downregulated lung production of pro-inflammatory chemokines and cytokines. These data support the proposal that activation of the cholinergic anti-inflammatory pathway may represent a useful addition to the therapy of acute respiratory distress syndrome.

Purpose: To determine the efficacy of preoperatively administered nicotine nasal spray (3 mg) for analgesia after third molar (TM) surgery., Materials and Methods: A single-center, prospective, randomized, double-blind, crossover trial was conducted. The study population consisted of 20 nonsmoking patients referred to the Department of Oral and Maxillofacial Surgery of Columbia University College of Dental Medicine for extraction of all 4 TMs. Each patient received nicotine nasal spray or placebo spray before TM surgery. At a subsequent visit the contralateral TMs were removed with prior administration of the alternate treatment. For an hour postoperatively, subjects reported information on pain and nausea, and hemodynamic variables were recorded at 15-minute intervals. Telephone follow-up was recorded for 5 days postoperatively, where patients reported information on pain, nausea, and use of hydrocodone/acetaminophen as rescue analgesia., Results: Nicotine treatment was associated with a highly significant decrease in pain reported during the 5 days after TM surgery. There was no difference in the amount of hydrocodone/acetaminophen used or amount of nausea reported. There was a small but significant increase in heart rate after nicotine treatment compared with placebo during the first hour after surgery. There was no difference in blood pressure between groups., Conclusion: Pain is well controlled by hydrocodone/acetaminophen in most patients after TM surgery. However, there is significant variability in pain reported. Nicotinic agonists represent a new class of analgesic that can be considered for patients who are expected to have significant opioid-resistant pain after TM surgery. Caution should be used with patients in whom a small increase in heart rate would be deleterious., (Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by increased deposition of beta-amyloid (Aβ) peptides and progressive cholinergic dysfunction in regions of the brain involved in learning and memory processing. In AD, progressive accumulation of Aβ peptide impairs nicotinic acetylcholine receptor (nAChR) function by an unknown mechanism believed to involve α(7)- and α(4)β(2)-nAChR blockade. The three approaches of the current study evaluated the effects of chronic nicotine treatment in the prevention of Aβ-induced impairment of learning and short-term memory. Rat AD model was induced by 14-day i.c.v. osmotic pump infusion of a 1:1 mixture of 300 pmol/day Aβ(1-40)/Aβ(1-42) or Aβ(40-1) (inactive peptide, control). The effect of nicotine (2 mg/(kg day)) on Aβ-induced spatial learning and memory impairments was assessed by evaluation of performance in the radial arm water maze (RAWM), in vivo electrophysiological recordings of early-phase long-term potentiation (E-LTP) in urethane-anesthetized rats, and immunoblot analysis to determine changes in the levels of beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), Aβ and memory-related proteins. The results indicate that 6 weeks of nicotine treatment reduced the levels of Aβ(1-40) and BACE1 peptides in hippocampal area CA1 and prevented Aβ-induced impairment of learning and short-term memory. Chronic nicotine also prevented the Aβ-induced inhibition of basal synaptic transmission and LTP in hippocampal area CA1. Furthermore, chronic nicotine treatment prevented the Aβ-induced reduction of α(7)- and α(4)-nAChR. These effects of nicotine may be due, at least in part, to upregulation of brain derived neurotropic factor (BDNF)., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cholinergic dysfunction and deposition of beta-amyloid (Aβ) in regions of the brain associated with learning and memory. The sporadic nature and late onset of most AD cases suggests that aside from biological determinants, environmental factors such as stress may also play a role in the progression of the disease. Behavioral and molecular studies were utilized to evaluate the effects of chronic nicotine treatment in the prevention of impairment of long-term memory. The rat model of AD was induced by i.c.v. osmotic pump infusion of Aβ peptides. Chronic psychosocial stress and chronic nicotine treatment were instituted for 6weeks. Spatial memory testing in the Radial Arm Water Maze revealed that, although stress, by itself, did not affect long-term memory, the combination of chronic stress and Aβ infusion impaired long-term memory significantly more than Aβ peptides infusion alone. Chronic nicotine treatment completely prevented Aβ- and stress/Aβ combination-induced memory impairment. Furthermore, molecular findings in hippocampal CA1 region of stress/Aβ rats indicated marked reduction in the protein levels of phosphorylated cAMP response element binding (p-CREB) and calcium-calmodulin-dependent protein kinase IV (CaMKIV), with significant increases in the levels of brain-derived neurotrophic factor (BDNF). These disturbances in signaling pathways, which may be the underlying mechanisms of impairment of long-term memory in these rats, were totally prevented by chronic nicotine treatment., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: to explore women's views surrounding the use of nicotine replacement therapy (NRT) to aid smoking cessation., Design and Setting: a qualitative approach using semi-structured interviews undertaken on 10 pregnant women in a semi-rural area of England., Findings: the two main themes that emerged from the study were that NRT was an important component in stopping smoking, but this was in conjunction with support given by the midwife advisor. Both themes appeared to be equally important to the women in aiding their attempts at smoking cessation. Also, the importance of tailored interventions should not be dismissed when aiding women in smoking cessation., Conclusions: exploring the views of women enabled the researchers to gain a greater understanding of the problems and achievements that women encountered when using NRT as an aid to stop smoking during pregnancy. The study also demonstrated that smoking cessation strategies can be successful if they are tailored to the individual needs of each woman, taking into account her dependency, domestic circumstances and willingness to change., Implications for Practice: the findings of this study add to the available research surrounding the efficacy of NRT in pregnancy. There is little evidence that the views of pregnant women have been taken into account prior to this study; as such, this report offers a different dimension to the available evidence. Although these findings could be adopted and utilized by practitioners, there is still the need for further research in this area on a larger scale., (Copyright 2008 Elsevier Ltd. All rights reserved.)

Objective: to review the literature of women's use of nicotine replacement therapy (NRT) during pregnancy. The review will examine NRT and nicotine, interventions and barriers to smoking cessation and the literature exploring women's views on using NRT in pregnancy., Method: a structured review of the literature was undertaken by accessing internet and library sources, restricted to English written articles between 1989 and 2003. Keywords were used to refine the search: pregnancy, smoking, NRT and smoking cessation., Findings: several papers had examined interventions employed to aid pregnant women in smoking cessation and the efficacy of NRT. However, papers exploring the views of women on the use of NRT during pregnancy were limited., Conclusions: smoking cessation is unique to individual women; as such, appropriate support and advice should be tailored accordingly. Further research is needed to explore the views of women using NRT during pregnancy to aid smoking cessation., Implications for Practice: the findings from this structured review raise awareness of the importance of smoking cessation during pregnancy, and the inclusion of women's views when discussing the use of NRT. Understanding women's views may enhance the care and advice given by midwives, thus improving smoking cessation rates in pregnancy., (Copyright 2008 Elsevier Ltd. All rights reserved.)

Objective: to develop a pragmatic service for pregnant smokers., Design: identification and referral of pregnant smokers to specialist services using self-report gathered on routine pregnancy booking questionnaire augmented by a carbon monoxide breath test. Engagement by specialist smoking cessation midwives using telephone contact with the offer of clinic-based counselling for women who want help. Telephone support and pharmacy provision of nicotine replacement therapy for women who decide to quit., Setting: three maternity units serving Glasgow in the West of Scotland., Participants: a relatively deprived population of 12,000 pregnant women each year in Glasgow., Interventions: at maternity booking, women with either a carbon monoxide breath test result >7 parts per million or self-reporting to be a current smoker during the routine pregnancy booking questionnaire were identified as smokers. All smokers were referred on to the specially trained midwives who provided an opt-out smoking cessation intervention. This involved motivational interviewing to engage pregnant smokers during telephone contact. Women considering quitting were invited for a follow-up face-to-face meeting in a clinic setting. Women who set a quit date were offered withdrawal oriented therapy augmented by pharmacy-based nicotine replacement therapy., Findings: booking midwives found it difficult to approach all pregnant women to talk about smoking. This was not made easier by the service requirement that all pregnant women should provide a carbon monoxide breath test at maternity booking. In one hospital, auxiliary nurses performed the carbon monoxide breath test and 2879 of 3219 (89%) women booking for antenatal care provided a sample, allowing most smokers to be identified. In another hospital where the carbon monoxide test was administered by midwives, only 1968 of 5570 (35%) women provided a carbon monoxide breath test sample; 61% of pregnant smokers were not identified and referred to specialist services. Of the 1936 pregnant smokers referred from all three hospitals, 386 (20%) attended a face-to-face appointment with specialist smoking cessation midwives, 370 (19%) set a quit date and 117 (6%) had quit 4 weeks after their quit date., Implications for Practice: this service development provides a pragmatic approach to identify nearly all pregnant smokers at maternity booking, and an opt-out model to refer them to specialist smoking cessation services. Further research is required to establish if extra auxiliary staff in maternity booking clinics can optimise the identification and referral of pregnant smokers to specialist smoking cessation services. This telephone- and clinic-based specialist service engaged 20% of referred pregnant smokers to attend a face-to-face appointment with a specialist smoking cessation midwife. Further research is required to assess if home-based support would engage a greater proportion of pregnant smokers, or if an incentive scheme would achieve the same aim. In total, 117 of 370 (32%) women who set a quit date had quit smoking 4 weeks later, which compares fairly well with a figure of 40% for pregnant smokers in the English smoking treatment services., (Copyright 2008 Elsevier Ltd. All rights reserved.)

Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.

Introduction: Smoking rates are higher among lesbian/gay/bisexual (LGB) than heterosexual (HT) individuals. However, there is scant information regarding smoking cessation treatments and outcomes in LGB populations. This study examined abstinence outcome in response to a high intensity smoking cessation program not specifically tailored to LGB smokers., Methods: A total of 54 gay/bisexual (GB) and 243 HT male smokers received 8-week open treatment with nicotine patch, bupropion, and counseling. Participants reported biologically verified abstinence at multiple time points during the study., Results: Demographic, smoking, and psychological characteristics at baseline were similar according to sexual orientation. During the first 2 weeks after quit day, abstinence rates were higher among GB smokers (Week 1: GB = 89%, HT = 82%; Week 2: GB = 77%, HT = 68%; ps < .05); abstinence rates converged subsequently, becoming nearly identical at the end of treatment (Week 8, GB = 59% vs. HT = 57%). In mixed effects longitudinal analysis of end-of-treatment outcome, sexual orientation (b = 1.40, SEM = 0.73, p = .056) and the Sexual Orientation x Time interaction (b = -0.146; SEM = 0.08, p = .058) approached statistical significance, reflecting the higher initial abstinence rates among GB smokers and the later convergence in abstinence rates by sexual orientation., Discussion: This first report comparing smoking cessation treatment response by sexual orientation found higher initial and similar end-of-treatment abstinence rates in GB and HT smokers. Further work is needed to determine whether these observations from GB smokers who displayed a willingness to attend a non-tailored program and broad similarity with their HT counterparts in many baseline characteristics will replicate in other groups of GB smokers.

Promoting cessation is a cornerstone of tobacco control efforts by public-health agencies. Economic information to support cessation programs has generally emphasized cost-effectiveness or the impact of cigarette pricing and smoking restrictions on quit rates. In contrast, this study provides empirical estimates of smoker preferences for increased efficacy and other attributes of smoking cessation therapies (SCTs). Choice data were collected through a national survey of Canadian smokers. We find systematic preference heterogeneity for therapy types and SCT attributes between light and heavy smokers, as well as random heterogeneity using random parameters logit models. Preference heterogeneity is greatest between length of use and types of SCTs. We estimate that light smokers would be willing to pay nearly $500 ($CAN) to increase success rates to 40% with the comparable figure for heavy smokers being near $300 ($CAN). Results from this study can be used to inform research and development for smoking cessation products and programs and suggest important areas of future inquiry regarding heterogeneity of smoker preferences and preferences for other health programs.

We tested whether a reduction of cigarette consumption obtained after 6 months of nicotine replacement therapy was maintained 5 years after the end of this treatment. Heavy smokers (mean = 30 cigarettes per day) who had no intention of quitting smoking were randomly assigned to a 6-month treatment of nicotine (15-mg patch, 4-mg gum, and/or 10-mg inhaler, n = 265), placebo (n = 269), or no intervention (n = 389). Products were sent by mail, and education was limited to a booklet. Of 923 participants, 879 (95%) were followed after 6 months and 671 (73%) after 5 years. After 6 months, smoking reduction was larger for nicotine (-10.9 cigarettes per day) than for placebo (-8.7) and no treatment (-4.9, all P or= 0.2) and smoking cessation rates (17% to 21%, all P > 0.2) were similar in all groups. In smokers, 5-year continuous abstinence was higher in those who had reduced their cigarette consumption by at least 50% between baseline and 6 months than in those who did not reduce (11.9% vs 5.6%; P = 0.011; odds ratio, 2.3; 95% confidence interval, 1.2-4.2). Thus, the initial effect of the treatment on smoking reduction was not maintained after 5 years. However, reducing cigarette consumption was associated with a higher chance of subsequently quitting smoking. Nicotine replacement therapy in unmotivated smokers had no deleterious effect on dependence levels and smoking behavior.

Nicotine intake via smoking is highly variable. Individualized dosing of nicotine replacement therapy (NRT) may improve product efficacy, but a better understanding of the within-day and within-subject relationships between smoking, NRT use, nicotine and cotinine concentrations in blood, and cravings and withdrawal symptoms is needed to inform dosing algorithms. A pilot study was undertaken to collect data on these relationships and to assess the feasibility of the methods needed for this type of research, including a sophisticated statistical modeling technique (a two-part mixed-effects model with correlated random effects that accounts for clumping at zero). Because nicotine metabolism varies by gender and race, the sample was homogeneous with respect to these characteristics. In a within-subjects study, 27 African American adult male smokers carried a computerized cigarette dispenser for 1 week, capturing the time each cigarette was smoked. Subjects then entered an inpatient setting for 1 day of scheduled smoking (matched to data from the cigarette dispenser to create an ecologically valid schedule) and 4 days of ad libitum nicotine nasal spray use, while tobacco abstinent. Eight times per day, at 2-hour intervals, blood was drawn and ratings of cigarette cravings and withdrawal symptoms were obtained. On average, subjects used less than half of the manufacturer's recommended minimum daily dose of nicotine nasal spray. Large differences in nicotine and cotinine levels were observed between individuals. When predicting nicotine, cotinine, withdrawal, and cravings, we observed significant interactions between route of nicotine intake and a variety of independent variables.

The relationship between CYP2A6 genotype and smoking status remains unclear although several studies have been reported. In this study, we have investigated the significance of CYP2A6 genotype on smoking habit and treatment of nicotine patch. Sixty-one smokers (1.7%) working in a Japanese company (n = 3585) participated in this smoking cessation program. Forty-four of 61 (72.1%) smokers were treated by nicotine patch. A genotyping analysis was carried out for 41 (40 men and 1 women) of 61 participants (67.2%). The smoking cessation rate at 90 days was 54.1% (33/61). Age and smoking years in re-smoking group are significantly lower than those in smoking cessation group. The smoking cessation rate of participants treated with nicotine patch (63.6%; 28/44) was significantly higher than that of the group non-treated with nicotine patch (29.4%; 5/17) at 90 days (p < 0.05). The incidence of homozygotes of CYP2A6 gene deletion (CYP2A619934/19934) in 41 cases (9.8%; 4/41) could be higher than that in 894 healthy controls (3.7%; 33/894) (p = 0.12), while no other variant alleles (CYP2A619932, CYP2A619933 and CYP2A619936) were found. Age and smoking years of participants with CYP2A619934/19934 are significantly higher than those with CYP2A619931 positive. The scores of Fagerstrom test, an analysis for nicotine-dependence, were slightly different between participants with CYP2A619934/19934 and CYP2A619931 positive. Although treatment of nicotine patch is efficacious to smoking cessation, cases with CYP2A619934/19934 might be more sensitive to nicotine adverse effects and more difficult to quit smoking once they have smoking habit.

Cognitive impairment has the greatest impact on illness outcome in schizophrenia. The most significant challenge in schizophrenia therapeutics, thus, is to develop an efficacious treatment for cognitive impairments. Acetylcholinesterase inhibitors, such as Physostigmine and Rivastigmine, are considered effective treatments for cognitive decline in Alzheimer's Disease, where the loss of cholinergic neurons is thought to be responsible for various cognitive deficits. The current study investigated the cognitive effects of Rivastigmine given as an add-on therapy to antipsychotic-treated schizophrenia patients in a placebo-controlled double-blind design. The study initially involved 40 patients, of which 21 patients (11 assigned to Rivastigmine and 10 assigned to placebo) agreed to continued participation, remained on the study drug, and underwent assessment of executive functioning, verbal skills, verbal and spatial working memory, attention and psychomotor speed on three occasions: (i) at baseline, and then (ii) after 12 weeks and (iii) 24 weeks of treatment with placebo or Rivastigmine. The results failed to reveal significant improvement on any cognitive measure with Rivastigmine treatment, compared with the placebo treatment. Some cognitive variables showed significant practice effects in both the placebo and Rivastigmine groups. No effects were noted in symptoms or side effects ratings. The beneficial cognitive effects of Rivastigmine seen in an open-label preliminary study are not substantiated by this study. Future studies should investigate the effects of other procholinergic drugs, such as Galantamine, which also act on the nicotine receptors and may produce stronger cognitive effects in schizophrenia.

We collected data from 5,857 adolescent (12-17 y) respondents in California to assess their perception about quitting smoking and nicotine replacement therapy use. In multivariate models, never smokers were less likely than established or experimenter smokers to believe that if they were to smoke they could quit anytime but were more likely to believe that nicotine replacement therapy is a sure way to quit.

Background and Purpose: Sleep disturbance is a common symptom of tobacco withdrawal and might contribute to early relapse vulnerability in abstinent smokers. This study was designed to compare the effects on sleep of nicotine patches applied either for 24 h (Nicopatch) or 16 h (Nicorette)., Patients and Methods: During a short smoking cessation period (48 h), this open-label, randomised, two-period crossover study compared the effects on sleep of the two nicotine patches in 20 heavy smokers (9 women, 11 men). During each period, polysomnographic recordings were performed from 12 pm to 7 am for two consecutive nights (baseline and treatment nights). Smoking cessation started from 8 pm the day of the baseline sleep recordings, and treatments were applied around 8 am the following morning., Results: Compared to the 16-h nicotine patch, smokers who received the 24-h nicotine patch experienced significantly less microarousals, a greater proportion of slow wave sleep, a higher REM density and higher rapid eye movement (REM) beta activities., Conclusions: The results of this study suggest that a 24-h nicotine patch is more efficient than a 16-h nicotine patch to alleviate tobacco withdrawal-induced sleep disturbances.

Nicotine Replacement Therapy (NRT) is the most frequently used pharmacological intervention for smoking cessation. Research on the effect of NRT showed serious nonadherence among users. We investigated adherence to NRT in cardiovascular patients. A number of 174 outpatients (N = 174), who smoked > 5 cigarettes a day, received free patches and intensive instructions from nurses. Questionnaires were sent to patients assessing patient characteristics, adherence to a 7-8 weeks time frame and appliance instructions, side effects/withdrawal symptoms, and reasons for nonadherence. Only 38% of the patients was adherent to the time frame. Appliance instructions were followed in 76-96% of the cases, except for smoking; 50% continued to smoke during NRT. In conclusion, despite considerable attention to appliance instructions, access to free patches and additional behavioral support, adherence to NRT in these patients is rather low.

The Food and Drug Administration approved over-the-counter (OTC) sale of nicotine gum and nicotine patches in 1996. We used data from the 1996 California Tobacco Survey to compare the rates of nicotine replacement therapy (NRT) use and smoking abstinence in California for each month during a period immediately preceding and immediately following the OTC availability of nicotine gum and patches. For smokers eligible to report a quit attempt, the proportion making a quit attempt using NRT and the proportion remaining abstinent was calculated for each of the 12 months prior to the survey interview. Multiple regression modeling of quit attempts and abstinence included a term for the number of months between the quit attempt and survey interview and dummy variables for the months before and after the OTC availability of NRT. Results showed a significant increase in the fraction of smokers using the patch (P < 0.01) and gum (P < 0.05) immediately following their availability OTC. There was also a significantly higher proportion of smokers reporting abstinence with gum use (P < 0.01) and a significant increase in reported abstinence with patch use (P < 0.01) during the period of time immediately following the availability of these products without a prescription. The results of this study suggest that removing the prescription status of NRT products resulted in an immediate increase in quit attempts and smoking abstinence with the use of nicotine gum or patches.

Objective: Studies of the efficacy of nicotine replacement therapy among alcoholic smokers have produced mixed findings. Our objective was to examine the smoking abstinence rate in smokers in sustained full remission from alcoholism (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who are receiving nicotine patch therapy with the dose tailored to the baseline serum cotinine concentration., Method: In this pharmacological relapse prevention study for 195 smokers with alcohol dependence in sustained full remission, the primary aim was to determine the 7-day point prevalence smoking abstinence rate at the end of 8 weeks of nicotine patch therapy in doses projected to achieve 100% venous replacement. Nicotine patch dose was based on the baseline serum venous cotinine as follows: (1) participants with < or = 200 ng/ml received a patch dose of 22 mg per day; (2) those with 201-300 ng/ml received a 33-mg dose per day, and (3) those with > 300 ng/ml received a 44-mg dose per day. A second (steady-state) serum cotinine concentration was obtained between weeks 2 and 7 to determine the percentage replacement., Results: The point prevalence smoking abstinence rate at the end of the 8 weeks of nicotine patch treatment was 51% (95% confidence interval [CI]: 45%-58%) which is higher than would be expected, and percent replacement of > 80% was achieved in 49 of 85 (58%) tobacco-abstinent subjects. Higher cigarettes per day (odds ratio [OR] = 1.030, 95% CI: 1.004-1.057, p = .023) and a history of depressed mood on the Diagnostic Interview Schedule (OR = 1.940, 95% CI: 1.044-3.605, p = .036) were found to be multivariate independent predictors of smoking at week 8. However, percentage replacement did not predict smoking abstinence., Conclusion: We achieved > 80% replacement in most subjects, and there was no evidence of severe nicotine toxicity associated with the tailored dose of nicotine patch therapy.

Background: Interventions for smoking cessation have been typically evaluated on reactively recruited samples in clinical trials (efficacy trials). However, to have an impact on smoking rates in a general population, the intervention should also be evaluated with proactively recruited representative samples (effectiveness trials)., Purpose: The characteristics of participants and two groups of nonparticipants recruited for a population-based nicotine replacement therapy study were compared., Methods: All members of a large New England Veterans' Administration Medical Center were contacted, and interviews were completed with 3,239 identified smokers (at least 10 cigarettes per day). At the end of the interview, all smokers were offered participation in a multiple intervention study. Of the interviewed smokers, 2,915 verbally agreed to participate in the study (90%). Of those who gave initial verbal consent, 2,054 returned the written informed consent form and became participants (70%)., Results: The participants (full consent group) differed significantly from both nonparticipant groups-that is, the smokers who were interviewed but declined participation by active refusal (survey only group) and those who gave verbal consent but passively refused participation by failing to return the written consent form (verbal consent only group). Participants were more likely to be married, younger, and female; to live with others; and to have previously used or considered using nicotine replacement therapy. The survey only group was also more likely to be in the precontemplation stage (54%), whereas the participants were more likely to be in the contemplation (46%) or preparation stage (35%). The verbal consent only group was intermediate of the other two groups in stage-of-change characteristics., Conclusions: An important finding was that it is possible to recruit a large proportion of a sample of identified smokers to an nicotine replacement therapy study. However, the participants are likely to differ in significant ways from those who either actively or passively decline participation.

An analysis of smokers admitted with acute coronary syndrome who received transdermal nicotine therapy and those who did not was performed. Propensity analysis was used to match patients. Transdermal nicotine therapy appears safe and does not have an effect on the mortality of patients with acute coronary syndromes.

Nicotine is a very widely used drug of abuse, which has many neurovegetative behavioural and psychological effects by interacting with neuronal nicotinic acetylcholine receptor. Cholinergic receptors can be divided into two types, muscarinic and nicotinic, based on the pharmacological action of various agonists and antagonists. This review summarises the major recent findings of nicotine effects in order to show the use of this drug in the neurophysiological research and namely as a potential tool for the treatment of some brain disorders.

Background: Nicotine replacement therapy (NRT) has been shown to assist smokers to stop smoking in randomized trials, but little is known about its use in the general population., Methods: As part of ongoing follow-up of a cohort established in 1989 in Washington County, Maryland, a questionnaire mailed in 1998 included a question about ever use of the two NRT products then available over-the-counter: nicotine gum and nicotine patch. This study reports on ever use of NRT among the 1,954 respondents who were current smokers in 1989 and subsequently provided data on NRT use and smoking habits in 1998., Results: Overall, 36% of the smokers in 1989 had ever used NRT in some form by 1998; 10% used gum only, 16% used patch only, and 10% used both gum and patch. Number of cigarettes smoked per day at baseline was the strongest predictor of ever use of NRT (ptrend < 0.001). Compared to nonusers, ever users of NRT were more likely to have more than 12 years of education (p < 0.01) and be 25-54 years old at baseline (p < 0.001). When NRT use was assessed in relation to smoking status in 1998, 30% of NRT ever users compared to 39% of nonusers had quit smoking (p < 0.01). Among persistent smokers, the likelihood of reducing the number of cigarettes smoked per day was similar between NRT ever users (40%) and nonusers (41%)., Conclusions: Ever use of NRT was common among this cohort of smokers, particularly among heavy smokers. Compared to nonusers, ever users of NRT were less likely to have stopped smoking and equally likely to cut down the frequency of smoking. This may reflect a tendency to turn to NRT for help after failing to quit by other means.

Sleep disturbance is commonly reported as a prominent subjective symptom by quitting smokers. However, little research on this issue has used objective measures of sleep quality. Previous research has relied mainly on retrospective report of sleep disturbance, with few studies investigating sleep during the initial period after quitting tobacco use. Studies that have used objective measurements suggest that sleep fragmentation is a common occurrence during the withdrawal period. In sleep medicine, sleep disturbance is viewed as a consequence of frequent arousals and is now considered to have particularly deleterious daytime consequences, including sleepiness and dysphoric mood. Recent work also indicates that such awakenings affect the cardiovascular system by providing repetitive bursts of sympathetic nervous system activation, possibly contributing to elevated levels of cardiovascular and cerebrovascular morbidity. Pharmacological treatments designed to facilitate smoking cessation are ineffective for sustained abstinence in many smokers, which may be related to sleep disturbance. Indeed, preliminary evidence suggests that the administration of nicotine replacement therapy (NRT) or bupropion can result in disrupted sleep, particularly in women. However, to better understand the role that nicotine withdrawal and bupropion or NRT treatment, independently and in combination, might play in sleep disturbance, it is necessary to develop a better understanding of the nature of the sleep disturbance than can be provided by self-report. This is particularly important for the development of treatment approaches targeted to ameliorate sleep disruption as part of an overall smoking cessation strategy. The present review seeks to report the current state of knowledge based on extant findings and argues for the need to conduct more detailed polysomnographic investigations of the potentially vicious cycle of smoking cessation leading to sleep disturbances that may prove iatrogenic to sustained cessation.

Modern functional neuroimaging techniques allow nicotine and tobacco researchers to investigate the neurobiological basis of addiction in humans. We introduce the methods and measures of the following neuroimaging techniques: Electroencephalography and event-related cortical potentials, positron emission tomography, and functional magnetic resonance imaging. We outline strengths and limitations across modalities and describe new and emerging technologies. We provide summaries of recent neuroimaging findings in the field of nicotine and tobacco research for neurochemistry, smoking and nicotine administration, craving and cue-reactivity, cognitive and affective information processing, and tobacco withdrawal. We address limitations of studies to date and identify opportunities for future research.

Many smoking cessation attempts are followed by failure or relapse. The optimal time to initiate a new quit attempt is not known. Administrative databases documenting recent use of a pharmacological aid for smoking cessation provide access to a population of smokers recently in the action phase of quitting. This study describes interest in further treatment among this population. A total of 2,340 smokers from the Minneapolis Veterans Administration Medical Center received prescriptions for a smoking cessation aid during an 18-month period. We conducted a cross-sectional survey of a random sample of this population a minimum of 3 months following the prescription, using a structured telephone interview (N=391). The response rate was 75.8%. The 1-month point-prevalent abstinence rate was 19.7%. Of continuing smokers, 98% were willing to make another quit attempt--50% immediately, and 28% within 1 month. There was no relationship between time since the last quit attempt and interest in trying again immediately. Some 95% of continuing smokers were willing to try a reduction strategy. Of these, 82.7% were interested in using nicotine replacement therapy (NRT) to accomplish this goal. Most cessation programs do not systematically approach participants who relapse. These data suggest that this population would welcome further help in quitting or reducing smoking shortly following failure, and that smokers do not commonly relapse to a precontemplation stage of change.

Smoking cessation attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant and anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking cessation treatment. We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy (six weeks) and transdermal nicotine patch(ten weeks). In a double-blind randomized trial of fluoxetine for smoking cessation, 150 daily smokers were assigned to placebo (n=48), 20 mg (n=51), or 40 mg fluoxetine (n=51). Fluoxetine did not significantly improve smoking cessation rates, either for those with or without major depressive disorder(MDD)histories or elevated current depression. Our results suggest that fluoxetine may moderate withdrawal symptoms, even if that was not manifested in improved smoking cessation rates. Our results, however, clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation.

Smoking-related death and disability rates for women have risen sharply recently. Despite lower smoking cessation success rates for women using behavioral therapies, data are limited on whether specific pharmacological therapies are equally efficacious in men and women. Using meta-analytic techniques, we examined whether significant differences in therapeutic efficacy of nicotine replacement therapy (NRT) for smoking cessation exist by sex. Out of the 31 randomized clinical trials of NRT that met inclusion criteria, 11 contributed to the analysis. The odds ratios for NRT vs. placebo were derived from each trial separately by sex for males and females, and these ratios were combined to give a pooled estimate of the effect of sex in response to NRT. NRT was effective at all time points in men (< 6 months: OR = 2.05, 95% CI= 1.61-2.60; 6 months: OR = 1.98, 95% CI = 1.51-2.60; 12 months: OR = 1.86, 95% CI = 1.39-2.50) and women (< 6 months: OR = 2.09, 95% CI = 1.65-2.65; 6 months, OR = 1.52, 95% CI = 1.17-1.98; 12 months: OR = 1.63, 95% CI = 1.22-2.18). At all time points, no significant difference was observed between sexes (< 6 months: OR = .97, 95% CI = .69-1.36; 6 months: OR = 1.33, 95% CI = .91-1.95; 12 months: OR = 1.21, 95% CI = .79-1.84). The results of this meta-analysis do not support the hypothesis that NRT has higher therapeutic efficacy for men than women.

This study of postmenopausal female smokers (N = 94) asked: During short-term smoking abstinence, do the beneficial effects of transdermal nicotine replacement therapy (NRT) on acute symptomatology (i.e., withdrawal, cigarette craving, smoking urges, mood, depressive symptoms, motor speed, and reaction time) differ in women who use and do not use hormone replacement therapy (HRT)? Participants were recruited according to HRT and non-HRT use (self-selecting), then randomized within strata to active nicotine or placebo nicotine patch. After 1 baseline week of smoking, participants quit smoking for 2 weeks. Women received cessation counseling and were monitored for abstinence. Dependent measures were collected during five clinic visits. Two-way analysis of covariance (ANCOVA) were run on change scores for dependent variables, with nicotine patch group (active/placebo) and HRT group (HRT/non-HRT) as independent variables and age as a covariate. No interactions were found between HRT and patch condition, but both showed specific effects. During the first abstinent week, women on active nicotine patch (compared with placebo) experienced less severe withdrawal, greater reductions in cigarette cravings, and lower (more favorable) Factor 1 scores on the Questionnaire of Smoking Urges. During the second abstinent week, women using HRT (compared with the non-HRT group) exhibited better mood (Profile of Mood States scores) and less depression (Beck Depression Inventory scores). These results suggest the following: First, the efficacy of transdermal nicotine replacement is not adversely modified by women's HRT use; second, ovarian hormones might influence women's responses to smoking cessation, and thus should be considered in developing effective strategies for women to quit smoking.

Patients who stop smoking often complain of aphthous (mouth) ulcers. This symptom is sometimes attributed to the use of smoking cessation medications, but little is known about it. We investigated the incidence, severity, and time course of mouth ulcers in abstaining smokers and the effect of different smoking cessation medications on the symptom. The sample consisted of 1234 smokers who sought treatment at a large smoking cessation clinic, maintained at least 1 week of continuous biochemically validated abstinence, and provided usable data. Participants assessed their mouth ulcers by rating a mouth ulcer item added to the Mood and Physical Symptoms Scale. Subjects made ratings weekly on three occasions while still smoking and over 4 weeks following smoking cessation. After stopping smoking, some 40% of patients developed mouth ulcers, mostly in the first 2 weeks. The problem was generally mild, but 8% reported severe ulceration. The ulcers resolved within 4 weeks in 60% of patients affected. The ulcer ratings in patients using oral nicotine replacement products were higher than in those using patch, nasal spray or bupropion in the first week of abstinence but not afterward. Mouth ulcers were more prevalent in more dependent smokers, and the occurrence of ulcers correlated with other tobacco withdrawal symptoms. Our results confirm that mouth ulcers are a common result of stopping smoking, affecting two in five quitters. Patients should be reassured that the lesions are a result of stopping smoking and not a side-effect of smoking cessation medication.

The rate of tobacco use is higher among First Nations (FN) peoples than among other Canadians. Cessation pharmacotherapy agents reduce tobacco use, but the appropriateness and effectiveness of these agents among FN smokers are not entirely clear. Rates of tobacco cessation pharmacotherapy use among FN smokers are unknown; such information would be useful for program planners and would indicate appropriateness of use. To examine cessation pharmacotherapy use, we extracted claims for nicotine gum, nicotine patch, and bupropion SR (Zyban) from the Non-Insured Health Benefits pharmacy database for FN persons living within British Columbia during 2001. A total of 3.8% (95% CI=3.6-4.0) of FN claimants filled a prescription for at least one tobacco cessation pharmacotherapy agent; 61.7% were female, and their mean age was 38.1 years. Most claims (60.5%) were for bupropion, followed by nicotine patch (40.7%) and nicotine gum (4.7%). A total of 4.6% of claimants used both nicotine patch and bupropion,.8% used nicotine gum and nicotine patch, and.5% used nicotine gum and bupropion. Pharmacotherapy agents appear to be used less often by FN smokers than by other Canadian smokers for several possible reasons. Additional research is needed related to FN populations and cessation pharmacotherapy use in terms of cultural appropriateness, barriers to use, and effectiveness.

Smokers not currently interested in quitting (N = 616) were randomized to receive telephone-based (a) reduction counseling plus nicotine replacement therapy (NRT) plus brief advice to quit, (b) motivational advice plus brief advice, or (c) no treatment. More smokers in the reduction (43%) and motivational (51%) conditions made a 24-hr quit attempt over 6 months than smokers in the no-treatment condition (16%; p < or = .01), but the 2 active conditions did not differ (p > or = .05). Similarly, 18%, 23%, and 4% of each condition were abstinent (7-day point prevalence) at 6 months (p < or = .01). Results indicate smoking reduction using NRT does not undermine cessation but rather increases the likelihood of quitting to a degree similar to motivational advice., ((c) 2004 APA, all rights reserved)

The subjective and reinforcing effects of drugs of abuse may depend partly on their rate of onset, with faster acting formulations typically producing stronger effects than slower ones. In this within-subjects study, we examined the acute effects of nicotine replacement therapy via nicotine nasal spray (fast delivery) vs. transdermal nicotine patch (slow delivery) on craving, withdrawal, cardiovascular responses, subjective ratings, and reinforcing effects of smoking. Smokers (N=30) not seeking treatment participated in three sessions, each after overnight smoking abstinence, involving 14-mg nicotine (Nicoderm) or placebo patch, followed 4 hr later by intermittent administration of nicotine (Nicotrol) or placebo nasal spray. Specifically, the three group comparisons were nicotine patch condition (with placebo spray), nicotine spray condition (with placebo patch), and placebo condition (placebo spray and patch). Nicotine patch and nicotine spray were never administered in the same session. Blood nicotine levels were similar between nicotine patch and nicotine spray conditions, by design. Heart rate and systolic blood pressure were higher following nicotine spray vs. the other conditions, as hypothesized. However, other than reductions in craving related to nicotine spray and patch at some points, no differences between conditions were observed in withdrawal, subjective effects of sprays and smoking, or smoking reinforcement assessed by a computer task. Thus, under these acute conditions, the speed of nicotine delivery from nasal spray vs. patch differentially affected cardiovascular responses and perhaps craving but did not influence withdrawal, subjective ratings, and smoking reinforcement.

Smokers (N=188) recruited from the local community completed a questionnaire that measured expected outcomes of using cigarettes, nicotine gum, nicotine patch, and nicotine nasal spray. Expectancy questions relating to negative affect, craving, weight, and health risks were derived from the Smoking Consequences Questionnaire-Adult. As predicted, smokers held much greater expectancies that cigarettes help control negative affect, craving, and weight relative to nicotine replacement therapy (NRT). All NRT products were expected to cause fewer health risks than cigarette smoking. As predicted, smokers held strong negative affect reduction expectancies for cigarette smoking. For NRT, although still relatively low, craving reduction was the strongest expectancy. Individuals who had experience using the nicotine patch had greater positive expectancies for NRT. Greater positive expectancies for NRT were correlated with more immediate plans to quit smoking. In summary, cigarette smokers' positive expectancies about cigarettes do not appear to generalize to NRT products, which may limit their use and effectiveness.

The present study examined several pharmacological and behavioral treatments designed to promote extinction of the responses to rewarding cigarette smoke cues. Pharmacological treatments comprised nicotine skin patches (21 mg/24 hr) and the nicotinic acetylcholine receptor antagonist mecamylamine (10 mg/day), administered separately or in combination. Behavioral manipulations included switching to denicotinized cigarettes, to cigarettes having different menthol flavor, or to ventilated-filter (low tar and nicotine) cigarettes. Smokers were assigned to the various treatments for 2 weeks before they quit smoking. During weekly test sessions, subjects rated the rewarding effects of their usual brands of cigarettes or cigarettes with different menthol content (mentholated vs. nonmentholated). Over the 2-week treatment period, all pharmacological treatments reduced ratings of reward for the usual-brand test cigarettes. Switching to smoking denicotinized cigarettes for 2 weeks similarly decreased rewarding effects of the usual-brand test cigarettes. Subjects also strongly preferred cigarettes with the same menthol content to which they were accustomed. However, manipulating the menthol content of the cigarettes smoked during the 2 weeks of treatment had different effects, depending on whether smokers habitually smoked mentholated or nonmentholated cigarettes. For menthol smokers, removal of the menthol cue hampered extinction of reward ratings for the usual-brand (mentholated) test cigarette. For nonmenthol smokers, addition of the menthol cue did not affect the progress of extinction of nonmenthol smoke cues. These findings demonstrate the importance of sensory cues in determining subjective reward and show that the reward value of these cues can be altered by removal of nicotine from tobacco or by pharmacological manipulations that interfere with the reinforcing effects of nicotine.

Evidence from pre-clinical infrahuman investigations, open-label clinical trials, and a single controlled trial found acute nicotine treatment potentiated up to 4 weeks neuroleptic-induced reductions of dyskinetic symptoms characterizing Tourette's syndrome (TS). Given the attentional disturbances associated with this syndrome, and the improvements in attentional processes reported with nicotine, this randomized, double-blind, placebo-controlled trial examined the acute (4 h) and sustained (2 weeks) effects of a single dose of transdermal nicotine on clinical (i.e., tics), attentional (continuous performance task, event-related potential, patient and parental reports) and behavioral symptoms in 23 children and adolescents with TS receiving neuroleptic treatment. In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 h but counteracted ERP-P300 signs of diminished attention seen 2 weeks following placebo treatment. Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention. Additional work with intermittent dosing schedules is required to characterize optimal clinical and cognitive effects with nicotine treatment.

This study evaluated the relationship between smoking cessation treatment outcome and the DRD2 polymorphism. Participants were 134 smokers who took part in a larger clinical trial evaluating the effects of an antidepressant medication (venlafaxine or placebo) plus standard care (brief counseling and nicotine replacement therapy). Venlafaxine is an antidepressant that inhibits the reuptake of serotonin and norepinephrine. A1 smokers were expected to quit significantly less often on placebo, although the abstinence rates between A1s and A2s on active drug were not expected to differ (i.e., an interaction between genotype and drug was hypothesized). In addition, antidepressant therapy was expected to have a similar genotype x treatment interaction on negative affect reduction. The results showed that smokers carrying the DRD2 A1 allele (A1/A1/A2) quit significantly less often than the homozygous A2s (OR=1.54, 95% CI=1.01-2.36). No interaction with treatment was observed. A significant pharmacogenetic effect of the drug on negative mood while quitting also was noted. Smokers absent the A1 allele (A2/A2) responded to the drug with a substantial reduction in negative affect, whereas those with the A1 allele showed no significant reduction in negative mood, F(1, 130)=5.95, p=.01. These results are contrary to expectations and suggest that although A1s may have more difficulty quitting, adding venlafaxine does not improve abstinence or mood. However, the results for the A2s provide evidence for a genotype-specific response to a pharmacological intervention, which could have implications for the development of future treatments.

We examined the ability of smokers who failed to quit smoking in the Lung Health Study to reduce the number of cigarettes per day and maintain this reduction and whether reduction predicted increased or decreased future cessation. In the Lung Health Study, among smokers with early lung disease who wished to stop smoking, 3923 were randomized to a special intervention of counseling and nicotine gum for smoking cessation and to bronchodilator therapy or placebo. Among the 1722 who were still smoking at the first year follow-up, 27% smoked the same, 43% smoked 1%-49% fewer, and 30% smoked at least 50% fewer cigarettes per day. Reduction in cigarettes per day was accompanied by reduction in expired-air carbon monoxide. About half of the less-than-50% reducers and one-fifth of the at-least-50% reducers maintained or exceeded this reduction over the next 4 years. Reduction was associated with nicotine gum use. Greater reduction at year 1 predicted more quit attempts in year 2 but not more point prevalence abstinence at year 2 nor more quits or abstinence between years 2 and 5. We conclude that reduction can be maintained but such reduction neither predicts an increased nor decreased probability of future cessation.

This preliminary study evaluated the potential efficacy of 50 mg of opioid antagonist naltrexone or placebo in combination with nicotine replacement therapy for smoking cessation, in a small sample of 32 smokers using one to one and a half packs of cigarettes per day. Addition of naltrexone resulted in an increase in continuous abstinence rates (9/16 for naltrexone vs. 5/16 for placebo). Naltrexone reduced the likelihood of relapse among participants who smoked during the first week of treatment, reduced desire to smoke, and prevented weight gain following smoking cessation. These preliminary results suggest that naltrexone augmentation of nicotine patch therapy using procedures designed to optimize the concurrent use of these two medications may be beneficial for smoking cessation.