Use of transdermal nicotine in a state-level prescription plan for the elderly. A first look at 'real-world' patch users.

PubMed

Orleans, C T; Resch, N; Noll, E; Keintz, M K; Rimer, B K; Brown, T V; Snedden, T M

1994-02-23

To assess transdermal nicotine use patterns and outcomes in a population of low-income older smokers. A 6-month telephone follow-up survey of smokers filling prescriptions for transdermal nicotine in the first 3 months of 1992. Pennsylvania's Pharmaceutical Assistance Plan for the Elderly, the nation's largest state-level prescription plan for the elderly. A total of 1070 noninstitutionalized male and female smokers aged 65 through 74 years. Self-reported physician/pharmacist advice and adjunctive treatments, concomitant smoking, and 6-month smoking abstinence. Respondents were predominantly long-term heavy smokers. They used nicotine patches for an average of 5 weeks, with few reporting use beyond 3 months or recalling bothersome side effects. Most of those with previous quit attempts rated quitting with the patch "easier." The 29% self-reported 6-month quit rate observed is encouraging. However, compliance with patch use guidelines was far from ideal in this high-risk population: only 54% of respondents received any initial advice or materials from their physicians or pharmacists, fewer than 2% took part in a formal clinic or one-to-one treatment program, and almost half (47%) smoked while using the patch, including 20% who smoked every day. Concomitant smoking was strongly associated with failure to achieve abstinence (P < .001). More frequent contact with physicians and/or pharmacists was associated with less concomitant smoking (P < .001) and higher quit rates (P = .005). This survey offers an important first look at problems and prospects for nicotine patch therapy in older adults, with implications for other groups as well. Prospective studies are needed to clarify optimal treatment regimens and adjuncts.

Addressing the evidence for FDA nicotine replacement therapy label changes: a policy statement of the Association for the Treatment of Tobacco use and Dependence and the Society for Research on Nicotine and Tobacco.

PubMed

Fucito, Lisa M; Bars, Matthew P; Forray, Ariadna; Rojewski, Alana M; Shiffman, Saul; Selby, Peter; West, Robert; Foulds, Jonathan; Toll, Benjamin A

2014-07-01

Cigarette smoking creates a substantial public health burden. Identifying new, effective smoking cessation interventions that optimize existing interventions and promoting effective use of approved medications is a priority. When used as directed, nicotine replacement therapy (NRT) aids smoking cessation, but there is opportunity for improving its effectiveness. Until recently, NRT use guidelines advised smokers to begin using NRT on their quit date, only to use 1 NRT formulation at a time, to refrain from using NRT while smoking, and to stop NRT within 3 months regardless of progress. The Food and Drug Administration (FDA) issued a recent announcement allowing for NRT labeling changes with applications from pharmaceutical companies for such changes, and we applaud this decision. Nevertheless, additional revisions are warranted by current research. There is robust evidence that combining a longer-acting form (e.g., patch) with a shorter-acting form (e.g., lozenge) is more effective than NRT monotherapy and is safe. Moreover, extant evidence suggests that NRT use prior to a quit attempt or for smoking reduction as part of a quit attempt is safe and as effective as starting NRT on quit date. Specifically, prequit nicotine patch increases quit rates and may engage additional recalcitrant smokers. Last, NRT use longer than 3 months is safe and may be beneficial for relapse prevention in some smokers. This report summarizes the FDA announcement, reviews the evidence for further revisions to current FDA NRT guidelines, and makes recommendations for over-the-counter (OTC) NRT labeling to allow for (1) combined use of faster-acting NRT medications with nicotine patch, (2) nicotine patch use prior to quit date or NRT for smoking reduction as part of a quit attempt, and (3) prolonged NRT for up to 6 months without healthcare provider consultation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

PubMed Central

Lindson, Nicola; Aveyard, Paul; Ingram, Jackie T; Inglis, Jennie; Beach, Jane; West, Robert; Michie, Susan

2009-01-01

Background The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy. Design/Methods We will conduct a non-inferiority randomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm, participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely. This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation. Outcomes/Follow-up The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day. Trial Registration Current Controlled Trials ISRCTN22526020 PMID:19682359

Addressing the Challenges of a Smoke-Free U.S. Navy Submarine Force

DTIC Science & Technology

2011-01-24

Trial  2007-9, CSP conducted a smoke-free trial.  Measured nicotine metabolite in non- smokers.  Non-smokers had 3x the amount of cotinine during... nicotine patch and gum replacement therapy ($500K).  2-3 personnel per submarine trained as smoking cessation facilitators.  Prior to 31 December...Conference held in San Diego  Utilized guidance provided in the 2008 Public Health Service (PHS) Tobacco Cessation (Treating Nicotine Dependence

Subsidised nicotine replacement therapy in a community pharmacy setting.

PubMed

Poder, Natasha; Perusco, Andrew; Hua, Myna

2005-08-01

Nicotine replacement therapies are effective, but are mostly under-utilised and often not used for an appropriate duration. The paper reports on a pilot project that used subsidies for NRT as a means to engage community pharmacists to deliver tobacco cessation to the Arabic-speaking community. Arabic-speaking community pharmacists were recruited through direct mail-outs and trained in tobacco cessation brief intervention. Fifteen selected pharmacies recruited Arabic smokers through their pharmacies. Pharmacy follow-up was conducted three months after the program was implemented. A total of 65 participants attended the seminar. A total of 31 pharmacy customers received at least one packet of subsidised NRT patches. Twenty (64.5%) clients received both the first and second subsidised pack. Fifteen clients continued to use patches after the third packet, however only three clients continued the patches to the eighth pack. The pilot was successful in improving recruitment of pharmacies into training for smoking cessation counselling as well as engaging community pharmacists to deliver tobacco cessation intervention with small incentive.

Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and Combined Pharmacotherapy.

PubMed

Loreto, Aline Rodrigues; Carvalho, Carlos Felipe Cavalcanti; Frallonardo, Fernanda Piotto; Ismael, Flavia; Andrade, Arthur Guerra de; Castaldelli-Maia, João Maurício

2017-01-01

The aim of this study was to investigate smoking treatment effectiveness and retention in a population with and without mental disorders (MD). Participants received cognitive behavioral therapy (CBT) plus nicotine patch alone or in combination with other medications (i.e., gum, bupropion, or nortriptyline) for smoking cessation treatment in a Brazilian Psychosocial Care Center unit (CAPS), taking into account sociodemographics and smoking profile covariates. The study involved comparison of treatment success (seven-day point prevalence abstinence at the end of the treatment) and retention (presence of the individual in all of the four medical consultations and six group sessions) in two subsamples of patients with MD (n = 267) and without MD (n = 397) who were included in a six-week treatment provided by a CAPS from 2007 to 2013. The treatment protocol comprised group CBT and pharmacotherapy (nicotine patches, nicotine gums, and bupropion and nortriptyline available, prescribed by psychiatrists). Within patients with MD, CBT plus nicotine patch plus bupropion (aOR = 2.00, 95% CI [1.14, 3.50], p = .015) and CBT plus nicotine patch plus gum (aOR = 2.10, 95% CI [1.04, 4.23], p = .036) were associated with treatment success. Within patients without MD, female gender (aOR = 0.60, 95% CI [0.37, 0.95], p = .031) and lower Heaviness of Smoking Index score (aOR = 0.80, 95% CI [0.65, 0.99], p = .048) were associated with treatment success. No variable was associated with dropout or retention within patients with or without MD. Our findings support the use of CBT plus nicotine patch plus bupropion as well as CBT plus nicotine patch plus gum in samples with high rates of medical, psychiatric, and addiction disorders. These findings support those of previous studies in the general population. Pharmacological treatment associated with group CBT based on cognitive-behavioral concepts and combined with ongoing MD treatment seems to be the best option for smoking cessation treatment among patients with MD. Units that deal with patients with MD, such as CAPS in Brazil, should be encouraged to treat smoking addiction in this population. Future studies should investigate retention rates in other samples of patients with MD.

A naturalistic cohort study on effectiveness, safety and usage pattern of an over-the-counter nicotine patch. Cohort study on smoking cessation.

PubMed

Hasford, Joerg; Fagerstrom, Karl Olov; Haustein, Knut-Olav

2003-09-01

INTRODUCTION. Nicotine replacement therapies (NRT) are effective for smoking cessation. After having received over-the-counter (OTC) status in Germany, concerns grew about effectiveness, increased risks, especially of adverse cardiovascular reactions, and inappropriate use of NRT. Thus, a pharmacy-based cohort study was launched. OBJECTIVES. To assess effectiveness, safety and appropriateness of use of an OTC nicotine patch (Nicotinell, Novartis Ltd.). Every customer who bought an OTC Nicotinell patch was eligible. All data were collected by self-administered questionnaires at weeks 2, 4, 8, 12 and 24 after inclusion. Six hundred and thirty-three customers were admitted, median duration of smoking was 19 years. Of the participants, 6% smoked up to 10 cigarettes per day, 43.6% between 11 and 20, 34.3% between 21 and 30, and 16.1% more than 30 cigarettes. Twenty-four weeks later, 351 participants replied: 28% (177 of 633) had quit smoking completely. Considering replies only the proportion of complete responders raised to 50.4%. There were no serious adverse events reported; 62.9% complied with the directions for use and did not use the patch for more than 3 months. About 45% smoked simultaneously with NRT. Pharmacy-based cohort studies are feasible. This study indicates that the nicotine patch is effective and safe in an OTC setting. There is still room to improve compliance with the directions for use.

Use of nicotine patches in breast-feeding mothers: transfer of nicotine and cotinine into human milk.

PubMed

Ilett, Kenneth F; Hale, Thomas W; Page-Sharp, Madhu; Kristensen, Judith H; Kohan, Rolland; Hackett, L Peter

2003-12-01

Our objective was to assess the extent of exposure to nicotine and cotinine in breast-fed infants during maternal smoking and later during maternal use of the nicotine transdermal patch to achieve smoking cessation. Fifteen lactating women (mean age, 32 years; mean weight, 72 kg) who were smokers (mean of 17 cigarettes per day) participated in a trial of the nicotine patch to assist in smoking cessation. Serial milk samples were collected from the women over sequential 24-hour periods when they were smoking and when they were stabilized on the 21-mg/d, 14-mg/d, and 7-mg/d nicotine patches. Nicotine and cotinine in milk were quantified by HPLC, and infant dose was calculated. Plasma concentrations of nicotine in the breast-fed infants were assessed, and the infants were also clinically assessed. Nicotine and cotinine concentrations in milk were not significantly different between smoking (mean of 17 cigarettes per day) and the 21-mg/d patch, but concentrations were significantly lower (P <.05) when patients were using the 14-mg/d and 7-mg/d patches than when smoking. There was also a downward trend in absolute infant dose (nicotine equivalents) from smoking or the 21-mg patch through to the 14-mg and 7-mg patches (P <.05 at both 14-mg and 7-mg doses, compared with smoking). Milk intake (shown as median and 25th to 75th percentile) by the breast-fed infants was similar while their mothers were smoking (585 mL/d [507-755 mL/d]) and subsequently when their mothers were using the 21-mg (717 mL/d [504-776 mL/d]), 14-mg (731 mL/d [535-864 mL/d]), and 7-mg (619 mL/d [520-706 mL/d]) patches (chi(2) = 3.19, P =.364). We conclude that the absolute infant dose of nicotine and its metabolite cotinine decreases by about 70% from when subjects were smoking or using the 21-mg patch to when they were using the 7-mg patch. In addition, use of the nicotine patch had no significant influence on the milk intake by the breast-fed infant. Undertaking maternal smoking cessation with the nicotine patch is, therefore, a safer option than continued smoking.

Impact of large-scale distribution and subsequent use of free nicotine patches on primary care physician interaction.

PubMed

Kushnir, Vladyslav; Sproule, Beth A; Cunningham, John A

2017-07-11

Large-scale distribution efforts of free nicotine replacement therapy (NRT) have been documented to be cost-effective interventions for increasing smoking quit rates. However, despite nearly a dozen studies evaluating their effectiveness, none have examined whether free NRT provision promotes further primary care help-seeking and the impact that it may have on cessation efforts. In the context of a randomized controlled trial, a secondary analysis was conducted on 1000 adult regular smokers randomized to be mailed a 5-week supply of nicotine patches or to a no intervention control group. Recipients and users of free nicotine patches at an 8 week follow-up were successfully case matched to controls based on age, gender, baseline level of nicotine dependence and intent to quit (n = 201 per group). Differences in physician interaction between the two groups were evaluated at both 8 week and 6 month follow-ups. The impact of physician interaction on self-reported smoking abstinence at each follow-up was also examined. Although no differences in physician interaction were noted between groups at the 8 week follow-up, at the 6 month follow-up, nicotine patch users reported greater frequency of discussing smoking with their physician (43.9%), as compared to the control group (30.3%) (p = 0.011). Across both groups, over 90% of those that discussed smoking with a physician were encouraged to quit and approximately 70% were provided with additional support. Separate ANOVAs revealed no significant impact of physician interaction on cessation (p > 0.05), regardless of group or follow-up period, however, at the 6 month follow-up, nicotine patch users who discussed cessation with a physician had made serious quit attempts at significantly greater rates (72.6%), compared to controls (49.1%) (p = 0.007). Irrespective of group, the majority of smokers in the present study did not discuss cessation with their physician. Recipients and users of nicotine patches however, were more likely to discuss smoking with their physician, suggesting that the provision of free NRT particularly to those who are likely to use it may facilitate opportunities for benefits beyond the direct pharmacological effects of the medication. clinicaltrials.gov , NCT01429129 . Registered: 2 September 2011.

Formulation and in vitro evaluation of xanthan gum or carbopol 934-based mucoadhesive patches, loaded with nicotine.

PubMed

Abu-Huwaij, Rana; Obaidat, Rana M; Sweidan, Kamal; Al-Hiari, Yusuf

2011-03-01

Bilayer nicotine mucoadhesive patches were prepared and evaluated to determine the feasibility of the formulation as a nicotine replacement product to aid in smoking cessation. Nicotine patches were prepared using xanthan gum or carbopol 934 as a mucoadhesive polymers and ethyl cellulose as a backing layer. The patches were evaluated for their thickness, weight and content uniformity, swelling behavior, drug-polymers interaction, adhesive properties, and drug release. The physicochemical interactions between nicotine and the polymers were investigated by Fourier transform infrared (FTIR) spectroscopy. Mucoadhesion was assessed using two-arm balance method, and the in vitro release was studied using the Franz cell. FTIR revealed that there was an acid base interaction between nicotine and carbopol as well as nicotine and xanthan. Interestingly, the mucoadhesion and in vitro release studies indicated that this interaction was strong between the drug and carbopol whereas it was weak between the drug and xanthan. Loading nicotine concentration to non-medicated patches showed a significant decrease in the mucoadhesion strength of carbopol patches and no significant effect on the mucoadhesion strength of xanthan patches. In vitro release studies of the xanthan patches showed a reasonable fast initial release profile followed by controlled drug release over a 10-h period. © 2010 American Association of Pharmaceutical Scientists

The Effect of Social Anxiety on Urge and Craving among Smokers with and without Anxiety Disorders

PubMed Central

Kimbrel, Nathan A.; Morissette, Sandra B.; Gulliver, Suzy B.; Langdon, Kirsten J.; Zvolensky, Michael J.

2014-01-01

Background Despite the often social nature of smoking, relatively little research has been conducted on the relationship between smoking and social anxiety disorder (SAD). Method Participants (N = 99) included 34 smokers without current mental health disorders, 37 smokers with SAD, and 28 smokers who met criteria for other anxiety disorder diagnoses (e.g., panic disorder or generalized anxiety disorder, but not SAD). Nicotine and placebo patches were administered to participants in a counterbalanced manner across two assessment days. Urge and craving were assessed before and after a 5-hour nicotine absorption/deprivation period. Results Compared to smokers without current mental health disorders, smokers with SAD did not report greater nicotine dependence, but did endorse greater motivation to use nicotine to avoid negative outcomes. In addition, after controlling for demographic variables, smoking characteristics, pre-deprivation urge and craving, and other anxiety/depression symptoms, social anxiety symptoms uniquely predicted urge and craving in the placebo patch condition; however, social anxiety had no influence on urge and craving in the nicotine patch condition. Conclusions These findings suggest that one potential reason that smokers with SAD may have worse cessation outcomes is that they may experience higher levels of craving and urge to smoke during quit attempts. Thus, during a quit attempt, particularly in the absence of nicotine replacement therapy, smokers with SAD are likely to benefit from additional treatment aimed at managing or reducing their social anxiety symptoms. PMID:24331637

The effect of social anxiety on urge and craving among smokers with and without anxiety disorders.

PubMed

Kimbrel, Nathan A; Morissette, Sandra B; Gulliver, Suzy B; Langdon, Kirsten J; Zvolensky, Michael J

2014-02-01

Despite the often social nature of smoking, relatively little research has been conducted on the relationship between smoking and social anxiety disorder (SAD). Participants (N=99) included 34 smokers without current mental health disorders, 37 smokers with SAD, and 28 smokers who met criteria for other anxiety disorder diagnoses (e.g., panic disorder or generalized anxiety disorder, but not SAD). Nicotine and placebo patches were administered to participants in a counterbalanced manner across two assessment days. Urge and craving were assessed before and after a 5-h nicotine absorption/deprivation period. Compared to smokers without current mental health disorders, smokers with SAD did not report greater nicotine dependence, but did endorse greater motivation to use nicotine to avoid negative outcomes. In addition, after controlling for demographic variables, smoking characteristics, pre-deprivation urge and craving, and other anxiety/depression symptoms, social anxiety symptoms uniquely predicted urge and craving in the placebo patch condition; however, social anxiety had no influence on urge and craving in the nicotine patch condition. These findings suggest that one potential reason that smokers with SAD may have worse cessation outcomes is that they may experience higher levels of craving and urge to smoke during quit attempts. Thus, during a quit attempt, particularly in the absence of nicotine replacement therapy, smokers with SAD are likely to benefit from additional treatment aimed at managing or reducing their social anxiety symptoms. Published by Elsevier Ireland Ltd.

Nicotine Transdermal Patch

MedlinePlus

... patches are used to help people stop smoking cigarettes. They provide a source of nicotine that reduces ... cause harm to the fetus.do not smoke cigarettes or use other nicotine products while using nicotine ...

Transdermal nicotine patches for eosinophilic pustular folliculitis.

PubMed

Yoshifuku, Asuka; Higashi, Yuko; Matsushita, Shigeto; Kawai, Kazuhiro; Kanekura, Takuro

2013-09-01

We previously reported the clinical effectiveness of transdermal nicotine patches for the treatment of skin disorders with eosinophilic infiltration such as Kimura's disease, erythema nodosum and eosinophilic pustular folliculitis (EPF). We assessed the efficacy and safety of transdermal nicotine patches for EPF. We treated eight patients with EPF with transdermal nicotine patches and evaluated the treatment response by performing overall lesional assessment. Excellent 77and good responses were obtained in five and one patient(s), respectively. In the other two patients, the lesions remained unchanged. No severe adverse effects were observed. Our results suggest that transdermal nicotine patches may be useful and safe in the treatment of EPF. © 2013 Japanese Dermatological Association.

[Interventions for smoking cessation in 2018].

PubMed

Abdul-Kader, J; Airagnes, G; D'almeida, S; Limosin, F; Le Faou, A-L

2018-06-01

Smoking cessation treatments have been proved effective to stop smoking. For pharmacological treatments, nicotine replacement therapies (NRT) as well as bupropion allow to increase 6 month-abstinence rates by more than 80% in comparison with placebo while varenicline prescription doubles success rates in the same conditions. These results mean that for 10 smokers who quit with placebo, 18 are expected to quit with NRT or bupropion and 28 are expected to quit with varenicline. Varenicline is 50% more effective than nicotine patch and 70% more effective than nicotine gum. Nevertheless, a combination including NRT patch and oral nicotine forms is as effective as varenicline, thus leading to encourage the prescription of a combination NRT when NRT are chosen. For these three pharmacological treatments, cardiovascular as well as neuropsychiatric tolerance were not found statistically different from placebo in randomized controlled trials. Yet, bupropion prescription leads to an increasing risk of seizure (1/1000 to 1/1500). For behavioral treatment, motivational interviewing as well as cognitive behavior therapies are been proven to be effective to stop smoking but few smokers have access to this treatment. Smoking cessation mobile application and smartphone application seem to be promising in terms of effectiveness and might be useful to reach more smokers. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A study of the use of free nicotine patches by Indigenous people.

PubMed

Ivers, Rowena G; Farrington, Melissa; Burns, Chris B; Bailie, Ross S; D'Abbs, Peter H; Richmond, Robyn L; Tipiloura, Eric

2003-10-01

To assess use of free nicotine patches by Indigenous people when offered a brief intervention for smoking cessation, and to assess changes in smoking behaviour at six months. We conducted a pre and post study in three Indigenous communities in the Northern Territory. Forty Indigenous smokers self-selected to receive free nicotine patches and a brief intervention for smoking cessation, and 71 chose the brief intervention only. Eighty-four per cent of participants were followed up; 14% of participants could not be located. Fifteen per cent of the nicotine patches group (10% with CO validation) and 1% (CO validated) of the brief intervention only group reported that they had quit at six months. Seventy-six per cent of the nicotine patches group and 51% of the brief intervention only group had reduced their consumption of tobacco. No participant completed a full course of patches. One possible side effect--the experience of bad dreams--was attributed in one community to the person concerned having been 'sung' or cursed. Free nicotine patches might benefit a small number of Indigenous smokers. Cessation rates for the use of both nicotine patches and brief intervention alone were lower than those in other populations, possibly because the study was conducted in a primary care setting and because of barriers to cessation such as widespread use of tobacco in these communities and the perception of tobacco use as non-problematic.

Randomized Clinical Trial of the Efficacy of Bupropion Combined with Nicotine Patch in the Treatment of Adolescent Smokers

ERIC Educational Resources Information Center

Killen, Joel D.; Robinson, Thomas N.; Ammerman, Seth; Hayward, Chris; Rogers, Jayna; Stone, Christi; Samuels, Deanne; Levin, Sara K.; Green, Sarah

2004-01-01

Adolescent smokers (N = 211) were randomized to 1 of 2 groups: (a) nicotine patch plus bupropion SR (sustained release; 150 mg per day) or (b) nicotine patch plus placebo. Group skills training sessions were conducted each week by research staff. Abstinence rates at Weeks 10 and 26 were as follows: (a) patch plus bupropion, 23% and 8%, (b) patch…

Randomized controlled trial of a web-based computer-tailored smoking cessation program as a supplement to nicotine patch therapy.

PubMed

Strecher, Victor J; Shiffman, Saul; West, Robert

2005-05-01

To assess the efficacy of World Wide Web-based tailored behavioral smoking cessation materials among nicotine patch users. Two-group randomized controlled trial. World Wide Web in England and Republic of Ireland. A total of 3971 subjects who purchased a particular brand of nicotine patch and logged-on to use a free web-based behavioral support program. Web-based tailored behavioral smoking cessation materials or web-based non-tailored materials. Twenty-eight-day continuous abstinence rates were assessed by internet-based survey at 6-week follow-up and 10-week continuous rates at 12-week follow-up. Using three approaches to the analyses of 6- and 12-week outcomes, participants in the tailored condition reported clinically and statistically significantly higher continuous abstinence rates than participants in the non-tailored condition. In our primary analyses using as a denominator all subjects who logged-on to the treatment site at least once, continuous abstinence rates at 6 weeks were 29.0% in the tailored condition versus 23.9% in the non-tailored condition (OR = 1.30; P = 0.0006); at 12 weeks continuous abstinence rates were 22.8% versus 18.1%, respectively (OR = 1.34; P = 0.0006). Moreover, satisfaction with the program was significantly higher in the tailored than in the non-tailored condition. The results of this study demonstrate a benefit of the web-based tailored behavioral support materials used in conjunction with nicotine replacement therapy. A web-based program that collects relevant information from users and tailors the intervention to their specific needs had significant advantages over a web-based non-tailored cessation program.

Nicotine increases brain functional network efficiency.

PubMed

Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

2012-10-15

Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

Nicotine Increases Brain Functional Network Efficiency

PubMed Central

Wylie, Korey P.; Rojas, Donald C.; Tanabe, Jody; Martin, Laura F.; Tregellas, Jason R.

2012-01-01

Despite the use of cholinergic therapies in Alzheimer’s disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting-state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network’s tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer’s disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. PMID:22796985

Gender, race, and education differences in abstinence rates among participants in two randomized smoking cessation trials.

PubMed

Piper, Megan E; Cook, Jessica W; Schlam, Tanya R; Jorenby, Douglas E; Smith, Stevens S; Bolt, Daniel M; Loh, Wei-Yin

2010-06-01

Smoking is the leading preventable cause of morbidity and mortality in the United States, but this burden is not distributed equally among smokers. Women, Blacks, and people with low socioeconomic status are especially vulnerable to the health risks of smoking and are less likely to quit. This research examined cessation rates and treatment response among 2,850 participants (57.2% women, 11.7% Blacks, and 9.0% with less than a high school education) from two large cessation trials evaluating: nicotine patch, nicotine lozenge, bupropion, bupropion + lozenge, and nicotine patch + lozenge. Results revealed that women, Blacks, and smokers with less education were less likely to quit smoking successfully than men, Whites, and smokers with more education, respectively. Women did not appear to benefit more from bupropion than from nicotine replacement therapy, but women and smokers with less education benefited more from combination pharmacotherapy than from monotherapy. Women, Blacks, and smokers with less education are at elevated risk for cessation failure, and research is needed to understand this risk and develop pharmacological and psychosocial interventions to improve their long-term cessation rates.

A novel tri-layered buccal mucoadhesive patch for drug delivery: assessment of nicotine delivery.

PubMed

Rao, Shasha; Song, Yunmei; Peddie, Frank; Evans, Allan M

2011-06-01

The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first-pass metabolism. A tri-layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro. Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri-layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min). The novel tri-layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Patterns of use of a free nicotine patch program for Medicaid and uninsured patients.

PubMed Central

Jaén, C. R.; Cummings, K. M.; Shah, D.; Aungst, W.

1997-01-01

This study assessed the use and effectiveness of a free nicotine patch program among Medicaid and uninsured smokers. Patterns of patch use, associated behaviors with quit attempt, side effects, and self-reported abstinence from smoking for 6 months were evaluated prospectively among patients from five urban family practice offices and a nicotine dependence clinic located in a comprehensive cancer center in Western New York. Results indicated that the majority of participants used the program as intended, and 90% of the participants found the patch useful in their quit attempt. Fourteen percent of participants were abstinent for 6 months or more. We found no support for inappropriate use of transdermal nicotine patches among patients with no health insurance or those on Medicaid. Transdermal nicotine patches are an effective cessation aid for smokers. Given the tall of the consequences of smoking on health costs, barriers to access to effective treatment for smoking cessation among individuals covered by Medicaid for health insurance need to be eliminated. PMID:9170833

The effect of transdermal nicotine patches on sleep and dreams.

PubMed

Page, F; Coleman, G; Conduit, R

2006-07-30

This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

Smoking cessation, smoking reduction, and delayed quitting among smokers given nicotine patches and a self-help pamphlet.

PubMed

Jolicoeur, Denise G; Richter, Kimber P; Ahluwalia, Jasjit S; Mosier, Michael C; Resnicow, Ken

2003-06-01

Over-the-counter nicotine replacement raises questions regarding its "real world" efficacy. This was an open-label, prospective study of 223 smokers who received 42 free nicotine patches and a self-help booklet via shopping mall distribution. The overall quit rate 6 months following distribution of the nicotine patches was 22% (50/223), almost the same quit rate found 6 weeks following patch distribution (21%, 47/223). Twelve percent (27/223) were abstinent at both 6 weeks and 6 months. Among the 83 participants who did not quit, cigarettes smoked per day dropped from 28 to 18. A substantial subgroup of quitters (14%) who, although still smoking at 6 weeks, were smoke free at 6 months, and it appears they had purposefully delayed a serious quit attempt. These results support the usefulness of nicotine patches in helping smokers quit, even with only minimal intervention such as a self-help manual.

Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling.

PubMed

Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

2014-11-01

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.

Nicotine and Non-Nicotine Smoking Factors Differentially Modulate Craving, Withdrawal and Cerebral Blood Flow as Measured with Arterial Spin Labeling

PubMed Central

Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

2014-01-01

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation. PMID:24820539

Brain indices of nicotine's effects on attentional bias to smoking and emotional pictures and to task-relevant targets.

PubMed

Gilbert, David G; Sugai, Chihiro; Zuo, Yantao; Rabinovich, Norka E; McClernon, F Joseph; Froeliger, Brett

2007-03-01

Aversive and smoking-related stimuli are related to smoking urges and relapse and can be potent distractors of selective attention. It has been suggested that the beneficial effect of nicotine replacement therapy may be mediated partly by the ability of nicotine to reduce distraction by such stimuli and thereby to facilitate attention to task-relevant stimuli. The present study tested the hypothesis that nicotine reduces distraction by aversive and smoking-related stimuli as indexed by the parietal P3b brain response to a task-relevant target digit. We assessed the effect of nicotine on distraction by emotionally negative, positive, neutral, and smoking-related pictures immediately preceding target digits during a rapid visual information processing task in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included two experimental sessions. After overnight smoking deprivation (12+ hr), active nicotine patches were applied to participants during one of the sessions and placebo patches were applied during the other session. Nicotine enhanced P3b responses associated with target digits immediately subsequent to negative emotional pictures bilaterally and subsequent to smoking-related pictures only in the right hemisphere. No effects of nicotine were observed for P3bs subsequent to positive and neutral distractor pictures. Another measure of attention, contingent negative variation amplitude in anticipation of the target digits also was increased by nicotine, especially in the left hemisphere and at posterior sites. Together, these findings suggest that nicotine reduces the distraction by emotionally negative and smoking-related stimuli and promotes attention to task-related stimuli by modulating somewhat lateralized and task-specific neural networks.

The Impact of Asking About Interest in Free Nicotine Patches on Smoker's Stated Intent to Change: Real Effect or Artefact of Question Ordering?

PubMed

Cunningham, John A; Kushnir, Vladyslav; McCambridge, Jim

2016-05-01

Stage of change questions are often included on general population surveys to assess the proportion of current smokers intending to quit. The current study reported on a methodological experiment to establish whether participant's self-reported stage of change can be influenced by asking about interest in free nicotine patches immediately prior to asking about intent to change. As part of an ongoing random digit dialing survey, a randomized half of participants were asked if they would be interested in receiving nicotine patches to help them quit smoking prior to being asked whether they intended to quit smoking in the next 6 months and 30 days. Participants who were first asked about interest in free nicotine patches were more likely to rate themselves as in preparation for change (asked first = 33%; not asked first = 19%), and less likely to rate themselves as in the precontemplation stage of change (asked first = 34%; not asked first = 47%), compared with participants who were not asked about their interest in free nicotine patches prior to being asked about their stage of change (P < .001). There are several possible explanations of the results. It is possible that offers of free nicotine patches increases smokers intentions to quit, at least temporarily. Alternatively, smokers being asked about interest in free nicotine patches may expect that the researchers would like to hear about people intending to quit, and respond accordingly. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gender, race, and education differences in abstinence rates among participants in two randomized smoking cessation trials

PubMed Central

Cook, Jessica W.; Schlam, Tanya R.; Jorenby, Douglas E.; Smith, Stevens S.; Bolt, Daniel M.; Loh, Wei-Yin

2010-01-01

Introduction: Smoking is the leading preventable cause of morbidity and mortality in the United States, but this burden is not distributed equally among smokers. Women, Blacks, and people with low socioeconomic status are especially vulnerable to the health risks of smoking and are less likely to quit. Methods: This research examined cessation rates and treatment response among 2,850 participants (57.2% women, 11.7% Blacks, and 9.0% with less than a high school education) from two large cessation trials evaluating: nicotine patch, nicotine lozenge, bupropion, bupropion + lozenge, and nicotine patch + lozenge. Results: Results revealed that women, Blacks, and smokers with less education were less likely to quit smoking successfully than men, Whites, and smokers with more education, respectively. Women did not appear to benefit more from bupropion than from nicotine replacement therapy, but women and smokers with less education benefited more from combination pharmacotherapy than from monotherapy. Discussion: Women, Blacks, and smokers with less education are at elevated risk for cessation failure, and research is needed to understand this risk and develop pharmacological and psychosocial interventions to improve their long-term cessation rates. PMID:20439385

Evaluating the effect of smoking cessation treatment on a complex dynamical system.

PubMed

Bekiroglu, Korkut; Russell, Michael A; Lagoa, Constantino M; Lanza, Stephanie T; Piper, Megan E

2017-11-01

To understand the dynamic relations among tobacco withdrawal symptoms to inform the development of effective smoking cessation treatments. Dynamical system models from control engineering are introduced and utilized to evaluate complex treatment effects. We demonstrate how dynamical models can be used to examine how distinct withdrawal-related processes are related over time and how treatment influences these relations. Intensive longitudinal data from a randomized placebo-controlled smoking cessation trial (N=1504) are used to estimate a dynamical model of withdrawal-related processes including momentary craving, negative affect, quitting self-efficacy, and cessation fatigue for each of six treatment conditions (nicotine patch, nicotine lozenge, bupropion, patch + lozenge, bupropion + lozenge, and placebo). Estimation and simulation results show that (1) withdrawal measurements are interrelated over time, (2) nicotine patch + nicotine lozenge showed reduced cessation fatigue and enhanced self-efficacy in the long-term while bupropion + nicotine lozenge was more effective at reducing negative affect and craving, and (3) although nicotine patch + nicotine lozenge had a better initial effect on cessation fatigue and self-efficacy, nicotine lozenge had a stronger effect on negative affect and nicotine patch had a stronger impact on craving. This approach can be used to provide new evidence illustrating (a) the total impact of treatment conditions (via steady state values) and (b) the total initial impact (via rate of initial change values) on smoking-related outcomes for separate treatment conditions, noting that the conditions that produce the largest change may be different than the conditions that produce the fastest change. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of nicotine replacement therapy in socioeconomically deprived young smokers: a community‐based pilot randomised controlled trial

PubMed Central

Roddy, Elin; Romilly, Nick; Challenger, Alison; Lewis, Sarah; Britton, John

2006-01-01

Background Smoking is common in young people, particularly in disadvantaged groups, and continued smoking has a major impact on quality and quantity of life. Although many young smokers want to stop smoking, little is known about the design and effectiveness of cessation services for them. Objective To determine whether nicotine replacement therapy (NRT) when combined with counselling is effective in young smokers in a deprived area of Nottingham, UK Methods and subjects We surveyed smoking prevalence and attitudes to smoking and quitting in young people accessing an open access youth project in a deprived area of Nottingham, and used the information gained to design a community based smoking cessation service incorporating a randomised controlled trial of nicotine patches against placebo given in association with individual behavioural support. We resurveyed smoking prevalence among project attendees after completing the pilot study. Results Of 264 young people surveyed (median age 14 years, range 11–21), 49% were regular smokers. A total of 98 young people were recruited and randomised to receive either active nicotine patches on a six week reducing dose regimen (49 participants), or placebo (49 participants). Adherence to therapy was low, the median duration being one week, and 63 participants did not attend any follow up. At four weeks, five subjects receiving active NRT and two receiving placebo were abstinent, and at 13 weeks none were. Adverse effects were more common in the active group but none were serious. Smoking prevalence among 246 youth project attendees surveyed after the trial was 44%. Conclusions This study suggests that NRT in this context is unlikely to be effective in young smokers, not least because of low adherence to therapy. It also suggests that young smokers want help with smoking cessation, but that establishing the efficacy of smoking cessation services for young people who need them most will be very difficult. PMID:16998171

Use of nicotine replacement therapy in socioeconomically deprived young smokers: a community-based pilot randomised controlled trial.

PubMed

Roddy, Elin; Romilly, Nick; Challenger, Alison; Lewis, Sarah; Britton, John

2006-10-01

Smoking is common in young people, particularly in disadvantaged groups, and continued smoking has a major impact on quality and quantity of life. Although many young smokers want to stop smoking, little is known about the design and effectiveness of cessation services for them. To determine whether nicotine replacement therapy (NRT) when combined with counselling is effective in young smokers in a deprived area of Nottingham, UK. We surveyed smoking prevalence and attitudes to smoking and quitting in young people accessing an open access youth project in a deprived area of Nottingham, and used the information gained to design a community based smoking cessation service incorporating a randomised controlled trial of nicotine patches against placebo given in association with individual behavioural support. We resurveyed smoking prevalence among project attendees after completing the pilot study. Of 264 young people surveyed (median age 14 years, range 11-21), 49% were regular smokers. A total of 98 young people were recruited and randomised to receive either active nicotine patches on a six week reducing dose regimen (49 participants), or placebo (49 participants). Adherence to therapy was low, the median duration being one week, and 63 participants did not attend any follow up. At four weeks, five subjects receiving active NRT and two receiving placebo were abstinent, and at 13 weeks none were. Adverse effects were more common in the active group but none were serious. Smoking prevalence among 246 youth project attendees surveyed after the trial was 44%. This study suggests that NRT in this context is unlikely to be effective in young smokers, not least because of low adherence to therapy. It also suggests that young smokers want help with smoking cessation, but that establishing the efficacy of smoking cessation services for young people who need them most will be very difficult.

The effect of a nicotine patch on cigarette craving over the course of the day: results from two randomized clinical trials.

PubMed

Shiffman, Saul; Ferguson, Stuart G

2008-10-01

The objective of this analysis was to assess the efficacy of a 21 mg/24-h nicotine patch for the reduction of craving throughout the waking day, compared both to placebo, and to a 15 mg/16-h patch differing pharmacokinetic profile over the day. The primary end-point was craving during the evening hours, because previous research suggested that smoking relapse was particularly likely at that time. Data were drawn from two similar randomized clinical trials among nicotine-dependent smokers who were quitting smoking: Study 1 compared the 21 mg/24-h patch to a placebo patch, while Study 2 compared the 21 mg/24-h patch to a 15 mg/16-h nicotine patch. In both studies, subjects (Study 1: n = 102; Study 2: n = 244) were prompted by an electronic diary to rate their craving multiple times per day during a 1 week baseline period, and for up to 2 weeks after quitting. For analysis, the day was divided into five blocks: morning (up to 10:59 a.m.), mid-day (11:00 a.m.-1:59 p.m.), afternoon (2:00 p.m.-4:59 p.m.), evening (5:00 p.m.-8:59 p.m.), and late night (9:00 p.m. onwards). The individual craving ratings were divided into three intervals based on time since quitting: Days 1-3, 4-7, and 8-14. The 21 mg/24-h nicotine patch resulted in significantly lower craving during all post-quit intervals, at each time of day, both compared to placebo (Study 1), and compared to the 15 mg/16-h nicotine patch (Study 2). Study 2 saw a significant treatment by interval interaction: in later time intervals, the difference in craving experience between 24- and 16-h patch conditions shrunk--while remaining significantly different--as overall levels of craving experienced by subjects in the two groups dropped. Adverse events reported in both studies tended to be mild and transient, consistent with the well characterized adverse event profile of nicotine patches. Study 1 demonstrated that a 21 mg/24-h patch was effective in reducing craving throughout the day, including the evening period when relapse risk is heightened. A further study comparing the 21 mg/24-h patch to a 15 mg/16-h nicotine patch found that craving was significantly lower at all times of day for smokers using the 21 mg/24-h patch. The studies were limited in that craving was only monitored for the first 2 weeks of quitting (when craving is most prominent), and cannot elucidate the impact of patch use on craving outside of this time. Also, there was substantial attrition of the sample over time, partly due to relapse in all conditions.

Effect of high-dose nicotine patch on craving and negative affect leading up to lapse episodes.

PubMed

Ferguson, Stuart G; Shiffman, Saul

2014-07-01

Nicotine patches have been reliably demonstrated to improve smoking cessation outcomes but most users still lapse, and then relapse, during treatment. While patch has been shown to alleviate background cravings, its effects on cue-induced cravings - which have been linked to the occurrence of lapse events - are poorly understood. Here we investigate the effect of nicotine patch on the intensity of craving and negative affect experienced during the hours immediately preceding lapse episodes. Participants were 185 smokers who had quit in the context of a randomized, double-blind trial of high-dose (35 mg) nicotine patch and who lapsed at least once during the first 5 weeks of treatment. Participants used electronic diaries to monitor their smoking, affect, and craving during their cessation attempt. The data suggest that developments on the lapse day - either external events or changes in internal states - caused craving and negative affect to rise, cumulating in the lapse. Nicotine is known to lower background craving and negative affect, but the difference between patch and placebo appeared to dissipate in the hours immediately preceding lapse episodes. Understanding the process by which these symptoms "spike" prior to a lapse - and developing treatments to counter it - are worthy research endeavors.

Free nicotine patches plus proactive telephone peer support to help low-income women stop smoking.

PubMed

Solomon, L J; Scharoun, G M; Flynn, B S; Secker-Walker, R H; Sepinwall, D

2000-07-01

This study tested the impact of free nicotine patches plus proactive telephone peer support to help low-income women stop smoking. A total of 214 Medicaid-eligible women smokers of childbearing age were randomized to receive free nicotine patches through the mail or free nicotine patches through the mail plus the provision of proactive support by telephone from a woman ex-smoker for up to 3 months. Assessments were conducted by telephone at baseline, 10 days, and 3 and 6 months after enrollment. At the 3-month follow-up, significantly more women in the patch plus proactive telephone support condition were abstinent (42%) compared to the patch only condition (28%) (P = 0.03). Similarly, more women in the experimental condition were abstinent at both the 10-day and 3-month assessments (32 v 19%, P = 0.02). However, differences were not found at the 6-month follow-up, suggesting that the addition of proactive telephone peer support enhanced short-term, but not long-term cessation. This is the first study to demonstrate a beneficial effect for the addition of proactive telephone support as an adjunct to free nicotine replacement in a low-income population. Copyright 2000 American Health Foundation and Academic Press.

Treating smokers before the quit date: can nicotine patches and denicotinized cigarettes reduce cravings?

PubMed

Rezaishiraz, Hamed; Hyland, Andrew; Mahoney, Martin C; O'Connor, Richard J; Cummings, K Michael

2007-11-01

The present study investigated whether treatment with the combination of denicotinized cigarettes and 21-mg nicotine patch for 2 weeks before a designated quit date could lessen cravings for smoking, thereby helping smokers abstain from smoking. The study was a randomized controlled clinical trial conducted at Roswell Park Cancer Institute, Buffalo, New York, in 2004 and 2005. Patients included 98 adult heavy smokers (using 20 or more cigarettes/day). Half of the subjects received 2 weeks of combination of denicotinized cigarettes (Quest 3) and 21-mg nicotine patch for 2 weeks before the quit date. The remaining smokers were switched to light cigarettes (Quest 1) during the 2 weeks before the quit date. After the quit date, all subjects received counseling for smoking cessation and were provided nicotine patches for up to 8 weeks after the quit date. Self-reported cravings for smoking, withdrawal symptoms, and smoking abstinence were measured at predetermined intervals using phone-based surveys and in clinical visits. The group that used denicotinized cigarettes and nicotine patch before quitting reported less frequent and less intense cravings for cigarettes in the 2 weeks before and after the designated quit date. Self-reported withdrawal symptoms and quit rates did not differ significantly between the groups. The use of a denicotinized cigarette combined with the nicotine patch appears to lessen cravings to smoke in the immediate postcessation period. A larger, better-powered study is needed to test if this treatment combination has merit for increasing quit rates.

Effects of Internet-Based Voucher Reinforcement and a Transdermal Nicotine Patch on Cigarette Smoking

ERIC Educational Resources Information Center

Glenn, Irene M.; Dallery, Jesse

2007-01-01

Nicotine replacement products are commonly used to promote smoking cessation, but alternative and complementary methods may increase cessation rates. The current experiment compared the short-term effects of a transdermal nicotine patch to voucher-based reinforcement of smoking abstinence on cigarette smoking. Fourteen heavy smokers (7 men and 7…

Escalating doses of transdermal nicotine in heavy smokers: effects on smoking behavior and craving.

PubMed

Selby, Peter; Andriash, Katherine; Zawertailo, Laurie; Persad, Desmond; Zack, Martin; Busto, Usoa E

2013-10-01

Fixed-dose nicotine replacement therapy (NRT) is efficacious for smoking cessation in the general population of smokers. However, it is less effective in populations with psychiatric comorbidities and/or severe tobacco dependence where the percent nicotine replacement is suboptimal. The objective of this pilot study was to determine the effectiveness of nicotine patch dose titration in response to continued smoking in heavily dependent smokers with psychiatric comorbidity. In a single-arm, open-label study adult smokers (mean cigarettes per day, 25.4 ± 13.4; range, 14-43; n = 12) willing to quit were treated with escalating doses of transdermal nicotine and brief counseling intervention if they continued to smoke over a 9-week treatment period. Plasma nicotine and cotinine, along with expired carbon monoxide levels, and the subjective effects of smoking, urge to smoke, demand elasticity, and mood symptoms were also assessed. The mean NRT dose was 32.7 (SD, 16.4) mg/d (range, 7-56 mg/d). Smokers reported significant reductions in both cigarettes per day (mean decrease, 18.4 ± 11.5) confirmed by expired carbon monoxide (mean decrease, 13.5 ± 13.0) with no significant changes in plasma nicotine concentrations during the course of NRT dose titration. There were significant effects on the subjective effects of smoking and measures of smoking behavior. Most commonly reported adverse events were respiratory infections, skin irritation at patch site, nausea, and sleep disturbances, which were generally mild and transient. Titrating doses of NRT to effect with brief intervention hold promise as an effective clinical strategy to assist heavily dependent psychiatrically ill smokers to change their smoking behavior.

The Influence of Social Support on Smoking Cessation Treatment Adherence Among HIV+ Smokers.

PubMed

de Dios, Marcel A; Stanton, Cassandra A; Cano, Miguel Ángel; Lloyd-Richardson, Elizabeth; Niaura, Raymond

2016-05-01

The high prevalence of smoking among people living with HIV is a significant problem. Nonadherence to smoking cessation pharmacotherapy is a barrier for successfully quitting. The current study investigated the extent to which social support variables impact adherence and cessation. Participants were 444 HIV+ smokers who provided data on nicotine patch adherence, social support, and smoking. We conducted a path analysis to estimate (1) the effects of six social support indicators at baseline on nicotine patch adherence; (2) the effect of patch adherence on 7-day point prevalence smoking at 6-month follow-up; and (3) the indirect effects of social support indicators on 7-day point prevalence smoking at 6-month follow-up via patch adherence. The tested model demonstrated good fit as indicated by the comparative fit index, root mean square error of approximation, and weighted root mean square residual (0.94, 0.02, and 0.51, respectively). Path analysis results indicated greater social support network contact was associated with higher levels of nicotine patch adherence (β = .13, P = .02), greater patch adherence was associated with a lower probability of 7-day point prevalence smoking at 6-month follow-up (β = -.47, P < .001) and greater social support network contact (β = -.06, P = .03) had a significant indirect effect on 7-day point prevalence smoking at 6-month follow-up via patch adherence. Findings have implications for smoking cessation interventions that seek to capitalize on the beneficial effects of social support. Such efforts should account for the role that frequency of contact may have on nicotine patch use and other treatment-related mechanisms. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Randomized controlled trial of mailed Nicotine Replacement Therapy to Canadian smokers: study protocol.

PubMed

Cunningham, John A; Leatherdale, Scott T; Selby, Peter L; Tyndale, Rachel F; Zawertailo, Laurie; Kushnir, Vladyslav

2011-09-28

Considerable public health efforts are ongoing Canada-wide to reduce the prevalence of smoking in the general population. From 1985 to 2005, smoking rates among adults decreased from 35% to 19%, however, since that time, the prevalence has plateaued at around 18-19%. To continue to reduce the number of smokers at the population level, one option has been to translate interventions that have demonstrated clinical efficacy into population level initiatives. Nicotine Replacement Therapy (NRT) has a considerable clinical research base demonstrating its efficacy and safety and thus public health initiatives in Canada and other countries are distributing NRT widely through the mail. However, one important question remains unanswered--do smoking cessation programs that involve mailed distribution of free NRT work? To answer this question, a randomized controlled trial is required. A single blinded, panel survey design with random assignment to an experimental and a control condition will be used in this study. A two-stage recruitment process will be employed, in the context of a general population survey with two follow-ups (8 weeks and 6 months). Random digit dialing of Canadian home telephone numbers will identify households with adult smokers (aged 18+ years) who are willing to take part in a smoking study that involves three interviews, with saliva collection for 3-HC/cotinine ratio measurement at baseline and saliva cotinine verification at 8-week and 6-month follow-ups (N = 3,000). Eligible subjects interested in free NRT will be determined at baseline (N = 1,000) and subsequently randomized into experimental and control conditions to receive versus not receive nicotine patches. The primary hypothesis is that subjects who receive nicotine patches will display significantly higher quit rates (as assessed by 30 day point prevalence of abstinence from tobacco) at 6-month follow-up as compared to subjects who do not receive nicotine patches at baseline. The findings from the proposed trial are timely and highly relevant as mailed distribution of NRT require considerable resources and there are limited public health dollars available to combat this substantial health concern. In addition, findings from this randomized controlled trial will inform the development of models to engage smokers to quit, incorporating proactive recruitment and the offer of evidence based treatment. ClinicalTrials.gov: NCT01429129.

Characteristics of COPD smokers and effectiveness and safety of smoking cessation medications.

PubMed

Jiménez Ruiz, Carlos A; Ramos Pinedo, Angela; Cicero Guerrero, Ana; Mayayo Ulibarri, Marisa; Cristobal Fernández, Maribel; Lopez Gonzalez, Gema

2012-09-01

Smoking is the main cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the only treatment shown to be effective in arresting the progression of COPD. Different epidemiological and population-based studies have shown smokers with COPD to have specific smoking characteristics that differentiate them from the rest of smokers and which complicate smoking cessation. The main objective of this study is to analyze the effectiveness and safety of drug treatments for smoking cessation in smokers with severe or very severe COPD. Smokers with severe or very severe COPD (Global Initiative for Chronic Obstructive Lung Disease stages III and IV) received treatment for smoking cessation. The treatment program consisted of a combination of behavioral therapy and drug treatment. Patients were followed up at 1, 2, 4, 6, 8, 10, 12, 18, and 24 weeks after the quit date. Four hundred seventy-two patients were seen, 65% were male, and their mean age was 58.3 (9.8). They smoked an average of 29.7 (13.4) cigarettes/day, and their mean Fagerström test for nicotine dependence score was 7.4 (2.1). Continuous abstinence rate from 9 to 24 weeks (CAR 9-24) was 48.5%. According to type of treatment used, CAR 9-24 for nicotine replacement therapy (NRT), bupropion, and varenicline were 38.2%, 55.6%, and 58.3%, respectively. Varenicline was more effective than nicotine patches: 61% versus 44.1% (odds ratio: 1.98; 95% CI: 1.25-3.12; p = .003). NRT was the treatment producing the fewest adverse effects. The onset of psychiatric symptoms due to medication was rare and evenly distributed across groups. This study shows that smokers with severe or very severe COPD are predominantly males with a high degree of physical dependence upon nicotine. CAR 9-24 was 48.5%. Varenicline and bupropion yielded higher abstinence rates than NRT. Varenicline was more effective than nicotine patches: all types of treatments were safe.

Differential Efficacy of Nicotine Replacement Among Overweight and Obese Women Smokers.

PubMed

Strong, David R; David, Sean P; Johnstone, Elaine C; Aveyard, Paul; Murphy, Michael F; Munafò, Marcus R

2015-07-01

Rates of obesity are higher among more dependent smokers and 37%-65% of smokers seeking cessation treatment are overweight or obese. Overweight or obese smokers may possess metabolic and neurobiological features that contribute to difficulty achieving cessation using front-line nicotine replacement products. Attention to factors that facilitate effective cessation treatment in this vulnerable population is needed to significantly reduce mortality risk among overweight and obese smokers. This secondary analysis of 2 large trials of transdermal nicotine replacement in general medical practices evaluated the hypothesis that higher body mass index (BMI) would moderate the efficacy of the nicotine patch. We examined the potential for gender to further moderate the relationship between BMI and treatment efficacy. In the placebo controlled trial (N = 1,621), 21-mg patch was no more effective than placebo for assisting biochemically verified point prevalence abstinence up to 1 year after quitting for women with higher BMI, but appeared to be effective for men at normal or high BMI (gender × BMI beta = -0.22, p = .004). We did not find differential long-term cessation outcomes among male or female smokers in the 15-mg patch trial (n = 705). However, we observed significantly higher rates of early lapse among women with higher BMI treated with nicotine patch across both trials. These results suggest that increased BMI may affect the efficacy of nicotine patch on reducing risk of early lapse in women. Additional research is needed to explore mechanisms of risk for decreased efficacy of this commonly used cessation aid. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Preferences among four combination nicotine treatments.

PubMed

Schneider, Nina G; Koury, Margaret A; Cortner, Chris; Olmstead, Richard E; Hartman, Neil; Kleinman, Leonard; Kim, Andrew; Chaya, Craig; Leaf, David

2006-09-01

Acute nicotine replacement treatments (NRTs) are disliked or misused, leading to insufficient nicotine intake and poor outcome. Patches provide steady nicotine but are slow and passive. Combining systems may improve efficacy with acute NRTs tailored for compliance. To test initial reactions to and use preferences among combinations of NRTs. Smokers (n=27) tested four combination NRTs in a 5-day crossover trial: 2/4-mg gum + 15-mg patch (G/P), 2/4-mg lozenges + 15-mg patch (L/P), inhaler + 15-mg patch (I/P), and 10 mg + 15-mg patches (P/P). Subjects rated an NRT combination each day after 5-6 h of use and ranked among the NRTs after testing all treatments. Double-patches (P/P) were ranked highest for "ease of use", "safety", and "use in public". However, for "help to quit", 70% preferred some form of acute-patch combination (A/P) compared to 30% choosing P/P. For "use under stress" (an immediate need), 93% preferred A/P systems compared to 7% choosing P/P. L/P ranked lowest for "ease of use", I/P and L/P were lowest on "safety", and I/P ranked lowest for "use in public". Expectations of NRTs changed with test experience for patches (better) and lozenges (worse). In brief testing, all combinations were acceptable. P/P was favored for ease, safety, and public use, but a majority chose A/P systems for help in quitting and use under stress. Combined use is viable and needs to be made known and accessible to smokers.

Examination of the mechanism of action of two pre-quit pharmacotherapies for smoking cessation.

PubMed

Ferguson, Stuart G; Walters, Julia A E; Lu, Wenying; Wells, Gudrun P; Schüz, Natalie

2015-12-21

There is substantial scope for improvement in the current arsenal of smoking cessation methods and techniques: even when front-line cessation treatments are utilized, smokers are still more likely to fail than to succeed. Studies testing the incremental benefit of using nicotine patch for 1-4 weeks prior to quitting have shown pre-quit nicotine patch use produces a robust incremental improvement over standard post-quit patch treatment. The primary objective of the current study is to test the mechanism of action of two pre-quit smoking cessation medications-varenicline and nicotine patch-in order to learn how best to optimize these pre-quit treatments. The study is a three group, randomized, open-label controlled clinical trial. Participants (n = 216 interested quitters) will be randomized to receive standard patch treatment (10 weeks of patch starting from a designated quit day), pre-quit patch treatment (two weeks of patch treatment prior to a quit day, followed by 10 weeks post-quit treatment) or varenicline (starting two weeks prior to quit day followed by 10 weeks post-quit). Participants will use study-specific modified smart-phones to monitor their smoking, withdrawal symptoms, craving, mood and social situations in near real-time over four weeks; two weeks prior to an assigned quit date and two weeks after this date. Smoking and abstinence will be assessed at regular study visits and biochemically verified. Understanding how nicotine patches and varenicline influence abstinence may allow for better tailoring of these treatments to individual smokers. Australian New Zealand Clinical Trials Registry, ACTRN12614000329662 (Registered: 27 March 2014).

Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats.

PubMed

Levin, Edward D; Hall, Brandon J; Chattopadhyay, Autri; Slade, Susan; Wells, Corinne; Rezvani, Amir H; Rose, Jed E

2016-08-01

Chronic nicotine infusion via transdermal patches has been widely shown to assist with smoking cessation. In particular, transdermal nicotine treatment prior to quitting smoking helps reduce ad libitum smoking and aids cessation Rose et al. (Nicotine Tob Res 11:1067-75, 2009). However, despite this success, the majority of smokers who use transdermal nicotine fail to permanently quit smoking. Additional treatments are needed. Tobacco addiction does not just depend on nicotinic receptor systems; a variety of neural systems are involved, including dopamine, norepinepherine, serotonin, and histamine. Given the involvement of a variety of neural systems in the circuits of addiction, combination therapy may offer improved efficacy for successful smoking cessation beyond single treatments alone. We have found that pyrilamine, an H1 histamine antagonist, significantly decreases nicotine self-administration in rats. The current study was conducted to confirm the effect of chronic nicotine infusion on ongoing nicotine self-administration and resumed access after enforced abstinence and to determine the interaction of chronic nicotine with an H1 antagonist treatment. Chronic nicotine infusion via osmotic minipump (2.5 and 5 mg/kg/day for 28 days) significantly reduced nicotine self-administration in a dose-dependent manner. Chronic nicotine infusion also reduced the resumption of nicotine self-administration after enforced abstinence. Chronic pyrilamine infusion (25 mg/kg/day for 14 days) also significantly reduced nicotine self-administration. The combination of chronic nicotine and pyrilamine reduced nicotine self-administration to a greater extent than treatment with either drug alone.

Toward precision smoking cessation treatment I: Moderator results from a factorial experiment.

PubMed

Piper, Megan E; Schlam, Tanya R; Cook, Jessica W; Smith, Stevens S; Bolt, Daniel M; Loh, Wei-Yin; Mermelstein, Robin; Collins, Linda M; Fiore, Michael C; Baker, Timothy B

2017-02-01

The development of tobacco use treatments that are effective for all smokers is critical to improving clinical and public health. The Multiphase Optimization Strategy (MOST) uses highly efficient factorial experiments to evaluate multiple intervention components for possible inclusion in an optimized tobacco use treatment. Factorial experiments permit analyses of the influence of patient characteristics on main and interaction effects of multiple, relatively discrete, intervention components. This study examined whether person-factor and smoking characteristics moderated the main or interactive effects of intervention components on 26-week self-reported abstinence rates. This fractional factorial experiment evaluated six smoking cessation intervention components among primary care patients (N=637): Prequit Nicotine Patch vs. None, Prequit Nicotine Gum vs. None, Preparation Counseling vs. None, Intensive Cessation In-Person Counseling vs. Minimal, Intensive Cessation Telephone Counseling vs. Minimal, and 16 vs. 8 Weeks of Combination Nicotine Replacement Therapy (NRT; nicotine patch+nicotine gum). Both psychiatric history and smoking heaviness moderated intervention component effects. In comparison with participants with no self-reported history of a psychiatric disorder, those with a positive history showed better response to 16- vs. 8-weeks of combination NRT, but a poorer response to counseling interventions. Also, in contrast to light smokers, heavier smokers showed a poorer response to counseling interventions. Heavy smokers and those with psychiatric histories demonstrated a differential response to intervention components. This research illustrates the use of factorial designs to examine the interactions between person characteristics and relatively discrete intervention components. Future research is needed to replicate these findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Influence of Nicotine on Lung Tumor Growth, Cancer Chemotherapy, and Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Kyte, S Lauren; Gewirtz, David A

2018-06-04

Studies in animal models have suggested that nicotine, an agonist of nicotinic acetylcholine receptors (nAChRs), may have the potential to prevent and/or reverse the peripheral neuropathy induced by cancer chemotherapeutic drugs, such as paclitaxel and oxaliplatin. However, a large body of evidence suggests that nicotine may also stimulate lung tumor growth and/or interfere with the effectiveness of cancer chemotherapy. While the reported proliferative effects of nicotine are highly variable, the antagonism of antitumor drug efficacy is more consistent, although this latter effect has been demonstrated primarily in cell culture studies. In contrast, in vitro and in vivo studies from our own laboratory indicate that nicotine fails to enhance the growth of non-small cell lung cancer cells or attenuate the effects of chemotherapy (paclitaxel). Given the inconsistencies in the literature, coupled with our own findings, the weight of evidence suggests that caution may be warranted in proposing to utilize nicotine to mitigate chemotherapy-induced peripheral neuropathy in cancer patients receiving chemotherapy. Conversely, clinical trials could be performed in patients who have completed therapy and are considered to be disease-free to determine whether nicotine, in the form of commercially available patches or gum, is effective in alleviating peripheral neuropathy symptoms. The American Society for Pharmacology and Experimental Therapeutics.

Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler.

PubMed

Hajek, P; West, R; Foulds, J; Nilsson, F; Burrows, S; Meadow, A

1999-09-27

There are several nicotine replacement products on the market, and physicians are likely to be asked with increasing frequency about which of these products their patients should use. To provide a basis for rational advice by comparing nicotine polacrilex (gum), a transdermal patch, nasal spray, and an inhaler. Randomized trial with assessments at the quit date and 1, 4, and 12 weeks later. Hospital smokers' clinic. Male and female community volunteers (N = 504) smoking 10 or more cigarettes per day and seeking help to stop smoking. Patients were given brief advice, and purchased their nicotine replacement treatment at approximately half the regular retail price. Nicotine replacement treatment use, ratings of withdrawal symptoms, ratings of product characteristics and helpfulness, and biochemically validated continuous lapse-free abstinence. The products did not differ in their effects on withdrawal discomfort, urges to smoke, or rates of abstinence. The continuous validated 12-week abstinence rates were 20%, 21%, 24%, and 24% in the gum, patch, spray, and inhaler groups, respectively. Compliance with recommended nicotine replacement treatment use was high for the patch, low for gum, and very low for the spray and the inhaler. The spray was underused because of adverse effects more often than the other products. In the subjects using the spray, the level of use among abstainers at week 1 predicted outcome at week 12. The inhaler was rated as more embarrassing to use than the other products, but provided at least as much nicotine as the gum. When asked about nicotine replacement treatment products available, physicians should note that, despite low compliance with the recommended dose of the spray and inhaler and differences in product ratings, overall, there are no notable differences between the products in their effects on withdrawal discomfort, perceived helpfulness, or general efficacy.

Predictors of nicotine withdrawal symptoms: findings from the first randomized smoking cessation trial in a low-income country setting.

PubMed

Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Jaber, Rana; Auf, Rehab; Maziak, Wasim

2016-07-01

To identify predictors of nicotine withdrawal symptoms among smokers who participated in a randomized cessation trial in a low-income country. We analyzed data from 269 smokers who participated in a randomized, placebo-controlled smoking cessation trial conducted in primary healthcare in Aleppo, Syria. All participants received behavioral counseling and were randomized to receive either 6 weeks of nicotine or placebo patch and were followed for one year. Throughout the study, lower total withdrawal score was associated with greater education (p = 0.044), older age of smoking initiation (p = 0.017), lower nicotine dependence (p = 0.024), higher confidence in ability to quit (p = 0.020), lower reported depression (p < 0.001), higher adherence to patch (p = 0.026), belief of receiving nicotine patches rather than placebo (p = 0.011), and waterpipe use (p = 0.047). Lower nicotine dependence, greater educational attainment, higher confidence in ability to quit and waterpipe use predict lower withdrawal severity. Waterpipe smoking may serve as a barrier to smoking cessation efforts in countries where its use is highly prevalent. Further, expectancies about the effects of pharmacotherapy appear to mediate the experience of nicotine withdrawal.

The impact of advertising on nicotine replacement therapy demand.

PubMed

Tauras, John A; Chaloupka, Frank J; Emery, Sherry

2005-05-01

While much is known about the economic determinants of tobacco use, very little is known about the economic determinants of nicotine replacement therapy (NRT) use. This paper is the first econometric study to examine the impact of advertising on NRT demand. Pooled cross-sectional time-series scanner-based data for 50 major metropolitan markets in the USA covering the period between the second quarter of 1996 and the second quarter of 2002 are used in the analysis. Fixed-effects modeling is employed to estimate the NRT demand equation. The estimates indicate that increased advertising of Nicoderm CQ transdermal patches and Nicotrol transdermal patches increases per-capita sales of established Nicoderm CQ and Nicotrol products, respectively. However, increased advertising of Nicorette polacrilex (gum) was found not to significantly increase sales of established Nicorette products. Moreover, decreases in the price of NRT and increases in the price of cigarettes were found to increase per-capita sales of NRT products. Given the documented efficacy of NRT, measures to increase peoples' awareness of NRT products through advertising, measures to decrease the price of NRT, and measures to increase the price of cigarettes would be effective means to increase the use of NRT, likely leading to decreased cigarette smoking and reductions in the future public health burden caused by tobacco use.

Tobacco Cessation Among Low-Income Smokers: Motivational Enhancement and Nicotine Patch Treatment

PubMed Central

2014-01-01

Introduction: Despite decades of tobacco use decline among the general population in the United States, tobacco use among low-income populations continues to be a major public health concern. Smoking rates are higher among individuals with less than a high school education, those with no health insurance, and among individuals living below the federal poverty level. Despite these disparities, smoking cessation treatments for low-income populations have not been extensively tested. In the current study, the efficacy of 2 adjunctive smoking cessation interventions was evaluated among low-income smokers who were seen in a primary care setting. Methods: A total of 846 participants were randomly assigned either to motivational enhancement treatment plus brief physician advice and 8 weeks of nicotine replacement therapy (NRT) or to standard care, which consisted of brief physician advice and 8 weeks of NRT. Tobacco smoking abstinence was at 1, 2, 6, and 12 months following baseline. Results: The use of the nicotine patch, telephone counseling, and positive decisional balance were predictive of increased abstinence rates, and elevated stress levels and temptation to smoke in both social/habit and negative affect situations decreased abstinence rates across time. Analyses showed intervention effects on smoking temptations, length of patch use, and number of telephone contacts. Direct intervention effects on abstinence rates were not significant, after adjusting for model predictors and selection bias due to perirandomization attrition. Conclusions: Integrating therapeutic approaches that promote use of and adherence to medications for quitting smoking and that target stress management and reducing negative affect may enhance smoking cessation among low-income smokers. PMID:24174612

Tobacco cessation among low-income smokers: motivational enhancement and nicotine patch treatment.

PubMed

Bock, Beth C; Papandonatos, George D; de Dios, Marcel A; Abrams, David B; Azam, Munawar M; Fagan, Mark; Sweeney, Patrick J; Stein, Michael D; Niaura, Raymond

2014-04-01

Despite decades of tobacco use decline among the general population in the United States, tobacco use among low-income populations continues to be a major public health concern. Smoking rates are higher among individuals with less than a high school education, those with no health insurance, and among individuals living below the federal poverty level. Despite these disparities, smoking cessation treatments for low-income populations have not been extensively tested. In the current study, the efficacy of 2 adjunctive smoking cessation interventions was evaluated among low-income smokers who were seen in a primary care setting. A total of 846 participants were randomly assigned either to motivational enhancement treatment plus brief physician advice and 8 weeks of nicotine replacement therapy (NRT) or to standard care, which consisted of brief physician advice and 8 weeks of NRT. Tobacco smoking abstinence was at 1, 2, 6, and 12 months following baseline. The use of the nicotine patch, telephone counseling, and positive decisional balance were predictive of increased abstinence rates, and elevated stress levels and temptation to smoke in both social/habit and negative affect situations decreased abstinence rates across time. Analyses showed intervention effects on smoking temptations, length of patch use, and number of telephone contacts. Direct intervention effects on abstinence rates were not significant, after adjusting for model predictors and selection bias due to perirandomization attrition. Integrating therapeutic approaches that promote use of and adherence to medications for quitting smoking and that target stress management and reducing negative affect may enhance smoking cessation among low-income smokers.

Composite HPMC and sodium alginate based buccal formulations for nicotine replacement therapy.

PubMed

Okeke, Obinna C; Boateng, Joshua S

2016-10-01

Smoking cessation is of current topical interest due to the significant negative health and economic impact in many countries. This study aimed to develop buccal films and wafers comprising HPMC and sodium alginate (SA) for potential use in nicotine replacement therapy via the buccal mucosa, as a cheap but effective alternative to currently used nicotine patch and chewing gum. The formulations were characterised using texture analyser (tensile and hardness, mucoadhesion), scanning electron microscopy, X-ray diffractometry, attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC) and swelling capacity. Drug loaded films and wafers were characterised for content uniformity (HPLC) whilst the drug loaded wafers only were further characterised for in vitro drug dissolution. SA modified and improved the functional properties of HPMC at optimum ratio of HPMC: SA of 1.25: 0.75. Generally, both films and wafers (blank and drug loaded) were amorphous in nature which impacted on swelling and mucoadhesive performance. HPMC-SA composite wafers showed a porous internal morphology with higher mucoadhesion, swelling index and drug loading capacity compared to the HPMC-SA composite films which were non-porous. The study demonstrates the potential use of composite HPMC-SA wafers in the buccal delivery nicotine. Copyright © 2016 Elsevier B.V. All rights reserved.

The impact of pharmaceutical company funding on results of randomized trials of nicotine replacement therapy for smoking cessation: a meta-analysis.

PubMed

Etter, Jean-François; Burri, Mafalda; Stapleton, John

2007-05-01

To assess whether source of funding affected the results of trials of nicotine replacement therapy (NRT) for smoking cessation. We reviewed all randomized controlled trials included in the Cochrane review. There were insufficient non-industry trials of the newer products for these to be included. We included 90 trials of either the nicotine gum (52) or nicotine patch (38). They comprised 18 238 treatment and 16 235 control participants. Forty-nine showed evidence of industry support (18 gum, 31 patch). Industry (31 of 49, 63%) compared with non-industry (seven of 41, 17%, P < 0.001) supported a higher proportion of nicotine patch studies and had larger sample sizes (479 versus 268, P = 0.04). Twenty-five (51%) industry trials reported statistically significant (P < 0.05) results, compared with nine (22%) non-industry trials (OR = 3.70, 95% CI = 1.46-9.35). This difference was not explained by trial characteristics. Industry-supported trials had a pooled odds ratio of 1.90 (1.67-2.16), compared with 1.61 (1.43-1.80) for other studies (chi(2) = 3.6, P = 0.058). There was evidence of funnel-plot asymmetry among industry trials (t = 4.35, P < 0.001), but not among other trials, indicating that several small null-effect industry trials may not have reached publication. After imputation adjustment, the odds ratio for industry trials reduced to 1.64 (1.43-1.89) and the overall NRT odds ratio reduced from 1.73 (1.60-1.90) to 1.62 (1.49-1.77). Compared with independent trials, industry-supported trials were more likely to produce statistically significant results and larger odds ratios. These differences persisted after adjustment for basic trial characteristics. Although we had no data on the amount of funding for each trial, it is possible that more resources led to higher treatment compliance and therefore greater efficacy in industry-supported trials. Differences can also possibly be explained by publication bias with several small, null-effect industry studies not having reached publication. After adjustment for this possible bias, results for industry trials were lower and similar to non-industry results. Similarly, the overall estimate of the net effect for these products reduces to about 5% attributable 1-year successes. This remains of considerable public health benefit. Registration of clinical trials has become mandatory in many countries since most of the trials considered here were conducted, and this should reduce the potential for publication bias in future.

Analyzing Milestones in Smoking Cessation: Illustration in a Nicotine Patch Trial in Adult Smokers

ERIC Educational Resources Information Center

Shiffman, Saul; Scharf, Deborah M.; Shadel, William G.; Gwaltney, Chad J.; Dang, Qianyu; Paton, Stephanie M.; Clark, Duncan B.

2006-01-01

Tests of addiction treatments seldom reveal where treatment exercises its effect (i.e., promoting initial abstinence, preventing lapses, and/or impeding progression from lapse to relapse). The authors illustrate analyses distinguishing effects on these milestones in a randomized trial of high-dose nicotine patch (35 mg; n = 188) versus placebo (n…

A randomized placebo-controlled clinical trial of five smoking cessation pharmacotherapies

PubMed Central

Piper, Megan E.; Smith, Stevens S.; Schlam, Tanya R.; Fiore, Michael C.; Jorenby, Douglas E.; Fraser, David; Baker, Timothy B.

2010-01-01

Context Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use. Objective The primary objective of this research was to assess the relative efficacies of five smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons. Design This was a randomized double-blind, placebo-controlled clinical trial. Setting Smokers were recruited from the community at two urban research sites. Patients Participants were 1504 adult smokers who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported: using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications. Interventions Participants were randomized to one of six treatment conditions: nicotine lozenge, nicotine patch, bupropion SR, nicotine patch + nicotine lozenge, bupropion + nicotine lozenge or placebo. In addition, all participants received six individual counseling sessions. Main Outcome Measures The main outcome measures were biochemically-confirmed 7-day point-prevalence abstinence assessed at 1 week post-quit, end of treatment (8 weeks post-quit) and 6 months post-quit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse. Results All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (OR’s = 1.63–2.34). With such protection, only the nicotine patch + nicotine lozenge (OR = 2.34, p < .001) produced significantly higher abstinence rates at 6-months post-quit than did placebo. Conclusions While the nicotine lozenge, bupropion, and bupropion + lozenge produced effects that were comparable to those reported in previous research, the nicotine patch + lozenge produced the greatest benefit relative to placebo for smoking cessation. PMID:19884613

Daily nicotine patch wear time predicts smoking abstinence in socioeconomically disadvantaged adults: An analysis of ecological momentary assessment data.

PubMed

Ma, Ping; Kendzor, Darla E; Poonawalla, Insiya B; Balis, David S; Businelle, Michael S

2016-12-01

Individuals who use the nicotine patch are more likely to quit smoking than those who receive placebo or no medication. However, studies have not yet examined the association between actual daily nicotine patch wear time during the early phase of a smoking cessation attempt and later smoking abstinence. The purpose of this study was to address this gap in the literature. Participants who enrolled in a safety-net hospital smoking cessation program were followed for 13 weeks (i.e., 1 week pre-quit through 12 weeks post-quit). Participants completed in-person assessments and daily ecological momentary assessments on study provided smartphones. Multivariate logistic regressions were used to determine if daily patch wear time during the first week post-quit predicted 7-day biochemically verified point prevalence smoking abstinence 4 and 12 weeks following the scheduled quit date. Demographic characteristics and smoking behaviors were adjusted as covariates. Participants (N=74) were primarily non-White (78.7%) and most (86%) had an annual household income of <$20,000. Greater average hours of daily nicotine patch wear time during the first week post-quit was associated with a greater likelihood of abstinence at the 4 and 12 week post-quit visits (aOR=2.22, 95% CI:1.17-4.23; aOR=2.24, 95% CI:1.00-5.03). Furthermore, more days of wearing the patch for ≥19h was associated with a greater likelihood of abstinence at the 4 and 12 week post-quit visits (aOR=1.81, 95% CI:1.01-3.22; aOR=2.18, 95% CI:1.03-4.63). Greater adherence to the nicotine patch early in a quit attempt may increase the likelihood of smoking cessation among socioeconomically disadvantaged adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of serum nicotine level on posterior spinal fusion in an in vivo rabbit model.

PubMed

Daffner, Scott D; Waugh, Stacey; Norman, Timothy L; Mukherjee, Nilay; France, John C

2015-06-01

Cigarette smoking has a deleterious effect on spinal fusion. Although some studies have implied that nicotine is primarily responsible for poor fusion outcomes, other studies suggest that nicotine may actually stimulate bone growth. Hence, there may be a dose-dependent effect of nicotine on posterior spinal fusion outcomes. The purpose of this study was to determine if such a relationship could be shown in an in vivo rabbit model. This is a prospective in vivo animal study. Twenty-four adult male New Zealand white rabbits were randomly divided into four groups. All groups received a single-level posterolateral, intertransverse process fusion at L5-L6 with autologous iliac crest bone. One group served as controls and only underwent the spine fusion surgery. Three groups received 5.25-, 10.5-, and 21-mg nicotine patches, respectively, for 5 weeks. Serum nicotine levels were recorded for each group. All animals were euthanized 5 weeks postoperatively, and spinal fusions were evaluated radiographically, by manual palpation, and biomechanically. Statistical analysis evaluated the dose response effect of outcomes variables and nicotine dosage. This study was supported by a portion of a $100,000 grant from the Orthopaedic Research and Education Foundation. Author financial disclosures were completed in accordance with the journal's guidelines; there were no conflicts of interests disclosed that would have led to bias in this work. The average serum levels of nicotine from the different patches were 7.8±1.9 ng/mL for the 5.25-mg patch group; 99.7±17.7 ng/mL for the 10.5-mg patch group; and 149.1±24.6 ng/mL for the 21-mg patch group. The doses positively correlated with serum concentrations of nicotine (correlation coefficient=0.8410, p<.001). The 5.25-mg group provided the best fusion rate, trabeculation, and stiffness. On the basis of the palpation tests, the fusion rates were control (50%), 5.25 mg (80%), 10.5 mg (50%), and 21 mg (42.8%). Radiographic assessment of trabeculation and bone incorporation and biomechanical analysis of bending stiffness ratio were also greatest in the 5.25-mg group. Radiographic evaluation showed a significant (p=.0446) quadratic effect of nicotine dose on spinal fusion. The effects of nicotine on spinal fusion are complex, may be dose dependent, and may not always be detrimental. The uniformly negative effects of smoking reported in patients undergoing spinal fusion may possibly be attributed to the other components of cigarette smoke. Copyright © 2015 Elsevier Inc. All rights reserved.

Allocation of resources between smoking cessation methods and lovastatin treatment of hypercholesterolaemia: based on cost effectiveness and the social welfare function.

PubMed

Plans-Rubió, Pedro

2004-01-01

To use the social welfare function to decide on allocation of resources between smoking cessation methods and lovastatin treatment of hypercholesterolaemia for the primary prevention of coronary heart disease. Three smoking cessation therapies (medical advice, nicotine gum and nicotine patch) were considered in smokers, and lovastatin 20, 40 and 80 mg/day was considered in individuals with hypercholesterolaemia (total cholesterol > 7.24 mmol/L [> 270 mg/dL]). Multiple logistic regression analysis was used to obtain parameter epsilon determining the exact form of the social welfare function in Catalonia, Spain. The preferable strategy was to give higher priority to the intervention that used one smoking cessation method and lovastatin treatment for hypercholesterolaemia and that was associated with a value of epsilon consistent with the social welfare function. A value of 1.58 (95% CI: 0.75-2.84) was obtained for parameter epsilon of the social welfare function, showing a nonutilitarian form. A higher priority should be given, based on the social welfare function, to the intervention using medical advice for smoking cessation and lovastatin 20-80 mg/day for hypercholesterolaemia, since this approach was associated with epsilon values of 2.8-2.9 in men and 1.8-2.4 in women, while interventions using nicotine substitution therapies were associated with epsilon values of < 0.9 in men and < 0.4 in women. The cost of treating all smokers and individuals with hypercholesterolaemia was 35% lower using medical advice for smoking cessation and lovastatin 20 mg/day, which was associated with epsilon values of 2.9 in men and 2.4 in women, than using a utilitarian solution consisting of nicotine patches for smoking cessation and lovastatin 20 mg/day. These results show that higher priority should be given to lovastatin treatment of hypercholesterolaemia than to nicotine substitution treatments for smoking cessation, based on cost effectiveness and the social welfare function. The study also showed the applicability of this method to decisions about resource allocation between competing treatments when society has a nonutilitarian social welfare function.

Cost-Effectiveness of Nicotine Patches for Smoking Cessation in Pregnancy: A Placebo Randomized Controlled Trial (SNAP).

PubMed

Essex, Holly N; Parrott, Steve; Wu, Qi; Li, Jinshuo; Cooper, Sue; Coleman, Tim

2015-06-01

Smoking during pregnancy is the most important, preventable cause of adverse pregnancy outcomes including miscarriage, premature birth, and low birth weight with huge financial costs to the National Health Service. However, there are very few published economic evaluations of smoking cessation interventions in pregnancy and previous studies are predominantly U.S.-based and do not present incremental cost-effectiveness ratios (ICER). A number of studies have demonstrated cost-effectiveness of nicotine replacement therapy (NRT) in the general population, but this has yet to be tested among pregnant smokers. A cost-effectiveness analysis was undertaken alongside the smoking, nicotine, and pregnancy trial to compare NRT patches plus behavioral support to behavioral support alone, for pregnant women who smoked. At delivery, biochemically verified quit rates were slightly higher at 9.4% in the NRT group compared to 7.6% in the control group (odds ratio = 1.26, 95% CI = 0.82-1.96), at an increased cost of around £90 per participant. Higher costs in the NRT group were mainly attributable to the cost of NRT patches (mean = £46.07). The incremental cost-effectiveness ratio associated with NRT was £4,926 per quitter and a sensitivity analysis including only singleton births yielded an ICER of £4,156 per quitter. However, wide confidence intervals indicated a high level of uncertainty. Without a specific willingness to pay threshold, and due to high levels of statistical uncertainty, it is hard to determine the cost-effectiveness of NRT in this population. Furthermore, future research should address compliance issues, as these may dilute any potential effects of NRT, thus reducing the cost-effectiveness. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements.

PubMed

Kasparbauer, Anna-Maria; Meyhöfer, Inga; Steffens, Maria; Weber, Bernd; Aydin, Merve; Kumari, Veena; Hurlemann, Rene; Ettinger, Ulrich

2016-11-01

Nicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. Eighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). There were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. The reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers. Copyright © 2016 Elsevier Inc. All rights reserved.

Study protocol for a randomised trial of nicotine-free cigarettes as an adjunct to usual NRT-based cessation practice, in people who wish to stop smoking

PubMed Central

2011-01-01

Background Current smoking cessation treatments focus on addressing the pharmacological dependence of smokers on nicotine. However, new strategies are needed that address both nicotine dependence and the psychological dependence on cigarettes as the source of nicotine. Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates. This paper describes the protocol for a large randomised-controlled trial to test the effect of using nicotine-free cigarettes together with NRT on long-term quit rates. Methods/design This single-blind, randomised trial aims to recruit 1,410 participants through the national telephone-based Quitline service in New Zealand. Participants in the treatment arm will be asked to stop smoking nicotine-containing cigarettes on their chosen Quit day and smoke ad libitum nicotine-free (Quest 3) cigarettes for six weeks. At the same time people in this group will be asked to start using NRT patches, gum and/or lozenges (as recommended by Quitline) for eight weeks. Participants in the control arm will be asked to stop smoking completely on their chosen Quit day and start using NRT patches, gum and/or lozenges (as recommended by Quitline) for eight weeks. Data collection will occur at baseline, three and six weeks, and three and six months after Quit day. The primary outcome is the proportion of participants who self-report seven-day point prevalence abstinence at six months since Quit date. Discussion Smoking prevalence in New Zealand has changed little in recent years (particularly in Māori, the indigenous people of New Zealand) and additional options for smokers who want to quit are needed. Although a variety of methods are available to help, many are expensive, have side effects, and despite their use most quit attempts still fail. This trial will test the balance of benefits and risks of a new strategy for people to overcome nicotine dependence. Since smoking is the leading cause of lost healthy life years in New Zealand, if proven effective this strategy is likely to have substantial public health benefits. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000410358 PMID:21232155

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

PubMed

Rabin, Rachel A; Ashare, Rebecca L; Schnoll, Robert A; Cinciripini, Paul M; Hawk, Larry W; Lerman, Caryn; Tyndale, Rachel F; George, Tony P

2016-06-01

Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296). © 2016 American Academy of Addiction Psychiatry.

Longitudinal Changes in Smoking Abstinence Symptoms and Alternative Reinforcers Predict Long-term Smoking Cessation Outcomes

PubMed Central

Schnoll, Robert A.; Hitsman, Brian; Blazekovic, Sonja; Veluz-Wilkins, Anna; Wileyto, E. Paul; Leone, Frank T.; Audrain-McGovern, Janet E.

2016-01-01

Background Transdermal nicotine, with behavioral counseling, is among the most popular approaches used to quit smoking. Yet, 6-month cessation rates rarely exceed 20–25%. Identifying factors associated with cessation success may help researchers and clinicians develop enhanced interventions that can improve quit rates. This study examined longitudinal changes in withdrawal, craving, depression and anxiety symptoms, and alternative reinforcers, from a baseline assessment to a 6-month outcome, as predictors of 6-month smoking cessation outcomes following 8 weeks of nicotine patch treatment and counseling. Methods A sample of 180 smokers, who completed an effectiveness trial that provided counseling and 8 weeks of 21mg nicotine patches, was analyzed. Generalized estimating equations evaluated changes in withdrawal and craving, depression and anxiety symptoms, and alternative reinforcers over time, between participants who were smoking at 6-months and participants who were abstinent (confirmed with carbon monoxide) at 6-months. Multiple logistic regression assessed changes in these variables as predictors of relapse. Results Controlling for covariates associated with cessation (i.e., nicotine dependence, patch adherence, and rate of nicotine metabolism), participants who were abstinent at 6 months showed significantly lower craving and withdrawal and significantly higher substitute reinforcers from baseline to 6 months, vs. those who were smoking at 6 months (p < .001). An increase in craving predicted relapse to smoking (p < .05). Conclusions These results support continued efforts to strengthen interventions that reduce withdrawal and craving and the development of interventions to address alternative reinforcers in order to promote long-term smoking abstinence following nicotine patch treatment. PMID:27372219

"I Smoke Like This to Suppress These Issues That Are Flaws of My Character": Challenges and Facilitators of Cessation Among Smokers With Bipolar Disorder.

PubMed

Heffner, Jaimee L; Watson, Noreen L; McClure, Jennifer B; Anthenelli, Robert M; Hohl, Sarah; Bricker, Jonathan B

2018-01-01

Smokers with bipolar disorder (BD) have low rates of successful quitting, yet no prior studies have evaluated the process of quitting among these smokers in the context of a current quit attempt. To facilitate development of more effective interventions, we conducted a qualitative exploration of challenges and facilitators of quitting in an intervention study for smokers with BD. Participants were adult daily smokers with BD (n = 10) who completed a 10-week smoking cessation intervention consisting of Acceptance and Commitment Therapy (ACT) and nicotine patch. We administered semistructured interviews focused on the quitting process at the end of treatment and used inductive content analysis to extract themes. Emergent themes representing challenges of quitting included social impediments, lack of awareness, avoidance, maladaptive beliefs, ambivalence, benefits of smoking, and difficulties with nicotine replacement. Themes representing change facilitators included positive treatment effects (ACT-specific, nonspecific, and nicotine patch-related), coping behaviors, reasons to quit, changes in self-perception, and social benefits. Results suggest a need for assistance with obtaining social support and handling social impediments, interrupting the automaticity of smoking, expanding the behavioral repertoire to handle aversive internal states that tend to be avoided by smoking, preventing maladaptive beliefs from interfering with quitting, taking meaningful action toward change while experiencing ambivalence, either replacing the benefits of smoking or accepting their loss, and troubleshooting difficulties with nicotine replacement. Findings regarding facilitators of quitting supported previous quantitative findings that the ACT intervention impacted theory-based targets and highlighted the importance of the counseling relationship.

Anxiety Sensitivity and Nicotine Replacement Therapy Side Effects: Examining the Role of Emotion Dysregulation Among Treatment-Seeking Smokers.

PubMed

Zvolensky, Michael J; Paulus, Daniel J; Garey, Lorra; Raines, Amanda M; Businelle, Michael; Shankman, Stewart A; Manning, Kara; Goodwin, Renee D; Schmidt, Norman B

2017-11-01

Nicotine replacement therapy (NRT) significantly increases the likelihood of quit success at least over the short term, yet some smokers prematurely discontinue use. NRT side effects are often cited as the primary reason for medication discontinuation. The current study examined a theoretical pathway by which two smoking-related emotional vulnerabilities (anxiety sensitivity and emotion dysregulation) were related to the number of NRT (nicotine patch) side effects reported 1 week following a scheduled quit attempt. It was hypothesized that anxiety sensitivity would have an indirect effect on NRT side effects through emotion dysregulation. A total of 179 treatment-seeking, adult daily smokers with elevated anxiety sensitivity (47.5% male; M age = 39.73 years, SD = 13.87) were enrolled in a smoking cessation trial. Covariate-adjusted analyses provided support for the hypothesized pathway, such that emotion dysregulation explained the association between anxiety sensitivity and NRT side effects (b = 0.02, SE = 0.01, 95% CI [0.002, 0.03]; completely standardized estimate = .15). The findings underscore the importance of developing cessation treatments that incorporate techniques to enhance emotion regulation, particularly among smokers higher in anxiety sensitivity, to decrease the risk of NRT side effects.

Smoking cessation interventions in clinical practice.

PubMed

Cornuz, J

2007-10-01

Physicians are in a unique position to advise smokers to quit by integrating the various aspects of nicotine dependence. This review provides an overview of interventions for smokers presenting in a clinical setting. Strategies used for smoking cessation counselling differ according to patient's readiness to quit. For smokers who do not intend to quit smoking, physicians should inform and sensitise them about tobacco use and cessation. For smokers who are dissonant, physicians should use motivational strategies, such as discussing barriers to cessation and their solutions. For smokers ready to quit, the physician should show strong support, help set a quit date, prescribe pharmaceutical therapies for nicotine dependence, such as nicotine replacement therapy (i.e., gum, transdermal patch, nasal spray, mouth inhaler, lozenges, micro and sublingual tablets) and/or bupropion (atypical antidepressant thought to work by blocking neural reuptake of dopamine and/or nor epinephrine), with instructions for use, and suggest behavioural strategies to prevent relapse. The efficacy of all of these pharmacotherapies is comparable, roughly doubling cessation rates over control conditions. Varenicline is a promising new effective drug recently approved by many health authorities. Physician counselling and pharmacotherapeutic interventions for smoking cessation are among the most cost-effective clinical interventions.

Use of pharmacy data to evaluate smoking regulations' impact on sales of nicotine replacement therapies in New York City.

PubMed

Metzger, Kristina B; Mostashari, Farzad; Kerker, Bonnie D

2005-06-01

Recently, New York City and New York State increased cigarette excise taxes and New York City implemented a smoke-free workplace law. To assess the impact of these policies on smoking cessation in New York City, we examined over-the-counter sales of nicotine replacement therapy (NRT) products. Pharmacy sales data were collected in real time as part of nontraditional surveillance activities. We used Poisson generalized estimating equations to analyze the effect of smoking-related policies on pharmacy-specific weekly sales of nicotine patches and gum. We assessed effect modification by pharmacy location. We observed increases in NRT product sales during the weeks of the cigarette tax increases and the smoke-free workplace law. Pharmacies in low-income areas generally had larger and more persistent increases in response to tax increases than those in higher-income areas. Real-time monitoring of existing nontraditional surveillance data, such as pharmacy sales of NRT products, can help assess the effects of public policies on cessation attempts. Cigarette tax increases and smoke-free workplace regulations were associated with increased smoking cessation attempts in New York City, particularly in low-income areas.

Designing a smoking cessation intervention for the unique needs of homeless persons: a community-based randomized clinical trial.

PubMed

Goldade, Kate; Whembolua, Guy-Lucien; Thomas, Janet; Eischen, Sara; Guo, Hongfei; Connett, John; Des Jarlais, Don; Resnicow, Ken; Gelberg, Lillian; Owen, Greg; Grant, Jon; Ahluwalia, Jasjit S; Okuyemi, Kolawole S

2011-12-01

Although smoking prevalence remains strikingly high in homeless populations (~70% and three times the US national average), smoking cessation studies usually exclude homeless persons. Novel evidence-based interventions are needed for this high-risk subpopulation of smokers. To describe the aims and design of a first-ever smoking cessation clinical trial in the homeless population. The study was a two-group randomized community-based trial that enrolled participants (n = 430) residing across eight homeless shelters and transitional housing units in Minnesota. The study objective was to test the efficacy of motivational interviewing (MI) for enhancing adherence to nicotine replacement therapy (NRT; nicotine patch) and smoking cessation outcomes. Participants were randomized to one of the two groups: active (8 weeks of NRT + 6 sessions of MI) or control (NRT + standard care). Participants attended six in-person assessment sessions and eight retention visits at a location of their choice over 6 months. Nicotine patch in 2-week doses was administered at four visits over the first 8 weeks of the 26-week trial. The primary outcome was cotinine-verified 7-day point-prevalence abstinence at 6 months. Secondary outcomes included adherence to nicotine patch assessed through direct observation and patch counts. Other outcomes included the mediating and/or moderating effects of comorbid psychiatric and substance abuse disorders. Lessons learned from the community-based cessation randomized trial for improving recruitment and retention in a mobile and vulnerable population included: (1) the importance of engaging the perspectives of shelter leadership by forming and convening a Community Advisory Board; (2) locating the study at the shelters for more visibility and easier access for participants; (3) minimizing exclusion criteria to allow enrollment of participants with stable psychiatric comorbid conditions; (4) delaying the baseline visit from the eligibility visit by a week to protect against attrition; and (5) regular and persistent calls to remind participants of upcoming appointments using cell phones and shelter-specific channels of communication. The study's limitations include generalizability due to the sample drawn from a single Midwestern city in the United States. Since inclusion criteria encompassed willingness to use NRT patch, all participants were motivated and were ready to quit smoking at the time of enrollment in the study. Findings from the self-select group will be generalizable only to those motivated and ready to quit smoking. High incentives may limit the degree to which the intervention is replicable. Lessons learned reflect the need to engage communities in the design and implementation of community-based clinical trials with vulnerable populations.

Nicotine patches and quitline counseling to help hospitalized smokers stay quit: study protocol for a randomized controlled trial.

PubMed

Cummins, Sharon; Zhu, Shu-Hong; Gamst, Anthony; Kirby, Carrie; Brandstein, Kendra; Klonoff-Cohen, Hillary; Chaplin, Edward; Morris, Timothy; Seymann, Gregory; Lee, Joshua

2012-08-01

Hospitalized smokers often quit smoking, voluntarily or involuntarily; most relapse soon after discharge. Extended follow-up counseling can help prevent relapse. However, it is difficult for hospitals to provide follow-up and smokers rarely leave the hospital with quitting aids (for example, nicotine patches). This study aims to test a practical model in which hospitals work with a state cessation quitline. Hospital staff briefly intervene with smokers at bedside and refer them to the quitline. Depending on assigned condition, smokers may receive nicotine patches at discharge or extended quitline telephone counseling post-discharge. This project establishes a practical model that lends itself to broader dissemination, while testing the effectiveness of the interventions in a rigorous randomized trial. This randomized clinical trial (N = 1,640) tests the effect of two interventions on long-term quit rates of hospitalized smokers in a 2 x 2 factorial design. The interventions are (1) nicotine patches (eight-week, step down program) dispensed at discharge and (2) proactive telephone counseling provided by the state quitline after discharge. Subjects are randomly assigned into: usual care, nicotine patches, telephone counseling, or both patches and counseling. It is hypothesized that patches and counseling have independent effects and their combined effect is greater than either alone. The primary outcome measure is thirty-day abstinence at six months; a secondary outcome is biochemically validated smoking status. Cost-effectiveness analysis is conducted to compare each intervention condition (patch alone, counseling alone, and combined interventions) against the usual care condition. Further, this study examines whether smokers' medical diagnosis is a moderator of treatment effect. Generalized linear (binomial) mixed models will be used to study the effect of treatment on abstinence rates. Clustering is accounted for with hospital-specific random effects. If this model is effective, quitlines across the U.S. could work with interested hospitals to set up similar systems. Hospital accreditation standards related to tobacco cessation performance measures require follow-up after discharge and provide additional incentive for hospitals to work with quitlines. The ubiquity of quitlines, combined with the consistency of quitline counseling delivery as centralized state operations, make this partnership attractive. Smoking cessation in hospitalized smokers NCT01289275. Date of registration February 1, 2011; date of first patient August 3, 2011.

Use and reimbursement costs of smoking cessation medication under the Quebec public drug insurance plan.

PubMed

Tremblay, Michèle; Payette, Yves; Montreuil, Annie

2009-01-01

Since October 2000, the nicotine patch, nicotine gum and bupropion have been reimbursed under Quebec's public drug insurance plan. The objective of this study is to describe use of these medications between October 2000 and December 2004 by smokers covered by the public plan, as well as the costs of reimbursing these medications. Data from the Régie de l'assurance maladie du Québec were used to analyze prescriptions for smoking cessation medication issued to persons insured under the public drug insurance plan. Between October 1, 2000, and December 31, 2004, more than 300,000 Quebeckers covered by the public drug insurance plan were reimbursed for smoking cessation medications. This corresponds to a yearly average of 14% of all smokers insured under the public plan. The proportion of employment assistance recipients who used these medications was higher than the proportion of seniors or "other" insurance plan participants. Nicotine patches were the treatment of choice for most users. A total of $55 million was reimbursed by the public drug insurance plan for the nicotine patch, nicotine gum and bupropion over this four-year period. The reimbursement provisions put in place in Quebec in 2000 were successful in reaching financially disadvantaged smokers, at a cost that was comparable with other effective smoking cessation services.

Development of procedures for early screening of smoking cessation medications in humans.

PubMed

Perkins, K A; Lerman, C; Stitzer, Ml; Fonte, C A; Briski, J L; Scott, J A; Chengappa, K N R

2008-08-01

Candidate medications for smoking cessation may be screened more efficiently if initial evaluations in humans combine the practical advantages of laboratory studies with the clinical validity of clinical trials, such as by increasing participants' "quit motivation" during brief testing. We manipulated "intrinsic" quit motivation by recruiting smokers who either did intend to quit soon ("treatment seekers," N = 47) or did not ("nonseekers," N = 93), and "extrinsic" quit motivation by providing or not providing reinforcement for abstinence ($12/day). All the subjects smoked as they would usually do during weeks 1 and 3, and tried to quit during weeks 2 and 4 using either a nicotine patch (21 mg) or a placebo patch, in accordance with the crossover design of the study. The nicotine patch increased abstinence in treatment seekers but not in nonseekers. Reinforcement had a main effect on abstinence but did not moderate the effects of the nicotine patch or treatment-seeking status. Intrinsic, but not extrinsic, quit motivation of participants may enhance the validity of brief tests of medication efficacy for smoking cessation.

Moderation of nicotine effects on covert orienting of attention tasks by poor placebo performance and cue validity.

PubMed

Hammersley, Jonathan J; Gilbert, David G; Rzetelny, Adam; Rabinovich, Norka E

2016-10-01

Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement. The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task. Compared to a placebo patch, a 14mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance. These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine's effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement. Copyright © 2016 Elsevier Inc. All rights reserved.

High-Throughput Patch Clamp Screening in Human α6-Containing Nicotinic Acetylcholine Receptors

PubMed Central

Armstrong, Lucas C.; Kirsch, Glenn E.; Fedorov, Nikolai B.; Wu, Caiyun; Kuryshev, Yuri A.; Sewell, Abby L.; Liu, Zhiqi; Motter, Arianne L.; Leggett, Carmine S.; Orr, Michael S.

2017-01-01

Nicotine, the addictive component of tobacco products, is an agonist at nicotinic acetylcholine receptors (nAChRs) in the brain. The subtypes of nAChR are defined by their α- and β-subunit composition. The α6β2β3 nAChR subtype is expressed in terminals of dopaminergic neurons that project to the nucleus accumbens and striatum and modulate dopamine release in brain regions involved in nicotine addiction. Although subtype-dependent selectivity of nicotine is well documented, subtype-selective profiles of other tobacco product constituents are largely unknown and could be essential for understanding the addiction-related neurological effects of tobacco products. We describe the development and validation of a recombinant cell line expressing human α6/3β2β3V273S nAChR for screening and profiling assays in an automated patch clamp platform (IonWorks Barracuda). The cell line was pharmacologically characterized by subtype-selective and nonselective reference agonists, pore blockers, and competitive antagonists. Agonist and antagonist effects detected by the automated patch clamp approach were comparable to those obtained by conventional electrophysiological assays. A pilot screen of a library of Food and Drug Administration–approved drugs identified compounds, previously not known to modulate nAChRs, which selectively inhibited the α6/3β2β3V273S subtype. These assays provide new tools for screening and subtype-selective profiling of compounds that act at α6β2β3 nicotinic receptors. PMID:28298165

Nicotine effects on brain function and functional connectivity in schizophrenia.

PubMed

Jacobsen, Leslie K; D'Souza, D Cyril; Mencl, W Einar; Pugh, Kenneth R; Skudlarski, Pawel; Krystal, John H

2004-04-15

Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Outcomes from a patient-centered residential treatment plan for tobacco dependence.

PubMed

Hodgkin, John E; Sachs, David P L; Swan, Gary E; Jack, Lisa M; Titus, Betsy L; Waldron, Susan J S; Sachs, Bonnie L; Brigham, Janet

2013-09-01

St. Helena Hospital launched the first US residential stop-smoking program, The St. Helena Center for a Smoke-Free Life, in 1969. This observational report describes the center's treatment outcome rate for using a patient-centered approach to the use of tobacco dependence medications and behavioral treatment for patients who participated in the program from January 1, 2005 through December 31, 2007. A total of 284 patients used long-acting (nicotine patch, bupropion, and varenicline) and/or short-acting medications (nicotine nasal spray, nicotine gum, nicotine lozenge, and nicotine oral inhaler) alone or in combination during treatment and after discharge. Seven patients chose to use no medications. Patients using nicotine patch received a mean ± SD dose of 33.3±15.7 mg of nicotine in 16 hours (range, 5-90 mg). The 12-month 7-day point prevalence smoking abstinence rate after participation in the intensive, 1-week, residential program was 57.0%. Recommendations are discussed for future research and for implementing aspects of the St. Helena program in other treatment settings. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Nicotine addiction management following surgery: a quality improvement approach in the post anesthesia care unit.

PubMed

Finegan, Barry A; Roblin, Daniel; Hammal, Fadi

2018-03-14

For smokers, hospital admission is accompanied by forced involuntary nicotine abstinence due to smoke-free site/grounds policies. An audit of patients admitted to our surgical wards revealed that identification of smoking status was inadequate and that nicotine addiction management (NAM) was infrequently offered. The project aimed to enhance both these metrics by initiating NAM in the post anesthesia care unit (PACU). Out of 744 patients admitted to our PACU in August 2015, 54% had their smoking status documented. The 200 patients (27%) out of the 744 were smokers and only 50% were offered NAM before discharge. PACU unit staff to determine the smoking status of every patient before discharge from the PACU (later changed to OR nursing staff) and, if a patient was identified as a smoker, to offer NRT (patch and mouth spray only) and initiate therapy prior to transfer of the patient to the ward. Data about number of patients admitted, presence of documented smoking status, number of identified smokers, and number offered/accepted nicotine replacement therapy (NRT) were collected at baseline and thereafter quarterly. Engaging video education sessions addressed the education gaps highlighted in a needs assessment. Identification of smoking status was made part of preoperative checklist and NRT was made available in post-operative recovery room. These interventions resulted in an increase in screening for tobacco use from 54% at baseline to 95% and the offer of NRT to smokers from 50 to 89%.

Moderation of Nicotine Effects on Covert Orienting of Attention Tasks by Poor Placebo Performance and Cue Validity

PubMed Central

Gilbert, David G.; Rzetelny, Adam; Rabinovich, Norka E.

2016-01-01

Introduction and Rationale Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement. Method The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task. Results Compared to a placebo patch, a 14 mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance. Conclusions These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine’s effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement. PMID:27461547

Nicotine dependence and psychiatric disorders.

PubMed

Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

2003-01-01

Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention, concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance.

Smoking Topography Characteristics of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls

PubMed Central

Cassidy, Rachel N.; Miller, Mollie E.

2016-01-01

Introduction: Reducing the nicotine content of cigarettes to a minimally addictive level has been proposed as a regulatory strategy for reducing tobacco dependence. However, smokers with schizophrenia (SS) may be prone to changing their smoking topography in efforts to compensate for the reduction in nicotine content. The aims of this study were to compare smoking topography characteristics of usual-brand and very low nicotine content (VLNC) cigarettes in SS and control smokers without psychiatric illness (CS), and to determine whether nicotine replacement reversed any changes in topography produced by VLNC cigarettes. Methods: Using a within-subjects, counter-balanced design, SS (n = 27) and CS (n = 23) smoked usual brand cigarettes, VLNC cigarettes while wearing placebo patches (VLNC + PLA), or VLNC cigarettes while wearing transdermal nicotine patches totaling 42mg (VLNC + NIC) during 5-hour ad libitum smoking sessions. Cigarettes were smoked through topography measurement devices. Results: Across conditions, SS smoked more puffs per session and per cigarette, had higher cigarette volumes, and had shorter inter-puff intervals than CS (Ps < .01). During VLNC cigarette sessions, puff duration increased and time between puffs decreased, but participants smoked fewer puffs, resulting in a net decrease in cigarette and total session volume (Ps < .001). There were no significant interactions between group and condition. Conclusions: These findings indicate that acute use of VLNC cigarettes does not increase intensity of smoking in SS, and support the feasibility of a nicotine reduction policy. Implications: Reducing the nicotine in cigarettes to a minimally addictive level has been proposed as a means of reducing tobacco dependence. However, smokers, particularly those with schizophrenia (SS) may alter their puffing in an attempt to extract more nicotine from VLNC cigarettes. This study compared smoking topography of usual brand versus VLNC cigarettes, combined with placebo or transdermal nicotine patches, in SS and controls. Although some changes in topography were indicative of compensatory smoking, total puffs and total cigarette volume were reduced with VLNC cigarettes, indicating that acute VLNC cigarette use does not increase smoking in SS. PMID:26995794

Treatment adherence in a lay health adviser intervention to treat tobacco dependence.

PubMed

Hood, N E; Ferketich, A K; Paskett, E D; Wewers, M E

2013-02-01

Lay health advisers (LHAs) are increasingly used to deliver tobacco dependence treatment, especially with low-socioeconomic status (SES) populations. More information is needed about treatment adherence to help interpret mixed evidence of LHA intervention effectiveness. This study examined adherence to behavioral counseling and nicotine patches in an LHA intervention with 147 Ohio Appalachian female daily smokers. Participants were randomly selected from clinics and randomized to the intervention condition of a randomized controlled trial. Overall, 75.5% of participants received all seven planned LHA visits, 29.3% used patches for >7 weeks and approximately half received high average ratings on participant responsiveness. Depressive symptoms and low nicotine dependence were associated with lower patch adherence while high poverty-to-income ratio was associated with high responsiveness. Compared with those with fewer visits, participants who received all visits were more likely to be abstinent (22.5 versus 2.8%, P=0.026) or have attempted quitting (85.0 versus 47.4%, P=0.009) at 3 months. High participant responsiveness was associated with 12-month abstinence. LHA interventions should focus on improving adherence to nicotine patches and managing depression because it is an independent risk factor for low adherence.

Smoking Topography Characteristics of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls.

PubMed

Tidey, Jennifer W; Cassidy, Rachel N; Miller, Mollie E

2016-09-01

Reducing the nicotine content of cigarettes to a minimally addictive level has been proposed as a regulatory strategy for reducing tobacco dependence. However, smokers with schizophrenia (SS) may be prone to changing their smoking topography in efforts to compensate for the reduction in nicotine content. The aims of this study were to compare smoking topography characteristics of usual-brand and very low nicotine content (VLNC) cigarettes in SS and control smokers without psychiatric illness (CS), and to determine whether nicotine replacement reversed any changes in topography produced by VLNC cigarettes. Using a within-subjects, counter-balanced design, SS (n = 27) and CS (n = 23) smoked usual brand cigarettes, VLNC cigarettes while wearing placebo patches (VLNC + PLA), or VLNC cigarettes while wearing transdermal nicotine patches totaling 42mg (VLNC + NIC) during 5-hour ad libitum smoking sessions. Cigarettes were smoked through topography measurement devices. Across conditions, SS smoked more puffs per session and per cigarette, had higher cigarette volumes, and had shorter inter-puff intervals than CS (Ps < .01). During VLNC cigarette sessions, puff duration increased and time between puffs decreased, but participants smoked fewer puffs, resulting in a net decrease in cigarette and total session volume (Ps < .001). There were no significant interactions between group and condition. These findings indicate that acute use of VLNC cigarettes does not increase intensity of smoking in SS, and support the feasibility of a nicotine reduction policy. Reducing the nicotine in cigarettes to a minimally addictive level has been proposed as a means of reducing tobacco dependence. However, smokers, particularly those with schizophrenia (SS) may alter their puffing in an attempt to extract more nicotine from VLNC cigarettes. This study compared smoking topography of usual brand versus VLNC cigarettes, combined with placebo or transdermal nicotine patches, in SS and controls. Although some changes in topography were indicative of compensatory smoking, total puffs and total cigarette volume were reduced with VLNC cigarettes, indicating that acute VLNC cigarette use does not increase smoking in SS. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Medications Development for the Treatment of Nicotine Dependence in Individuals with Schizophrenia

PubMed Central

Montoya, Ivan D.; Vocci, Frank

2008-01-01

The development of medications for the treatment of nicotine dependence in patients with schizophrenia is a public health priority due to its high prevalence rates, devastating medical consequences, and difficulty to treat. It has been hypothesized that the high prevalence of nicotine dependence among patients with schizophrenia may be due to a shared neurobiological vulnerability. This shared vulnerability has been evidenced in reports showing that nicotine improves neuropsychological deficits associated with schizophrenia such as in the P50 evoked auditory potentials, spatial working memory, and attention. The common pathophysiologic pathways of smoking and schizophrenia may serve as the basis for the pharmacological evaluation of medications for the treatment of these concurrent disorders. Currently, little research of medications for the treatment of this comorbidity has been conducted. Studies have evaluated the efficacy of smoking cessation medications in patients with schizophrenia. These include the nicotine replacement therapy (patch, nasal spray) and sustained release bupropion. Others have evaluated the anti-smoking effect of medications (e.g., clozapine, haloperidol) used for the treatment of schizophrenia. In both cases, the results have not been conclusive. Newer smoking cessation approaches such as varenicline, selegiline, rimonabant, and nicotine vaccine, among others, have yet to be tested in this population. The purpose of this article is to review the results of the studies conducted to date and propose some potential pharmacotherapies based on the current knowledge of the pathophysiology of both disorders. PMID:19194522

Smoking cessation treatment outcomes among people with and without mental and substance use disorders: An observational real-world study.

PubMed

Castaldelli-Maia, João Mauricio; Loreto, Aline Rodrigues; Guimarães-Pereira, Bruna Beatriz Sales; Carvalho, Carlos Felipe Cavalcanti; Gil, Felipe; Frallonardo, Fernanda Piotto; Ismael, Flávia; Andrade, Arthur Guerra de; Ventriglio, Antonio; Richter, Kimber P; Bhugra, Dinesh

2018-03-30

There is a lack of studies evaluating smoking cessation treatment protocols which include people with and without mental and substance use disorders (MSUD), and which allows for individuals with MSUD undergoing their psychiatric treatment. We compared treatment success between participants with (n = 277) and without (n = 419) MSUD among patients in a 6-week treatment provided by a Brazilian Psychosocial Care Center (CAPS) from 2007 to 2013. Sociodemographic, medical and tobacco use characteristics were assessed at baseline. Tobacco treatment consisted of 1) group cognitive behavior therapy, which included people with and without MSUD in the same groups, and 2) pharmacotherapy, which could include either nicotine patches, nicotine gum, bupropion or nortriptyline. For participants with MSUD, tobacco treatment was integrated into their ongoing mental health treatment. The main outcome was 30-day point prevalence abstinence, measured at last day of treatment. Abstinence rates did not differ significantly between participants with and without MSUD (31.1% and 34.4%, respectively). Variables that were significantly associated with treatment success included years smoking, the Heaviness of Smoking Index, and use of nicotine patch or bupropion. The inclusion of individuals with and without MSUD in the same protocol, allowing for individuals with MSUD undergoing their psychiatric treatment, generates at least comparable success rates between the groups. Predictors of treatment success were similar to those found in the general population. Facilities that treat patients with MSUD should treat tobacco use in order to reduce the disparities in morbidity and mortality experienced by this population. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Step Care treatment for smoking cessation

PubMed Central

Ebbert, Jon O.; Little, Melissa A.; Klesges, Robert C.; Bursac, Zoran; Johnson, Karen C.; Thomas, Fridtjof; Vander Weg, Mark W.

2017-01-01

Abstract We compared the effectiveness of a ‘stepped care’ approach with increasing treatment intensity (‘Step Care’) to one with repeated treatments (‘Recycle’) among cigarette smokers interested in quitting smoking. Step 1 of the Step Care intervention consisted of a single counseling session, nicotine patch for six weeks and telephonic contact. For smokers not achieving tobacco abstinence 6 months after randomization with Step 1, the intensity of the intervention increased to four counseling sessions, bupropion sustained-release, nine telephone calls and three mailings (Step 2). For those not achieving tobacco abstinence 12 months after randomization, smokers received six behavioral counseling sessions, nicotine patch and nicotine gum, nine telephone calls and three mailings (Step 3). The Recycle participants received one session of health behavior counseling, six weeks of the nicotine patch and a telephone call at each step. 270 cigarette smokers were randomized. At 24 months after randomization using an intention to treat analysis, no statistically significant difference was observed in prolonged smoking abstinence between the Step Care and Recycle condition (16.9% versus 9.4%; adjusted OR = 1.88; 95% CI 0.88–4.01; P =0.10). Additional research is needed to explore whether a stepped care intervention increases long-term smoking abstinence rates compared with repeating the same intervention. PMID:28158558

Separate and Combined Effects of Very Low Nicotine Cigarettes and Nicotine Replacement in Smokers with Schizophrenia and Controls

PubMed Central

Rohsenow, Damaris J.; Kaplan, Gary B.; Swift, Robert M.; AhnAllen, Christopher G.

2013-01-01

Introduction: The prevalence of smoking among people with schizophrenia in the United States is about 3 times that of the general population. Novel approaches are needed to reduce rates of smoking-related morbidity and mortality among these smokers. Methods: This study used a within-subjects design to investigate the separate and combined effects of sensorimotor replacement for smoking (very low nicotine content [VLNC] cigarettes vs. no cigarettes) and transdermal nicotine replacement (42 mg nicotine [NIC] vs. placebo [PLA] patches) in smokers with schizophrenia (SS; n = 30) and control smokers without psychiatric illness (CS; n = 26). Each session contained a 5-hr controlled administration period in which participants underwent the following conditions, in counterbalanced order: VLNC + NIC, VLNC + PLA, no cigarettes + NIC, no cigarettes + PLA, usual-brand cigarettes + no patches. Next, participants completed measures of cigarette craving, nicotine withdrawal, smoking habit withdrawal, and cigarette subjective effects, followed by a 90-min period of ad libitum usual-brand smoking. Results: Smoking VLNC cigarettes during the controlled administration periods reduced cigarette craving, nicotine withdrawal symptoms, habit withdrawal symptoms, and usual-brand smoking in SS and CS relative to the no cigarette conditions. VLNC cigarettes were well accepted by both groups and did not affect psychiatric symptom levels in SS. Transdermal nicotine significantly reduced cigarette craving but did not affect usual-brand smoking. Conclusions: These findings suggest that reducing the nicotine content of cigarettes to nonaddictive levels may be a promising approach for reducing nicotine dependence among people with schizophrenia. PMID:22517190

What can we do in secondary prevention of cigarette smoking?

PubMed

Haustein, Knut-Olaf

2003-12-01

Cigarette smoking kills about six million smokers per year worldwide, and the cigarette has become a symbol of threat to mankind, particularly in industrialized countries. Tobacco smoking causes signs of addiction due to nicotine, but it is the inhaled and exhaled smoke that causes damage to health if cigarette smoking is continued for one or more decades. It is very difficult to attain a high efficacy of stopping smoking using methods of primary prevention in children and young adults. Secondary and tertiary prevention methods use medical and psychological support to the smoker (behavioural and aversion therapy) as well as medical advice in combination with drugs such as nicotine replacement or bupropion. Using a combination of these methods can increase effectiveness up to 45%. Use of nicotine replacement therapy (NRT) in combination with medical advice is the method of smoking cessation recommended by the World Health Organization. Bupropion causes several severe side effects which are not observed with NRT. This article reviews various NRT formulations, including chewing gum, patch, nasal spray, tablet and inhaler, and our experience of using NRT in medical practice, such as adverse events, withdrawal symptoms and the efficacy of NRT in patients with coronary heart disease (angina pectoris, cardiac arrhythmias, etc.), are briefly mentioned. Overall, we need greater efforts in practising primary and secondary prevention among current and future physicians to solve the health problems associated with tobacco use in many nations.

Lessons learned from the implementation of a time-limited, large-scale nicotine replacement therapy giveaway program in New York City.

PubMed

Davis, Karen A; Coady, Micaela H; Mbamalu, Ijeoma G; Sacks, Rachel; Kilgore, Elizabeth A

2013-09-01

Since 2006, the New York City (NYC) Department of Health and Mental Hygiene has conducted the Nicotine Patch and Gum Program (NPGP) in collaboration with 311, NYC's non-emergency information line. In two prior years, the program was conducted in collaboration with the New York State (NYS) Smokers' Quitline and with community-based organizations. The NPGP is an annual, brief, population-based nicotine replacement therapy (NRT) giveaway for NYC residents, complementing the NYS Quitline's year-round NRT distribution program. Since 2006, 168,000 smokers have enrolled, with the largest number of enrollees in 2010 (n = 40,000) and the smallest number in 2009 (n = 28,000). A 2003 program evaluation demonstrated that smokers who received NRT through the NPGP had higher quit rates than smokers who did not receive NRT; these results were replicated in 2006 and 2008. Lessons learned from implementing the NPGP include: 1) time-limited NRT interventions are important complements to year-round NRT distribution; 2) expanding NRT distribution to light smokers increases treatment reach; and 3) employing multiple enrollment mechanisms, including telephone and online options, extends program reach to diverse groups of smokers. The NPGP provides a model for other jurisdictions considering implementing time-limited, population-based NRT programs as a complementary strategy to enhance ongoing tobacco control efforts.

Efficacy and safety of an over-the-counter transdermal nicotine patch as an aid for smoking cessation.

PubMed

Davidson, M; Epstein, M; Burt, R; Schaefer, C; Whitworth, G; McDonald, A

1998-01-01

To evaluate the efficacy and safety of a transdermal nicotine patch as an aid for smoking cessation in an over-the-counter setting. Multicenter, double-blind, randomized, placebo-controlled trial of 6-week duration with 18 weeks of follow-up. Four shopping mall precincts. The randomized sample consisted of 802 adults (mean age, 39 years) and was 89% white and 54% female. A smoking history of at least 20 cigarettes per day for 1 year and a score of 5 (on a 10-point scale) on a motivational assessment questionnaire were required for enrollment. Poststudy follow-up was limited to those who had quit smoking at the end of 6 weeks. Nicotine patches were provided at the shopping mall. Guidance consisted only of package instructions and a smoking cessation self-help booklet. Quit rates were defined as total abstinence from smoking for 4 consecutive weeks (treatment weeks 3-6), point prevalence smoking status at week 6, or nonsmoker at week 6 and week 24 (6-month postquit date). Smoking status was assessed by diaries, and verification for the first 2 quit rates was obtained by confirmation of carbon monoxide of 8 ppm or less in expired breath. Safety was evaluated by self-reported adverse events. Quit rate was 12% for the active treatment group and 5.5% for the placebo group, based on total abstinence for 4 consecutive weeks (P = .001) compared with quit rates of 19.5% and 7.5% for active treatment and placebo groups, respectively, based on point prevalence data at week 6. At 24 weeks, 8.2% of nonsmokers in the active treatment group and 4.0% in the placebo group remained nonsmokers. At least 1 adverse event was reported by 57% receiving the nicotine patch and 39% receiving placebo (P<.001). When the nicotine patch was used in an over-the-counter setting, quit rates were comparable to those reported for medical settings. A 2:1 quit rate advantage was achieved at week 6 and was maintained at 24 weeks.

[Drugs used to treat nicotine addiction].

PubMed

Zieleń, Iwona; Sliwińska-Mossoń, Mariola; Milnerowicz, Halina

2012-01-01

Tobacco smoking in Poland is fairly widespread on a large scale. Research suggests that the early twenty-first century, the percentage of female daily smokers aged 20 and above was 26%, and men the same age 43%. In addition, epidemiological studies have shown that smoking was the cause of approximately sixty-nine thousand deaths in Poland (including fifty-seven thousand men and twelve thousand women). It is common ground that cigarette smoking has a negative effect on our body. It represents one of the main and most commonly defined risk factors for many diseases that can be eliminated. Smoking often leads to addiction, and nicotine is an addictive drug. Nicotine addiction is characterized by symptoms such as: "hunger" smoking, difficulty in controlling behavior on smoking or the number of cigarettes smoked, nicotine withdrawal, the occurrence of tolerance, neglect of interests, as well as devoting more time on activities related to smoking, follow-up smoking despite knowledge of its dangers. The most commonly used in Poland, a questionnaire to identify nicotine dependence is a test Fagerstöma. Currently assigned some importance, "the doctor a conversation the patient" and motivating him to stop smoking and maintain abstinence as long as possible. But beyond the "conversation" is also used as an aid to medical treatment for the patient to stop smoking, especially to alleviate withdrawal symptoms. The first attempts of pharmacological help in the effort to weaning from smoking began in the thirties. Were conducted fairly successful, although uncontrolled trials with lobeline, an alkaloid of action similar to nicotine. In Poland, the drugs of first choice in the treatment of nicotine dependence are nicotine replacement therapies (nicotine gum and patches that contain nicotine) and bupropion SR. Quite a popular drugs to help in the fight against addiction are also cytisine and varenicline. The choice of the drug is usually the result of medical experience in the use of a particular product, as well as the presence of contraindications, and preferences as well as individual patient characteristics. Development of knowledge about the neurobiology of addiction in a broader sense, including dependence on nicotine, contributed to a better understanding of the mechanism of smoking and allowed to search for more effective pharmacological treatments. Current research and clinical trials carried out in two main directions - a) the administration of non-nicotine alone, and b) in combination with nicotine replacement therapy. Publication focuses on the characteristics of the preparations for the treatment of nicotine dependence, including for example mechanism of action, method and duration of use, effectiveness in the treatment and side effects that may occur during the use of these substances.

78 FR 19718 - Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

...] Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use AGENCY: Food...-counter nicotine replacement therapy products, related to concomitant use with other nicotine-containing... over-the- counter nicotine replacement therapy products for their approved intended use as aids to...

Cigarette smoking and the periodontal patient.

PubMed

Johnson, Georgia K; Hill, Margaret

2004-02-01

Evidence from cross-sectional and case-control studies in various populations demonstrates that adult smokers are approximately three times as likely as non-smokers to have periodontitis. The association between smoking and attachment loss is even stronger when the definition of periodontitis is restricted to the most severely affected subjects. Smokers have a diminished response to periodontal therapy and show approximately half as much improvement in probing depths and clinical attachment levels following non-surgical and various surgical modalities of therapy. Implant failures in smokers are twice those of non-smokers, with a higher failure rate in the maxillary arch accounting for the majority of the difference. Tobacco-induced alterations in microbial and host factors contribute to these deleterious effects of smoking on the periodontium. In longitudinal studies, the rate of periodontal disease progression is increased in smokers, but decreases to that of a non-smoker following tobacco cessation. Likewise, recent non-smokers respond to periodontal therapy in a manner similar to patients who have never smoked. Data regarding the impact of smoking on periodontal status included in this review will be helpful to dental health professionals as they counsel their patients regarding tobacco use. The role of dental health professionals in tobacco cessation is discussed, including the use of the five A's: ask--identify tobacco users; advise--advise them to quit; assess--evaluate the patient's readiness to quit; assist--offer assistance in cessation; and arrange--follow up on the patient's cessation efforts. The addition of pharmacotherapy to behavioral therapy, including nicotine replacement therapy and bupropion, can increase cessation rates. The most popular form of nicotine replacement therapy is the patch, and its use has been shown to double cessation rates compared to behavioral therapy alone. Use of bupropion in combination with nicotine replacement therapy may be particularly helpful for heavy smokers or smokers who have experienced multiple failed attempts at cessation. The American Academy of Periodontology Parameters of Care include tobacco cessation as a part of periodontal therapy, and the 2000 Surgeon General's Report on Oral Health in America encourages dental professionals to become more active in tobacco cessation counseling. Doing so will have far-reaching positive effects on our patients' oral and general health.

Bupropion: pharmacological and clinical profile in smoking cessation.

PubMed

Haustein, K O

2003-02-01

Chemistry, pharmacokinetics, pharmacology, clinical efficacy, adverse effects and dosage of bupropion hydrochloride (BP), an aminoketone antidepressant used in smoking cessation, are reviewed. The nicotinergic acetylcholine receptors are inhibited at clinically relevant concentrations of BP. BP does not inhibit monoamine oxidase, and it has minimal inhibitory effects on presynaptic noradrenaline and dopamine uptake. BP is rapidly absorbed after oral administration and demonstrates biphasic elimination with an elimination half-life of 11 - 14 hours. BP is extensively metabolized by oxidation and reduction to at least 6 metabolites, 2 of which may be active. The plasma levels of the erythro-amino alcohol of BP correlate with several side effects such as insomnia and dry mouth. Efficacy of BP(SR) in smoking cessation has been examined in several double-blind, randomized trials in which daily doses of 150 or 300 mg have been administered for 7 or 9 weeks. In addition, 1 study examined the combination of BP(SR) plus nicotine patch. The point prevalences of stopping smoking reached values between 21.2 and 38%, but they did not exceed those after nicotine replacement therapy alone. Long-term administration (52 weeks) of BP did not improve abstinence compared with placebo after a 2-year follow-up period. Thus, the efficacy of BP in smoking cessation is comparable to that of nicotine replacement therapy. However, BP possesses a broad spectrum of infrequent adverse effects and interferes with the degradation of several drugs such as tricyclic antidepressants, beta-recpetor blocking agents, class Ic-antiarrhythmics etc. As the risk-benefit ratio of BP is smaller than that of nicotine replacement, BP should be considered as a second-line treatment in smoking cessation.

A randomized clinical trial of counseling and nicotine replacement therapy for treatment of African American non-daily smokers: Design, accrual, and baseline characteristics.

PubMed

Nollen, Nicole L; Cox, Lisa Sanderson; Mayo, Matthew S; Ellerbeck, Edward F; Madhusudhana, Sheshadri; Ahluwalia, Jasjit S

2018-05-19

Non-daily smokers (NDS) who smoke on some but not all days are a growing subset of United States (US) tobacco users. Racial/ethnic minorities are more likely to be NDS. African American NDS have strikingly high levels of nicotine and carcinogen exposure, making treatment of this high risk group a priority. The current study is one of three ongoing federally-funded clinical trials of NDS and, to our knowledge the only RCT focused on racial/ethnic minority NDS. The design has been guided by input from Patient and Stakeholder Advisory Panels who helped develop the research questions, design the intervention, and select the outcomes. The objective is to compare the effectiveness of smoking cessation counseling alone (C) or smoking cessation counseling plus participant's choice of nicotine replacement therapy (NRT; C + NRT) for African American NDS. Two-hundred seventy-eight African American NDS will be randomized in a 2:1 fashion to C + NRT or C. All participants receive five sessions of smoking cessation counseling; those randomized to C + NRT receive their choice of nicotine gum, patch, and/or lozenge. Treatment in both groups lasts for 12 weeks. We hypothesize that C + NRT will be more effective than C on the primary outcome of biochemically-confirmed abstinence from smoking at week 12. Secondary aims will compare C + NRT and C on patient- and provider-desired outcomes including abstinence from smoking at week 26, change in biochemically-verified nicotine and carcinogen exposure, days abstinent, and treatment process measures (e.g., NRT use and side effects). Predictors of abstinence will also be explored. Findings will illuminate effective treatment options for African American NDS and contribute to development of evidence-based guidelines for treating the 8.9 million US adult NDS for whom no guidelines currently exist. ClinicalTrials.gov: NCT02244918. Copyright © 2017. Published by Elsevier Inc.

Evaluation of P-Listed Pharmaceutical Residues in Empty ...

EPA Pesticide Factsheets

Under the Resource Conservation and Recovery Act (RCRA), some pharmaceuticals are considered acute hazardous wastes because their sole active pharmaceutical ingredients are P-listed commercial chemical products (40 CFR 261.33). Hospitals and other healthcare facilities have struggled with RCRA's empty container requirements when it comes to disposing of visually empty warfarin and nicotine containers, and this issue is in need of investigation. For example, nicotine gums, patches and lozenges are hazardous wastes because nicotine and its salts are listed as P075, and Coumadin (also known as warfarin) is hazardous because warfarin and its salts are listed as P001 (when warfarin is present at concentrations greater than 0.3%). Therefore, when unused nicotine-based smoking cessation products (e.g., patches, gum and lozenges) and Coumadin are discarded, they are acute hazardous wastes and must be managed in accordance with all applicable RCRA regulations. Furthermore, due to additional management requirements for P-listed wastes, any acute hazardous water residues remaining in containers (and therefore the container itself) must be managed as hazardous unless the container has been rendered

Pharmacogenetic Association of the Galanin Receptor (GALR1) SNP rs2717162 with Smoking Cessation

PubMed Central

Gold, Allison B; Wileyto, E Paul; Lori, Adriana; Conti, David; Cubells, Joseph F; Lerman, Caryn

2012-01-01

Galanin modulates dopaminergic neurotransmission in the mesolimbic dopamine system, thereby influencing the rewarding effects of nicotine. Variants in the galanin receptor 1 (GALR1) gene have been associated with retrospective craving severity and heaviness of smoking in prior research. We investigated pharmacogenetic associations of the previously studied GALR1 polymorphism, rs2717162, in 1217 smokers of European ancestry who participated in one of three pharmacogenetic smoking cessation clinical trials and were treated with nicotine patch (n=623), nicotine nasal spray (n=189), bupropion (n=213), or placebo (n=192). The primary endpoint was abstinence (7-day point prevalence, biochemically confirmed) at the end of treatment. Cravings to smoke were assessed on the target quit day (TQD). The longitudinal regression model revealed a significant genotype by treatment interaction (P=0.03). There was a reduced odds of quitting success with the presence of at least one minor (C) allele in the bupropion-treated group (OR=0.43; 95% CI=0.22–0.77; P=0.005) but equivalent quit rates by genotype in the nicotine-replacement therapy groups. This genotype by treatment interaction was reproduced in a Cox regression model of time to relapse (P=0.04). In the bupropion trial, smokers carrying the C allele also reported more severe TQD cravings. Further research to identify functional variants in GALR1 and to replicate pharmacogenetic associations is warranted. PMID:22373943

The SNAP trial: a randomised placebo-controlled trial of nicotine replacement therapy in pregnancy--clinical effectiveness and safety until 2 years after delivery, with economic evaluation.

PubMed

Cooper, Sue; Lewis, Sarah; Thornton, James G; Marlow, Neil; Watts, Kim; Britton, John; Grainge, Matthew J; Taggar, Jaspal; Essex, Holly; Parrott, Steve; Dickinson, Anne; Whitemore, Rachel; Coleman, Tim

2014-08-01

Smoking during pregnancy causes many adverse pregnancy and birth outcomes. Nicotine replacement therapy (NRT) is effective for cessation outside pregnancy but efficacy and safety in pregnancy are unknown. We hypothesised that NRT would increase smoking cessation in pregnancy without adversely affecting infants. To compare (1) at delivery, the clinical effectiveness and cost-effectiveness for achieving biochemically validated smoking cessation of NRT patches with placebo patches in pregnancy and (2) in infants at 2 years of age, the effects of maternal NRT patch use with placebo patch use in pregnancy on behaviour, development and disability. Randomised, placebo-controlled, parallel-group trial and economic evaluation with follow-up at 4 weeks after randomisation, delivery and until infants were 2 years old. Randomisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio. Participants, site pharmacies and all study staff were blind to treatment allocation. Seven antenatal hospitals in the Midlands and north-west England. Women between 12 and 24 weeks' gestation who smoked ≥ 10 cigarettes a day before and ≥ 5 during pregnancy, with an exhaled carbon monoxide (CO) reading of ≥ 8 parts per million (p.p.m.). NRT patches (15 mg per 16 hours) or matched placebo as an 8-week course issued in two equal batches. A second batch was dispensed at 4 weeks to those abstinent from smoking. self-reported, prolonged abstinence from smoking between a quit date and childbirth, validated at delivery by CO measurement and/or salivary cotinine (COT) (primary outcome). Infants, at 2 years: absence of impairment, defined as no disability or problems with behaviour and development. Economic: cost per 'quitter'. One thousand and fifty women enrolled (521 NRT, 529 placebo). There were 1010 live singleton births and 12 participants had live twins, while there were 14 fetal deaths and no birth data for 14 participants. Numbers of adverse pregnancy and birth outcomes were similar in trial groups, except for a greater number of caesarean deliveries in the NRT group. Smoking: all participants were included in the intention-to-treat (ITT) analyses; those lost to follow-up (7% for primary outcome) were assumed to be smoking. At 1 month after randomisation, the validated cessation rate was higher in the NRT group {21.3% vs. 11.7%, odds ratio [OR], [95% confidence interval (CI)] for cessation with NRT, 2.05 [1.46 to 2.88]}. At delivery, there was no difference between groups' smoking cessation rates: 9.4% in the NRT and 7.6% in the placebo group [OR (95% CI), 1.26 (0.82 to 1.96)]. Infants: at 2 years, analyses were based on data from 888 out of 1010 (87.9%) singleton infants (including four postnatal infant deaths) [445/503 (88.5%) NRT, 443/507 (87.4%) placebo] and used multiple imputation. In the NRT group, 72.6% (323/445) had no impairment compared with 65.5% (290/443) in placebo (OR 1.40, 95% CI 1.05 to 1.86). The incremental cost-effectiveness ratio for NRT use was £4156 per quitter (£4926 including twins), but there was substantial uncertainty around these estimates. Nicotine replacement therapy patches had no enduring, significant effect on smoking in pregnancy; however, 2-year-olds born to women who used NRT were more likely to have survived without any developmental impairment. Further studies should investigate the clinical effectiveness and safety of higher doses of NRT. Current Controlled Trials ISRCTN07249128. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 54. See the NIHR Journals Library programme website for further project information.

E-Cigarette Liquid Nicotine Ingestion in a Child: Case Report and Discussion.

PubMed

Gill, Natasha; Sangha, Gurinder; Poonai, Naveen; Lim, Rodrick

2015-11-01

Nicotine poisoning is well described in the pediatric population, and even small oral doses may result in toxic effects. The source of nicotine is usually tobacco products and nicotine replacement products such as gum and patches. With the more frequent use of novel products such as e-cigarettes, concern has arisen regarding liquid nicotine. As there are no regulations regarding childproof bottling and packaging, there may be increased potential for unintentional ingestion of these colorfully and appealingly packaged products by children. We present and discuss a case of this nature, as we feel emergency physicians should be aware of this new mode of poisoning, and public health efforts should be made to minimize such exposures.

Effect on smoking cessation of switching nicotine replacement therapy to over-the-counter status.

PubMed

Thorndike, Anne N; Biener, Lois; Rigotti, Nancy A

2002-03-01

This study examined whether the change in nicotine replacement therapy sales from prescription to over the counter (OTC) status affected smoking cessation. We used the 1993-1999 Massachusetts Tobacco Surveys to compare data from adult current smokers and recent quitters before and after the OTC switch. No significant change over time occurred in the proportion of smokers who used nicotine replacement therapy at a quit attempt in the past year (20.1% pre-OTC vs 21.4% post-OTC), made a quit attempt in the past year (48.1% vs 45.2%), or quit smoking in the past year (8.1% vs 11.1%). Fewer non-Whites used nicotine replacement therapy after the switch (20.7% pre-OTC vs 3.2% post-OTC, P =.002), but the proportion of Whites using nicotine replacement therapy did not change significantly (20.6% vs 24.0%). We observed no increase in Massachusetts smokers' rates of using nicotine replacement therapy, making a quit attempt, or stopping smoking after nicotine replacement therapy became available for OTC sale. There appear to be other barriers to the use of nicotine replacement therapy besides visiting a physician, especially among minority smokers.

The effect of varenicline and nicotine patch on smoking rate and satisfaction with smoking: an examination of the mechanism of action of two pre-quit pharmacotherapies.

PubMed

Lu, Wenying; Chappell, Kate; Walters, Julia A E; Jacobson, Glenn A; Patel, Rahul; Schüz, Natalie; Ferguson, Stuart G

2017-07-01

In recent years, there has been growing research interest in using nicotine replacement medications to aid smoking reduction prior to a quit attempt. Gaining a better understanding of how treatments influence smoking reduction may allow for better tailoring of treatments and, ultimately, better cessation outcomes. The objective of the current study was to test the effects of the pre-quit use of varenicline and nicotine patch on smoking rate and satisfaction with smoking. All participants were required to attend up to five study visit sections. Participants (n = 213) who were interested in quitting were randomised (open-label) to receive either pre-quit patch or varenicline (both treatments started 2 weeks prior to an assigned quit day, followed by 10 weeks post-quit) or standard patch (10 weeks starting from an assigned quit day). Participants used modified smartphones to monitor their smoking in real time for 4 weeks. Participants in the two pre-quit treatment groups reported significant reductions in both their satisfaction with smoking (p < 0.001) and smoking rate (p < 0.001) from baseline to the end of pre-quit period; participants in the standard patch group did not. The observed reduction of smoking rate was associated with the satisfaction with smoking (p < 0.01), although the mediation effect of satisfaction was small. Pre-quit treatment caused reductions in satisfaction with smoking and smoking rate. Satisfaction was associated with changes in smoking rate, but the relationship was weak. As such, monitoring reductions in satisfaction do not appear to be a viable method of evaluating responsiveness to treatment.

Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial.

PubMed

Koegelenberg, Coenraad F N; Noor, Firdows; Bateman, Eric D; van Zyl-Smit, Richard N; Bruning, Axel; O'Brien, John A; Smith, Clifford; Abdool-Gaffar, Mohamed S; Emanuel, Shaunagh; Esterhuizen, Tonya M; Irusen, Elvis M

2014-07-01

Behavioral approaches and pharmacotherapy are of proven benefit in assisting smokers to quit, but it is unclear whether combining nicotine replacement therapy (NRT) with varenicline to improve abstinence is effective and safe. To evaluate the efficacy and safety of combining varenicline and a nicotine patch vs varenicline alone in smoking cessation. Randomized, blinded, placebo-controlled clinical trial with a 12-week treatment period and a further 12-week follow-up conducted in 7 centers in South Africa from April 2011 to October 2012. Four hundred forty-six generally healthy smokers were randomized (1:1); 435 were included in the efficacy and safety analyses. Nicotine or placebo patch treatment began 2 weeks before a target quit date (TQD) and continued for a further 12 weeks. Varenicline was begun 1 week prior to TQD, continued for a further 12 weeks, and tapered off during week 13. Tobacco abstinence was established and confirmed by exhaled carbon monoxide measurements at TQD and at intervals thereafter up to 24 weeks. The primary end point was the 4-week exhaled carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 of treatment, ie, the proportion of participants able to maintain complete abstinence from smoking for the last 4 weeks of treatment, as assessed using multiple imputation analysis. Secondary end points included point prevalence abstinence at 6 months, continuous abstinence rate from weeks 9 through 24, and adverse events. Multiple imputation also was used to address loss to follow-up. The combination treatment was associated with a higher continuous abstinence rate at 12 weeks (55.4% vs 40.9%; odds ratio [OR], 1.85; 95% CI, 1.19-2.89; P = .007) and 24 weeks (49.0% vs 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) and point prevalence abstinence rate at 6 months (65.1% vs 46.7%; OR, 2.13; 95% CI, 1.32-3.43; P = .002). In the combination treatment group, there was a numerically greater incidence of nausea, sleep disturbance, skin reactions, constipation, and depression, with only skin reactions reaching statistical significance (14.4% vs 7.8%; P = .03); the varenicline-alone group experienced more abnormal dreams and headaches. Varenicline in combination with NRT was more effective than varenicline alone at achieving tobacco abstinence at 12 weeks (end of treatment) and at 6 months. Further studies are needed to assess long-term efficacy and safety. clinicaltrials.gov Identifier: NCT01444131.

Effect on Smoking Cessation of Switching Nicotine Replacement Therapy to Over-the-Counter Status

PubMed Central

Thorndike, Anne N.; Biener, Lois; Rigotti, Nancy A.

2002-01-01

Objectives. This study examined whether the change in nicotine replacement therapy sales from prescription to over the counter (OTC) status affected smoking cessation. Methods. We used the 1993–1999 Massachusetts Tobacco Surveys to compare data from adult current smokers and recent quitters before and after the OTC switch. Results. No significant change over time occurred in the proportion of smokers who used nicotine replacement therapy at a quit attempt in the past year (20.1% pre-OTC vs 21.4% post-OTC), made a quit attempt in the past year (48.1% vs 45.2%), or quit smoking in the past year (8.1% vs 11.1%). Fewer non-Whites used nicotine replacement therapy after the switch (20.7% pre-OTC vs 3.2% post-OTC, P = .002), but the proportion of Whites using nicotine replacement therapy did not change significantly (20.6% vs 24.0%). Conclusions. We observed no increase in Massachusetts smokers' rates of using nicotine replacement therapy, making a quit attempt, or stopping smoking after nicotine replacement therapy became available for OTC sale. There appear to be other barriers to the use of nicotine replacement therapy besides visiting a physician, especially among minority smokers. (Am J Public Health. 2002;92:437–442) PMID:11867326

Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.

PubMed

Lesage, Elise; Aronson, Sarah E; Sutherland, Matthew T; Ross, Thomas J; Salmeron, Betty Jo; Stein, Elliot A

2017-06-01

Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline. Similarly, decreased mesocorticolimbic activity associated with cognitive flexibility in abstinent smokers was restored to the level of nonsmokers following stimulation of nicotinic acetylcholine receptors (familywise error-corrected P < .05). Conversely, neural signatures of decreased reward sensitivity in smokers (vs nonsmokers; familywise error-corrected P < .05) in the dorsal striatum and anterior cingulate cortex were not mitigated by nicotine or varenicline. There was a double dissociation between the effects of chronic nicotine dependence on neural representations of reward sensitivity and acute effects of stimulation of nicotinic acetylcholine receptors on behavioral and neural signatures of cognitive flexibility in smokers. These chronic and acute pharmacologic effects were observed in overlapping mesocorticolimbic regions, suggesting that available pharmacotherapies may alleviate deficits in the same circuitry for certain mental computations but not for others. clinicaltrials.gov Identifier: NCT00830739.

The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

PubMed

McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E; Kozink, Rachel V; Addicott, Merideth A; Sweitzer, Maggie M; Westman, Eric C; Van Wert, Dana M

2016-07-01

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. © 2015 Society for the Study of Addiction.

The future of nicotine replacement.

PubMed

Russell, M A

1991-05-01

Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether.

[Difference in action sites between mecamylamine and hexamethonium on nicotinic receptors of sympathetic neurons].

PubMed

Liu, Wei; Zheng, Jian-Quan; Liu, Zhen-Wei; Li, Li-Jun; Wan, Qin; Liu, Chuan-Gui

2002-12-25

To compare the difference in action sites between mecamylamine (MEC) and hexamethonium (HEX) on nicotinic receptors of sympathetic neurons, we investigated the effects of MEC and HEX on the nicotine-induced currents in cultured superior cervical ganglion neurons by whole-cell patch clamp technique. The IC(50) of MEC and HEX for antagonizing the effect of 0.08 mmol/L nicotine was 0.0012 and 0.0095 mmol/L, respectively. Both MEC and HEX accelerated the desensitization of nicotinic receptors. Furthermore, by comparing their effects at holding potentials 30, 70 and 110 mV, it was indicated that their suppressing effect on the nicotine-induced currents was voltage-dependent. However, different from that of HEX, the inhibitory effect of MEC increased with administering the mixture of MEC and nicotine at intervals of 3 min, indicating a use-dependent effect of MEC. It is concluded that the action site of MEC on nicotinic receptors of sympathetic neurons is different from that of HEX.

The Effects of Nicotinic and Muscarinic Receptor Activation on Patch-Clamped Cells in the Optic Tectum of Rana Pipiens

PubMed Central

Yu, C.-J.; Debski, E. A.

2008-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 μM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 μM) and bicuculline (25 μM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 μM). Muscarinic receptor-mediated responses, induced by carbachol (100 μM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input. PMID:12676145

The effects of nicotinic and muscarinic receptor activation on patch-clamped cells in the optic tectum of Rana pipiens.

PubMed

Yu, C-J; Debski, E A

2003-01-01

Both nicotinic and muscarinic cholinergic receptors are present in the optic tectum. To begin to understand how the activation of these receptors affects visual activity patterns, we have determined the types of physiological responses induced by their activation. Using tectal brain slices from the leopard frog, we found that application of nicotine (100 microM) evoked long-lasting responses in 60% of patch-clamped tectal cells. Thirty percent of these responses consisted of an increase in spontaneous postsynaptic currents (sPSCs) and had both a glutamatergic and GABAergic component as determined by the use of 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) and bicuculline (25 microM), respectively. Remaining response types consisted of an inward membrane current (16%) and an increase in sPSCs combined with an inward membrane current (14%). All responses could be elicited in the presence of tetrodotoxin (0.5 microM). Muscarinic receptor-mediated responses, induced by carbachol (100 microM) application after nicotinic receptor desensitization, produced responses in 70% of tectal cells. In contrast to responses elicited by nicotine, carbachol-induced responses could be evoked multiple times without significant decrement. Responses consisted of either an outward current (57%), a decrease in sPSCs (5%) or an increase in sPSCs, with (almost 6%) or without (almost 3%) an outward current. The response elicited by carbachol was not predicted by the response of the cell to nicotine. Our results suggest that nicotinic receptors are found predominantly at presynaptic locations in the optic tectum while muscarinic receptors are most often present at postsynaptic sites. We conclude that both of these receptor types could substantially modulate visual activity by changing either the input to tectal neurons or the level of their response to that input.

Anxiety Diagnoses in Smokers Seeking Cessation Treatment: Relations with Tobacco Dependence, Withdrawal, Outcome, and Response to Treatment

PubMed Central

Piper, Megan E.; Cook, Jessica W.; Schlam, Tanya R.; Jorenby, Douglas E.; Baker, Timothy B.

2010-01-01

Aims To understand the relations amongst anxiety disorders and tobacco dependence, withdrawal symptoms, response to smoking cessation pharmacotherapy, and ability to quit smoking. Design Randomized placebo-controlled clinical trial. Participants received six 10-minute individual counseling sessions and either: placebo, bupropion SR, nicotine patch, nicotine lozenge, bupropion SR+nicotine lozenge, or nicotine patch+nicotine lozenge. Setting Two urban research sites. Participants Data were collected from 1504 daily smokers (>9 cigarettes per day) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use. Measurements Participants completed baseline assessments, the Composite International Diagnostic Interview and ecological momentary assessments for two weeks. Findings A structured clinical interview identified participants who ever met criteria for a panic attack (n=455), social anxiety (n=199), or generalized anxiety disorder (n=99), and those who qualified for no anxiety diagnosis (n=891). Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms. Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect. Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8-weeks and 6-months postquit and showed no benefit from single-agent or combination-agent pharmacotherapies. Conclusions Anxiety diagnoses were common amongst treatment-seeking smokers and were related to increased motivation to smoke, elevated withdrawal, lack of response to pharmacotherapy, and impaired ability to quit smoking. These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses. PMID:20973856

New Product Marketing Blurs the Line Between Nicotine Replacement Therapy and Smokeless Tobacco Products.

PubMed

Kostygina, Ganna; England, Lucinda; Ling, Pamela

2016-07-01

Tobacco companies have begun to acquire pharmaceutical subsidiaries and recently started to market nicotine replacement therapies, such as Zonnic nicotine gum, in convenience stores. Conversely, tobacco companies are producing tobacco products such as tobacco chewing gum and lozenges that resemble pharmaceutical nicotine replacement products, including a nicotine pouch product that resembles snus pouches. This convergence of nicotine and tobacco product marketing has implications for regulation and tobacco cessation.

Effects of smoking cessation on heart rate variability among long-term male smokers.

PubMed

Harte, Christopher B; Meston, Cindy M

2014-04-01

Cigarette smoking has been shown to adversely affect heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. Conversely, smoking cessation is posited to improve cardiac regulation. The aim of the present study was to examine the effects of smoking cessation on HRV among a community sample of chronic smokers. Sixty-two healthy male smokers enrolled in an 8-week smoking cessation program involving a nicotine transdermal patch treatment. Participants were assessed at baseline (while smoking regularly), at mid-treatment (while using a high-dose patch), and at follow-up, 4 weeks after patch discontinuation. Both time-domain (standard deviation of normal-to-normal (NN) intervals (SDNN), square root of the mean squared difference of successive NN intervals (RMSSD), and percent of NN intervals for which successive heartbeat intervals differed by at least 50 ms (pNN50)) and frequency-domain (low frequency (LF), high frequency (HF), LF/HF ratio) parameters of HRV were assessed at each visit. Successful quitters (n = 20), compared to those who relapsed (n = 42), displayed significantly higher SDNN, RMSSD, pNN50, LF, and HF at follow-up, when both nicotine and smoke free. Smoking cessation significantly enhances HRV in chronic male smokers, indicating improved autonomic modulation of the heart. Results suggest that these findings may be primarily attributable to nicotine discontinuation rather than tobacco smoke discontinuation alone.

Programmable carbon nanotube membrane-based transdermal nicotine delivery with microdialysis validation assay.

PubMed

Gulati, Gaurav Kumar; Chen, Tao; Hinds, Bruce Jackson

2017-01-01

To evaluate the performance of switchable carbon nanotubes (CNT) membrane devices for transdermal nicotine delivery, we have developed an in-vitro microdialysis method that allow us to detect variable transdermal fluxes of nicotine through CNT devices and can be applied directly to in-vivo studies. Microdialysis membranes were placed beneath the porcine skin and its nicotine levels increased 6-8 times when the CNT membrane on skin was turned from OFF to ON state by application of bias. Fluxes in the ON state were approximately 3 times that of commercial nicotine patches and switching times were less than two hours, thus suggesting the improved therapeutic potential of our device. Blue tooth enabled CNT devices that can be programmed by smartphone and coupled with remote counseling application for enhanced smoking cessation treatments. Copyright © 2016. Published by Elsevier Inc.

Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction.

PubMed

Benowitz, N L

1991-05-01

Rational treatment of the pharmacologic aspects of tobacco addiction includes nicotine substitution therapy. Understanding the pharmacodynamics of nicotine and its role in the addiction process provides a basis for rational therapeutic intervention. Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks.

Chronic Disease Management for Tobacco Dependence

PubMed Central

Joseph, Anne M.; Fu, Steven S.; Lindgren, Bruce; Rothman, Alexander J.; Kodl, Molly; Lando, Harry; Doyle, Brandon; Hatsukami, Dorothy

2014-01-01

Background Tobacco dependence disorder is a chronic relapsing condition, yet treatment is delivered in discrete episodes of care that yield disappointing long-term quit rates. Methods We conducted a randomized controlled trial from June 1, 2004, through May 31, 2009, to compare telephone-based chronic disease management (1 year; longitudinal care [LC]) with evidence-based treatment (8 weeks; usual care [UC]) for tobacco dependence. A total of 443 smokers each received 5 telephone counseling calls and nicotine replacement therapy by mail for 4 weeks. They were then randomized to UC(2 additional calls) or LC(continued counseling and nicotine replacement therapy for an additional 48 weeks). Longitudinal care targeted repeat quit attempts and interim smoking reduction for relapsers. The primary outcome was 6 months of prolonged abstinence measured at 18 months of follow-up. Results At 18 months, 30.2% of LC participants reported 6 months of abstinence from smoking, compared with 23.5% in UC (unadjusted, P=.13). Multivariate analysis showed that LC (adjusted odds ratio, 1.74; 95% CI, 1.08–2.80), quit attempts in past year (1.75; 1.06–2.89), baseline cigarettes per day (0.95; 0.92–0.99), and smoking in the 14- to 21-day interval post-quit (0.23; 0.14–0.38) predicted prolonged abstinence at 18 months. The LC participants who did not quit reduced smoking more than UC participants (significant only at 12 months). The LC participants received more counseling calls than UC participants (mean, 16.5 vs 5.8 calls; P<.001), longer total duration of counseling (283 vs 117 minutes; P<.001), and more nicotine replacement therapy (4.7 vs 2.4 boxes of patches; P<.001). Conclusion A chronic disease management approach increases both short- and long-term abstinence from smoking. Trial Registration clinicaltrials.gov Identifier: NCT00309296 PMID:22123795

Bone graft

MedlinePlus

... dry. Follow instructions about showering. DO NOT smoke. Smoking slows or prevents bone healing. If you smoke, the graft is more likely to fail. Be aware that nicotine patches slow healing just like smoking does.

Comparison of the effectiveness of virtual cue exposure therapy and cognitive behavioral therapy for nicotine dependence.

PubMed

Park, Chan-Bin; Choi, Jung-Seok; Park, Su Mi; Lee, Jun-Young; Jung, Hee Yeon; Seol, Jin-Mi; Hwang, Jae Yeon; Gwak, Ah Reum; Kwon, Jun Soo

2014-04-01

Previous studies have reported promising results regarding the effect of repeated virtual cue exposure therapy on nicotine dependence. This study aimed to compare the effectiveness of virtual cue exposure therapy (CET) and cognitive behavioral therapy (CBT) for nicotine dependence. Thirty subjects with nicotine dependence participated in 4 weeks of treatment with either virtual CET (n=15) or CBT (n=15). All patients were male, and none received nicotine replacement treatment during the study period. The main setting of the CET used in this study was a virtual bar. The primary foci of the CBT offered were (a) smoking cessation education, (b) withdrawal symptoms, (c) coping with high-risk situations, (d) cognitive reconstruction, and (e) stress management. Daily smoking count, level of expiratory carbon monoxide (CO), level of nicotine dependence, withdrawal symptoms, and subjective craving were examined on three occasions: week 0 (baseline), week 4 (end of treatment), and week 12 (follow-up assessment). After treatment, the daily smoking count, the expiratory CO, and nicotine dependence levels had significantly decreased. These effects continued during the entire study period. Similar changes were observed in both virtual CET and CBT groups. We found no interaction between type of therapy and time of measurement. Although the current findings are preliminary, the present study provided evidence that virtual CET is effective for the treatment of nicotine dependence at a level comparable to CBT.

The Effect of Repeated Virtual Nicotine Cue Exposure Therapy on the Psychophysiological Responses: A Preliminary Study

PubMed Central

Choi, Jung-Seok; Park, Sumi; Lee, Jun-Young; Jung, Hee-Yeon; Lee, Hae-Woo; Jin, Chong-Hyeon

2011-01-01

Objective Smoking related cues may elicit smoking urges and psychophysiological responses in subjects with nicotine dependence. This study aimed to investigate the effect of repeated virtual cue exposure therapy using the surround-screen based projection wall system on the psychophysiological responses in nicotine dependence. Methods The authors developed 3-dimensional neutral and smoking-related environments using virtual reality (VR) technology. Smoking-related environment was a virtual bar, which comprised both object-related and social situation cues. Ten subjects with nicotine dependence participated in 4-week (one session per week) virtual cue exposure therapy. Psychophysiological responses [electromyography (EMG), skin conductance (SC), and heart rate] and subjective nicotine craving were acquired during each session. Results VR nicotine cue elicited greater psychophysiological responses and subjective craving for smoking than did neutral cue, and exposure to social situation cues showed greater psychophysiological responses in SC and EMG than did object-related cues. This responsiveness decreased during the course of repeated therapy. Conclusion The present study found that both psychophysiological responses and subjective nicotine craving were greater to nicotine cue exposure via projection wall VR system than to neutral cues and that enhanced cue reactivity decreased gradually over the course of repeated exposure therapy. These results suggest that VR cue exposure therapy combined with psychophysiological response monitoring may be an alternative treatment modality for smoking cessation, although the current findings are preliminary. PMID:21852993

Dispelling Myths about Nicotine Replacement Therapy

MedlinePlus

... of nicotine gum is associated with hyperinsulinemia and insulin resistance. Circulation. 1996;94:878-881. 16. Epifano L, ... R, Shafer Z, Fainaru M. Weight gain and insulin resistance during nicotine replacement therapy. Clin Cardiol. 1999;22: ...

A review of the pharmacological and psychopharmacological aspects of smoking and smoking cessation in psychiatric patients.

PubMed

Haustein, K O; Haffner, S; Woodcock, B G

2002-09-01

The data reviewed confirm that mentally ill patients smoke twice as many cigarettes as patients without mental illness. The secretion of neurotransmitters such as noradrenaline, serotonin, dopamine, acetylcholine, gamma-amino-butyric acid and glutamate is increased by the binding of nicotine to central nicotine receptors. There are also data showing that serotonin formation and secretion in patients with mental illness are influenced by chronic smoking. Cigarette smoke inhibits the activity of monoamine oxidase B, which is responsible for the catabolism of several brain neurotransmitters. Patients suffering from major depression show a comorbidity between heavy smoking and the disease. In patients with schizophrenia treated with neuroleptics, increased cigarette smoking reduces adverse reactions to the drug therapy presumably because of an increase in metabolism of the neuroleptics. There is also evidence suggesting that quitting smoking is more difficult for mentally ill patients than patients without psychiatric disease. Several studies have been carried out on smoking cessation in psychiatric patients. The alternative method of harm reduction, e.g. reducing the number of cigarettes smoked using nicotine patches or chewing gum, is necessary in patients not able to quit. The data indicate that strategies such as the coupling of smoking prohibition with administration of nicotine preparations are useful in smoking cessation. A no-smoking policy in psychiatric clinics, even when this leads to withdrawal symptoms in the patients affected, has no negative effect on mental illness. Because patients with mental diseases are particularly vulnerable to the marketing strategies of the tobacco industry, this chronically ill section of the population requires special protection by the law-makers.

Effects of transdermally administered nicotine on aspects of attention, task load, and mood in women and men.

PubMed

Trimmel, Michael; Wittberger, Susanne

2004-07-01

This double-blind placebo-controlled study was conducted to determine nicotine effects on diverse types of attentional performance, task load, and mood considering sex effects as suggested by animal studies. Twelve smokers, 12 deprived smokers and 12 nonsmokers (6 females, 6 males in each group) were investigated. Participants were treated either by 5 mg/16 h nicotine patches (Nicorette) or placebo. Effects of treatment were examined by a computerized attention-test battery; mood was assessed by the Berliner-Alltagssprachliches-Stimmungs-Inventar and task load by the NASA Task Load Index (NASA-TLX). Results showed that nicotine significantly increased the number of hits and decreased reaction time (RT) in the vigilance task. In the selective attention task combined with irrelevant speech as background noise, nicotine enhanced rate of hits. Although it was indicated that nicotine leads to a generally higher accuracy in attention tasks, response time of visual search was prolonged, contradicting a universal facilitation by nicotine. Participants experienced mental demand and temporal demand lower and rated alertness higher when in the nicotine condition. These effects were independent of smoking status, indicating "true" nicotine effects. Females took significant advantage of nicotine in the vigilance task, reaching the performance level of males, accompanied by a higher rated alertness. Results indicate task- and sex-dependent nicotine effects.

Electronic cigarettes in North America: history, use, and implications for smoking cessation.

PubMed

Franck, Caroline; Budlovsky, Talia; Windle, Sarah B; Filion, Kristian B; Eisenberg, Mark J

2014-05-13

Designed to mimic the look and feel of tobacco cigarettes, electronic cigarettes (e-cigarettes) may facilitate smoking cessation. However, the efficacy and safety of e-cigarette use for this purpose remain poorly understood. Our objectives were to review the available data on the efficacy and safety of e-cigarettes for smoking cessation and to consider issues relevant to the context in which they are used, including product awareness and regulatory and ethical concerns. We systematically searched PubMed for randomized controlled trials and uncontrolled, experimental studies involving e-cigarettes. Included studies were limited to English or French language reports. Quality assessment was performed according to the Cochrane Risk of Bias tool. We identified 169 publications, of which 7 studies were included. Studies have concluded that e-cigarettes can help reduce the number of cigarettes smoked and may be as effective for smoking cessation as the nicotine patch. Although there is a lack of data concerning the safety and efficacy of e-cigarettes as a smoking cessation therapy, available evidence showed no significant difference in adverse event rates between e-cigarettes and the nicotine patch. E-cigarettes are widely used among smokers attempting to quit. However, significant international variation remains in the regulatory mechanisms governing the sale and distribution of e-cigarettes. Ethical concerns surround the use of e-cigarettes among minors and their potential to undermine efforts to reduce cigarette smoking. Given the limited available evidence on the risks and benefits of e-cigarette use, large, randomized, controlled trials are urgently needed to definitively establish their potential for smoking cessation.

Quit Intentions Moderate Subjective and Physiological Responses to Acute Nicotine Replacement Therapy Administration in Dependent Smokers.

PubMed

Schlagintweit, Hera E; Campbell, Niamh K; Barrett, Sean P

2017-08-01

This study assessed the impact of expectancy and administration components of acute nicotine inhaler use on craving, heart rate, and smoking behavior in smokers with varying intentions to quit. 47 dependent smokers that differed in self-reported intention to quit (no intention to quit during the next month N = 26 vs. intention to initiate a quit attempt within 2 weeks N = 21) were randomly administered a 4 mg nicotine or nicotine-free inhaler across two sessions. Instructions regarding the inhaler's nicotine content (expect nicotine vs. expect nicotine-free; nicotine expectancy) and flavor (mint vs. citrus) varied across sessions. Craving and heart rate were assessed before and after inhaler administration (two-second inhalations every 10 seconds over 20 minutes). Next, participants were offered an opportunity to self-administer puffs of their preferred tobacco brand during an hour-long progressive ratio task. Across participants, nicotine expectancy independently reduced withdrawal related craving (p = .018), but no comparable effects of nicotine administration were evident. In quitting motivated smokers, nicotine expectancy and administration interacted to reduce intention to smoke (p = .040), while nicotine expectancy (p = .047) and administration (p = .025) independently reduced intention to smoke in quitting unmotivated smokers. Blunted heart rate reactivity to nicotine administration was observed in quitting motivated relative to unmotivated smokers (p = .042); however, neither expectancy nor administration impacted smoking behavior in either group (p values > .25). Findings indicate that participant quitting intentions moderate acute nicotine replacement therapy responses. In quitting motivated smokers, a combination of pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving. Findings from this study demonstrate that motivations to quit smoking moderate subjective and physiological responses to acute nicotine administration and expectancy in dependent cigarette smokers. Quitting motivated smokers showed blunted heart rate reactivity to nicotine administration, suggesting that they may be less sensitive to the rewarding aspects of nicotine consumption. Nicotine administration and expectancy were found to interact to reduce craving in quitting motivated but not in unmotivated smokers, suggesting that pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving in smokers who plan to quit. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transdermal nicotine for induction of remission in ulcerative colitis.

PubMed

McGrath, J; McDonald, J W D; Macdonald, J K

2004-10-18

Ulcerative colitis is largely a disease of nonsmokers. Intermittent smokers often experience improvement in their symptoms while smoking. Nonsmokers with ulcerative colitis who begin smoking may go into remission. Randomized controlled trials were developed to test the efficacy of transdermal nicotine for the induction of remission in ulcerative colitis. (1) To determine the efficacy of transdermal nicotine for induction of remission in ulcerative colitis. (2) To assess adverse events associated with transdermal nicotine therapy for ulcerative colitis The MEDLINE (via PubMed) and EMBASE databases were searched using the search criteria "ulcerative colitis" and "transdermal nicotine" or "nicotine" to identify relevant papers published between 1970 and December 2003. Manual searches of reference lists from potentially relevant papers were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched. We included only randomized controlled trials in which patients with active mild to moderate ulcerative colitis were randomly allocated to receive transdermal nicotine (15 to 25 mg/day) or a placebo or another treatment (corticosteroids or mesalamine). Data extraction and assessment of the methodological quality of each trial were independently performed by each author. Any disagreement among reviewers was resolved by consensus. The primary outcome measure was the number of patients achieving clinical or sigmoidoscopic remission as defined by the primary studies (e.g. no symptoms of ulcerative colitis), and expressed as a percentage of the patients randomized (intention to treat analysis). Secondary outcomes included clinical response, adverse events and withdrawal because of adverse events. Seven studies were identified, five of which met the inclusion criteria. A meta-analysis of two trials in which 71 patients were randomized to nicotine and 70 to placebo showed a statistically significant benefit for nicotine treatment. After four to six weeks of treatment 19 of 71 patients treated with transdermal nicotine were in clinical remission compared to 9 of 70 treated with placebo (OR=2.56, 95% CI 1.02-6.45). In the same group of patients improvement or remission was noted in 29 of the 71 patients assigned to nicotine compared to 14 of 70 patients assigned to placebo (OR=2.72, 95% CI 1.28 - 5.81). For patients with left sided colitis the odds ratio was 2.31 (95% CI 1.05-5.10). When transdermal nicotine was compared to standard medical therapy no significant benefit for nicotine was observed. After four to six weeks of standard therapy (oral prednisone or mesalamine), 34 of 63 patients were in clinical or sigmoidoscopic remission compared to 33 of 66 patients treated with transdermal nicotine (OR=0.77, 95% CI 0.37-1.60). A meta-analysis of all five studies which included 137 patients treated with transdermal nicotine and 133 patients treated with a placebo or standard therapy demonstrated no statistically significant benefit of nicotine therapy (OR=1.23; 95% CI 0.71-2.14). Patients treated with transdermal nicotine were significantly more likely to withdrawal due to adverse events than patients treated with placebo or standard medical therapy (OR=5.82, 95% CI, 1.66 - 20.47) and were significantly more likely to suffer from an adverse event than patients treated with placebo or standard medical therapy (OR=3.54, 95% CI, 2.07 - 6.08). The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.

Acute effects of nicotine on processing of complex stimuli in smokers and nonsmokers

NASA Astrophysics Data System (ADS)

Harkrider, Ashley; Hedrick, Mark

2004-05-01

Effects of nicotine in the auditory system of normal-hearing smokers and nonsmokers were investigated both behaviorally and physiologically. Discrimination of consonant-vowel speech in quiet and noise was assessed in the presence and absence of a transdermal nicotine patch by measuring categorical boundaries and mismatch negativity (MMN). Data indicate that the effects of nicotine on both behavioral and physiological measures increased with an increase in severity of nicotine-induced symptoms. Smokers showed improved CV discrimination in quiet and noise with nicotine. Additionally, smokers exhibited more measurable and significantly sharper boundaries as well as larger MMN areas than nonsmokers in quiet and noise for both placebo and nicotine sessions. MMN data acquired for both quiet and noise, and behavioral data acquired in quiet, indicate that smokers show the greatest improvements in discrimination during nicotine exposure, followed by symptomatic nonsmokers. Asymptomatic nonsmokers show little improvement with nicotine and, on occasion, show decrements in performance. These data may contribute to our understanding of the role of nAChRs in the auditory system, the neural mechanisms that underlie the recognition of sound in quiet and noise, and mechanisms mediating improved information processing and enhanced cognitive performance that serve as reinforcement for continued tobacco use by smokers.

Performance effects of nicotine during selective attention, divided attention, and simple stimulus detection: an fMRI study.

PubMed

Hahn, Britta; Ross, Thomas J; Wolkenberg, Frank A; Shakleya, Diaa M; Huestis, Marilyn A; Stein, Elliot A

2009-09-01

Attention-enhancing effects of nicotine appear to depend on the nature of the attentional function. Underlying neuroanatomical mechanisms, too, may vary depending on the function modulated. This functional magnetic resonance imaging study recorded blood oxygen level-dependent (BOLD) activity in minimally deprived smokers during tasks of simple stimulus detection, selective attention, or divided attention after single-blind application of a transdermal nicotine (21 mg) or placebo patch. Smokers' performance in the placebo condition was unimpaired as compared with matched nonsmokers. Nicotine reduced reaction time (RT) in the stimulus detection and selective attention but not divided attention condition. Across all task conditions, nicotine reduced activation in frontal, temporal, thalamic, and visual regions and enhanced deactivation in so-called "default" regions. Thalamic effects correlated with RT reduction selectively during stimulus detection. An interaction with task condition was observed in middle and superior frontal gyri, where nicotine reduced activation only during stimulus detection. A visuomotor control experiment provided evidence against nonspecific effects of nicotine. In conclusion, although prefrontal activity partly displayed differential modulation by nicotine, most BOLD effects were identical across tasks, despite differential performance effects, suggesting that common neuronal mechanisms can selectively benefit different attentional functions. Overall, the effects of nicotine may be explained by increased functional efficiency and downregulated task-independent "default" functions.

A Critical Evaluation of Nicotine Replacement Therapy for Teenage Smokers.

ERIC Educational Resources Information Center

Patten, Christi A.

2000-01-01

Evaluates the appropriateness and feasibility of nicotine replacement therapy (NRT) in teenage smokers. Available forms of NRT, theoretical rationale and efficacy of NRT, ethical considerations, and the feasibility of NRT in teenage smokers are addressed. Several characteristics similar to adult nicotine dependent smokers have been found in teen…

Acetylcholine-evoked currents in cultured neurones dissociated from rat parasympathetic cardiac ganglia.

PubMed Central

Fieber, L A; Adams, D J

1991-01-01

1. The properties of acetylcholine (ACh)-activated ion channels of parasympathetic neurones from neonatal rat cardiac ganglia grown in tissue culture were examined using patch clamp recording techniques. Membrane currents evoked by ACh were mimicked by nicotine, attenuated by neuronal bungarotoxin, and unaffected by atropine, suggesting that the ACh-induced currents are mediated by nicotinic receptor activation. 2. The current-voltage (I-V) relationship for whole-cell ACh-evoked currents exhibited strong inward rectification and a reversal (zero current) potential of -3 mV (NaCl outside, CsCl inside). The rectification was not alleviated by changing the main permeant cation or by removal of divalent cations from the intracellular or extracellular solutions. Unitary ACh-activated currents exhibited a linear I-V relationship with slope conductances of 32 pS in cell-attached membrane patches and 38 pS in excised membrane patches with symmetrical CsCl solutions. 3. Acetylcholine-induced currents were reversibly inhibited in a dose-dependent manner by the ganglionic antagonists, mecamylamine (Kd = 37 nM) and hexamethonium (IC50 approximately 1 microM), as well as by the neuromuscular relaxant, d-tubocurarine (Kd = 3 microM). Inhibition of ACh-evoked currents by hexamethonium could not be described by a simple blocking model for drug-receptor interaction. 4. The amplitude of the ionic current through the open channel was dependent on the extracellular Na+ concentration. The direction of the shift in reversal potential upon replacement of NaCl by mannitol indicates that the neuronal nicotinic receptor channel is cation selective and the magnitude suggests a high cation to anion permeability ratio. The cation permeability (PX/PNa) followed the ionic selectivity sequence Cs+ (1.06) greater than Na+ (1.0) greater than Ca2+ (0.93). Anion substitution experiments showed a relative anion permeability, PCl/PNa less than or equal to 0.05. 5. The nicotinic ACh-activated channels described mediate the responses of postganglionic parasympathetic neurones of the mammalian heart to vagal stimulation. PMID:1708819

Paths to tobacco abstinence: A repeated-measures latent class analysis.

PubMed

McCarthy, Danielle E; Ebssa, Lemma; Witkiewitz, Katie; Shiffman, Saul

2015-08-01

Knowledge of smoking change processes may be enhanced by identifying pathways to stable abstinence. We sought to identify latent classes of smokers based on their day-to-day smoking status in the first weeks of a cessation attempt. We examined treatment effects on class membership and compared classes on baseline individual differences and 6-month abstinence rates. In this secondary analysis of a double-blind randomized placebo-controlled clinical trial (N = 1,433) of 5 smoking cessation pharmacotherapies (nicotine patch, nicotine lozenge, bupropion SR, patch and lozenge, or bupropion SR and lozenge), we conducted repeated-measures latent class analysis of daily smoking status (any smoking vs. none) for the first 27 days of a quit attempt. Treatment and covariate relations with latent class membership were examined. Distal outcome analysis compared confirmed 6-month abstinence rates among the latent classes. A 5-class solution was selected. Three-quarters of smokers were in stable smoking or abstinent classes, but 25% were in classes with unstable abstinence probabilities over time. Active treatment (compared to placebo), and particularly the patch and lozenge combination, promoted early quitting. Latent classes differed in 6-month abstinence rates and on several baseline variables, including nicotine dependence, quitting history, self-efficacy, sleep disturbance, and minority status. Repeated-measures latent class analysis identified latent classes of smoking change patterns affected by treatment, related to known risk factors, and predictive of distal outcomes. Tracking behavior early in a change attempt may identify prognostic patterns of change and facilitate adaptive treatment planning. (c) 2015 APA, all rights reserved).

Smoking cessation in smokers who smoke menthol and non-menthol cigarettes.

PubMed

Smith, Stevens S; Fiore, Michael C; Baker, Timothy B

2014-12-01

To assess the relations of menthol cigarette use with measures of cessation success in a large comparative effectiveness trial (CET). Participants were randomized to one of six medication treatment conditions in a randomized double-blind, placebo-controlled clinical trial. All participants received six individual counseling sessions. Community-based smokers in two communities in Wisconsin, USA. A total of 1504 adult smokers who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. The analysis sample comprised 1439 participants: 814 white non-menthol smokers, 439 white menthol smokers and 186 African American (AA) menthol smokers. There were too few AA non-menthol smokers (n = 16) to be included in the analyses. Nicotine lozenge, nicotine patch, bupropion sustained release, nicotine patch + nicotine lozenge, bupropion + nicotine lozenge and placebo. Biochemically confirmed 7-day point-prevalence abstinence assessed at 4, 8 and 26 weeks post-quit. In longitudinal abstinence analyses (generalized estimating equations) controlling for cessation treatment, menthol smoking was associated with reduced likelihood of smoking cessation success relative to non-menthol smoking [model-based estimates of abstinence = 31 versus 38%, respectively; odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.59, 0.86]. In addition, among menthol smokers, AA women were at especially high risk of cessation failure relative to white women (estimated abstinence = 17 versus 35%, respectively; OR = 2.63, 95% CI = 1.75, 3.96; estimated abstinence rates for AA males and white males were both 30%, OR = 1.06, 95% CI = 0.60, 1.66). In the United States, smoking menthol cigarettes appears to be associated with reduced cessation success compared with non-menthol smoking, especially in African American females. © 2014 Society for the Study of Addiction.

Smoking Cessation in Smokers Who Smoke Menthol and Non-Menthol Cigarettes

PubMed Central

Smith, Stevens S.; Fiore, Michael C.; Baker, Timothy B.

2015-01-01

Aims To assess the relations of menthol cigarette use with measures of cessation success in a large comparative effectiveness trial (CET). Design Participants were randomized to one of six medication treatment conditions in a randomized double-blind, placebo controlled clinical trial. All participants received six individual counseling sessions. Setting Community-based smokers in two communities in Wisconsin, USA. Participants 1504 adult smokers who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. The analysis sample comprised 1439 participants: 814 White non-menthol smokers, 439 White menthol smokers, and 186 African American (AA) menthol smokers. There were too few AA non-menthol smokers (n=16) to be included in the analyses. Interventions Nicotine lozenge, nicotine patch, bupropion sustained release, nicotine patch + nicotine lozenge, bupropion + nicotine lozenge, and placebo. Measurements Biochemically-confirmed 7-day point-prevalence abstinence assessed at 4, 8, and 26 weeks post-quit. Findings In longitudinal abstinence analyses (generalized estimating equations) controlling for cessation treatment, menthol-smoking was associated with reduced likelihood of smoking cessation success relative to non-menthol smoking (model-based estimates of abstinence = 31% vs. 38%, respectively; odds ratio [OR] =0.71, 95% confidence interval [CI]=0.59, 0.86). In addition, amongst menthol smokers, AA women were at especially high risk of cessation failure relative to White women (estimated abstinence =17% vs. 35%, respectively; OR=2.63, 95% CI=1.75, 3.96); estimated abstinence rates for AA males and White males were both 30%, OR=1.06, 95% CI=0.60, 1.66). Conclusion In the USA, smoking menthol cigarettes appears to be associated with reduced cessation success compared with non-menthol smoking, especially in African-American females. PMID:24938369

Randomised trial of two nicotine patch protocols distributed through a state quitline.

PubMed

Burns, Emily K; Hood, Nancy E; Goforth, Emma; Levinson, Arnold H

2016-03-01

Most telephone quitlines provide free nicotine replacement therapy (NRT). An 8-week course is recommended, but few users complete it. Information is needed to help quitlines distribute NRT cost-effectively. Randomised two-group trial. Colorado QuitLine callers who smoked 16-20 cigarettes per day at enrolment and who were eligible for and agreed to receive free NRT. Provision of 4-week versus 8-week NRT supply; the 8-week supply was shipped in halves and required participants to request the second half (split-shipment protocol). Enrolment occurred during March 2010-February 2011, follow-up concluded in November 2011, and analysis was performed in 2012. Point abstinence (7 and 30 day) and prolonged abstinence (6 month) from tobacco use. Overall, 1495 study participants were enrolled and 57.7% completed follow-up. Abstinence rates did not differ significantly between study conditions: 13.8% versus 12.4% in 4-week versus 8-week arms, respectively, (30-day point abstinence, non-respondents treated as smokers). NRT duration was similar in both groups, due in part to purchase of additional patches in the 4-week group. About one-third of the 8-week group requested the full 8-week supply and had higher abstinence rates. Cost per quit was lower in the 4-week (compared to 8-week) group. A randomised trial did not find worse cessation outcomes among quitline users who received half the minimum recommended course of NRT, but offering the full recommended course using a split-shipment protocol may be reasonably cost-effective and supportive of NRT adherers. NCT01889771. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

What Do Mothers Think about Concurrent Breastfeeding and Smoking?

PubMed Central

Bogen, Debra L.; Davies, Erin D.; Barnhart, Wesley C.; Lucero, Cynthia A.; Moss, Deborah R.

2008-01-01

Background According to newer AAP policies, smoking is not contraindicated with breastfeeding, yet smokers initiate and maintain breastfeeding less than non-smokers. Objectives 1) Describe maternal knowledge and 2) attitudes regarding concurrent breastfeeding and smoking or nicotine replacement therapy (NRT) and 3) evaluate the association between maternal smoking and infant feeding practices. Methods Mothers bringing children <13 months old for an appointment completed a 24-item, anonymous survey which addressed knowledge, attitudes and practices about concurrent breastfeeding and smoking/NRT. Results Among 204 survey completers, 63% were African American, 52% had never breastfed and 54% had never smoked. Knowledge: Regardless of smoking status, 19% were aware of the recommendation to smoke after breastfeeding; most did not know that nicotine gum (42%) or patch (40%) transfers less or about the same amount of nicotine into breast milk than smoking a pack per day. Attitudes: Most mothers (80%) believe that women should not smoke any cigarettes if breastfeeding; current smokers (25%) were more likely than former (10%) or never smokers (11%) to find it acceptable to smoke one or more cigarettes per day (p=.03). Only 2% found it acceptable to use NRT while breastfeeding. Practice: Among ever breastfeeders, 10% stopped breastfeeding because of smoking. Over half of recent or current smokers reported that smoking impacted their infant feeding decision. Conclusions Mothers in this sample believe that women who smoke or take NRT should not breastfeed. Smoking status impacted women’s infant feeding practices. Correction of misinformation could increase breastfeeding rates. PMID:18501868

Neuronal effects of nicotine during auditory selective attention.

PubMed

Smucny, Jason; Olincy, Ann; Eichman, Lindsay S; Tregellas, Jason R

2015-06-01

Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.

Dependence on Tobacco and Nicotine Products: A Case for Product-Specific Assessment

PubMed Central

Eissenberg, Thomas

2012-01-01

The International Classification of Diseases and the Diagnostic and Statistical Manual for diagnosing tobacco/nicotine dependence emphasize the dependence-producing drug nicotine. These diagnostic tools have been challenged on grounds of poor predictive validity, and they do not differentiate across various forms of nicotine-containing products. In fact, nicotine-containing products (e.g., tobacco cigarettes, smokeless tobacco [ST], waterpipe, electronic cigarettes [ECIGs], and nicotine replacement [NR] products) have very different characteristics both in terms of sensory and behavioral involvement and also in pharmacokinetic and pharmacodynamic effects. For example, a cigarette and a nicotine patch are very different on almost every one of these dimensions. When ability to stop using a nicotine/tobacco product is used as a criterion for dependence, success rates vary considerably across products: Tobacco cigarette cessation is more difficult than ST cessation that in turn is more difficult than NR product cessation. Based on these results, we hypothesize that there is a continuum of dependence as much as there is a continuum of harm, with tobacco cigarettes and NR products on opposite ends of both continua and other products (waterpipe and ECIGs) somewhere in between. In order to capture more precisely the dependence produced by both nicotine and its administration forms, product-specific instruments may be required. The pros and cons of this approach are discussed. PMID:22459798

Medication Guide

MedlinePlus

... before starting any new medication. First-Line Medications: Nicotine Replacement Therapy (NRT) These medications are called "first- ... they might try a "second-line" medication instead. Nicotine replacement therapy (NRT) helps smokers quit by reducing ...

Extended treatment for cigarette smoking cessation: a randomized control trial.

PubMed

Laude, Jennifer R; Bailey, Steffani R; Crew, Erin; Varady, Ann; Lembke, Anna; McFall, Danielle; Jeon, Anna; Killen, Diana; Killen, Joel D; David, Sean P

2017-08-01

To test the potential benefit of extending cognitive-behavioral therapy (CBT) relative to not extending CBT on long-term abstinence from smoking. Two-group parallel randomized controlled trial. Patients were randomized to receive non-extended CBT (n = 111) or extended CBT (n = 112) following a 26-week open-label treatment. Community clinic in the United States. A total of 219 smokers (mean age: 43 years; mean cigarettes/day: 18). All participants received 10 weeks of combined CBT + bupropion sustained release (bupropion SR) + nicotine patch and were continued on CBT and either no medications if abstinent, continued bupropion + nicotine replacement therapy (NRT) if increased craving or depression scores, or varenicline if still smoking at 10 weeks. Half the participants were randomized at 26 weeks to extended CBT (E-CBT) to week 48 and half to non-extended CBT (no additional CBT sessions). The primary outcome was expired CO-confirmed, 7-day point-prevalence (PP) at 52- and 104-week follow-up. Analyses were based on intention-to-treat. PP abstinence rates at the 52-week follow-up were comparable across non-extended CBT (40%) and E-CBT (39%) groups [odds ratio (OR) = 0.99; 95% confidence interval (CI) = 0.55, 1.78]. A similar pattern was observed across non-extended CBT (39%) and E-CBT (33%) groups at the 104-week follow-up (OR = 0.79; 95% CI= 0.44, 1.40). Prolonging cognitive-behavioral therapy from 26 to 48 weeks does not appear to improve long-term abstinence from smoking. © 2017 Society for the Study of Addiction.

Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current.

PubMed

Wang, H; Shi, H; Zhang, L; Pourrier, M; Yang, B; Nattel, S; Wang, Z

2000-09-05

Nicotine is a main constituent of cigarette smoke and smokeless tobacco, known to increase the risk of sudden cardiac death. This study aimed at establishing ionic mechanisms underlying potential electrophysiological effects of nicotine. Effects of nicotine on Kv4.3 and Kv4.2 channels expressed in Xenopus oocytes were studied at the whole-cell and single-channel levels. The effects of nicotine on the transient outward K(+) current (I:(to)) were studied by use of whole-cell patch-clamp techniques in canine ventricular myocytes. Nicotine potently inhibited Kv4 current. The concentration for half-maximal inhibition (IC(50)) was 40+/-4 nmol/L, and the current was abolished by 100 micromol/L nicotine. The IC(50) for block of native I:(to) was 270+/-43 nmol/L. The steady-state activation properties of Kv4.3 and I:(to) were unaltered by nicotine, whereas positive shifts of the inactivation curves were observed. Of the total inhibition of Kv4.3 and I:(to) by nicotine, 40% was due to tonic block and 60% was attributable to use-dependent block. Activation, inactivation, and reactivation kinetics were not significantly changed by nicotine. Nicotine reduced single-channel conductance, open probability, and open time but increased the closed time of Kv4.3. The effects of nicotine were not altered by antagonists to various neurotransmitter receptors, indicating direct effects on I:(to) channels. Nicotine is a potent inhibitor of cardiac A-type K(+) channels, with blockade probably due to block of closed and open channels. This action may contribute to the ability of nicotine to affect cardiac electrophysiology and induce arrhythmias.

Predictors of Adherence to Nicotine Replacement Therapy (Nicotine Patch) Among Homeless Persons Enrolled in a Randomized Controlled Trial Targeting Smoking Cessation.

PubMed

Ojo-Fati, O; Thomas, J L; Vogel, R I; Ogedegbe, O; Jean-Louis, G; Okuyemi, K S

2016-01-01

Adherence to smoking cessation treatment is generally low, especially among socio-economically disadvantaged groups including individuals experiencing homelessness and those with mental illnesses. Despite the high smoking rates in homeless populations (~70%) no study to date has systematically examined predictors of adherence to nicotine replacement therapy (NRT) in this population. The aim of this secondary analysis was to identify predictors of adherence to NRT in a smoking cessation trial conducted among homeless smokers. Secondary analysis of data from a randomized controlled trial enrolling 430 persons who were homeless and current cigarette smokers. Participants were assigned to one of the two study conditions to enhance smoking cessation: Motivational Interviewing (MI; 6 sessions of MI + 8 weeks of NRT) or Standard Care (Brief advice to quit+ 8 weeks of NRT). The primary outcome for the current analysis was adherence to NRT at end of treatment (8 weeks following randomization). Adherence was defined as a total score of zero on a modified Morisky adherence scale). Demographic and baseline psychosocial, tobacco-related, and substance abuse measures were compared between those who did and did not adhere to NRT. After adjusting for confounders, smokers who were depressed at baseline (OR=0.58, 95% CI, 0.38-0.87, p=0.01), had lower confidence to quit (OR=1.10, 95% CI, 1.01-1.19, p=0.04), were less motivated to adhere (OR=1.04, 95% CI, 1.00-1.07, p=0.04), and were less likely to be adherent to NRT. Further, age of initial smoking was positively associated with adherence status (OR= 0.83, 95% CI, 0.69-0.99, p=0.04). These results suggest that smoking cessation programs conducted in this population may target increased adherence to NRT by addressing both depression and motivation to quit. clinicaltrials.gov: NCT00786149.

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

PubMed Central

Christensen, Mark H.; Ishibashi, Masaru; Nielsen, Michael L.; Leonard, Christopher S.; Kohlmeier, Kristi A.

2015-01-01

The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on several parameters affecting LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine was found to induce larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age. PMID:24863041

Double dissociation of working memory and attentional processes in smokers and non-smokers with and without nicotine.

PubMed

Grundey, Jessica; Amu, Rosa; Ambrus, Géza Gergely; Batsikadze, Georgi; Paulus, Walter; Nitsche, Michael A

2015-07-01

Nicotine has been shown to affect cortical excitability measured using transcranial magnetic stimulation in smoking and non-smoking subjects in different ways. In tobacco-deprived smokers, administration of nicotine restores compromised cortical facilitation while in non-smokers, it enhances cortical inhibition. As cortical excitability and activity are closely linked to cognitive processes, we aimed to explore whether nicotine-induced physiological alterations in non-smokers and smokers are associated with cognitive changes. Specifically, we assessed the impact of nicotine on working memory performance (n-back letter task) and on attentional processes (Stroop interference test) in healthy smokers and non-smokers. Both tasks have been shown to rely on prefrontal areas, and nicotinic receptors are relevantly involved in prefrontal function. Sixteen smoking and 16 non-smoking subjects participated in the 3-back letter task and 21 smoking and 21 non-smoking subjects in the Stroop test after the respective application of placebo or nicotine patches. The results show that working memory and attentional processes are compromised in nicotine-deprived smokers compared to non-smoking individuals. After administration of nicotine, working memory performance in smokers improved, while non-smoking subjects displayed decreased accuracy with increased number of errors. The effects have been shown to be more apparent for working memory performance than attentional processes. In summary, cognitive functions can be restored by nicotine in deprived smokers, whereas non-smokers do not gain additional benefit. The respective changes are in accordance with related effects of nicotine on cortical excitability in both groups.

Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine.

PubMed

Ren, Zuo Jun; Mummalaneni, Shobha; Qian, Jie; Baumgarten, Clive M; DeSimone, John A; Lyall, Vijay

2015-01-01

Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol.

Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine

PubMed Central

Ren, Zuo Jun; Mummalaneni, Shobha; Qian, Jie; Baumgarten, Clive M.; DeSimone, John A.; Lyall, Vijay

2015-01-01

Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol. PMID:26039516

Nicotine Induces Resistance to Chemotherapy by Modulating Mitochondrial Signaling in Lung Cancer

PubMed Central

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D.; Upadhyay, Daya

2009-01-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 μM) followed by cisplatin (35 μM) plus etoposide (20 μM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4′diisothiocyanatostilbene-2,2′disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-ρ0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer. PMID:18676776

Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.

PubMed

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D; Upadhyay, Daya

2009-02-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer.

Novel delivery systems for nicotine replacement therapy as an aid to smoking cessation and for harm reduction: rationale, and evidence for advantages over existing systems.

PubMed

Shahab, Lion; Brose, Leonie S; West, Robert

2013-12-01

Nicotine replacement therapy (NRT) has been used in the treatment of tobacco dependence for over three decades. Whilst the choice of NRT was limited early on, in the last ten years there has been substantial increase in the number of nicotine delivery devices that have become available. This article briefly summarises existing forms of NRT, evidence of their efficacy and use, and reviews the rationale for the development of novel products delivering nicotine via buccal, transdermal or pulmonary routes (including nicotine mouth spray, nicotine films, advanced nicotine inhalers and electronic cigarettes). It presents available evidence on the efficacy, tolerability and abuse potential of these products, with a focus on their advantages as well as disadvantages compared with established forms of NRT for use as an aid to both smoking cessation as well as harm reduction.

Step Care Treatment for Smoking Cessation

ERIC Educational Resources Information Center

Ebbert, Jon O.; Little, Melissa A.; Klesges, Robert C.; Bursac, Zoran; Johnson, Karen C.; Thomas, Fridtjof; Vander Weg, Mark W.

2017-01-01

We compared the effectiveness of a "stepped care" approach with increasing treatment intensity ("Step Care") to one with repeated treatments ("Recycle") among cigarette smokers interested in quitting smoking. Step 1 of the Step Care intervention consisted of a single counseling session, nicotine patch for six weeks…

Effect of nicotine patches in pregnancy on infant and maternal outcomes at 2 years: follow-up from the randomised, double-blind, placebo-controlled SNAP trial.

PubMed

Cooper, Sue; Taggar, Jaspal; Lewis, Sarah; Marlow, Neil; Dickinson, Anne; Whitemore, Rachel; Coleman, Tim

2014-09-01

The SNAP (Smoking and Nicotine in Pregnancy) trial compared nicotine replacement therapy (NRT) patches with placebo in pregnant smokers; although NRT doubled cessation rates in the first 4 weeks, by delivery no differences in maternal smoking or birth outcomes were noted. As a result, NRT used in standard doses during pregnancy is considered ineffective for smoking cessation. Subsequent effects of NRT on the children of treated mothers are unknown because no trials have investigated the effect of gestational NRT use beyond birth. To assess whether NRT use in pregnancy might cause harm to infants, we aimed to compare effects of NRT and placebo on infant development 2 years after delivery. 1050 pregnant smokers aged 16-45 years, at 12-24 weeks' gestation, and smoking at least five cigarettes per day were recruited from seven hospitals in England between May 1, 2007, and Feb 26, 2010, and followed up until their infants were 2 years old. Participants were randomly assigned (1:1) to receive up to 8-weeks treatment with NRT (15 mg/16 h transdermal patches) or identically packaged and visually matched placebo patches (all patches manufactured by and purchased at market rate from United Pharmaceuticals, Amman, Jordan), issued as two 4-week supplies (521 for NRT group, 529 for placebo group) [Corrected]. Randomisation was stratified by site with participants, health-care professionals, and research staff masked to treatment allocation. The primary results for participants and infants at delivery were published in 2012; we present results from the trial cohort 2 years after birth. After delivery, questionnaires were posted to participants and, if there was no response, to family physicians. The primary outcome at 2 years was infants' survival without developmental impairment (ie, no disability or problems with behaviour or development). Treatment groups were compared on an intention-to-treat basis. The trial is registered with Controlled-Trials.com, number ISRCTN07249128. Questionnaires were returned at 2 years for 891 (88%) of 1010 live singleton births (445 of (88%) 503 given NRT and 446 (88%) of 507 given placebo). Because of missing data, developmental outcomes, including four infant deaths, were documented for 888 of (88%) 1010 singleton infants; 445 (88%) of 503 infants in NRT group and 443 (87%) of 507 infants in placebo. In the NRT group, 323 (73%) of 445 infants had no impairment compared with 290 (65%) of 443 infants in the placebo group (odds ratio [OR] 1.40, 95% CI 1.05-1.86, p=0.023). At 2 years, 15 (3%) of 521 mothers in the NRT group and nine (2%) of 529 mothers in the placebo groups self-reported prolonged smoking abstinence since a quit date set in pregnancy (OR 1.71, 95% CI 0.74-3.94, p=0.20). Adverse events were not collected after delivery, but previously reported adverse pregnancy and birth outcomes were similar in the two groups. Infants born to women who used NRT for smoking cessation in pregnancy were more likely to have unimpaired development. NRT had no effect on prolonged abstinence from smoking but did cause a temporary doubling of smoking cessation shortly after randomisation during pregnancy, which could explain findings. If findings are confirmed by subsequent research, this has potential implications for the management of smoking in pregnancy. National Institute for Health Research Health Technology Assessment Programme. Copyright © 2014 Cooper et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

Withdrawal-oriented therapy for smokers.

PubMed

Hajek, P

1989-06-01

The treatment approach of the Maudsley Hospital Smokers Clinic is described. It stems from the notion that smokers seeking help are dependent on nicotine, and that withdrawal discomfort is a major block to their success in quitting. Accordingly, therapy focuses on helping clients overcome nicotine deprivation. It uses nicotine replacement and a special format of group treatment. Details are given of preparation of clients, use of nicotine chewing gum, use of group-oriented groupwork, use of information about withdrawal, and training in withdrawal-oriented therapy. Data are presented concerning characteristics of the clientele, treatment adherence, and treatment results. A number of controversial issues are addressed, such as the optimal duration of treatment, timing of the quit date, the value of educational input, and the value of individualization of treatment goals.

Activation of muscle nicotinic acetylcholine receptor channels by nicotinic and muscarinic agonists

PubMed Central

Akk, Gustav; Auerbach, Anthony

1999-01-01

The dose-response parameters of recombinant mouse adult neuromuscular acetylcholine receptor channels (nAChR) activated by carbamylcholine, nicotine, muscarine and oxotremorine were measured. Rate constants for agonist association and dissociation, and channel opening and closing, were estimated from single-channel kinetic analysis.The dissociation equilibrium constants were (mM): ACh (0.16)carbamylcholine (5.1)>oxotremorine M (0.6)>nicotine (0.5)>muscarine (0.15).Rat neuronal α4β2 nAChR can be activated by all of the agonists. However, detailed kinetic analysis was impossible because the recordings lacked clusters representing the activity of a single receptor complex. Thus, the number of channels in the patch was unknown and the activation rate constants could not be determined.Considering both receptor affinity and agonist efficacy, muscarine and oxotremorine are significant agonists of muscle-type nAChR. The results are discussed in terms of structure-function relationships at the nAChR transmitter binding site. PMID:10602325

Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior.

PubMed

Eppolito, Amy K; Bachus, Susan E; McDonald, Craig G; Meador-Woodruff, James H; Smith, Robert F

2010-01-01

Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96mg/kg/day or 2.0mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the alpha4, alpha7, and beta2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.

Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

PubMed

Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

2017-05-01

Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach) , a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

Nicotine during pregnancy: changes induced in neurotransmission, which could heighten proclivity to addict and induce maladaptive control of attention.

PubMed

Kohlmeier, K A

2015-06-01

Prenatal exposure to nicotine, occurring either via maternal smoking or via use of transdermal nicotine patches to facilitate cigarette abstinence by pregnant women, is associated with ∼ 13% of pregnancies worldwide. Nicotine exposure during gestation has been correlated with several negative physiological and psychosocial outcomes, including heightened risk for aberrant behaviors involving alterations in processing of attention as well as an enhanced liability for development of drug dependency. Nicotine is a terotogen, altering neuronal development of various neurotransmitter systems, and it is likely these alterations participate in postnatal deficits in attention control and facilitate development of drug addiction. This review discusses the alterations in neuronal development within the brain's major neurotransmitter systems, with special emphasis placed on alterations within the laterodorsal tegmental nucleus, in light of the role this cholinergic nucleus plays in attention and addiction. Changes induced within this nucleus by gestational exposure to nicotine, in combination with changes induced in other brain regions, are likely to contribute to the transgenerational burden imposed by nicotine. Although neuroplastic changes induced by nicotine are not likely to act in isolation, and are expected to interact with epigenetic changes induced by preconception exposure to drugs of abuse, unraveling these changes within the developing brain will facilitate eventual development of targeted treatments for the unique vulnerability for arousal disorders and development of addiction within the population of individuals who have been prenatally exposed to nicotine.

Smoking characteristics and comorbidities in the power to quit randomized clinical trial for homeless smokers.

PubMed

Okuyemi, Kolawole S; Goldade, Kate; Whembolua, Guy-Lucien; Thomas, Janet L; Eischen, Sara; Guo, Hongfei; Connett, John E; Grant, Jon; Ahluwalia, Jasjit S; Resnicow, Ken; Owen, Greg; Gelberg, Lillian; Jarlais, Don Des

2013-01-01

Smoking prevalence in homeless populations is strikingly high (∼70%); yet, little is known about effective smoking cessation interventions for this population. We conducted a community-based clinical trial, Power To Quit (PTQ), to assess the effects of motivational interviewing (MI) and nicotine patch (nicotine replacement therapy [NRT]) on smoking cessation among homeless smokers. This paper describes the smoking characteristics and comorbidities of smokers in the study. Four hundred and thirty homeless adult smokers were randomized to either the intervention arm (NRT + MI) or the control arm (NRT + Brief Advice). Baseline assessment included demographic information, shelter status, smoking history, motivation to quit smoking, alcohol/other substance abuse, and psychiatric comorbidities. Of the 849 individuals who completed the eligibility survey, 578 (68.1%) were eligible and 430 (74.4% of eligibles) were enrolled. Participants were predominantly Black, male, and had mean age of 44.4 years (S D = 9.9), and the majority were unemployed (90.5%). Most participants reported sleeping in emergency shelters; nearly half had been homeless for more than a year. Nearly all the participants were daily smokers who smoked an average of 20 cigarettes/day. Nearly 40% had patient health questionnaire-9 depression scores in the moderate or worse range, and more than 80% screened positive for lifetime history of drug abuse or dependence. This study demonstrates the feasibility of enrolling a diverse sample of homeless smokers into a smoking cessation clinical trial. The uniqueness of the study sample enables investigators to examine the influence of nicotine dependence as well as psychiatric and substance abuse comorbidities on smoking cessation outcomes.

What do mothers think about concurrent breast-feeding and smoking?

PubMed

Bogen, Debra L; Davies, Erin D; Barnhart, Wesley C; Lucero, Cynthia A; Moss, Deborah R

2008-01-01

According to newer policies of the American Academy of Pediatrics, smoking is not contraindicated with breast-feeding, yet smokers initiate and maintain breast-feeding less often than nonsmokers. We sought to describe maternal knowledge and attitudes regarding concurrent breast-feeding and smoking or nicotine replacement therapy (NRT) and to evaluate the association between maternal smoking and infant feeding practices. Mothers bringing children <13 months old for an appointment completed a 24-item anonymous survey that addressed knowledge, attitudes, and practices about concurrent breast-feeding and smoking/NRT. Among 204 survey completers, 63% were African American, 52% had never breast-fed, and 54% had never smoked. Regardless of smoking status, 19% were aware of the recommendation to smoke after breast-feeding; most did not know that nicotine gum (42%) or patch (40%) transfers less or about the same amount of nicotine into breast milk than smoking a pack per day. Most mothers (80%) believed that women should not smoke any cigarettes if breast-feeding; current smokers (25%) were more likely than former (10%) or never smokers (11%) to find it acceptable to smoke one or more cigarettes per day (P = .03). Only 2% found it acceptable to use NRT while breast-feeding. Among ever breast-feeders, 10% stopped breast-feeding because of smoking. Over half of recent or current smokers reported that smoking affected their infant feeding decision. Mothers in this sample believe that women who smoke or take NRT should not breast-feed. Smoking status affected women's infant feeding practices. Correction of misinformation could increase breast-feeding rates.

Evaluating Nicotine Replacement Therapy and Stage-Based Therapies in a Population-Based Effectiveness Trial

ERIC Educational Resources Information Center

Velicer, Wayne F.; Friedman, Robert H.; Fava, Joseph L.; Gulliver, Suzy B.; Keller, Stefan; Sun, Xiaowu; Ramelson, Harley; Prochaska, James O.

2006-01-01

Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England…

Effects of nicotine exposure during prenatal or perinatal period on cell numbers in adult rat hippocampus and cerebellum: a stereology study.

PubMed

Chen, Wei-Jung A; King, Karen A; Lee, Ruby E; Sedtal, Christopher S; Smith, Andrew M

2006-11-02

Smoking during pregnancy poses a potential risk to unborn children. The present study examined the long-term effects of early nicotine exposure on the number of pyramidal and granule cells in the hippocampus, and Purkinje cells in the cerebellar vermis. The loss of neurons is the most severe form of brain injury with significant functional implications. In this study, rats were exposed to nicotine during either the prenatal (PRE) period or both the prenatal and early postnatal (PERI) period. It was hypothesized that nicotine treatment would result in long-term decreases in neuronal numbers, and that PERI treatment would be more detrimental to these cell populations than the PRE treatment. The results showed that neither PRE nor PERI nicotine exposure reduces the numbers of pyramidal, granule or Purkinje cells. Neither the regions where these cells reside, nor the cell densities were affected by nicotine. Although no significant cell loss was observed, the current nicotine exposure regimens may lead to alterations in cellular functions or cytoarchitectures. The present results in conjunction with previous reports showing significant cell loss from nicotine exposure during the brain growth spurt suggest that "patch-like" nicotine exposure during prenatal period may alter the sensitivity or the responsiveness of the developing brain to the injurious effects of nicotine during the most vulnerable stage of brain development - the brain growth spurt. Furthermore, the current stereology cell counting results are not in agreement with some reports in the literature, and this discrepancy may simply be a function of different cell counting techniques used.

Nicotine Withdrawal; Measure Your Symptoms (Quiz)

MedlinePlus

... Free Resources Medications Can Help You Quit Using Nicotine Replacement Therapy Busting NRT Myths Smokefree Phone Apps ... Withdrawal Understanding Withdrawal Quiz: How Strong is Your Nicotine Addiction? Quiz: What Are Your Withdrawal Symptoms? Dealing ...

[Health consequences of smoking electronic cigarettes are poorly described].

PubMed

Tøttenborg, Sandra Søgaard; Holm, Astrid Ledgaard; Wibholm, Niels Christoffer; Lange, Peter

2014-09-01

Despite increasing popularity, health consequences of vaping (smoking electronic cigarettes, e-cigarettes) are poorly described. Few studies suggest that vaping has less deleterious effects on lung function than smoking conventional cigarettes. One large study found that e-cigarettes were as efficient as nicotine patches in smoking cessation. The long-term consequences of vaping are however unknown and while some experts are open towards e-cigarettes as a safer way of satisfying nicotine addiction, others worry that vaping in addition to presenting a health hazard may lead to an increased number of smokers of conventional cigarettes.

77 FR 70955 - FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products; Report to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-28

.... FDA-2012-N-1148] FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products... comments. SUMMARY: The Food and Drug Administration (FDA) is announcing a 1-day public hearing to obtain...

Use of nicotine replacement therapy and stop-smoking medicines in a national sample of Aboriginal and Torres Strait Islander smokers and ex-smokers.

PubMed

Thomas, David P; Briggs, Viki L; Couzos, Sophia; Panaretto, Kathryn S; van der Sterren, Anke E; Stevens, Matthew; Borland, Ron

2015-06-01

To examine the use of nicotine replacement therapy (NRT) and the stop-smoking medicines (SSMs) varenicline and bupropion in a national sample of Aboriginal and Torres Strait Islander smokers and recent ex-smokers. The Talking About The Smokes (TATS) project used a quota sampling design to recruit a nationally representative sample of 1721 smokers and ex-smokers who had quit ≤ 12 months before from communities served by 34 Aboriginal community-controlled health services and one community in the Torres Strait. Baseline surveys were conducted from April 2012 to October 2013. These were compared with 1017 daily smokers from the general Australian population surveyed by the International Tobacco Control Policy Evaluation Project (ITC Project) from July 2010 to May 2011. Past and intended use of NRT and SSMs, duration of use, and whether participants thought NRT and SSMs help smokers to quit. Compared with other daily Australian smokers, lower proportions of Aboriginal and Torres Strait Islander daily smokers had ever used any NRT or SSMs (TATS, 37% v ITC, 58.5%) or used them in the past year (TATS, 23% v ITC, 42.1%). Nicotine patches were most commonly used by Aboriginal and Torres Strait Islander smokers and recent ex-smokers (24%), followed by varenicline (11%) and nicotine gum (10%); most (74%) had got their last NRT at no cost. Among dependent Aboriginal and Torres Strait Islander daily smokers, those who were more socioeconomically advantaged were more likely than the disadvantaged to have used NRT or SSMs. Similar proportions of Aboriginal and Torres Strait Islander daily smokers and other Australian daily smokers said that NRT or SSMs help smokers to quit (TATS, 70% v ITC, 74.2%). Dependent Aboriginal and Torres Strait Islander smokers who had previously used NRT or SSMs were more likely to believe they help in quitting and to intend to use them in the future. Aboriginal and Torres Strait Islander daily smokers, particularly those who are most disadvantaged, are less likely to have used NRT or SSMs than other Australian daily smokers. Some of the barriers to use, including cost, are being overcome, but further improvements are possible.

Treatment Adherence in a Lay Health Adviser Intervention to Treat Tobacco Dependence

ERIC Educational Resources Information Center

Hood, N. E.; Ferketich, A. K.; Paskett, E. D.; Wewers, M. E.

2013-01-01

Lay health advisers (LHAs) are increasingly used to deliver tobacco dependence treatment, especially with low-socioeconomic status (SES) populations. More information is needed about treatment adherence to help interpret mixed evidence of LHA intervention effectiveness. This study examined adherence to behavioral counseling and nicotine patches in…

Enabling access to new WHO essential medicines: the case for nicotine replacement therapies

PubMed Central

2010-01-01

Nicotine replacement therapies (NRT) are powerful tools for the successful treatment of nicotine addiction and tobacco use. The medicines are clinically effective, supported by the Framework Convention on Tobacco Control, and are now World Health Organization-approved essential medicines. Enabling global access to NRT remains a challenge given ongoing confusion and misperceptions about their efficacy, cost-effectiveness, and availability with respect to other tobacco control and public health opportunities. In this commentary, we review existing evidence and guidelines to make the case for global access to NRT highlighting the smoker's right to access treatment to sensibly address nicotine addiction. PMID:21092092

New mechanisms and perspectives in nicotine withdrawal

PubMed Central

Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

2014-01-01

Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

Knowledge and Perceptions about Nicotine, Nicotine Replacement Therapies and Electronic Cigarettes among Healthcare Professionals in Greece.

PubMed

Moysidou, Anastasia; Farsalinos, Konstantinos E; Voudris, Vassilis; Merakou, Kyriakoula; Kourea, Kallirrhoe; Barbouni, Anastasia

2016-05-20

Introduction. The purpose of this study was to evaluate the knowledge and perceptions of Greek healthcare professionals about nicotine, nicotine replacement therapies and electronic cigarettes. Methods. An online survey was performed, in which physicians and nurses working in private and public healthcare sectors in Athens-Greece were asked to participate through email invitations. A knowledge score was calculated by scoring the correct answers to specific questions with 1 point. Results. A total of 262 healthcare professionals were included to the analysis. Most had daily contact with smokers in their working environment. About half of them considered that nicotine has an extremely or very important contribution to smoking-related disease. More than 30% considered nicotine replacement therapies equally or more addictive than smoking, 76.7% overestimated their smoking cessation efficacy and only 21.0% would recommend them as long-term smoking substitutes. For electronic cigarettes, 45.0% considered them equally or more addictive than smoking and 24.4% equally or more harmful than tobacco cigarettes. Additionally, 35.5% thought they involve combustion while the majority responded that nicotine in electronic cigarettes is synthetically produced. Only 14.5% knew about the pending European regulation, but 33.2% have recommended them to smokers in the past. Still, more than 40% would not recommend electronic cigarettes to smokers unwilling or unable to quit smoking with currently approved medications. Cardiologists and respiratory physicians, who are responsible for smoking cessation therapy in Greece, were even more reluctant to recommend electronic cigarettes to this subpopulation of smokers compared to all other participants. The knowledge score of the whole study sample was 7.7 (SD: 2.4) out of a maximum score of 16. Higher score was associated with specific physician specialties. Conclusions. Greek healthcare professionals appear to overestimate the adverse effects of nicotine, and many would not recommend any nicotine-containing product as a long-term smoking substitute. Additionally, they have poor knowledge about the function and characteristics of electronic cigarettes.

Chewing Tobacco: Not a Safe Alternative to Cigarettes

MedlinePlus

... chewed, sucked on or sniffed, rather than smoked. Nicotine is absorbed through the soft tissues of the mouth ... replacement therapy with nicotine gum or lozenges, a nicotine replacement that is also absorbed through the lining of the mouth, ...

The effect of switching pharmacological intervention during extinction on nicotine-evoked conditioned responding in rats.

PubMed

Pittenger, Steven T; Zeplin, Lindsey C; Dwoskin, Linda P; Bevins, Rick A

2015-12-01

Pharmacotherapies are often utilized to aid in smoking cessation, and switching medication when treating nicotine dependence has become more commonplace. Although common, little is known about the impact of the initial therapy on the effects of the subsequent therapy. To begin to fill this gap in our understanding, this project determined how switching compounds that share stimulus elements with nicotine during extinction altered extinction responding and generalization of this extinction back to nicotine. Rats were trained in a discriminated goal-tracking task where nicotine administration was followed by intermittent sucrose access; sucrose was withheld following saline administration. In experiment 1, nornicotine supplanted nicotine in extinction sessions 1-3 and then a switch to varenicline on extinction sessions 4-6 was examined. In experiment 2, the reverse was investigated; varenicline to start extinction and then a switch to nornicotine. Generalization of extinction back to the nicotine stimulus was then assessed by generating a cumulative dose-effect curve. Generalization of extinction back to the training nicotine stimulus was greater if nornicotine had been received at any point in extinction compared to only receiving varenicline. Whereas, extinction with varenicline alone showed more generalization to lower doses of nicotine. A switch in cessation pharmacotherapy during extinction did not impede or enhance generalization back to the nicotine-training stimulus. The nornicotine stimulus appears to share more stimulus overlap with the 0.4 mg/kg nicotine stimulus and varenicline may share more overlap with lower nicotine doses.

Genetic variation in the serotonin pathway and smoking cessation with nicotine replacement therapy: New data from the Patch in Practice trial and pooled analyses

PubMed Central

David, Sean P.; Johnstone, Elaine C.; Murphy, Michael F.G.; Aveyard, Paul; Guo, Boliang; Lerman, Caryn; Munafò, Marcus R.

2015-01-01

The serotonin pathway has been implicated in nicotine dependence and may influence smoking cessation. Therefore, 792 cigarette smokers from the Patch in Practice trial were genotyped for the tryptophan hydroxylase (TPH1 A779C), serotonin transporter (SLC6A4 5-HTTLPR), and 5-HT1A (HTR1A C-1019G) polymorphisms. Cox regression analysis did not demonstrate significant effects of any of the three genotypes on relapse to smoking: TPH1 (Reference AA; AC: hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.78, 1.24, p = 0.90; CC: HR 0.93, 95% CI 0.73, 1.18, p = 0.55); 5-HTTLPR (Reference LL; SL: HR 1.01, 95% CI 0.85, 1.20, p = 0.90; SS: HR 1.13, 95% CI 0.91, 1.39, p = 0.27); HTR1A (Reference CC; CG: HR 1.04, 95% CI 0.86, 1.25, p = 0.70; GG: HR 1.01, 95% CI 0.82, 1.24, p = 0.93). Moreover, pooled analyses of data from all three extant pharmacogenetic NRT trials (N= 1398) found no significant effect of 5-HTTLPR genotype on continuous abstinence at 12-week (Reference LL; SL: odds ratio (OR) = 1.25, 95% CI 0.89, 1.74, p = 0.19; SS: OR= 1.31, 95% CI 0.86, 1.98, p = 0.21) or 26-week follow-up (Reference LL; SL: OR= 0.93, 95% CI 0.64, 1.33, p = 0.68; SS: OR= 1.00, 95% CI 0.63, 1.58, p = 1.00). These data do not support a statistically or clinically significant moderating effect of these specific 5-HT pathway genetic variants on smoking cessation. However, the possibility remains that other variants in these or other 5-HT genes may influence NRT efficacy for smoking cessation in treatment seeking smokers. PMID:18562131

Extended Treatment with Bupropion SR for Cigarette Smoking Cessation

ERIC Educational Resources Information Center

Killen, Joel D.; Fortmann, Stephen P.; Murphy, Greer M.; Hayward, Chris; Arredondo, Christina; Cromp, DeAnn; Celio, Maria; Abe, Laurie; Wang, Yun; Schatzberg, Alan F.

2006-01-01

The authors present results of a randomized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation. Adult smokers (N = 362) received open-label treatment (11 weeks) that combined relapse prevention training, bupropion SR, and nicotine patch followed by extended treatment (14…

[Tobacco reduction in a prison of France].

PubMed

Harcouët, L; Balanger, S; Meunier, N; Mourgues, A; Grabar, S; Haouili, B; Guillevin, L

2008-05-01

Little is known about free nicotine transdermal patch efficacy on tobacco reduction in prisoners. The objective is to study this efficacy in prison as well as motivations to reduce and influence of socioeconomic conditions and other addictions in prisoners' aspiration to stop smoking. A prospective study was proposed to prisoners candidate to tobacco cessation. Assessment was made by questionnaires and visits to physicians working at the prison. Nicotinic patches were systematically proposed to patients with a starting 15 mg/16 h dose (or 10 mg/16 h if the dependence was low), followed by a 10 and 5 mg/16 h dose reduction. Prisoners motivated to smoking cessation (N=73) generally had multiaddictive behaviours and precarious socioeconomic profile. Thirty percent of prisoners self-reported a reduction of 50% of their cigarettes consumption until they left prison. Median duration of this successful treatment was 45 days. Median duration of treatment response for patients who relapsed in prison (15 %) was 75 days. No predictive factor of success was found. Tobacco reduction is possible in prison even if living conditions are not favourable.

Motivation and patch treatment for HIV+ smokers: a randomized controlled trial.

PubMed

Lloyd-Richardson, Elizabeth E; Stanton, Cassandra A; Papandonatos, George D; Shadel, William G; Stein, Michael; Tashima, Karen; Flanigan, Timothy; Morrow, Kathleen; Neighbors, Charles; Niaura, Raymond

2009-11-01

To test the efficacy of two smoking cessation interventions in a HIV positive (HIV+) sample: standard care (SC) treatment plus nicotine replacement therapy (NRT) versus more intensive motivationally enhanced (ME) treatment plus NRT. Randomized controlled trial. HIV+ smoker referrals from eight immunology clinics in the northeastern United States. A total of 444 participants enrolled in the study (mean age = 42.07 years; 63.28% male; 51.80% European American; mean cigarettes/day = 18.27). SC participants received two brief sessions with a health educator. Those setting a quit date received self-help quitting materials and NRT. ME participants received four sessions of motivational counseling and a quit-day counseling call. All ME intervention materials were tailored to the needs of HIV+ individuals. Biochemically verified 7-day abstinence rates at 2-month, 4-month and 6-month follow-ups. Intent-to-treat (ITT) abstinence rates at 2-month, 4-month and 6-month follow-ups were 12%, 9% and 9%, respectively, in the ME condition, and 13%, 10% and 10%, respectively, in the SC condition, indicating no between-group differences. Among 412 participants with treatment utilization data, 6-month ITT abstinence rates were associated positively with low nicotine dependence (P = 0.02), high motivation to quit (P = 0.04) and Hispanic American race/ethnicity (P = 0.02). Adjusting for these variables, each additional NRT contact improved the odds of smoking abstinence by a third (odds ratio = 1.32, 95% confidence interval = 0.99-1.75). Motivationally enhanced treatment plus NRT did not improve cessation rates over and above standard care treatment plus NRT in this HIV+ sample of smokers. Providers offering brief support and encouraging use of nicotine replacement may be able to help HIV+ patients to quit smoking.

A critical evaluation of a nicotine vaccine within a self-administration behavioral model.

PubMed

Moreno, Amira Y; Azar, Marc R; Warren, Noelle A; Dickerson, Tobin J; Koob, George F; Janda, Kim D

2010-04-05

(S)-Nicotine is a psychostimulant legal drug responsible for causing addiction to tobacco smoking. Tobacco smoking has been irrevocably linked to a number of serious diseases and at present is considered the leading cause of preventable death in the United States. Despite well-documented adverse medical consequences, nicotine addiction has historically been one of the hardest to break. Current therapies have offered limited success and show high rates of relapse, emphasizing the need to engineer alternative therapies to aid nicotine cessation. The current study presents a protein-based immunopharmacotherapy approach for the treatment of nicotine addiction. Immunopharmacotherapy aims to use highly specific antibodies to blunt passage of drug into the brain thus minimizing reinforcing effects on the reward pathways of the central nervous system. Generation of a successful vaccine heavily relies on appropriate optimization of hapten design, immunogenic carrier and adjuvant. Modification of a classical nicotine hapten in conjugation with three distinct carrier proteins allowed for priming of a nicotine vaccine able to elicit significant amounts of nicotine-specific antibodies. Increased self-administration with use of a high drug dose (0.03 mg/kg/infusion; approximately 2 cigarettes in human) was observed in the vaccinated versus control animals suggesting a compensatory pattern and possibly reduced passage of nicotine to the brain. These results support the hypothesis that proper optimization of vaccine formulations could lead to successful nicotine vaccines for human use.

Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptor.

PubMed

Jozwiak, Krzysztof; Targowska-Duda, Katarzyna M; Kaczor, Agnieszka A; Kozak, Joanna; Ligeza, Agnieszka; Szacon, Elzbieta; Wrobel, Tomasz M; Budzynska, Barbara; Biala, Grazyna; Fornal, Emilia; Poso, Antti; Wainer, Irving W; Matosiuk, Dariusz

2014-12-15

9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards α3β4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the micromolar range. Homology modeling, molecular docking and molecular dynamics of ligand-receptor complexes in POPC membrane are used to find the mode of interactions of N-alkylated dextromethorphan derivatives with α3β4 nAChR. The compounds, similarly as dextromethorphan, interact with the middle portion of α3β4 nAChR ion channel. Finally, behavioral tests confirmed potential application of the studied compounds for the treatment of addiction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Electronic Cigarettes for Smoking Cessation.

PubMed

Orellana-Barrios, Menfil A; Payne, Drew; Medrano-Juarez, Rita M; Yang, Shengping; Nugent, Kenneth

2016-10-01

The use of electronic cigarettes (e-cigarettes) is increasing, but their use as a smoking-cessation aid is controversial. The reporting of e-cigarette studies on cessation is variable and inconsistent. To date, only 1 randomized clinical trial has included an arm with other cessation methods (nicotine patches). The cessation rates for available clinical trials are difficult to compare given differing follow-up periods and broad ranges (4% at 12 months with non-nicotine e-cigarettes to 68% at 4 weeks with concomitant nicotine e-cigarettes and other cessation methods). The average combined abstinence rate for included prospective studies was 29.1% (combination of 6-18 months׳ rates). There are few comparable clinical trials and prospective studies related to e-cigarettes use for smoking cessation, despite an increasing number of citations. Larger randomized clinical trials are essential to determine whether e-cigarettes are effective smoking-cessation devices. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Nicotine dependence and smoking cessation.

PubMed

Tan, Linxiang; Tang, Quansheng; Hao, Wei

2009-11-01

Tobacco use is the single most preventable cause of death, disability and disease in the world and is projected to be the leading cause of death and disability across all developed and developing countries by 2020. Nicotine, the primary active ingredient of cigarettes that contributes to physical dependence, acts on nicotine receptors in the central nervous system and leads to the release of neurotransmitters (such as dopamine). Like other drugs of abuse, nicotine is thought to produce reinforcing effect by activating the mesocorticolimbic dopamine system. A wide variety of cessation treatments of nicotine dependence is commercially available, yet only 2 general approaches have received empirical validation: behavioral intervention (including 5 As brief intervention) and pharmacotherapy. The evidences show that 5 As brief intervention is one of the most cost-effective treatments in clinical work for busy physicians. Three types of medications have been available in market for smoking cessation treatment: nicotine replacement treatment (NRT, i.e., transdermal patch, gum, inhaler, nasal spray, and lozenge), sustained release bupropion and varenicline. Varenicline, a novel alpha4beta2 nicotinic receptor partial agonist, is effective for tobacco dependence. Phase III trials suggest that it is more effective than NRT and bupropion SR. The safety profile of varenicline is excellent, with the most commonly occurring adverse events, nausea, typically mild and well tolerated. However, new safety warnings are added to the varenicline label because of post-marketing report including agitation, depression and suicidality. A causal connection between varenicline use and these symptoms has not been established.

Chronic nicotine differentially alters spontaneous recovery of contextual fear in male and female mice.

PubMed

Tumolo, Jessica M; Kutlu, Munir Gunes; Gould, Thomas J

2018-04-02

Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigating the role of ion-pair strategy in regulating nicotine release from patch: Mechanistic insights based on intermolecular interaction and mobility of pressure sensitive adhesive.

PubMed

Li, Qiaoyun; Wan, Xiaocao; Liu, Chao; Fang, Liang

2018-07-01

The aim of this study was to prepare a drug-in-adhesive patch of nicotine (NIC) and use ion-pair strategy to regulate drug delivery rate. Moreover, the mechanism of how ion-pair strategy regulated drug release was elucidated at molecular level. Formulation factors including pressure sensitive adhesives (PSAs), drug loading and counter ions (C 4 , C 6 , C 8 , C 10 , and C 12 ) were screened. In vitro release experiment and in vitro transdermal experiment were conducted to determine the rate-limiting step in drug delivery process. FT-IR and molecular modeling were used to characterize the interaction between drug and PSA. Thermal analysis and rheology study were conducted to investigate the mobility variation of PSA. The optimized patch prepared with NIC-C 8 had the transdermal profile fairly close to that of the commercial product (p > 0.05). The release rate constants (k) of NIC, NIC-C 4 and NIC-C 10 were 21.1, 14.4 and 32.4, respectively. Different release rates of NIC ion-pair complexes were attributed to the dual effect of ion-pair strategy on drug release. On one hand, ion-pair strategy enhanced the interaction between drug and PSA, which inhibited drug release. On the other hand, using ion-pair strategy improved the mobility of PSA, which facilitated drug release. Drug release behavior was determined by combined effect of two aspects above. These conclusions provided a new idea for us to regulate drug release behavior from patch. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of the effects of combined nicotine replacement therapy vs. cigarette smoking in males.

PubMed

Haustein, Knut-Olaf; Krause, Jörn; Haustein, Heidi; Rasmussen, Thomas; Cort, Nicholas

2003-04-01

This open study assessed the effects of nicotine replacement therapy (NRT) on the normalizing of exhaled carbon monoxide (CO), transcutaneous partial oxygen tension (tcpO(2)), plasma cotinine and thiocyanate levels, and cardiovascular risk markers in abstinent subjects compared with untreated smokers after 4, 8, 12, and 26 weeks. The trial enrolled 197 subjects in two parallel groups: 164 subjects who received NRT (patch plus gum) for 12 weeks and 33 untreated smokers (controls). At 26 weeks, 123/164 participants in the treatment group had completed the study; 51/123 (41.5%) sustained abstinence from smoking, whereas 72/123 (58.5%) had relapsed. Changes in cotinine (abstainers: 291.6 ng/ml at baseline vs. 27.3 ng/ml at week 26; p<.0001) and thiocyanate levels (abstainers: 10.4 ng/ml at baseline vs. 6.2 ng/ml at week 26; p<.0001) and expired CO (abstainers: 30.4 ppm at baseline vs. 4.2 ppm at week 26; p<.0001) accurately reflected the changes in smoking and/or NRT use in both abstainers and relapsers. After they stopping smoking, tcpO(2) significantly improved in abstainers (34.9 mmHg at baseline vs. 50.4 mmHg at week 26; p<0.0001). Inverse correlations between the number of daily cigarettes and plasma cotinine, thiocyanate, and exhaled CO levels were observed in both relapsers and smokers. A clinically significant increase in HDL cholesterol (39.0 vs. 44.7 mg/dl; p<.0001) occurred in the abstainers between baseline and study end. Use of combination NRT to achieve abstinence resulted in marked improvements in biochemical parameters in abstainers and partial improvements in relapsers. The safety of combination NRT was confirmed by the absence of overdose-related adverse events.

Effects of varenicline versus transdermal nicotine replacement therapy on cigarette demand on quit day in individuals with substance use disorders.

PubMed

Murphy, Cara M; MacKillop, James; Martin, Rosemarie A; Tidey, Jennifer W; Colby, Suzanne M; Rohsenow, Damaris J

2017-08-01

Cigarette demand is a behavioral economic measure of the relative value of cigarettes. Decreasing the value of cigarette reinforcement may help with quitting smoking. This study aimed to evaluate the effects of initial use of varenicline (VAR) versus nicotine replacement therapy (NRT) on demand for cigarettes on quit day among smokers with substance use disorders (SUD) and to determine whether reduced demand was associated with subsequent abstinence from smoking at 1 and 3 months. Participants (N = 110) were randomized to double-blind, double-placebo conditions: VAR with placebo NRT or NRT with placebo capsules. The cigarette purchase task (CPT) was used to assess demand for cigarettes at baseline and on quit day, following a 1-week medication dose run-up/placebo capsule lead-in and first day use of the patch. Demand for cigarettes decreased from baseline to quit day without significant differences between medications. Reductions in CPT intensity (number of cigarettes that would be smoked if they were free) and CPT breakpoint (lowest price at which no cigarettes would be purchased) predicted greater likelihood of abstaining on quit day. Reduced intensity predicted length of abstinence at 1 and 3 months while reduced breakpoint predicted only 1 month length of abstinence. Initial therapeutic doses of VAR and NRT resulted in similar reductions in cigarette reinforcement. Larger initial reductions in demand on quit day were associated with early success with abstaining from cigarettes. Behavioral economic approaches may be useful for identifying individuals who benefit less from pharmacotherapy and may need additional treatment resources. https://clinicaltrials.gov/ct2/show/NCT00756275.

Increased reach and effectiveness of a statewide tobacco quitline after the addition of access to free nicotine replacement therapy

PubMed Central

An, Lawrence C; Schillo, Barbara A; Kavanaugh, Annette M; Lachter, Randi B; Luxenberg, Michael G; Wendling, Ann H; Joseph, Anne M

2006-01-01

Background Tobacco users receiving behavioural and pharmacological assistance are more likely to quit. Although telephone quitlines provide population access to counselling, few offer pharmacotherapy. Objective To assess change in cessation rates and programme impact after the addition of free nicotine replacement therapy (NRT) to statewide quitline services. Design, setting, participants An observational study of cohorts of callers to the Minnesota QUITPLANSM Helpline before (n  =  380) and after (n  =  373) the addition of access to free NRT. Intervention Mailing of NRT (patch or gum) to callers enrolling in multi‐session counselling. Main outcome measure Thirty‐day abstinence six months after programme registration. Results The number of callers increased from 155 (SD 75) to 679 (180) per month pre‐NRT to post‐NRT (difference 524, 95% confidence interval (CI) 323 to 725). Post‐NRT, the proportion of callers enrolling in multi‐session counselling (23.4% v 90.1%, difference 66.6%, 95% CI 60.8% to 71.6%) and using pharmacotherapy (46.8% v 86.8%, difference 40.0%, 95% CI 31.3% to 47.9%) increased. Thirty‐day abstinence at six months increased from 10.0% pre‐NRT to 18.2% post‐NRT (difference 8.2%, 95% CI 3.1% to 13.4%). Post‐NRT the average number of new ex‐smokers per month among registrants increased from 15.5 to 123.6 (difference 108.1, 95% CI 61.1 to 155.0). The cost per quit pre‐NRT was $1362 (SD $207). The cost per quit post‐NRT was $1934 ($215) suggesting a possible increase in cost per quit (difference $572, 95% CI −$12 to $1157). Conclusion The addition of free NRT to a state quitline is followed by increases in participation and abstinence rates resulting in an eightfold increase in programme impact. These findings support the addition of access to pharmacological therapy as part of state quitline services. PMID:16885577

Anhedonia: Its Dynamic Relations With Craving, Negative Affect, and Treatment During a Quit Smoking Attempt.

PubMed

Cook, Jessica W; Lanza, Stephanie T; Chu, Wanghuan; Baker, Timothy B; Piper, Megan E

2017-06-01

Research shows that abstinence from tobacco leads to a withdrawal-related decrement in responsivity to nondrug rewards (ie, anhedonia). However, it remains unclear how anhedonia relates to other key withdrawal symptoms and withdrawal-related constructs over time. We analyzed ecological momentary assessment data to examine whether a decrement in response to rewards during a 10-day period following quitting shows a pattern of associations with other variables (ie, treatment, tobacco dependence, negative affect, and craving) that is consistent with anhedonia being a tobacco withdrawal symptom. As part of a randomized controlled trial of smoking cessation therapies, 1122 adults (58% female) were assigned to: placebo (n = 131), bupropion (alone or with nicotine lozenge; n = 401), or nicotine replacement therapy (NRT; lozenge, patch, both; n = 590). Participants completed 4 ecological momentary assessments per day for 10 days postquit, resulting in 22 575 assessments. Time-varying effect modeling showed that anhedonia was significantly greater among those high in dependence relative to lower dependent smokers out to day 9 postquit. The placebo group showed elevated anhedonia immediately postquit, which fell to levels similar to the treatment groups by day 7. NRT effectively reduced anhedonia and its time-varying association with craving early in the quit attempt. The positive association between negative affect and anhedonia was moderate and stable over time for both active treatment groups. These results provide additional support that anhedonia following quitting smoking is a manifestation of the tobacco withdrawal syndrome. This study supported the hypothesis that diminished responsivity to nondrug rewards (ie, anhedonia) is a symptom of the tobacco withdrawal syndrome. Results showed that anhedonia: (1) was significantly associated with dependence, especially during the early postquit period when withdrawal was at its peak intensity; (2) showed significant time-varying associations with other withdrawal symptoms, especially craving; and (3) was significantly suppressed by agonist administration as was its association with craving over time. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cue-Provoked Craving and Nicotine Replacement Therapy in Smoking Cessation

ERIC Educational Resources Information Center

Waters, Andrew J.; Shiffman, Saul; Sayette, Michael A.; Paty, Jean A.; Gwaltney, Chad J.; Balabanis, Mark H.

2004-01-01

Cue exposure paradigms have been used to examine reactivity to smoking cues. However, it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy (NRT) in clinical samples. Cue-provoked craving ratings and reaction time responses were…

Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer's disease.

PubMed

Gao, Jie; Adam, Bao-Ling; Terry, Alvin V

2014-03-15

The currently available therapies for Alzheimer's disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association of nicotine metabolism and sex with relapse following varenicline and nicotine replacement therapy.

PubMed

Glatard, Anaïs; Dobrinas, Maria; Gholamrezaee, Mehdi; Lubomirov, Rubin; Cornuz, Jacques; Csajka, Chantal; Eap, Chin B

2017-10-01

Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine, mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of varenicline in women and in nicotine normal metabolizers phenotypically determined by nicotine-metabolite ratio. Our objective was to study the influence of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine replacement therapy and varenicline. Data were extracted from a longitudinal study which included smokers participating in a smoking cessation program. Response to treatment was defined by the absence of relapse when a set threshold of reduction in cigarettes per day relative to the week before the study was no more reached. The analysis considered total and partial reduction defined by a diminution of 100% and of 90% in cigarettes per day, respectively. The hazard ratio of relapsing was estimated in multivariate Cox regression models including the sex and the nicotine metabolism determined by the phenotype or by CYP2A6 genotyping (rs1801272 and rs28399433). In the normal metabolizers determined by phenotyping and in women, the hazard ratio for relapsing was significantly lower with varenicline for a partial decrease (HR = 0.33, 95% CI [0.12, 0.89] and HR = 0.20, 95% CI [0.04, 0.91], respectively) and nonsignificantly lower for a total cessation (HR = 0.45, 95% CI [0.20, 1.0] and HR = 0.38, 95% CI [0.14, 1.0]). When compared with the normal metabolizers determined by phenotyping, the hazard ratio for a partial decrease was similar in the normal metabolizers determined by genotyping (HR = 0.42, 95% CI [0.18, 0.94]) while it was significantly lower with varenicline for a total cessation (HR = 0.50, 95% CI [0.26, 0.98]). Women and normal nicotine metabolizers may benefit more from varenicline over nicotine replacement therapy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

PubMed

de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

2018-04-01

Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Effects on abstinence of nicotine patch treatment before quitting smoking: parallel, two arm, pragmatic randomised trial.

PubMed

2018-06-13

To examine the effectiveness of a nicotine patch worn for four weeks before a quit attempt. Randomised controlled open label trial. Primary care and smoking cessation clinics in England, 2012-15. 1792 adults who were daily smokers with tobacco dependence. 899 were allocated to the preloading arm and 893 to the control arm. Participants were randomised 1:1, using concealed randomly permuted blocks stratified by centre, to either standard smoking cessation pharmacotherapy and behavioural support or the same treatment supplemented by four weeks of 21 mg nicotine patch use before quitting: "preloading." The primary outcome was biochemically confirmed prolonged abstinence at six months. Secondary outcomes were prolonged abstinence at four weeks and 12 months. Biochemically validated abstinence at six months was achieved by 157/899 (17.5%) participants in the preloading arm and 129/893 (14.4%) in the control arm: difference 3.0% (95% confidence interval -0.4% to 6.4%), odds ratio 1.25 (95% confidence interval 0.97 to 1.62), P=0.08 in the primary analysis. There was an imbalance between arms in the frequency of varenicline use as post-cessation treatment, and planned adjustment for this gave an odds ratio for the effect of preloading of 1.34 (95% confidence interval 1.03 to 1.73), P=0.03: difference 3.8% (0.4% to 7.2%). At four weeks, the difference in prolonged abstinence unadjusted for varenicline use was odds ratio 1.21 (1.00 to 1.48), difference 4.3% (0.0% to 8.7%), P=0.05, and adjusted for varenicline use was 1.32 (1.08 to 1.62) P=0.007. At 12 months the odds ratio was 1.28 (0.97 to 1.69), difference 2.7% (-0.4% to 5.8%), P=0.09 unadjusted for varenicline use and after adjustment was 1.36 (1.02 to 1.80) P=0.04. 5.9% of participants discontinued preloading owing to intolerance. Gastrointestinal symptoms-chiefly nausea-occurred in 4.0% (2.2% to 5.9%) more people in the preloading arm than control arm. Eight serious adverse events occurred in the preloading arm and eight in the control arm (odds ratio 0.99, 0.36 to 2.75). Evidence was insufficient to confidently show that nicotine preloading increases subsequent smoking abstinence. The beneficial effect seems to have been masked by a concurrent reduction in the use of varenicline in people using nicotine preloading, and future studies should explore ways to mitigate this unintended effect. Current Controlled Trials ISRCTN33031001. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Nicotine Inhibits Memory CTL Programming

PubMed Central

Sun, Zhifeng; Smyth, Kendra; Garcia, Karla; Mattson, Elliot; Li, Lei; Xiao, Zhengguo

2013-01-01

Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development. PMID:23844169

Evaluation of smoking cessation behaviors and interventions among Latino smokers at low-income clinics in a US-Mexico border county.

PubMed

Sias, Jeri J; Urquidi, Ulysses J; Bristow, Zuzanne M; Rodriguez, José C; Ortiz, Melchor

2008-02-01

A descriptive study of 94 Latino smokers receiving nicotine replacement therapy (NRT) in US-Mexico border clinics in El Paso County, Texas was conducted. A baseline questionnaire and two follow-up telephone surveys (8-12 weeks and 6 months) were administered to evaluate smoking habits, behaviors, and cessation interventions. Participants reported an average daily cigarette consumption of 15 cigarettes and smoked within 30 min of waking (44%). Primary motivations for quitting were personal health (95%), family's health (74%), and doctor's advice (71%). Female smokers were more likely to smoke due to being anxious (p=0.012), not being able to sleep (p=0.02), or to feel thin (p=0.002). Male smokers were more likely to smoke when drinking alcohol (p=0.005). Nearly 40% of smokers reported they had never tried to quit before. Medication use at baseline was 82% patch, 53% lozenge, 29% gum, and 24% bupropion (combination therapy permitted). At 8-12 weeks, nearly two-thirds of patients were quit and 44% remained quit at six months. Smoking habits, behaviors, and successful cessation interventions among Latinos in a US-Mexico border community were identified.

Nicotine restores functional connectivity of the ventral attention network in schizophrenia.

PubMed

Smucny, Jason; Olincy, Ann; Tregellas, Jason R

2016-09-01

While previous work has suggested that nicotine may transiently improve attention deficits in schizophrenia, the neuronal mechanisms are poorly understood. This study is the first to examine the effects of nicotine on connectivity within the ventral attention network (VAN) during a selective attention task in schizophrenia. Using a crossover design, 17 nonsmoking patients with schizophrenia and 20 age/gender-matched nonsmoking healthy controls performed a go/no-go task with environmental noise distractors during application of a 7 mg nicotine or placebo patch. Psychophysiological interaction analysis was performed to analyze task-associated changes in connectivity between a ventral parietal cortex (VPC) seed and the inferior frontal gyrus (IFG), key components of the human VAN. Effects of nicotine on resting state VAN connectivity were also examined. A significant diagnosis × drug interaction was observed on task-associated connectivity between the VPC seed and the left IFG (F(1,35) = 8.03, p < 0.01). This effect was driven by decreased connectivity after placebo in patients and greater connectivity after nicotine. Resting state connectivity analysis showed a significant main effect of diagnosis between the seed and right IFG (F = 4.25, p = 0.023) due to increased connectivity in patients during placebo, but no drug × diagnosis interactions or main effects of drug. This study is the first to demonstrate that 1) the VAN is disconnected in schizophrenia during selective attention, and 2) nicotine may normalize this pathological state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nicotine Vapor Method to Induce Nicotine Dependence in Rodents.

PubMed

Kallupi, Marsida; George, Olivier

2017-07-05

Nicotine, the main addictive component of tobacco, induces potentiation of brain stimulation reward, increases locomotor activity, and induces conditioned place preference. Nicotine cessation produces a withdrawal syndrome that can be relieved by nicotine replacement therapy. In the last decade, the market for electronic cigarettes has flourished, especially among adolescents. The nicotine vaporizer or electronic nicotine delivery system is a battery-operated device that allows the user to simulate the experience of tobacco smoking without inhaling smoke. The device is designed to be an alternative to conventional cigarettes that emits vaporized nicotine inhaled by the user. This report describes a procedure to vaporize nicotine in the air to produce blood nicotine levels in rodents that are clinically relevant to those that are observed in humans and produce dependence. We also describe how to construct the apparatus to deliver nicotine vapor in a stable, reliable, and consistent manner, as well as how to analyze air for nicotine content. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Smoking topography and abstinence in adult female smokers

PubMed Central

McClure, Erin A.; Saladin, Michael E.; Baker, Nathaniel L.; Carpenter, Matthew J.; Gray, Kevin M.

2013-01-01

Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e. smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated, but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad-libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4 weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers. PMID:24018226

Anxiety and smoking cessation outcomes in alcohol-dependent smokers.

PubMed

Kelly, Megan M; Grant, Christoffer; Cooper, Sharon; Cooney, Judith L

2013-02-01

Anxiety-related characteristics, including anxiety sensitivity and trait anxiety, are elevated in individuals with alcohol and nicotine dependence and associated with greater difficulties with quitting smoking. However, little is known about how anxiety-related characteristics are related to smoking cessation outcomes in alcohol-dependent smokers. The present study, part of a larger smoking cessation clinical trial, examined associations between anxiety sensitivity, trait anxiety, nicotine withdrawal symptoms, smoking urges, and smoking cessation outcomes in a sample of 83 alcohol-dependent smokers. Participants were enrolled in concurrent alcohol and tobacco treatment as part of a substance-abuse intensive outpatient program. Smoking cessation treatment was administered in a 3-week cognitive-behavioral format that included 8 weeks of open-label nicotine patch treatment. Information on nicotine withdrawal, smoking urges, and CO-confirmed smoking consumption rates was collected at baseline, quit date, end of behavioral treatment, and at a 1-month follow-up. Higher levels of anxiety sensitivity were associated with more smoking urges due to anticipation of negative affect relief at quit date. Higher levels of trait anxiety were associated with more smoking urges due to positive reinforcement and anticipation of relief of negative affect at quit date, as well as more severe nicotine withdrawal symptoms at the end of treatment. Levels of anxiety sensitivity and trait anxiety were not associated with Cox regression survival times to relapse. These results indicate that for alcohol-dependent smokers, levels of anxiety sensitivity and trait anxiety are important to consider in the assessment and treatment of nicotine dependence.

Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis.

PubMed

Ditre, Joseph W; Heckman, Bryan W; Zale, Emily L; Kosiba, Jesse D; Maisto, Stephen A

2016-07-01

Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered through tobacco smoke and other delivery systems (eg, patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges g = 0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Sex composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions. Current smoking has been associated with more severe chronic pain and physical impairment. Acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should use dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action.

Assessing Constituent Levels in Smokeless Tobacco Products: A New Approach to Engaging and Educating the Public

PubMed Central

Loken, Barbara; Williams, Allison L.; Vitriol, Joseph; Stepanov, Irina; Hatsukami, Dorothy

2015-01-01

Introduction: Providing accurate information about the constituents in nicotine-containing products may help tobacco users make informed decisions about product choices. An experimental study examined a novel approach for presenting accurate constituent information about brands and types of smokeless tobacco (SLT) that could be understood by the general public. Methods: Participants were recruited through Amazon’s Mechanical Turk and presented information online about 2 constituent dimensions of SLT products—nicotine and/or toxicity (for simplicity, “toxicity” in this study refers to carcinogenic constituents) Participants completed measures of knowledge and tobacco health risks at 2 time points: before and after exposure to constituent information. Results: Participants were found to increase their knowledge that toxicity contributes to disease risk and nicotine contributes to addiction, that SLT products vary in their levels of nicotine and toxicity, and that both SLT and cigarette products have higher toxicity than medicinal nicotine replacement therapies (e.g., nicotine lozenges). Study results showed no differences when presenting toxicity information alone versus presenting it in conjunction with nicotine information, and found no misperceptions or confusions about the relative harmfulness of cigarettes, SLT, or nicotine replacement therapy. Conclusions: Providing tobacco constituent information to smokers and nonsmokers will improve their knowledge about the relative toxicity across products and variations within a class of tobacco products without compromising the health risks associated with tobacco use. PMID:25634934

Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria

PubMed Central

Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Bahelah, Raed; Maziak, Wasim

2015-01-01

Introduction The development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. Methods Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. Results Of the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. Conclusion Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages. PMID:26077603

Adverse Reaction to Nicotine Gum in Malay Female Smoker: A Case Report

ERIC Educational Resources Information Center

Noorzurani, Md Haris Robson; Bond, Alyson; Wolff, Kim

2008-01-01

Nicotine replacement therapies (NRT) are prescribed in smoking cessation programmes to help smokers stop smoking. The ideal dosage of NRT should control cravings and withdrawal symptoms but avoid adverse reactions. This report describes a case of adverse reaction to nicotine gum in a female Malay smoker. Assays taken 2 h after the gum, showed that…

Anthropometric and body composition changes in smokers vs abstainers following an exercise-aided pharmacotherapy smoking cessation trial for women.

PubMed

Prapavessis, Harry; De Jesus, Stefanie; Fitzgeorge, Lyndsay; Rollo, Scott

2018-06-07

Post-cessation weight gain contributes to smoking relapse, especially for women. Furthermore, excess weight in the form of android or visceral fat is associated with metabolic health problems. For this study, a secondary analysis was conducted in 2015 to determine whether quitting status, achieved through a 14 week supervised exercise-aided nicotine replacement therapy (NRT) cessation program [Getting Physical on Cigarette Trial-2009 to 2013; Prapavessis, et al., 2016], affects anthropometric and body composition parameters in female smokers (N = 413, M age = 42.39 years). Anthropometric (weight and BMI) and body composition (% total body fat, % android fat, lean mass and visceral fat) indices were assessed at baseline and end of treatment. Smoking status was confirmed weekly from expired breath carbon monoxide. Adherence to exercise and NRT patch was calculated from the number of exercise sessions attended and patches worn to the number of exercise sessions offered and patches supplied, respectively. Factorial (smoking status) ANCOVAs controlling for baseline anthropometric and body composition parameters as well as adherence to exercise and NRT revealed significant differences in weight (p = .033; ɳ p 2  = 0.017) and BMI (p = .020; ɳ p 2  = 0.020) at week 14. This equated to abstainers weighing 1.26 kg more and having a 0.52 higher BMI than smokers. No significant differences were found for any of the body composition parameters at week 14 (ɳ p 2 range from 0.001-0.007). Abstainers gain modest weight compared to smokers. This weight gain is related to increases in lean mass and not total, android, or visceral fat. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of ceftriaxone on conditioned nicotine reward in rats.

PubMed

Philogene-Khalid, Helene L; Simmons, Steven J; Muschamp, John W; Rawls, Scott M

2017-09-01

Nicotine is the addictive compound in tobacco products which exerts psychosomatic effects that contribute to abuse and to low rates of abstinence in treatment-seeking smokers. At present, the most successful smoking cessation aide helps one in four individuals quit smoking at 1 year postcessation. New adjunctive therapies are needed to improve status of smoking-related public health crises, and β-lactam antibiotics are one class of potential therapies as they favorably augment extrasynaptic glutamate clearance. Our study used two-chamber place conditioning to assess effects of ceftriaxone (CTX) on persistence of conditioned nicotine reward. Rats were conditioned to associate nicotine (0.4 mg/kg, subcutaneous) with one context and vehicle with an alternative context. After initial post-test, rats received either daily ceftriaxone (200 mg/kg, intraperitoneal) or saline. All rats showed nicotine place preference during post-test 1. CTX-treated rats meeting extinction criterion by post-test 7 showed significantly reduced preference for the nicotine-paired context during post-test 2 compared with vehicle-treated rats. We interpret these data to support the further study of CTX as a smoking cessation aide. Our results suggest that CTX reduces persistence of conditioned nicotine reward and may be helpful for improving abstinence rates in a subset of treatment-seeking smokers.

Characteristics of Australian smokers using bupropion and nicotine-replacement therapies.

PubMed

Doran, Christopher; Stafford, Jennifer; Shanahan, Marian; Mattick, Richard P

2007-02-01

Smokers were surveyed using a computer-assisted telephone interview to explore behaviors associated with the use of bupropion and nicotine-replacement therapies, using a convenient sample of Australian smokers. With assistance from the Pharmacy Guild of Australia, smokers were recruited through pharmacies and interviewed at baseline and after 3 months. A total of 508 smokers were recruited, 396 were interviewed at baseline and 318 completed a 3-month computer-assisted telephone interview. At 3 months, over two-thirds of participants were still smoking, the majority daily. However, the number of cigarettes smoked per week reduced and the time taken before smoking the first cigarette after waking increased. Nearly all participants started their medication (94%), while only 39% completed the full course. The main reasons for not completing the full course were adverse side effects, such as abnormal dreams and sleep disturbance. Despite Australian guidelines for bupropion and nicotine-replacement therapies to be used within a comprehensive treatment program, only 11% of patients were recommended behavioral support for nicotine dependence by their doctor or pharmacist. The results of the study shed light on patient utilization of the medication in terms of uptake and completion, possible side effects experienced and use of adjuncts. A better understanding of the use and experience of bupropion and nicotine-replacement therapies, and the lack of behavioral support offered with these, provides policy makers with a stronger evidence base to refine and improve the use of such pharmacotherapies.

Tobacco Harms, Nicotine Pharmacology, and Pharmacologic Tobacco Cessation Interventions for Women.

PubMed

Baraona, L Kim; Lovelace, Dawn; Daniels, Julie L; McDaniel, Linda

2017-05-01

Firsthand and secondhand tobacco use is linked to a multitude of harmful illnesses, adverse perinatal outcomes, and death. Cessation attempts among women may be hampered by their unique biologic response to nicotine. Current research has revealed epigenetic changes from intrauterine nicotine exposure that have intergenerational consequences. Multiple studies have demonstrated the efficacy of various pharmacologic tobacco cessation interventions in conjunction with behavioral counseling. Based on this evidence, the US Preventative Services Task Force (USPSTF) 2015 guideline recommends pharmacologic therapy for all nonpregnant persons who smoke in addition to behavioral counseling. The effectiveness of pharmacologic treatments among pregnant women is less clear, with far fewer studies evaluating potential benefits and harms. While exposure to pharmacologic therapies raises concerns for fetal safety, these potential risks must be weighed against those of continued tobacco use, which guarantees fetal exposure to nicotine. First-line tobacco cessation medications include nicotine replacement therapy (NRT), bupropion, and varenicline. Second-line medications include nortriptyline and clonidine. Pharmacokinetics, effectiveness, regimens, and safety profiles for nonpregnant, pregnant, and lactating women are reviewed. Alternative tobacco cessation options and potential new pharmacologic tobacco cessation agents are discussed. Initiating brief interventions, using the 5A's and 5R's model is described. © 2017 by the American College of Nurse-Midwives.

Antimicrobial photodynamic therapy minimizes the deleterious effect of nicotine in female rats with induced periodontitis.

PubMed

Gualberto, Erivan Clementino; Theodoro, Letícia Helena; Longo, Mariellén; Novaes, Vivian Cristina Noronha; Nagata, Maria José Hitomi; Ervolino, Edilson; Garcia, Valdir Gouveia

2016-01-01

The aim of this study was to compare the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) in the treatment of experimentally induced periodontitis in female rats that were systemically treated with or without nicotine. Female rats (n = 180) were divided into two groups: vehicle administration (Veh) and nicotine administration (Nic). Mini-pumps containing either vehicle or nicotine were implanted in the rats 30 days before the induction of experimental periodontitis (EP). EP was induced by placing a cotton ligature around the left mandibular first molar. After 7 days, the ligature was removed, and the rats were randomly divided into three treatment subgroups: SRP (only SRP), DL (SRP plus diode laser), and aPDT (SRP plus aPDT). The aPDT consisted of phenothiazine photosensitizer deposition followed by diode laser irradiation. Ten rats from each subgroup were euthanized at 7, 15, and 30 days after treatment. Alveolar bone loss (ABL) in the furcation region was evaluated using histological, histometric, and immunohistochemical analyses. The rats that were treated with nicotine showed more ABL compared to those treated with vehicle. In both the Veh and Nic groups, SRP plus aPDT treatment resulted in reduced ABL, smaller numbers of both TRAP- and RANKL-positive cells, and higher numbers of PCNA-positive cells compared to SRP treatment alone. aPDT was an effective adjunctive therapy for the treatment of periodontitis in female rats regardless of whether they received nicotine.

Meta-Analysis of the Efficacy of Nicotine Replacement Therapy for Smoking Cessation: Differences between Men and Women

ERIC Educational Resources Information Center

Cepeda-Benito, Antonio; Reynoso, Jose T.; Erath, Stephen

2004-01-01

Gender differences in the efficacy of nicotine replacement therapies (NRTs) were examined in a meta-analytical review of 90 effect sizes obtained from a sample of 21 double-blind, placebo-controlled randomized studies. Although NRT was more effective for men than placebo at 3-month, 6-month, and 12-month follow-ups, the benefits of NRT for women…

Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

PubMed Central

Moaddel, Ruin; Abdrakhmanova, Galia; Kozak, Joanna; Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Rosenberg, Avraham; Tran, Thao; Xiao, Yingxian; Zarate, Carlos A.; Wainer, Irving W.

2012-01-01

The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)- hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC50 = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤1μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [125I]-α-bungarotoxin and [3H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC50 3.1 and 9.1μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC50 >100μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [3H]-MK-801. The calculated Ki values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and > 100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug. PMID:23183107

Rapid relief of block by mecamylamine of neuronal nicotinic acetylcholine receptors of rat chromaffin cells in vitro: an electrophysiological and modeling study.

PubMed

Giniatullin, R A; Sokolova, E M; Di Angelantonio, S; Skorinkin, A; Talantova, M V; Nistri, A

2000-10-01

The mechanism responsible for the blocking action of mecamylamine on neuronal nicotinic acetylcholine receptors (nAChRs) was studied on rat isolated chromaffin cells recorded under whole-cell patch clamp. Mecamylamine strongly depressed (IC(50) = 0.34 microM) inward currents elicited by short pulses of nicotine, an effect slowly reversible on wash. The mecamylamine block was voltage-dependent and promptly relieved by a protocol combining membrane depolarization with a nicotine pulse. Either depolarization or nicotine pulses were insufficient per se to elicit block relief. Block relief was transient; response depression returned in a use-dependent manner. Exposure to mecamylamine failed to block nAChRs if they were not activated by nicotine or if they were activated at positive membrane potentials. These data suggest that mecamylamine could not interact with receptors either at rest or at depolarized level. Other nicotinic antagonists like dihydro-beta-erythroidine or tubocurarine did not share this action of mecamylamine although proadifen partly mimicked it. Mecamylamine is suggested to penetrate and block open nAChRs that would subsequently close and trap this antagonist. Computer modeling indicated that the mechanism of mecamylamine blocking action could be described by assuming that 1) mecamylamine-blocked receptors possessed a much slower, voltage-dependent isomerization rate, 2) the rate constant for mecamylamine unbinding was large and poorly voltage dependent. Hence, channel reopening plus depolarization allowed mecamylamine escape and block relief. In the presence of mecamylamine, therefore, nAChRs acquire the new property of operating as coincidence detectors for concomitant changes in membrane potential and receptor occupancy.

Development of Culturally Appropriate Support Strategies to Increase Uptake of Nicotine Replacement Therapy Among Russian- and Chinese-Speaking Smokers in New York City.

PubMed

Quinn, Erin C; Sacks, Rachel; Farley, Shannon M; Thihalolipavan, Sayone

2017-06-01

Approximately 80,000 New York City smokers are Chinese or Russian speakers. To increase utilization of smoking cessation services among these populations, the Department of Health and Mental Hygiene developed linguistically and culturally tailored outreach strategies to promote and enhance its annual Nicotine Patch and Gum Program. In 2010, online web applications in Chinese and Russian were introduced. In 2011, input was sought from the community to develop Russian-language radio and newspaper ads, and a Russian-speaking liaison provided phone-assisted online enrollment support. In 2012, Chinese newspaper ads were introduced, and a Cantonese- and Mandarin-speaking liaison was hired to provide enrollment support. In 2010, 51 Russian speakers and 40 Chinese speakers enrolled in the program via web application. In 2011, 510 Russian speakers applied via the web application, with 463 assisted by the Russian-speaking liaison; forty-four Chinese speakers applied online. In 2012, 394 Russian speakers applied via the web application; 363 were assisted by the Russian-speaking liaison. Eighty-five Chinese smokers applied online via the web application; seventy were assisted by the Chinese-speaking liaison. Following the implementation of culturally tailored cessation support interventions, ethnic Russian smokers' uptake of cessation support increased tenfold, while Chinese smokers' uptake doubled. Although linguistically appropriate resources are an essential foundation for reaching immigrant communities with high smoking rates, devising culturally tailored strategies to increase quit rates is critical to programmatic success.

Availability and range of tobacco products for sale in Massachusetts pharmacies.

PubMed

Seidenberg, Andrew B; Hong, Weiwei; Liu, Jiayue; Noel, Jonathan K; Rees, Vaughan W

2013-11-01

New tobacco control policies have been introduced in Massachusetts which restrict tobacco product sales in pharmacies. The purpose of this investigation was to outline the scope of pharmacy involvement in the tobacco market by assessing the availability and range of tobacco products sold in Massachusetts pharmacies. Public listings of licenced pharmacies and tobacco retailers in Massachusetts were examined to determine the proportion of pharmacies licenced to sell tobacco, and the proportion of tobacco retailers possessing a pharmacy licence. Telephone interviews were conducted with a random sample (n=70) of pharmacies possessing a tobacco licence to assess the availability and range of tobacco products for sale. The availability of nicotine replacement therapy (NRT) products was assessed as a comparison. The majority of pharmacies in Massachusetts possessed a tobacco licence (69%), and pharmacies made up 9% of licenced tobacco retailers. Among pharmacies surveyed that reported selling tobacco (90%), cigarettes were the most available tobacco product for sale (100%), followed by cigars (69%), little cigars/cigarillos (66%), moist snuff (53%), pipe tobacco (49%), roll-your-own tobacco (34%), snus (14%), dissolvable tobacco (11%) and electronic cigarettes (2%). Nearly all pharmacies selling tobacco offered the nicotine patch (100%), gum (100%) and lozenge (98%). Tobacco-free pharmacy policies would affect a majority of Massachusetts pharmacies and remove a variety of tobacco products from their store shelves. Further, nearly one in ten tobacco retailers would be eliminated by prohibiting tobacco sales in Massachusetts pharmacies statewide.

Assessing Constituent Levels in Smokeless Tobacco Products: A New Approach to Engaging and Educating the Public.

PubMed

Borgida, Eugene; Loken, Barbara; Williams, Allison L; Vitriol, Joseph; Stepanov, Irina; Hatsukami, Dorothy

2015-11-01

Providing accurate information about the constituents in nicotine-containing products may help tobacco users make informed decisions about product choices. An experimental study examined a novel approach for presenting accurate constituent information about brands and types of smokeless tobacco (SLT) that could be understood by the general public. Participants were recruited through Amazon's Mechanical Turk and presented information online about 2 constituent dimensions of SLT products-nicotine and/or toxicity (for simplicity, "toxicity" in this study refers to carcinogenic constituents) Participants completed measures of knowledge and tobacco health risks at 2 time points: before and after exposure to constituent information. Participants were found to increase their knowledge that toxicity contributes to disease risk and nicotine contributes to addiction, that SLT products vary in their levels of nicotine and toxicity, and that both SLT and cigarette products have higher toxicity than medicinal nicotine replacement therapies (e.g., nicotine lozenges). Study results showed no differences when presenting toxicity information alone versus presenting it in conjunction with nicotine information, and found no misperceptions or confusions about the relative harmfulness of cigarettes, SLT, or nicotine replacement therapy. Providing tobacco constituent information to smokers and nonsmokers will improve their knowledge about the relative toxicity across products and variations within a class of tobacco products without compromising the health risks associated with tobacco use. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Using free patches to improve reach of the Oregon Quit Line.

PubMed

Deprey, Mona; McAfee, Tim; Bush, Terry; McClure, Jennifer B; Zbikowski, Susan; Mahoney, Lisa

2009-01-01

For 2 1/2 months, the Oregon Tobacco Quit Line (ORQL) offered a free 2-week starter kit of nicotine patches to all callers. The promotional plan, utilizing Roger's Diffusion of Innovation theory, targeted health plans, local policy makers, media sources, and referral sources, such as healthcare providers. Word-of-mouth advertising was also encouraged using a free patch card, which could be handed out to tobacco users. Six weeks prior to the public launch, information about the initiative was disseminated by e-mailing and sending letters to public and private sector partners. Call volume to the ORQL was monitored 6 months prior to the Free Patch Initiative and immediately following the launch. Demographic characteristics of callers pre- and postinitiative were compared using ORQL data. A media firm tracked earned media generated by the initiative. The Initiative generated free "earned" media attention, increased calls to the ORQL by 12-fold, and reached 1.3% of the smoking population within a 3-month period. Offering a short course of free NRT is an effective way to promote the use of quitlines.

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delijewski, Marcin; Beberok, Artur; Otręba, Michał

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanizationmore » process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.« less

Pharmacological treatment of tobacco dependence.

PubMed

Jarvik, M E; Henningfield, J E

1988-05-01

Pharmacologically based approaches for the treatment of tobacco dependence are reviewed. The rational basis for pharmacologic treatment approaches is that tobacco dependence is partially, and critically, mediated by the actions of tobacco-delivered nicotine to the central nervous system. These actions include direct reinforcing properties of nicotine itself, tolerance and physiologic dependence, possible beneficial effects of nicotine in the alleviation of anxiety and control of weight, and neurohormonal regulation which can become important to the maintenance of emotional well-being and performance at work. Insofar as tobacco abstinence leads to negative consequences, via these biobehavioral mechanisms, pharmacologic intervention should be able to assist in initial tobacco detoxification and help tobacco abstinent persons to avoid subsequent relapse. The purpose of this review is to survey some of the efforts to develop such interventions, as well as to elucidate some of the issues relevant to such development. Four distinct approaches are discussed: (1) Nicotine replacement, in which physiologic dependence is transferred to a safer and more therapeutically manageable nicotine delivering formulation; this category includes nicotine polacrilex gum; (2) Blockade therapy, in which a drug is taken that blocks the reinforcing properties of nicotine should relapse occur; (3) Nonspecific pharmacotherapy, in which the biobehaviorally mediated correlates of tobacco abstinence are treated on a symptomatic basis; (4) Deterrent therapy, in which a drug is taken prior to smoking such that any tobacco use would produce reliable aversive effects.

Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells.

PubMed

Hone, Arik J; Michael McIntosh, J; Rueda-Ruzafa, Lola; Passas, Juan; de Castro-Guerín, Cristina; Blázquez, Jesús; González-Enguita, Carmen; Albillos, Almudena

2017-01-01

Varenicline is a nicotinic acetylcholine receptor (nAChR) agonist used to treat nicotine addiction, but a live debate persists concerning its mechanism of action in reducing nicotine consumption. Although initially reported as α4β2 selective, varenicline was subsequently shown to activate other nAChR subtypes implicated in nicotine addiction including α3β4. However, it remains unclear whether activation of α3β4 nAChRs by therapeutically relevant concentrations of varenicline is sufficient to affect the behavior of cells that express this subtype. We used patch-clamp electrophysiology to assess the effects of varenicline on native α3β4* nAChRs (asterisk denotes the possible presence of other subunits) expressed in human adrenal chromaffin cells and compared its effects to those of nicotine. Varenicline and nicotine activated α3β4* nAChRs with EC 50 values of 1.8 (1.2-2.7) μM and 19.4 (11.1-33.9) μM, respectively. Stimulation of adrenal chromaffin cells with 10 ms pulses of 300 μM acetylcholine (ACh) in current-clamp mode evoked sodium channel-dependent action potentials (APs). Under these conditions, perfusion of 50 or 100 nM varenicline showed very little effect on AP firing compared to control conditions (ACh stimulation alone), but at higher concentrations (250 nM) varenicline increased the number of APs fired up to 436 ± 150%. These results demonstrate that therapeutic concentrations of varenicline are unlikely to alter AP firing in chromaffin cells. In contrast, nicotine showed no effect on AP firing at any of the concentrations tested (50, 100, 250, and 500 nM). However, perfusion of 50 nM nicotine simultaneously with 100 nM varenicline increased AP firing by 290 ± 104% indicating that exposure to varenicline and nicotine concurrently may alter cellular behavior such as excitability and neurotransmitter release. © 2016 International Society for Neurochemistry.

E-cigarettes and smoking cessation. Similar efficacy to other nicotine delivery devices, but many uncertainties.

PubMed

2015-11-01

E-cigarettes, marketed as an alternative to conventional cigarettes, are designed to transform a solution of variable composition, with or without nicotine, into an aerosol that the user inhales. How effective are e-cigarettes as an aid to smoking cessation, and what are their known adverse effects? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. A randomised trial involving 657 individuals who wanted to stop smoking compared e-cigarettes (with or without nicotine) with nicotine patches. There was no difference between the groups after 6 months, with an overall quit rate of about 5%. A double-blind randomised trial including 300 smokers compared the impact of e-cigarettes with or without nicotine on tobacco consumption. After 3 months, 14% of those using e-cigarettes with nicotine had quit completely, compared to 4% of those using e-cigarettes without nicotine. Adverse events reported in these trials were mild and transient, and mainly included dry mouth, irritation of the mouth and throat, dizziness, and nausea. When the solution ("e-liquid") contains nicotine, the main adverse effects are those of nicotine. Bronchial disorders, neuropsychiatric disorders and ocular irritation have been reported with inhaled propylene glycol. The effects of propylene glycol and glycerol, when heated and inhaled over long periods, are not known. The addictive effect is difficult to determine. Long-term use of e-cigarettes has been observed in about one-third of people who stopped smoking. Toxic or carcinogenic substances have been found in some e-cigarette aerosols, but at lower concentrations than in tobacco smoke. The diversity in the composition of e-liquids and the lack of proper controls make it difficult to assess the associated dangers. In early 2015, e-cigarettes containing nicotine appear to have efficacy similar to that of other nicotine delivery systems as an aid to smoking cessation. Apart from the effects of nicotine, there are few known adverse effects. However, there are many uncertainties as to the composition of the different e-liquids and the long-term effects of the substances when they are heated and inhaled. There is no reason to discourage smokers from substituting the proven, serious harms of tobacco smoke with the potential and poorly defined harms associated with e-cigarettes.

Predictors of adherence to pharmacological and behavioral treatment in a cessation trial among smokers in Aleppo, Syria.

PubMed

Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Bahelah, Raed; Maziak, Wasim

2015-08-01

The development of evidence-based smoking cessation programs is in its infancy in developing countries, which continue to bear the main brunt of the tobacco epidemic. Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs, but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries settings. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country. Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site, two-group, parallel-arm, double-blind, randomized, placebo-controlled smoking cessation trial in primary care clinics in Aleppo, Syria. Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions, and were randomized to either 6 weeks of nicotine or placebo patch. Of the 269 participants, 68% adhered to pharmacological treatment, while 70% adhered to behavioral counseling. In logistic regression modeling, lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline, greater withdrawal symptoms, and perception of receiving placebo instead of active nicotine patch. Women showed lower adherence than men to behavioral treatment, while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment. Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence, and address concurrent waterpipe use at all stages. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence.

PubMed

Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

2017-08-01

Because electronic cigarettes (e-cigs) containing nicotine may relieve smoking abstinence symptoms similar to nicotine replacement therapy medication, we used within-subjects designs to test these effects with a first-generation e-cig in nonquitting and quitting smokers. In Study 1, 28 nontreatment-seeking smokers abstained overnight prior to each of 3 sessions. Minnesota Nicotine Withdrawal Scale (MNWS) withdrawal (and craving item) relief was assessed following 4 exposures (each 10 puffs) over 2 hr to e-cigs that either did (36 mg/ml) or did not (i.e., placebo, 0 mg/ml) contain nicotine or after no e-cig. Relief was greater after nicotine versus placebo e-cig (p < .05) but not after placebo versus no e-cig, showing relief was due to nicotine per se and not simple e-cig use behavior. Using a crossover design in Study 2, smokers preparing to quit soon engaged in 2 experimental 4-day quit periods on separate weeks. In weeks 1 and 3, all received a nicotine or placebo e-cig on Monday to use ad libitum while trying to abstain from smoking on Tuesday through Friday. (Week 2 involved resumption of ad libitum smoking.) MNWS and Questionnaire of Smoking Urges (QSU) craving were assessed at daily visits following 24-hr abstinence. Of 17 enrolled, 12 quit for ≥24 hr at least once, allowing test of relief because of e-cig use on quit days. Withdrawal and craving were reduced because of nicotine versus placebo e-cig use (both p < .05). In sum, compared with placebo e-cigs, nicotine e-cigs can relieve smoking abstinence symptoms, perhaps in a manner similar to Food and Drug Administration-approved nicotine replacement therapy products, although much more research with larger samples is needed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Smoking topography and abstinence in adult female smokers.

PubMed

McClure, Erin A; Saladin, Michael E; Baker, Nathaniel L; Carpenter, Matthew J; Gray, Kevin M

2013-12-01

Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e., smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers. © 2013 Elsevier Ltd. All rights reserved.

Disrupting nicotine reinforcement: from cigarette to brain.

PubMed

Rose, Jed E

2008-10-01

Cigarette smoking is a tenacious addiction that is maintained to a significant extent by the reinforcing effects of nicotine. An emerging theme in smoking cessation treatment is the development of methods for interfering with these reinforcing effects. By attenuating nicotine reinforcement, treatments may enhance a smoker's chances of successfully remaining abstinent. Several treatment approaches will be described, including the use of denicotinized cigarettes, nicotine vaccines, nicotinic receptor agonists and antagonists, and modulators of brain reinforcement processes. These techniques highlight the numerous sites along the path between the cigarette and the brain that can be targeted for intervention. In addition to unimodal therapies, treatment combinations will be discussed that might more effectively block cigarette reward and thereby further enhance smoking abstinence.

Comparative Effectiveness of Motivation Phase Intervention Components for Use with Smokers Unwilling to Quit: A Factorial Screening Experiment

PubMed Central

Cook, Jessica W.; Collins, Linda M.; Fiore, Michael C.; Smith, Stevens S.; Fraser, David; Bolt, Daniel M.; Baker, Timothy B.; Piper, Megan E.; Schlam, Tanya R.; Jorenby, Douglas; Loh, Wei-Yin; Mermelstein, Robin

2015-01-01

Aims To screen promising intervention components designed to reduce smoking and promote abstinence in smokers initially unwilling to quit. Design A balanced, 4-factor, randomized factorial experiment. Setting Eleven primary care clinics in southern Wisconsin, USA. Participants 517 adult smokers (63% women, 91% White) recruited during primary care visits who were willing to reduce their smoking but not quit. Interventions Four factors contrasted intervention components designed to reduce smoking and promote abstinence: 1) nicotine patch vs. none; 2) nicotine gum vs. none; 3) motivational interviewing (MI) vs. none; and 4) behavioral reduction counseling (BR) vs. none. Participants could request cessation treatment at any point during the study. Measurements The primary outcome was percent change in cigarettes smoked per day at 26 weeks post-study enrollment; the secondary outcomes were percent change at 12 weeks and point-prevalence abstinence at 12 and 26 weeks post-study enrollment. Findings There were few main effects, but a significant 4-way interaction at 26-weeks post-study enrollment (p=.01, β = .12) revealed relatively large smoking reductions by two component combinations: nicotine gum combined with BR and BR combined with MI. Further, BR improved 12-week abstinence rates (p=.04), and nicotine gum, when used without MI, increased abstinence after a subsequent aided quit attempt (p=.01). Conclusions Motivation-phase nicotine gum and behavioral reduction counseling are promising intervention components for smokers who are initially unwilling to quit. PMID:26582140

Combination nicotine replacement therapy: strategies for initiation and tapering.

PubMed

Hsia, Stephanie L; Myers, Mark G; Chen, Timothy C

2017-04-01

Several studies and meta-analyses have demonstrated the efficacy of combination nicotine replacement therapy (NRT) for patients who wish to quit smoking. However, there is limited guidance with respect to initiation and tapering of combination NRT. We attempt to review the evidence and rationale behind combination NRT, present the dosing used in combination NRT studies, and propose a step-down approach for tapering of combination NRT with integration of behavioral strategies. Copyright © 2017. Published by Elsevier Inc.

Electrophysiological investigation of the effect of structurally different bispyridinium non-oxime compounds on human α7-nicotinic acetylcholine receptor activity-An in vitro structure-activity analysis.

PubMed

Scheffel, Corinna; Niessen, Karin V; Rappenglück, Sebastian; Wanner, Klaus T; Thiermann, Horst; Worek, Franz; Seeger, Thomas

2018-09-01

Organophosphorus compounds, including nerve agents and pesticides, exert their toxicity through irreversible inhibition of acetylcholinesterase (AChE) resulting in an accumulation of acetylcholine and functional impairment of muscarinic and nicotinic acetylcholine receptors. Current therapy comprises oximes to reactivate AChE and atropine to antagonize effects induced by muscarinic acetylcholine receptors. Nicotinic malfunction leading to depression of the central and peripheral respiratory system is not directly treated calling for alternative therapeutic interventions. In the present study, we investigated the electrophysiological properties of the human nAChR subtype α7 (hα7-nAChR) and the functional effect of the 4-tert-butyl bispyridinium (BP) compound MB327 and of a series of novel substituted bispyridinium compounds on the receptors by an automated patch clamp technique. Activation of hα7-nAChRs was induced by nicotine and acetylcholine demonstrating rapid cationic influx up to 100μM. Agonist-induced currents decayed within a few milliseconds revealing fast desensitization of the receptors. Application of higher agonist concentrations led to a decline of current amplitudes which seemed to be due to increasing receptor desensitization. When 100μM of agonist was coapplied with low concentrations of the well characterized α7-specific positive allosteric modulator PNU-120596 (1μM-10μM), the maximum response and duration of nAChR activation were markedly augmented indicating an elongated mean open-time of receptors and prevention of receptor desensitization. However, co-application of increasing PNU-120596 concentrations (>10μM) with agonist induced a decline of potentiated current responses. Although less pronounced than PNU-120596, six of the twenty tested substituted BP compounds, in particular those with a substituent at 3-position and 4-position at the pyridinium moieties, were found to potentiate current responses of hα7-nAChRs, most pronounced MB327.This effect was clearly depended on the presence of the agonist indicating a positive allosteric mechanism of these compounds. Besides potentiation at low concentrations, these compounds seem to interact at different binding sites on hα7-nAChRs since enhancement decreased at high concentrations. The residual fourteen BP compounds, possessing either an isopropyl-group or more than one group at the pyridinium moiety, antagonized nicotinic currents exhibiting IC 50 of low up to high micromolar concentrations (∼1μM-300μM). Copyright © 2017 Elsevier B.V. All rights reserved.

The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens [corrected].

PubMed

Balfour, David J K

2004-12-01

It is now widely accepted that nicotine is the primary addictive component of tobacco smoke and that a majority of habitual smokers find it difficult to quit smoking because of their dependence upon this component of the smoke. However, although nicotine replacement therapy elicits a clinically valuable and significant improvement in the number of quit attempts that are ultimately successful, its efficacy remains disappointingly low. This review considers some of the reasons for this problem. It focuses on the hypothesis that stimulation of the dopamine (DA) projections to the medial shell and the core of the nucleus accumbens play complementary roles in the development of nicotine dependence. The hypothesis proposes that increased extra-synaptic DA in the medial shell of the accumbens confers hedonic properties on behaviors, such as smoking, which deliver nicotine, and thereby increase the probability that the response is learned. It also summarizes the evidence that the primary role of the increased DA overflow, observed in the accumbal core of nicotine-pretreated individuals, challenged with nicotine, is the attribution of incentive salience to cues associated with delivery of the drug and the transition to Pavlovian responding to these conditioned stimuli. The review argues that sensitization of the DA projections to the accumbal core, and the behaviors that depend upon this process, play a pivotal role in the maintenance of the tobacco smoking habit and that it is this component of the dependence that is inadequately addressed by nicotine replacement therapy.

Nicotinic receptors as CNS targets for Parkinson's disease.

PubMed

Quik, Maryka; Bordia, Tanuja; O'Leary, Kathryn

2007-10-15

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal alpha6beta2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, alpha4beta2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to alpha6beta2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics.

The relevance and treatment of cue-induced cravings in tobacco dependence.

PubMed

Ferguson, Stuart G; Shiffman, Saul

2009-04-01

Craving to smoke is often conceptualized and measured as a tonic, slowly changing state induced by abstinence. In this article, we review the literature on the existence, causes, and treatment of cue-induced cravings: intense, episodic cravings typically provoked by situational cues associated with drug use. In laboratory research, smokers exposed to smoking-related cues demonstrate increased craving as well as distinct patterns of brain activation. Observational field studies indicate that such cue-induced cravings are substantially responsible for relapse to smoking but that smoking can often be averted by coping responses. The effects of pharmacological interventions are mixed. Steady-state medications (bupropion, varenicline, nicotine patch) do not appear to protect smokers from cue-induced cravings. However, acutely administered nicotine medications (such as nicotine gum and lozenge), used after cue exposure as "rescue medications," can help a smoker's recovery from cue-induced cravings. Cue-induced craving plays an important role in smoking and relapse and likely in other addictions as well. Treatments to mitigate the effect of cue-induced craving are both important and needed.

The role of nicotine content information in smokers' subjective responses to nicotine and placebo inhalers.

PubMed

Darredeau, Christine; Barrett, Sean P

2010-11-01

A growing body of evidence suggests that non-pharmacological factors may play an important role in smoking cessation outcomes using nicotine replacement therapies. This study examined the role of information about nicotine content in smokers' subjective responses to nicotine and placebo inhalers, using the four conditions of the balanced-placebo design in a mixed within/between-subjects design. Twenty-four adult smokers (12 male) completed two laboratory sessions following overnight abstinence from smoking. Participants were randomly assigned to receive either nicotine inhalers or placebo inhalers in both sessions but were told that they received a nicotine-containing inhaler in one session and a nicotine-free inhaler in the other. In each session participants completed subjective assessments before and after inhaler administration using visual analogue scales and the Brief Questionnaire of Smoking Urges. While neither nicotine content nor information about it significantly affected cigarette craving associated with withdrawal relief, participants reported a greater reduction in craving associated with intention to smoke when told the inhalers contained nicotine than when told the inhalers were nicotine-free, regardless of actual nicotine content. Findings suggest that psychological factors play an important role in smokers' subjective responses to nicotine inhalers, the effects of which cannot be solely attributed to the direct pharmacological effects of nicotine. Copyright © 2011 John Wiley & Sons, Ltd.

Treating nicotine dependence by targeting attention-deficit/ hyperactivity disorder (ADHD) with OROS methylphenidate: the role of baseline ADHD severity and treatment response.

PubMed

Nunes, Edward V; Covey, Lirio S; Brigham, Gregory; Hu, Mei-Chen; Levin, Frances R; Somoza, Eugene C; Winhusen, Theresa M

2013-10-01

To determine whether treatment of attention-deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. This is a secondary analysis of data from a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites; the original trial was sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n = 127) or matching placebo (n = 128). All participants received nicotine patches (21 mg/d) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline ADHD Rating Scale-IV (ADHD-RS) score, change in ADHD-RS score during treatment, and their interactions. Treatment interacted with both ADHD-RS score at baseline (P = .01) and change in ADHD-RS score during treatment (P = .008). Among patients with higher ADHD-RS scores (> 36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score ≥ 24), 70.0% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo (P = .02). In contrast, among patients with the lowest ADHD-RS baseline scores (≤ 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo (P = .02). OROS methylphenidate, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD and more robust response of ADHD symptoms to medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD. ClinicalTrials.gov identifier: NCT00253747. © Copyright 2013 Physicians Postgraduate Press, Inc.

Urushiol Patch Test Using the T.R.U.E. TEST System.

PubMed

Kim, Yesul; Longenecker, Amy; ElSohly, Mahmoud A; Gul, Waseem; Hage, Raymond J; Hamann, Curtis P; Marks, James G

Poison ivy, poison oak, and poison sumac are the most common causes of allergic contact dermatitis in North America. Although extensive efforts have been made to develop therapies that prevent and treat allergic contact dermatitis to these plants, there lacks an entirely effective method, besides complete avoidance. Efforts to develop a more effective preventive therapy, such as a vaccine, are ongoing. To accurately evaluate the efficacy of these new therapies, an appropriate assessment tool is needed. The aim of this study was to evaluate the safety and appropriate doses of urushiol required for a patch test based on the hydrogel delivery system of the Thin-Layer Rapid Use Epicutaneous Patch Test. Nine subjects were patch tested with various doses of urushiol and a negative control on day 0. Patch test sites were inspected for any local reaction on days 2, 4, 7, 14, and 21 after the initial exposure and graded by standard morphology. All 9 subjects did not have any significant adverse effects. The urushiol patch test using the hydrogel delivery method demonstrated urushiol sensitivity. All doses of urushiol resulted in a local reaction, and severity of reactions was correlated with dosage of urushiol used in the patch test.

Connections of nicotine to cancer.

PubMed

Grando, Sergei A

2014-06-01

This Opinion article discusses emerging evidence of direct contributions of nicotine to cancer onset and growth. The list of cancers reportedly connected to nicotine is expanding and presently includes small-cell and non-small-cell lung carcinomas, as well as head and neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical, urinary bladder and kidney cancers. The mutagenic and tumour-promoting activities of nicotine may result from its ability to damage the genome, disrupt cellular metabolic processes, and facilitate growth and spreading of transformed cells. The nicotinic acetylcholine receptors (nAChRs), which are activated by nicotine, can activate several signalling pathways that can have tumorigenic effects, and these receptors might be able to be targeted for cancer therapy or prevention. There is also growing evidence that the unique genetic makeup of an individual, such as polymorphisms in genes encoding nAChR subunits, might influence the susceptibility of that individual to the pathobiological effects of nicotine. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the evaluation of regulations on nicotine product manufacturing, distribution and marketing.

Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective.

PubMed

Roze, S; Ferrières, J; Bruckert, E; Van Ganse, E; Chapman, M J; Liens, D; Renaudin, C

2007-11-01

To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C < 40 mg/dl (1.03 mmol/l) on statin alone. The second submodel used standard Markov techniques to evaluate long-term clinical and economic outcomes based on Framingham risk estimates. Direct medical costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (< 50,000 euros per life year gained) considered good value for money in Western Europe. Raising HDL-C by adding PR nicotinic acid to statin therapy in CHD patients was cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes.

A Pragmatic Approach to Patch Testing Atopic Dermatitis Patients: Clinical Recommendations Based on Expert Consensus Opinion.

PubMed

Chen, Jennifer K; Jacob, Sharon E; Nedorost, Susan T; Hanifin, Jon M; Simpson, Eric L; Boguniewicz, Mark; Watsky, Kalman L; Lugo-Somolinos, Aida; Hamann, Carsten R; Eberting, Cheryl Lee; Silverberg, Jonathan I; Thyssen, Jacob P

2016-01-01

Allergic contact dermatitis (ACD) may complicate the clinical course of atopic dermatitis (AD), and patch testing remains the criterion standard for diagnosing ACD. To date, there have been no guidelines or consensus recommendations on when and how to patch test individuals with AD. Failure to patch test when appropriate may result in overlooking an important and potentially curable complicating comorbidity. In this article, we present consensus recommendations regarding when to perform patch testing in the AD patient, best practices, and common pitfalls. Patch testing should be considered in AD patients with dermatitis that fails to improve with topical therapy; with atypical/changing distribution of dermatitis, or pattern suggestive of ACD; with therapy-resistant hand eczema in the working population; with adult- or adolescent-onset AD; and/or before initiating systemic immunosuppressants for the treatment of dermatitis. A suggested patch testing algorithm for AD patients is provided.

Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers.

PubMed

Gu, Xiaosi; Lohrenz, Terry; Salas, Ramiro; Baldwin, Philip R; Soltani, Alireza; Kirk, Ulrich; Cinciripini, Paul M; Montague, P Read

2016-01-01

Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told "nicotine" vs. told "no nicotine") with the nicotine content in a cigarette (nicotine vs. placebo) which participants smoked immediately before performing a fMRI task involving reward learning. Subjects' reported craving was measured both before smoking and after the fMRI session. We found that first, in the presence of nicotine, smokers demonstrated significantly reduced craving after smoking when told "nicotine in cigarette" but showed no change in craving when told "no nicotine." Second, neural activity in the insular cortex related to craving was only significant when smokers were told "nicotine" but not when told "no nicotine." Both effects were absent in the placebo condition. Third, insula activation related to computational learning signals was modulated by belief about nicotine regardless of nicotine's presence. These results suggest that belief about nicotine has a strong impact on subjective craving and insula responses related to both craving and learning in deprived smokers, providing insights into the complex nature of belief-drug interactions.

Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial.

PubMed

Toll, Benjamin A; White, Marney; Wu, Ran; Meandzija, Boris; Jatlow, Peter; Makuch, Robert; O'Malley, Stephanie S

2010-10-01

Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting. Smokers (N=172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date. The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43). For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Efficacy of electronic cigarettes for smoking cessation.

PubMed

Orr, Katherine Kelly; Asal, Nicole J

2014-11-01

To review data demonstrating effective smoking cessation with electronic cigarettes (e-cigarettes). A literature search of MEDLINE/PubMed (1946-March 2014) was performed using the search terms e-cigarettes, electronic cigarettes, and smoking cessation. Additional references were identified from a review of literature citations. All English-language clinical studies assessing efficacy of e-cigarettes compared with baseline, placebo, or other pharmacological methods to aid in withdrawal symptoms, smoking reduction, or cessation were evaluated. A total of 6 clinical studies were included in the review. In small studies, e-cigarettes significantly decreased desire to smoke, number of cigarettes smoked per day, and exhaled carbon monoxide levels. Symptoms of nicotine withdrawal and adverse effects were variable. The most common adverse effects were nausea, headache, cough, and mouth/throat irritation. Compared with nicotine patches, e-cigarettes were associated with fewer adverse effects and higher adherence. Most studies showed a significant decrease in cigarette use acutely; however, long-term cessation was not sustained at 6 months. There is limited evidence for the effectiveness of e-cigarettes in smoking cessation; however, there may be a place in therapy to help modify smoking habits or reduce the number of cigarettes smoked. Studies available provided different administration patterns such as use while smoking, instead of smoking, or as needed. Short-term studies reviewed were small and did not necessarily evaluate cessation with a focus on parameters associated with cessation withdrawal symptoms. Though long-term safety is unknown, concerns regarding increased poisoning exposures among adults in comparison with cigarettes are alarming. © The Author(s) 2014.

Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Mei-Fang

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O{sub 2} demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp,more » and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation and, possibly, normal blood flow in the brainstem. - Highlights: • Ketamine/amphetamines inhibit nicotine-induced cerebral neurogenic vasdilation. • Ketamine/amphetamines block cerebral perivascular sympathetic nAChR-mediated current. • The inhibitory potency is ketamine > D-amphetamine > methamphetamine > OH-amphetamine.« less

Age-dependent differences in nicotine reward and withdrawal in female mice.

PubMed

Kota, D; Martin, B R; Damaj, M I

2008-06-01

Adolescent smoking is an increasing epidemic in the US. Research has shown that the commencement of smoking at a young age increases addiction and decreases the probability of successful cessation; however, limited work has focused on nicotine dependence in the female. The goal of the present study was to identify the biological and behavioral factors that may contribute to nicotine's increased abuse liability in female adolescents using animal models of nicotine dependence. Early adolescent (PND 28) and adult (PND 70) female mice were compared in various aspects of nicotine dependence using reward and withdrawal models following sub-chronic nicotine exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were examined. In the conditioned place preference model, adolescents demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit rewarding effects. Furthermore, adolescents displayed increased physical, but not affective, withdrawal signs in three models. Upon acute exposure to nicotine, adolescent mice showed increased sensitivity in an analgesic measure as well as hypothermia. After chronic nicotine exposure, both adults and adolescents displayed tolerance to nicotine with adolescents having a lower degree of tolerance to changes in body temperature. These data indicate that differences in nicotine's rewarding and aversive effects may contribute to variations in certain components of nicotine dependence between adult and adolescent female mice. Furthermore, this implies that smoking cessation therapies may not be equally effective across all ages.

Effects on agitation with rivastigmine patch monotherapy and combination therapy with memantine in mild to moderate Alzheimer's disease: a multicenter 24-week prospective randomized open-label study (the Korean EXelon Patch and combination with mEmantine Comparative Trial study).

PubMed

Yoon, Soo J; Choi, Seong H; Na, Hae R; Park, Kyung-Won; Kim, Eun-Joo; Han, Hyun J; Lee, Jae-Hong; Shim, Young S; Na, Duk L

2017-03-01

Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients. This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms. Factor analyses showed two symptom clusters: factor A - aggressive agitated behaviors - versus factor B - non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms. In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494-499. © 2016 Japan Geriatrics Society.

Review of the evidence that pH is a determinant of nicotine dosage from oral use of smokeless tobacco.

PubMed

Tomar, S L; Henningfield, J E

1997-01-01

To determine whether manipulation of the pH of moist-snuff products by manufacturers could control the delivery of nicotine. Medline database 1966-97 using the following subject headings and keywords: nicotine, absorption, mouth mucosa, skin, hydrogen-ion concentration, smokeless tobacco, biological transport, and membranes; computer database of the tobacco bibliography maintained by the US Centers for Disease Control and Prevention's Office on Smoking and Health; bibliographies of pertinent journal articles, books, and governmental reports; personal communications with experts in nicotine pharmacology and addiction; and Brown & Williamson Tobacco Corporation documents in the Tobacco Control Archives of the University of California, San Francisco. Included all relevant animal studies, in-vitro studies, nicotine replacement therapy trials, and human observational studies. We found that the effects of pH on drug absorption have been well established in animal models for nicotine and many other acidic or basic compounds. Increased alkalinity promotes the absorption of nicotine and increases its physiological effects. Human studies, which are more limited, confirm these processes. For example, nicotine absorption is directly related to the pH when nicotine is delivered in either tobacco smoke or nicotine polacrilex gum. Although other factors could influence the rate of nicotine absorption from oral tobacco, manipulating tobacco pH appears to be the primary means by which the speed of nicotine absorption is determined in moist-snuff products.

Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective.

PubMed

Cheah, Nuan Ping; Chong, Norman Wee Lin; Tan, Jing; Morsed, Faridatul Akmam; Yee, Shen Kuan

2014-03-01

Many electronic nicotine delivery systems (ENDS) are marketed as safer tobacco alternative products or effective cessation therapies. ENDS samples were evaluated for design features, including nicotine and glycols content. This could be useful in developing a legal framework to handle ENDS. Identification of the nicotine, glycerol and propylene glycol (PPG) contents was conducted using gas chromatography mass spectrometry with quantification performed using flame ionisation techniques. Varying nicotine amounts were found in ENDS cartridges which were labelled with the same concentration. Chemicals such as PPG and glycerol were found to be present in the nicotine-containing liquid of the cartridges. ENDS varied in their contents and packaging information. Limited information was available on the contents of nicotine and other chemicals present in a variety of ENDS sampled. Based on samples tested in this study, many contain misleading information on product ingredients. The results show poor consistency between actual nicotine content analysed on ENDS cartridges and the amount labelled. These findings raise safety and efficacy concerns for current and would-be recreational users or those trying to quit smoking.

Comparison of the efficacies of patching and penalization therapies for the treatment of amblyopia patients

PubMed Central

Cabi, Cemalettin; Sayman Muslubas, Isil Bahar; Aydin Oral, Ayse Yesim; Dastan, Metin

2014-01-01

AIM To compare the efficacies of patching and penalization therapies for the treatment of amblyopia patients. METHODS The records of 64 eyes of 50 patients 7 to 16y of age who had presented to our clinics with a diagnosis of amblyopia, were evaluated retrospectively. Forty eyes of 26 patients who had received patching therapy and 24 eyes of 24 patients who had received penalization therapy included in this study. The latencies and amplitudes of visual evoked potential (VEP) records and best corrected visual acuities (BCVA) of these two groups were compared before and six months after the treatment. RESULTS In both patching and the penalization groups, the visual acuities increased significantly following the treatments (P<0.05). The latency measurements of the P100 wave obtained at 1.0°, 15 arc min. Patterns of both groups significantly decreased following the 6-months-treatment. However, the amplitude measurements increased (P<0.05). CONCLUSION The patching and the penalization methods, which are the main methods used in the treatment of amblyopia, were also effective over the age of 7y, which has been accepted as the critical age for the treatment of amblyopia. PMID:24967195

Comparative effectiveness of motivation phase intervention components for use with smokers unwilling to quit: a factorial screening experiment.

PubMed

Cook, Jessica W; Collins, Linda M; Fiore, Michael C; Smith, Stevens S; Fraser, David; Bolt, Daniel M; Baker, Timothy B; Piper, Megan E; Schlam, Tanya R; Jorenby, Douglas; Loh, Wei-Yin; Mermelstein, Robin

2016-01-01

To screen promising intervention components designed to reduce smoking and promote abstinence in smokers initially unwilling to quit. A balanced, four-factor, randomized factorial experiment. Eleven primary care clinics in southern Wisconsin, USA. A total of 517 adult smokers (63.4% women, 91.1% white) recruited during primary care visits who were willing to reduce their smoking but not quit. Four factors contrasted intervention components designed to reduce smoking and promote abstinence: (1) nicotine patch versus none; (2) nicotine gum versus none; (3) motivational interviewing (MI) versus none; and (4) behavioral reduction counseling (BR) versus none. Participants could request cessation treatment at any point during the study. The primary outcome was percentage change in cigarettes smoked per day at 26 weeks post-study enrollment; the secondary outcomes were percentage change at 12 weeks and point-prevalence abstinence at 12 and 26 weeks post-study enrollment. There were few main effects, but a significant four-way interaction at 26 weeks post-study enrollment (P = 0.01, β = 0.12) revealed relatively large smoking reductions by two component combinations: nicotine gum combined with BR and BR combined with MI. Further, BR improved 12-week abstinence rates (P = 0.04), and nicotine gum, when used without MI, increased 26-week abstinence after a subsequent aided quit attempt (P = 0.01). Motivation-phase nicotine gum and behavioral reduction counseling are promising intervention components for smokers who are initially unwilling to quit. © 2015 Society for the Study of Addiction.

Cessation of Alcohol Consumption Decreases Rate of Nicotine Metabolism In Male Alcohol-Dependent Smokers#

PubMed Central

Gubner, Noah R.; Kozar-Konieczna, Aleksandra; Szoltysek-Boldys, Izabela; Slodczyk-Mankowska, Ewa; Goniewicz, Jerzy; Sobczak, Andrzej; Jacob, Peyton; Benowitz, Neal L.; Goniewicz, Maciej L.

2016-01-01

Background Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. Methods Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). Results and conclusions There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6 ± 1.3 vs. 4.1 ± 0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increases the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population. PMID:27107849

Cessation of alcohol consumption decreases rate of nicotine metabolism in male alcohol-dependent smokers.

PubMed

Gubner, Noah R; Kozar-Konieczna, Aleksandra; Szoltysek-Boldys, Izabela; Slodczyk-Mankowska, Ewa; Goniewicz, Jerzy; Sobczak, Andrzej; Jacob, Peyton; Benowitz, Neal L; Goniewicz, Maciej L

2016-06-01

Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6±1.3 vs 4.1±0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increase the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Knowledge about nicotine among HIV-positive smokers: Implications for tobacco regulatory science policy.

PubMed

Pacek, Lauren R; Rass, Olga; Johnson, Matthew W

2017-02-01

The present paper describes the general knowledge of smoking and nicotine among a sample of current smokers living with HIV (n=271) who were recruited via Amazon Mechanical Turk. Descriptive statistics were used to report sociodemographic and smoking characteristics, as well as knowledge about smoking and nicotine. The sample was comprised of relatively light smokers, both in terms of cigarettes per day (M=8.1, SD=9.7) and dependence (67.5% had low dependence according to the Heaviness of Smoking Index). The majority of participants correctly identified smoking as being a potential cause of various smoking-related conditions and correctly identified constituents in cigarette smoke. However, a majority of participants also misattributed nicotine as being a potential cause of smoking-related illness. Accurate knowledge about nicotine was low. These misperceptions are of particular concern for vulnerable populations, such as persons living with HIV, who are disproportionately burdened by the prevalence of smoking and associated morbidities and mortality. These misperceptions could have unintended consequences in the wake of a potential nicotine reduction policy, such that reduced nicotine content products are perceived as safer than normal nicotine content products currently available for sale. Additionally, incorrect knowledge about nicotine has implications for the uptake and continued use of nicotine replacement therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

PubMed Central

Yildirim, Emre; Connor, David A.; Gould, Thomas J.

2015-01-01

Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose–response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. PMID:25426579

In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

PubMed

Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P; Lichtman, Aron H; Carroll, F Ivy; Greenwald, Mark; Miles, Michael F; Damaj, M Imad

2017-05-15

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo Interactions between α7 Nicotinic Acetylcholine Receptor and Nuclear Peroxisome Proliferator-Activated Receptor-α: Implication for Nicotine Dependence

PubMed Central

Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P.; Lichtman, Aron H.; Carroll, F. Ivy; Greenwald, Mark; Miles, Michael F.; Damaj, M. Imad

2017-01-01

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. PMID:28279662

Dextromethorphan Interactions with Histaminergic and Serotonergic Treatments to Reduce Nicotine Self-administration in Rats

PubMed Central

Briggs, Scott A.; Hall, Brandon J.; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H.; Rose, Jed E.; Levin, Edward D.

2015-01-01

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2c agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with a lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, the acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with dextromethorphan and pyrilamine as well as lorcaserin. These findings suggest that combination therapy may be more effective smoking cessation treatments than monotherapy. PMID:26704812

Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

PubMed

Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

2016-03-01

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with dextromethorphan and pyrilamine as well as lorcaserin. These findings suggest that combination therapy may be more effective smoking cessation treatments than monotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Opioid Analgesics and Nicotine: More Than Blowing Smoke.

PubMed

Yoon, Jin H; Lane, Scott D; Weaver, Michael F

2015-09-01

Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

For Nicotine, Dose Matters | Center for Cancer Research

Cancer.gov

Nicotine replacement therapy (NRT) is frequently part of a person’s regimen for smoking cessation. The U.S. Food and Drug Administration has approved use of this approach for 12 weeks in supervised quitting programs. Unfortunately for some patients, though, this length of time is not long enough to break their addiction to tobacco. 

Tobacco Industry Research on Nicotine Replacement Therapy: "If Anyone Is Going to Take Away Our Business It Should Be Us".

PubMed

Apollonio, Dorie; Glantz, Stanton A

2017-10-01

Nicotine replacement therapy (NRT) is recommended for tobacco cessation on the basis of pharmaceutical industry research showing its effectiveness when combined with counseling. The tobacco industry opposed NRT when it first appeared in the 1980s but by 2016 was marketing its own NRT products. We used internal tobacco industry documents dated 1960 through 2010 to identify the industry's perceptions of NRT. As early as the 1950s, tobacco companies developed nonsmoked nicotine replacements for cigarettes, but they stopped out of concern that marketing such products would trigger Food and Drug Administration regulation of cigarettes. In the 1990s, after pharmaceutical companies began selling prescription NRT, tobacco companies found that many smokers used NRT to supplement smoking rather than to quit. In 2009, once the Food and Drug Administration began regulating tobacco, tobacco companies restarted their plans to capture the nicotine market. Although the tobacco industry initially viewed NRT as a threat, it found that smokers often combined NRT with smoking rather than using it as a replacement and began marketing their own NRT products.

[Post marketing surveillance study with an analgesic (transdermal buprenorphine patch) in patients with moderate to severe chronic pain].

PubMed

Tschirner, M; Ritzdorf, I; Brünjes, R

2008-09-18

To obtain information on the efficacy, tolerability and safetyofa transdermal buprenorphine patch (Transtec PRO) in patients with moderate to severe chronic pain. In addition it should be evaluated to what extent the two fixed patch change days per weekare simplifyingthe therapy. In this prospective multi-center post marketing surveillance study patients with chronic cancer and non-cancer pain were treated with transdermal buprenorphine for up to eight weeks. The evaluation included pain intensity, the dosage of the applied analgesics and additional therapies, the renal function (by serum creatinine) and adverse events. 3654 patients were treated for a mean of 50.4 days. Using the NRS-11 the mean pain intensity decreased from 6.3 at the time when patients were switched to the transdermal buprenorphine patch to 2.6 at the last treatment evaluation. The matrix patch was safe and well tolerated also in patients with advanced renal insufficiency. Adverse events were reported in 6.7% of the patients. 89.3% of the physicians quoted to prefer transdermal buprenorphine with the two fixed patch change days per week compared to the pre-treatment. The buprenorphine-containing matrix patch was effective and well tolerated in patients with moderate to severe chronic cancer and noncancer pain. From the physicians view the two fixed patch change days per week facilitate the guidance of therapy. In patients with advanced renal insufficiency a dose adjustment is not necessary.

The endocrine effects of nicotine and cigarette smoke

PubMed Central

Tweed, Jesse Oliver; Hsia, Stanley H.; Lutfy, Kabirullah; Friedman, Theodore C.

2012-01-01

With a current prevalence of approximately 20%, smoking continues to impact negatively upon health. Tobacco or nicotine use influences the endocrine system, with important clinical implications. In this review we critically evaluate the literature concerning the impact of nicotine as well as tobacco use on several parameters of the endocrine system and on glucose and lipid homeostasis. Emphasis is on the effect of smoking on diabetes mellitus and obesity and the consequences of smoking cessation on these disorders. Understanding the effects of nicotine and cigarettes on the endocrine system and how these changes contribute to the pathogenesis of various endocrine diseases will allow for targeted therapies and more effective approaches for smoking cessation. PMID:22561025

Tobacco Cessation Strategies: It Takes a Village.

PubMed

Chiu Qua, Debbie Anne

2017-01-01

Smoking is the leading cause of preventable death and chronic diseases in the U.S. Identifying smokers and providing appropriate intervention is therefore an integral part of each clinic visit. A combination of pharmacotherapy as well as behavioral counseling provides the best results. Pharmacotherapy includes nicotine replacement (patch, gum, lozenges), bupropion and varenicline. More recently, electronic nicotinic delivery systems (such as e-cigarettes, vaporizers/vape pens, and hookah pens) have become popular. Behavioral counseling includes identifying barriers to quitting or risk factors for relapse, and developing effective strategies to deal with these issues. A successful program requires a team-based approach, enlisting the help of adjuvant staff to reinforce cessation counseling and provide support services. The South Dakota Quitline is one of many good resources that the clinician can utilize to help with cessation and has one of the best quit rates in the nation. Copyright© South Dakota State Medical Association.

Varenicline for Tobacco Dependence

PubMed Central

Hays, J. Taylor; Ebbert, Jon O.

2010-01-01

A 57-year-old man with a 60-pack-year history visits his primary care provider because he wants to quit smoking. He has a history of stable coronary artery disease, peripheral vascular disease, and hypertension. He also has severe obstructive lung disease (forced expiratory volume in 1 second, 39% of the predicted value) with a progressive increase in dyspnea. He has quit smoking and has had numerous relapses; the longest duration of abstinence from smoking was 7 months. Each relapse involved casual smoking to “test himself.” During previous attempts to quit, he has used a nicotine patch, a nicotine inhaler, and sustained-release bupropion. He feels motivated to quit smoking because he recently heard about a new medication to aid in quitting, and he wants to improve his health. The patient and his physician discuss the therapeutic options and agree that varenicline (Chantix) may be an option. PMID:18987369

Is there a role for e-cigarettes in smoking cessation?

PubMed

Leduc, Charlotte; Quoix, Elisabeth

2016-04-01

The use of e-cigarettes has dramatically increased over the past few years and their role in smoking cessation remains controversial. Several clinical studies have evaluated their efficacy in smoking cessation but most of them are prospective cohort studies. Only two randomized, controlled trials have compared e-cigarettes versus placebo or patches. A meta-analysis of these two randomized, controlled trials has been performed. Nicotine-containing e-cigarettes appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo. However, these results are rated 'low' by GRADE standards. Many cohort studies have been conducted, with contradictory results. For some, e-cigarettes could increase the risk of nonsmokers developing nicotine dependence and of current smokers maintaining their dependence. The debate remains open and more randomized trials are needed with long-term data about the efficacy and safety of e-cigarettes. © The Author(s), 2015.

What happens when GPs proactively prescribe NRT patches in a disadvantaged community.

PubMed

Copeland, L; Robertson, R; Elton, R

2005-05-01

The high prevalence of smoking in disadvantaged communities gives serious cause for concern in terms of adverse effects on health and social outcomes. In Scotland, smoking -related lung cancer rates are particularly high and compare less favourably with the rest of the U.K. and Europe. GPs are increasingly being recognised as having an important role in smoking cessation and are allowed to prescribe NRT to those on a low income. This study aimed to follow up a group patientsfrom a disadvantaged area who had been prescribed nicotine patches by their GP. An initial self-complete questionnaire gathered details on age, sex, motivation, marital status, employment history, contact with other smokers, concern about weight gain, and nicotine dependence. (Nicotine dependence was assessed by using the Fagerstrom Test). Follow up was carried out at three months after commencing NRT prescription. Data was also gathered from patient case notes as to whether the participant had a smoking-related diagnosis, periods of depression, drug and/or alcohol problems. Outcome was measured in terms of "smoke the same", "smoke less" and "stopped". The statistical methods used for testing each factor against smoking were Spearman rank correlation, chi-squared test for trend and Kruskal-Wallis test. Basic descriptive statistics were used to report general outcomes of the study. The study enrolled 120 patients but 19 were lost to follow up. Out of 101 who used their prescription, 35 were smoking the same, 46 were smoking less and 20 had stopped. The variables most strongly affecting outcome were age, with older smokers having more success (p < 0.001), and those who had a diagnosis of depression having a worse outcome in terms of smoking cessation (p < 0.05). This study's findings indicate that encouraging GPs to take a proactive approach in prescribing NRT is effective, even in an area of socio-economic deprivation, and particularly with older smokers.

A special role for binocular visual input during development and as a component of occlusion therapy for treatment of amblyopia.

PubMed

Mitchell, Donald E

2008-01-01

To review work on animal models of deprivation amblyopia that points to a special role for binocular visual input in the development of spatial vision and as a component of occlusion (patching) therapy for amblyopia. The studies reviewed employ behavioural methods to measure the effects of various early experiential manipulations on the development of the visual acuity of the two eyes. Short periods of concordant binocular input, if continuous, can offset much longer daily periods of monocular deprivation to allow the development of normal visual acuity in both eyes. It appears that the visual system does not weigh all visual input equally in terms of its ability to impact on the development of vision but instead places greater weight on concordant binocular exposure. Experimental models of patching therapy for amblyopia imposed on animals in which amblyopia had been induced by a prior period of early monocular deprivation, indicate that the benefits of patching therapy may be only temporary and decline rapidly after patching is discontinued. However, when combined with critical amounts of binocular visual input each day, the benefits of patching can be both heightened and made permanent. Taken together with demonstrations of retained binocular connections in the visual cortex of monocularly deprived animals, a strong argument is made for inclusion of specific training of stereoscopic vision for part of the daily periods of binocular exposure that should be incorporated as part of any patching protocol for amblyopia.

A Pilot Randomized Clinical Trial of Intermittent Occlusion Therapy Liquid Crystal Glasses versus Traditional Patching for Treatment of Moderate Unilateral Amblyopia

PubMed Central

Wang, Jingyun; Neely, Daniel E.; Galli, Jay; Schliesser, Joshua; Graves, April; Damarjian, Tina G.; Kovarik, Jessica; Bowsher, James; Smith, Heather A.; Donaldson, Dana; Haider, Kathryn M.; Roberts, Gavin J.; Sprunger, Derek T.; Plager, David A.

2017-01-01

INTRODUCTION This pilot study was designed to compare the effectiveness of intermittent occlusion therapy (IO-Therapy) using liquid crystal glasses versus continuous occlusion therapy using traditional adhesive patches for treating amblyopia. DESIGN A randomized controlled trial. Children 3–8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn optimal refractive correction (if needed) for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO-Therapy Group with liquid crystal glasses (Amblyz™), set at 30-second opaque/transparent intervals (occluded 50% of wear time) or a 2-hour continuous Patching Group (occluded 100% of wear time). For each patient, visual acuity was measured with the ATS-HOTV method before and after 12 weeks of treatment. RESULTS At the conclusion of the first 12 week-treatment interval, data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15±0.12 (95% CI=0.09 to 0.15) logMAR in the IO-Therapy Group (N=19) and 0.15±0.11 (95% CI=0.1 to 0.15) logMAR in the Patching Group (N=15). Improvements in both groups were significant. The difference between groups was not statistically significant (P=0.73). No adverse effects were reported. CONCLUSION In this pilot study, IO-Therapy with Amblyz liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3–8 years of age with moderate amblyopia. A larger randomized clinical trial is needed to confirm results in future. PMID:27418249

A pilot randomized clinical trial of intermittent occlusion therapy liquid crystal glasses versus traditional patching for treatment of moderate unilateral amblyopia.

PubMed

Wang, Jingyun; Neely, Daniel E; Galli, Jay; Schliesser, Joshua; Graves, April; Damarjian, Tina G; Kovarik, Jessica; Bowsher, James; Smith, Heather A; Donaldson, Dana; Haider, Kathryn M; Roberts, Gavin J; Sprunger, Derek T; Plager, David A

2016-08-01

To compare the effectiveness of intermittent occlusion therapy (IO therapy) using liquid crystal glasses and continuous occlusion therapy using traditional adhesive patches for treating amblyopia. Children 3-8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled in this randomized controlled trial. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn any optimal refractive correction for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO therapy group with liquid crystal glasses (Amblyz), set at 30-second opaque/transparent intervals (occluded 50% of wear time), and a 2-hour continuous patching group (occluded 100% of wear time). For each patient, visual acuity was measured using ATS-HOTV before and after 12 weeks of treatment. Data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15 ± 0.12 logMAR (95% CI, 0.09-0.15) in the IO therapy group (n = 19) and 0.15 ± 0.11 logMAR (95% CI, 0.1-0.15) in the patching group (n = 15). In both groups improvement was significant, but the difference between groups was not (P = 0.73). No adverse effects were reported. In this pilot study, IO therapy with liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3-8 years of age with moderate amblyopia. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Design and characterization of an adhesive matrix based on a poly(ethyl acrylate, methyl methacrylate).

PubMed

Cilurzo, Francesco; Minghetti, Paola; Pagani, Stefania; Casiraghi, Antonella; Montanari, Luisa

2008-01-01

The main issue in the development of transdermal patches made of poly(ethyl acrylate, methyl methacrylate) (Eudragit NE 40D, PMM) is the shrinkage phenomenon during the spreading of the latex onto the release liner. To solve this problem, the latex is usually freeze-dried and then re-dissolved in an organic solvent (method 1). To simplify the production process, we prepared an adhesive matrix by adding to the commercial PMM latex a plasticizer and an additive (anti-shrinkage agent) that avoids the shrinkage of the water dispersion spread onto the release liner (method 2). In some cases the active ingredient itself, such as potassium diclofenac (DK) and nicotine (NT), works as anti-shrinkage agent. In this work, the effects of the preparation method, types and concentrations of the plasticizer (triacetin and tributyl citrate) on the adhesive properties of the transdermal patches were investigated. The adhesive properties of the prepared patch were determined by texture analysis, peel adhesion test and shear adhesion. The PMM/plasticizer interactions were evaluated by ATR-FTIR spectroscopy. Furthermore, the in vitro skin permeation profiles of DK and NT released from the patch were determined by Franz cell method. Generally speaking, the variables that mainly modify the adhesive properties are the concentration and type of the plasticizer. The skin permeation profiles of DK and NT from the patch prepared by method 2 overlapped with those obtained with the commercial products. The results underline that the PMM latex can be used conveniently in the development of transdermal patches.

Adverse effects of perinatal nicotine exposure on reproductive outcomes.

PubMed

Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

2015-12-01

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

Cue Reactivity in Nicotine and Alcohol Addiction: A Cross-Cultural View

PubMed Central

Lv, Wanwan; Wu, Qichao; Liu, Xiaoming; Chen, Ying; Song, Hongwen; Yang, Lizhuang; Zhang, Xiaochu

2016-01-01

A wealth of research indicates that cue reactivity is critical to understanding the neurobiology of nicotine and alcohol addiction and developing treatments. Functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) studies have shown abnormal cue reactivity in various conditions between nicotine or alcohol addicts and the healthy. Although the causes of these abnormalities are still unclear, cultural effect can not be ignored. We conduct an review of fMRI and EEG studies about the cue reactivity in nicotine and alcohol addiction and highlight the cultural perspective. We suggest that cultural cue reactivity is a field worth of exploring which may has an effect on addictive behavior through emotion and attention. The cultural role of nicotine and alcohol addiction would provide new insight into understanding the mechanisms of nicotine and alcohol addiction and developing culture-specific therapies. We consider that culture as a context may be a factor that causes confusing outcomes in exploring nicotine and alcohol addiction which makes it possible to control the cultural influences and further contribute to the more consistent results. PMID:27635123

Cue Reactivity in Nicotine and Alcohol Addiction: A Cross-Cultural View.

PubMed

Lv, Wanwan; Wu, Qichao; Liu, Xiaoming; Chen, Ying; Song, Hongwen; Yang, Lizhuang; Zhang, Xiaochu

2016-01-01

A wealth of research indicates that cue reactivity is critical to understanding the neurobiology of nicotine and alcohol addiction and developing treatments. Functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) studies have shown abnormal cue reactivity in various conditions between nicotine or alcohol addicts and the healthy. Although the causes of these abnormalities are still unclear, cultural effect can not be ignored. We conduct an review of fMRI and EEG studies about the cue reactivity in nicotine and alcohol addiction and highlight the cultural perspective. We suggest that cultural cue reactivity is a field worth of exploring which may has an effect on addictive behavior through emotion and attention. The cultural role of nicotine and alcohol addiction would provide new insight into understanding the mechanisms of nicotine and alcohol addiction and developing culture-specific therapies. We consider that culture as a context may be a factor that causes confusing outcomes in exploring nicotine and alcohol addiction which makes it possible to control the cultural influences and further contribute to the more consistent results.

Noribogaine reduces nicotine self-administration in rats

PubMed Central

Chang, Qing; Hanania, Taleen; Mash, Deborah C

2015-01-01

Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats’ levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

The impact of nicotine lozenges and stimulus expectancies on cigarette craving.

PubMed

Schlagintweit, Hera E; Good, Kimberley P; Barrett, Sean P

2014-08-01

Reduced craving associated with nicotine replacement therapy use is frequently attributed to the effects of nicotine pharmacology, however non-pharmacological factors may also play a role. This study examined the impact of nicotine pharmacology and non-pharmacological components of an acute nicotine lozenge (4 mg) on cigarette craving, mood and heart rate in 70 daily smokers (36 male). Smoking-related stimuli were used to assess cue-induced craving. Participants were randomly assigned to one of four conditions in a balanced placebo design where half the participants were provided deceptive information regarding the nicotine content of a lozenge. Subjective ratings of craving and mood were collected and heart rate was assessed before and after neutral and smoking cues. Nicotine expectancy reduced withdrawal-related craving (p = 0.006) regardless of actual nicotine administration while combined nicotine expectancy and administration reduced intentions to smoke (p = 0.046) relative to each of the other conditions. Exposure to smoking-related stimuli increased cigarette craving (p ≤ 0.001) and negative affect (p ≤ 0.001) regardless of expectancy or pharmacology. Following the smoking cue, women reported a greater increase in withdrawal-related craving than men (p = 0.027). Findings suggest that both pharmacological and non-pharmacological components of nicotine lozenge administration contribute to its acute effects on craving, yet neither appears effective in preventing craving triggered by exposure to environmental smoking stimuli. © The Author(s) 2014.

Artemin growth factor increases nicotinic cholinergic receptor subunit expression and activity in nociceptive sensory neurons.

PubMed

Albers, Kathryn M; Zhang, Xiu Lin; Diges, Charlotte M; Schwartz, Erica S; Yang, Charles I; Davis, Brian M; Gold, Michael S

2014-05-22

Artemin (Artn), a member of the glial cell line-derived growth factor (GDNF) family, supports the development and function of a subpopulation of peptidergic, TRPV1-positive sensory neurons. Artn (enovin, neublastin) is elevated in inflamed tissue and its injection in skin causes transient thermal hyperalgesia. A genome wide expression analysis of trigeminal ganglia of mice that overexpress Artn in the skin (ART-OE mice) showed elevation in nicotinic acetylcholine receptor (nAChR) subunits, suggesting these ion channels contribute to Artn-induced sensitivity. Here we have used gene expression, immunolabeling, patch clamp electrophysiology and behavioral testing assays to investigate the link between Artn, nicotinic subunit expression and thermal hypersensitivity. Reverse transcriptase-PCR validation showed increased levels of mRNAs encoding the nAChR subunits α3 (13.3-fold), β3 (4-fold) and β4 (7.7-fold) in trigeminal ganglia and α3 (4-fold) and β4 (2.8-fold) in dorsal root ganglia (DRG) of ART-OE mice. Sensory ganglia of ART-OE mice had increased immunoreactivity for nAChRα3 and exhibited increased overlap in labeling with GFRα3-positive neurons. Patch clamp analysis of back-labeled cutaneous afferents showed that while the majority of nicotine-evoked currents in DRG neurons had biophysical and pharmacological properties of α7-subunit containing nAChRs, the Artn-induced increase in α3 and β4 subunits resulted in functional channels. Behavioral analysis of ART-OE and wildtype mice showed that Artn-induced thermal hyperalgesia can be blocked by mecamylamine or hexamethonium. Complete Freund's adjuvant (CFA) inflammation of paw skin, which causes an increase in Artn in the skin, also increased the level of nAChR mRNAs in DRG. Finally, the increase in nAChRs transcription was not dependent on the Artn-induced increase in TRPV1 or TRPA1 in ART-OE mice since nAChRs were elevated in ganglia of TRPV1/TRPA1 double knockout mice. These findings suggest that Artn regulates the expression and composition of nAChRs in GFRα3 nociceptors and that these changes contribute to the thermal hypersensitivity that develops in response to Artn injection and perhaps to inflammation.

Nicotine receptor partial agonists for smoking cessation.

PubMed

Cahill, Kate; Stead, Lindsay F; Lancaster, Tim

2008-07-16

Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). Varenicline was developed as a nicotine receptor partial agonist from cytisine, a drug widely used in central and eastern Europe for smoking cessation. The first trial reports of varenicline were released in 2006, and further trials have now been published or are currently are underway. The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('varenicline' or 'cytisine' or 'Tabex' or 'nicotine receptor partial agonist') and 'smoking' in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, PsycINFO and CINAHL using MeSH terms and free text, and we contacted authors of trial reports for additional information where necessary. The latest search was in March 2008. We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. We extracted data in duplicate on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow up. The main outcome measured was abstinence from smoking after at least six months from the beginning of treatment. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we performed meta-analysis to produce a risk ratio, using the Mantel-Haenszel fixed-effect model. We found seven trials of varenicline compared with placebo for smoking cessation; three of these also included a bupropion experimental arm. We found one relapse prevention trial, comparing varenicline with placebo. We also found one open-label trial comparing varenicline with nicotine replacement therapy. The nine trials covered 7267 participants, 4744 of whom used varenicline. We identified one trial of cytisine (Tabex) for inclusion. The pooled risk ratio (RR) for continuous abstinence at six months or longer for varenicline versus placebo was 2.33 (95% confidence interval [CI] 1.95 to 2.80). The pooled RR for varenicline versus bupropion at one year was 1.52 (95% CI 1.22 to 1.88). The RR for varenicline versus NRT at one year was 1.31 (95% CI 1.01 to 1.71). The two trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The main adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Post-marketing safety data suggest that varenicline may be associated with depressed mood, agitation, and suicidal behaviour or ideation. The labelling of varenicline has been amended, and the FDA is conducting a safety review. The one cytisine trial included in this review found that more participants taking cytisine stopped smoking compared with placebo at two-year follow up, with an RR of 1.61 (95% CI 1.24 to 2.08). Varenicline increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. More participants quit successfully with varenicline than with bupropion. One open-label trial of varenicline versus nicotine replacement therapy demonstrated a modest benefit of varenicline. The effectiveness of varenicline as an aid to relapse prevention has not been clearly established. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including depressed mood, agitation and suicidal thoughts, are currently under review. There is a need for independent community-based trials of varenicline, to test its efficacy and safety in smokers with varying co-morbidities and risk patterns. There is a need for further trials of the efficacy of treatment extended beyond 12 weeks. Cytisine may also increase the chances of quitting, but the evidence at present is inconclusive.

Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers

PubMed Central

Gu, Xiaosi; Lohrenz, Terry; Salas, Ramiro; Baldwin, Philip R.; Soltani, Alireza; Kirk, Ulrich; Cinciripini, Paul M.; Montague, P. Read

2016-01-01

Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told “nicotine” vs. told “no nicotine”) with the nicotine content in a cigarette (nicotine vs. placebo) which participants smoked immediately before performing a fMRI task involving reward learning. Subjects’ reported craving was measured both before smoking and after the fMRI session. We found that first, in the presence of nicotine, smokers demonstrated significantly reduced craving after smoking when told “nicotine in cigarette” but showed no change in craving when told “no nicotine.” Second, neural activity in the insular cortex related to craving was only significant when smokers were told “nicotine” but not when told “no nicotine.” Both effects were absent in the placebo condition. Third, insula activation related to computational learning signals was modulated by belief about nicotine regardless of nicotine’s presence. These results suggest that belief about nicotine has a strong impact on subjective craving and insula responses related to both craving and learning in deprived smokers, providing insights into the complex nature of belief–drug interactions. PMID:27468271

Inpatient smoking cessation therapy: truth or dare?

PubMed

Boehm, Gabriela; Schroeder, Yvonne; Schoberberger, Rudolf

2015-10-01

This study aims to answer the question to which extent even very heavy nicotine-dependent smokers can benefit from a 3-week inpatient smoking cessation program. A particular focus lies on analyzing the positive effects, which go above and beyond normally anticipated health benefits. This is a descriptive study observing 270 patients over a 1-year period consisting of recruitment, therapy, and two post-therapy follow-up visits at 6-month interval. Gender differences, changes in body weight, and factors relating to addiction and the nicotine withdrawal process are analyzed. In comparing successful participants-post-therapy nonsmokers-with less successful ones, our analysis identifies benefits and advantages an inpatient smoking cessation therapy can bring to even the heaviest smokers. At the 12-month post-therapy follow-up visit, 42.6% of participants were identified as nonsmokers. A total of 34.0% of participants took up smoking again. No data is available on the remaining participants. Nonsmokers experienced significant reduction in nicotine craving and withdrawal symptoms. In terms of body weight, increases were found in both, men and women, nonsmokers and smokers. Successful quitters fail to report of an unbearable strong desire to smoke. Such unfounded fear should be communicated. Weight gain remains an undesired side effect. Hence, it is crucial to diagnose individuals more prone to weight gain and offer coping strategies thus reducing the risk of developing obesity. Nevertheless, the outcome of the study should be an encouragement to also heavy smokers and empower them to undertake smoking cessation.

Bidirectional modulation of visual plasticity by cholinergic receptor subtypes in the frog optic tectum

PubMed Central

Yu, Chuan-Jiang; Butt, Christopher M.; Debski, Elizabeth A.

2008-01-01

Cholinergic input to the optic tectum is necessary for visual map maintenance. To understand why, we examined the effects of activation of the different cholinergic receptor subtypes in tectal brain slices and determined whether the retinotectal map was affected by manipulations of their activity in vivo. Both α-bungarotoxin sensitive and insensitive nicotinic receptor agonists increased spontaneous postsynaptic currents (sPSCs) in a subpopulation of patch-clamped tectal cells; application of subtype selective receptor antagonists reduced nicotine-induced increases in sPSCs. Activation of α-bungarotoxin insensitive nicotinic receptors also induced substantial inward current in some cells. Muscarinic receptor mediated outward current responses were blocked by the M2-like muscarinic receptor antagonists himbacine or AF-DX 384 and mimicked by application of the M2-like agonist oxotremorine. A less frequently observed muscarinic response involving a change in sPSC frequency appeared to be mediated by M1-like muscarinic receptors. In separate experiments, pharmacological manipulation of cholinergic receptor subtype activation led to changes in the activity-dependent visual map created in the tectum by retinal ganglion cell terminals. Chronic exposure of the tectum to either α-bungarotoxin insensitive, α-bungarotoxin sensitive or M1-like receptor antagonists resulted in map disruption. However, treatment with the M2-like receptor antagonist, AF-DX 384, compressed the map. We conclude that nicotinic or M1-like muscarinic receptors control input to tectal cells while α-bungarotoxin insensitive nicotinic receptors and M2-like muscarinic receptors change tectal cell responses to that input. Blockade of the different cholinergic receptor subtypes can have opposing effects on map topography that are consistent with expected effects on tectal cell activity levels. PMID:12670313

Age-related changes in functional postsynaptic nicotinic acetylcholine receptor subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction.

PubMed

Christensen, Mark H; Kohlmeier, Kristi A

2016-03-01

The earlier an individual initiates cigarette smoking, the higher the likelihood of development of dependency to nicotine, the addictive ingredient in cigarettes. One possible mechanism underlying this higher addiction liability is an ontogenetically differential cellular response induced by nicotine in neurons mediating the reinforcing or euphoric effects of this drug, which could arise from age-related differences in the composition of nicotinic acetylcholine receptor (nAChR) subunits. In the current study, we examined whether the subunit composition of nAChRs differed between neurons within the laterodorsal tegmentum (LDT), a nucleus importantly involved in drug addiction associated behaviours, across two periods of ontogeny in which nicotine-mediated excitatory responses were shown to depend on age. To this end, whole-cell patch-clamp recordings in mouse brain slices from identified LDT neurons, in combination with nAChR subunit-specific receptor antagonists, were conducted. Comparison of the contribution of different nAChR subunits to acetylcholine (ACh)-induced inward currents indicated that the contributions of the β2 and/or β4 and α7 nAChR subunits alter across age. Taken together, we conclude that across a limited ontogenetic period, there is plasticity in the subunit composition of nAChRs in LDT neurons. In addition, our data indicate, for the first time, functional presence of α6 nAChR subunits in LDT neurons within the age ranges studied. Changes in subunit composition of nAChRs across ontogeny could contribute to the age-related differential excitability induced by nicotine. Differences in the subunit composition of nAChRs within the LDT would be expected to contribute to ontogenetic-dependent outflow from the LDT to target regions, which include reward-related circuitry. © 2014 Society for the Study of Addiction.

Validation of a LC-MS/MS Method for Quantifying Urinary Nicotine, Six Nicotine Metabolites and the Minor Tobacco Alkaloids—Anatabine and Anabasine—in Smokers' Urine

PubMed Central

McGuffey, James E.; Wei, Binnian; Bernert, John T.; Morrow, John C.; Xia, Baoyun; Wang, Lanqing; Blount, Benjamin C.

2014-01-01

Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling—i.e., metabolite ratios. In addition, the minor tobacco alkaloids—anabasine and anatabine—can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides) and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme) that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1′-N-oxide, anatabine, and anabasine) are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76–99%), specificity, accuracy (0–10% bias) and reproducibility (2–9% C.V.) make this method ideal for large high through-put studies. PMID:25013964

The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro.

PubMed

Peacock, M E; Sutherland, D E; Schuster, G S; Brennan, W A; O'Neal, R B; Strong, S L; Van Dyke, T E

1993-07-01

The ability of fibroblasts to reproduce and attach to teeth is of paramount importance in re-establishing the lost connective tissue attachment after periodontal therapy. This study examined the effect of nicotine, a major component of the particulate phase of tobacco smoke, on human gingival fibroblast (HGF) reproduction and attachment to tissue culture surfaces. Pooled HGF cultures made from explants of gingival biopsies were utilized between passages 5 and 10 and plated in 96-well plates at 1.0 x 10(4) cells per well. Cell numbers were determined using 3-(4,5-dimethylthiazol-2-y)-2,5-diphenyl tetrazolium bromide (MTT), which is a reflection of mitochondrial dehydrogenase activity. The concentrations of nicotine used were 0.025, 0.05, 0.1, 0.2, and 0.4 microM, the average serum concentration for a smoker being approximately 0.1 microM. The effect of continuous nicotine exposure on HGF reproduction was determined by incubating cell cultures and media containing nicotine for up to 48 hours. Residual toxicity was determined by preincubating cells with nicotine for 1 or 6 hours. HGF suspensions and increasing concentrations of nicotine were added together to determine the effect on attachment. Results showed an enhanced effect of nicotine on HGF attachment, with increasing numbers of cells attaching with increasing nicotine concentrations, compared to the control. Low concentrations of nicotine had a stimulatory effect on cell replication, while higher concentrations of nicotine appear to have no significant effect on HGF reproduction. The responses of cells to some concentrations of nicotine may persist after its removal.

Decreased nicotinic receptor availability in smokers with slow rates of nicotine metabolism

PubMed Central

Dubroff, Jacob G.; Doot, Robert K.; Falcone, Mary; R, Robert A. Schnoll; Ray, Riju; Tyndale, Rachel F.; Brody, Arthur L.; Hou, Catherine; Schmitz, Alexander; Lerman, Caryn

2015-01-01

The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR availability (α4β2* subtype) using positron emission tomography (PET) imaging of the radiotracer 2-18F-FA-85380 (2-18F-FA). Methods Twenty four smokers, 12 slow metabolizers (NMR <0.26) and 12 normal metabolizers (NMR ≥0.26), underwent 2-18F-FA-PET brain imaging following overnight nicotine abstinence (18 hours prior to scanning), using a validated bolus plus infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest (VOIs), with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed prior to and following the scans. Results Thalamic nAChR α4β2* availability was significantly reduced in slow (versus normal) nicotine metabolizers (P=0.04). Slow metabolizers exhibited greater reductions in craving than normal metabolizers from pre- to post-scanning; however, craving was unrelated to availability. Conclusion The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies differences in treatment response between slow and normal metabolizers of nicotine. PMID:26272810

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

PubMed

Dubroff, Jacob G; Doot, Robert K; Falcone, Mary; Schnoll, Robert A; Ray, Riju; Tyndale, Rachel F; Brody, Arthur L; Hou, Catherine; Schmitz, Alexander; Lerman, Caryn

2015-11-01

The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (α4β2* subtype) availability using PET imaging of the radiotracer 2-(18)F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-(18)F-FA-85380, or 2-(18)F-FA). Twenty-four smokers-12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR ≥ 0.26)-underwent 2-(18)F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans. Thalamic nAChR α4β2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability. The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Modifying Risk Factors for Total Joint Arthroplasty: Strategies That Work Nicotine.

PubMed

Springer, Bryan D

2016-08-01

Smoking and nicotine use remain a major health care crisis in the United States. Although rates have dropped dramatically over the last 50 years, approximately 18% of the US adult population still smokes. The musculoskeletal effects of nicotine and other byproducts of smoking place patients at increased risk for perioperative complications including medical complication, wound healing problems, infection, and death. A comprehensive behavioral modification program with or without the use of nicotine replacement therapy has been shown to be most effective at smoking cessation around the time of planned surgery. Although literature suggests that smoking cessation 4-6 weeks before surgery can diminish risk, both current and former smokers are at increased risk for perioperative complications compared with those that have never smoked. Cotinine, a metabolite of nicotine, can be used to monitor smoking cessation before surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Naltrexone on Smoking Cessation Outcomes and Weight Gain in Nicotine-Dependent Men and Women

PubMed Central

King, Andrea C.; Cao, Dingcai; O'Malley, Stephanie S.; Kranzler, Henry R.; Cai, Xiaochen; deWit, Harriet; Matthews, Alicia K.; Stachoviak, Ryan J.

2015-01-01

This study examined whether the opioid receptor antagonist naltrexone is efficacious in smoking cessation and whether sex moderates the response. We assessed smoking quit rates and weight gain in a double-blind randomized trial comparing oral naltrexone (n = 162) with placebo (n = 154) in nicotine-dependent participants who wanted to quit smoking. The medication was gradually titrated up to 50 mg during the week before the quit date and then maintained at this dose for 12 weeks. For the first 4 weeks after the quit date, all participants received a nicotine patch to mitigate tobacco withdrawal and attended weekly individual cognitive-behavioral smoking cessation counseling sessions. After this time, participants continued with naltrexone or placebo through 12 weeks. Follow-up assessments were conducted at 26 and 52 weeks. During treatment, naltrexone (vs placebo) increased quit rates, attenuated smoking urge, and reduced weight gain. At follow-up, after medication discontinuation, the effect of naltrexone on improving quit rates was no longer evident. Men and women experienced different benefits from naltrexone; men showed greater reductions in smoking, whereas women showed greater reductions in weight gain. In sum, naltrexone showed acute efficacy in treating nicotine dependence, but after the medication was discontinued, the effect on quit rate was not maintained. Further study of naltrexone in smoking cessation treatment and reduction of cessation-related weight gain, as well as preclinical investigation of mechanisms underlying sex differences, is warranted. PMID:22926596

Chronic Nicotine Consumption does not Influence 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induced Lung Tumorigenesis

PubMed Central

Murphy, Sharon E.; von Weymarn, Linda B.; Schutten, Melissa M.; Kassie, Fekadu; Modiano, Jaime F.

2011-01-01

Nicotine replacement therapy (NRT) is often used to maintain smoking cessation. However, concerns exist about the safety of long term NRT use in ex-smokers and its concurrent use in smokers. In this study, we determined the effect of nicotine administration on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors in A/J mice. Female mice were administered a single dose of NNK (10 μmol) and 0.44 μmol/ml nicotine in the drinking water. Nicotine was administered 2 weeks prior to NNK, 44 weeks after NNK, throughout the experiment, or without NNK treatment. The average weekly consumption of nicotine-containing water was 15 ± 3 mls/mouse, resulting in an estimated daily nicotine dose of 0.9 μmol (0.15 mg) per mouse. Nicotine administration alone for 46 weeks did not increase lung tumor multiplicity (0.32 ± 0.1 tumor/mouse versus 0.53 ± 0.1 tumors/mouse). Lung tumor multiplicity in NNK-treated mice was 18.4 ± 4.5 and was not different than for mice consuming nicotine before or after NNK administration, 21.9 ± 5.3 and 20.0 ± 5.4 tumors per mouse, respectively. Lung tumor multiplicity in animals consuming nicotine both before and after NNK administration was 20.4 ± 5.4. Tumor size and progression of adenomas to carcinomas was also not affected by nicotine consumption. In addition, nicotine consumption had no effect on the level of O6-methylguanine in the lung of NNK-treated mice. These negative findings in a commonly used model of human lung carcinogenesis should lead us to question the interpretation of the many in vitro studies that find nicotine stimulates cancer cell growth. PMID:22027684

Light transmission and preference of eye patches for occlusion treatment.

PubMed

Heo, Hwan; Park, Jung Won; Park, Sang Woo

2013-01-01

To investigate light transmission and preference for six eye patches for occlusion therapy. Six patches were examined, including; Ortopad Fun Pack, Ortopad Flesh, Kawamoto A-1, Kawamoto A-2, 3M Opticlude, and Everade Eye Guard. The size and the presence of a light blocking pad of patches were investigated. The amount of light transmitted through the patches was evaluated, using a digital light meter and a model eye, in three different environments; indoors with fluorescent light, outdoors on a sunny day, and strong light from illuminator. After patching the normal eye, the flash visual evoked potential (VEP) was measured. Thirty patients with amblyopia or horizontal strabismus, who received occlusion therapy as initial treatment, were included. After using all six patches, patients completed a 7-item questionnaire regarding the patch preference for size, color and shape, adhesive power, pain with removal, skin irritation after removing patch, parent's preference and overall opinion. All patches had a light-blocking pad, except the 3M Nexcare. Ortopad had the strongest light blocking power in the three environments, and the 3M Nexcare had the weakest power. In flash VEP, Ortopad and Kawamoto patches showed flat, but 3M Nexcare and Everade Eye Guard showed normal response. There were significant preferential differences among the patches in all the items of the questionnaire (P<0.05). In comparison between the patches respectively, 3M Nexcare received the lowest satisfaction in pain when removing a patch and skin irritation after removing a patch. Kawamoto A-2 received the lowest score in the overall satisfaction. We found differences in the light-blocking power and in the preference of the various patches for the occlusion treatment. This is a pilot study regarding only characteristics and preferences of patches. Further clinical studies regarding the relationship between characteristics or preferences of patches and outcomes of occlusion treatment are needed.

Assigned versus Perceived Placebo Effects in Nicotine Replacement Therapy for Smoking Reduction in Swiss Smokers

ERIC Educational Resources Information Center

Dar, Reuven; Stronguin, Florencia; Etter, Jean-Francois

2005-01-01

In this report, the authors explore the relationships of perceived treatment to outcome in a large, placebo-controlled trial of nicotine replacement treatment for smoking reduction. In the original study (J. F. Etter, E. Laszlo, J. P. Zellweger, C. Perrot, & T. V. Perneger, 2002), which was conducted in French-speaking Switzerland, smokers were…

Effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 osteoblast-like cells.

PubMed

Torshabi, Maryam; Esfahrood, Zeinab Rezaei; Gholamin, Parisan; Karami, Elahe

2016-11-01

Evidence shows that oxidative stress induced by nicotine plays an important role in bone loss. Vitamin E with its antioxidative properties may be able to reverse the effects of nicotine on bone. This study aimed to assess the effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 (osteosarcoma) human osteoblast-like cells. We treated the cells with 5 mM nicotine. The viability and morphology of cells were evaluated respectively using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) and crystal violet assays. The effect of nicotine on osteogenic gene expression in MG-63 cells was assessed by real-time reverse-transcription polymerase chain reaction of osteoblast markers, namely, alkaline phosphatase, osteocalcin and bone sialoprotein. The results revealed that survival and proliferation of MG-63 cells were suppressed following exposure to nicotine, and cytoplasm vacuolization occurred in the cells. Nicotine significantly down-regulated the expression of osteogenic marker genes. Such adverse effects on morphology, viability and osteogenic gene expression of MG-63 cells were reversed by vitamin E therapy. In conclusion, vitamin E supplementation may play a role in proliferation and differentiation of osteoblasts, and vitamin E can be considered as an anabolic agent to treat nicotine-induced bone loss.

Internal tobacco industry research on olfactory and trigeminal nerve response to nicotine and other smoke components.

PubMed

Megerdichian, Christine L; Rees, Vaughan W; Wayne, Geoffrey Ferris; Connolly, Gregory N

2007-11-01

Evidence has shown that factors other than the central pharmacological effects of nicotine are important in promoting smoking behavior. One such non-nicotine effect includes sensory stimulation, which may promote smoking by developing learned associations with nicotine's rewarding effects, or by constituting a rewarding experience independent of nicotine. The present study used internal tobacco industry documents to examine industry efforts to understand and manipulate stimulation of the sensory nerves by tobacco smoke, and the influence of sensory stimulation on smoker behavior. Research focused on sensory nerves of the head and neck, including the olfactory nerve, which carries flavor and odor, and the trigeminal nerve, which carries irritant information. The tobacco industry maintained a systematic research program designed to elucidate an understanding of responses of sensory nerves to nicotine and other components of tobacco smoke, and attempted to develop nicotine-like compounds that would enhance sensory responses in smokers. Industry research appeared intended to aid in the development of new products with greater consumer appeal. The potential influence of sensory response in enhancing nicotine dependence through an associative mechanism was acknowledged by the tobacco industry, but evidence for research in this area was limited. These findings add to evidence of industry manipulation of sensory factors to enhance smoking behavior and may have implications for development of more effective treatment strategies, including more "acceptable" nicotine replacement therapies.

Interactions between the endocannabinoid and nicotinic cholinergic systems: preclinical evidence and therapeutic perspectives.

PubMed

Scherma, Maria; Muntoni, Anna Lisa; Melis, Miriam; Fattore, Liana; Fadda, Paola; Fratta, Walter; Pistis, Marco

2016-05-01

Several lines of evidence suggest that endocannabinoid and nicotinic cholinergic systems are implicated in the regulation of different physiological processes, including reward, and in the neuropathological mechanisms of psychiatric diseases, such as addiction. A crosstalk between these two systems is substantiated by the overlapping distribution of cannabinoid and nicotinic acetylcholine receptors in many brain structures. We will review recent preclinical data showing how the endocannabinoid and nicotinic cholinergic systems interact bidirectionally at the level of the brain reward pathways, and how this interaction plays a key role in modulating nicotine and cannabinoid intake and dependence. Many behavioral and neurochemical effects of nicotine that are related to its addictive potential are reduced by pharmacological blockade or genetic deletion of type-1 cannabinoid receptors, inhibition of endocannabinoid uptake or metabolic degradation, and activation of peroxisome proliferator-activated-receptor-α. On the other hand, cholinergic antagonists at α7 nicotinic acetylcholine receptors as well as endogenous negative allosteric modulators of these receptors are effective in blocking dependence-related effects of cannabinoids. Pharmacological manipulation of the endocannabinoid system and endocannabinoid-like neuromodulators shows promise in the treatment of nicotine dependence and in relapse prevention. Likewise, drugs acting at nicotinic acetylcholine receptors might prove useful in the therapy of cannabinoid dependence. Research by Steven R. Goldberg has significantly contributed to the progress in this research field.

Nicotine does not enhance tumorigenesis in mutant K-ras-driven mouse models of lung cancer.

PubMed

Maier, Colleen R; Hollander, M Christine; Hobbs, Evthokia A; Dogan, Irem; Linnoila, R Ilona; Dennis, Phillip A

2011-11-01

Smoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiologic levels of nicotine on lung tumor formation, tumor growth, or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Tumors that develop in this model have mutations in K-ras, which is commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras-driven lung cancer, nicotine did not increase tumor number or size and did not affect overall survival. Likewise, in a syngeneic model using lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable with those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiologic data showing that NRT does not enhance lung cancer risk in former smokers.

A comparative multicenter study of two transdermal estradiol replacement therapies in the treatment of postmenopausal symptoms.

PubMed

Van Leusden, H A; Albertyn, G; Verlaine, C; Van Ruymbeke, J

1993-01-01

Comparison of the effects of treatment of two transdermal therapeutic systems for estrogen replacement therapy with regard to efficacy, tolerability, and acceptance. Open randomized. Multicenter. A study population of 104 postmenopausal women was randomized on a 1:1 basis to treatment with one of two estradiol patches, System (Cilag) and Estraderm (Ciba-Geigy). Systolic and diastolic BP, hot flushes, night sweating, fatigue, insomnia, depression, nervousness, headache, vaginal discomfort (efficacy variables); bleeding, dermatological symptoms, comfort and adhesiveness of patch, and other possible causes of discontinuation (tolerability); general evaluation by patient (acceptance). Considering all efficacy variables, 53% of Systen and 46% of Estraderm patients found the therapy satisfactory. Tolerability was somewhat higher in the Systen group. Adhesiveness of the patch was significantly better for Systen. Overall, 79% of Systen patients and 62% of Estraderm patients evaluated treatment as "good" or "very good." The majority of patients in both groups found the patch very comfortable or only slightly obtrusive.

An intervention to reduce the number of convenience stores selling tobacco: feasibility study.

PubMed

Paynter, Janine; Glover, Marewa; Bullen, Chris; Sonia, Deepika

2016-05-01

Reduction of the availability of tobacco has been proposed as a means of reducing and denormalising tobacco use. Some retailers have stopped selling tobacco. Therefore, we investigated how willing New Zealand convenience store owners were to stop selling tobacco or sell nicotine replacement therapy. Promotion of their stores was offered as an incentive to stop selling tobacco. We asked convenience store owners in the Auckland metropolitan region of New Zealand to choose one of three actions. The first was to stop selling tobacco for a short period of time; the second was to restrict the hours that they sold tobacco; the third was to display and sell nicotine replacement therapy. All participating retailers completed a short interview about selling tobacco. We also surveyed customers about nicotine replacement and cessation. One-third of eligible retailers agreed to participate. Most who participated (93%) were unwilling to stop or restrict tobacco sales and 2 (7%) had already stopped selling tobacco. Tobacco was perceived as a key product for their businesses. Very few customers who purchased cigarettes noticed nicotine replacement therapy or obtained it from convenience stores. Substantially reducing the availability of tobacco in communities is likely to require legislative approaches, underpinned by sustained community pressure and support for convenience store owners who are willing to change their business model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Mirtazapine attenuates the expression of nicotine-induced locomotor sensitization in rats.

PubMed

Barbosa-Méndez, Susana; Jurado, Noé; Matus-Ortega, Maura; Martiñon, Susana; Heinze, Gerardo; Salazar-Juárez, Alberto

2017-10-05

Nicotine is the primary psychoactive component of tobacco. Many addictive nicotinic actions are mediated by an increase in the activity of the serotonin (5-HT) system. Some studies show that the 5-HT 2A , 5-HT 2C , and 5-HT 3 receptors have a central role in the induction and expression of nicotine-induced locomotor sensitization. Mirtazapine, an antagonist of the α 2- adrenergic receptors, the 5-HT 2A/C , and the 5-HT 3 receptors, has proven effective in reducing behavioral effects induced by drugs like cocaine and methamphetamines in human and animal. In this study, we evaluated the effect of mirtazapine on the locomotor activity and on the expression of nicotine-induced locomotor sensitization. We used the nicotine locomotor sensitization paradigm to assess the effects of mirtazapine on nicotine-induced locomotor activity and locomotor sensitization. Mirtazapine (30mg/kg, i.p.) was administered during extinction. Our study found that mirtazapine attenuated the expression of locomotor sensitization induced by different nicotine doses, decreased the duration of locomotor effects and locomotor activity induced by binge administration of nicotine. In addition, our study revealed that treatment with mirtazapine for 60 days produced an enhanced attenuation of nicotine-induced locomotor activity during the expression phase of behavioral sensitization, compared to that obtained when mirtazapine was administered for 30 days. This suggests that use of mirtazapine in controlled clinical trials may be a useful therapy to maintain abstinence for long periods. Copyright © 2017 Elsevier B.V. All rights reserved.

Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

PubMed

Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

2017-01-01

Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

The effects of acute doses of nicotine on video lottery terminal gambling in daily smokers.

PubMed

McGrath, Daniel S; Barrett, Sean P; Stewart, Sherry H; Schmid, Evan A

2012-03-01

A growing body of evidence suggests that gambling frequently co-occurs with smoking, yet little is known about the degree to which nicotine and/or tobacco use influences gambling behavior. Nonetheless, an increasing number of studies suggest that acute administration of nicotine may alter other reinforcing behaviors in both animal and human models, raising the possibility that nicotine may also influence gambling behavior and craving. The purpose of this study was to examine the acute effects of nicotine on subjective and behavioral gambling responses. Twenty-eight (15 male) regular gamblers who smoke daily completed two double-blind laboratory sessions where their subjective and behavioral responses to video lottery terminal (VLT) gambling were assessed, following the administration of nicotine inhalers (NI; 4 mg deliverable) or placebo inhalers. NI significantly decreased tobacco-related cravings (p < 0.05) but did not affect gambling-related cravings, VLT betting patterns, or subjective responses (ps > 0.1). NI were found to acutely suppress tobacco-related cravings without influencing gambling. These results suggest that use of nicotine replacement therapies may be a safe option for gamblers who are attempting to quit smoking.

Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy?

PubMed Central

Suter, Melissa A.; Mastrobattista, Joan; Sachs, Maike; Aagaard, Kjersti

2016-01-01

Background Use of electronic cigarettes (e-cigarettes) and other nicotine containing products is increasing among women of reproductive age. The short- and long-term effects of these products on both mother and fetus are unknown. Methods Because e-cigarettes are nicotine delivery systems, we sought to conduct a comprehensive review of the effects of nicotine on the fetus. Results In utero nicotine exposure in animal models is associated with adverse effects for the offspring lung, cardiovascular system and brain. In the lung, this included reduced surface area, weight, and volume, as well as emphysema-like lesions. In adulthood, exposed offspring demonstrate elevated blood pressure and increased perivascular adipose tissue. In the brain, exposure alters offspring serotonergic, dopaminergic, and norepinephrine networks, which in turn are associated with behavioral and cognitive impairments. We also review current data on the lack of efficacy of nicotine replacement therapy in pregnant women, and highlight different nicotine containing products such as snuff, snus, and hookah. Conclusion We conclude that no amount of nicotine is known to be safe during pregnancy, and studies specifically addressing this risk are crucial and an imminent public health issue. PMID:25366492

Is there evidence for potential harm of electronic cigarette use in pregnancy?

PubMed

Suter, Melissa A; Mastrobattista, Joan; Sachs, Maike; Aagaard, Kjersti

2015-03-01

Use of electronic cigarettes (e-cigarettes) and other nicotine containing products is increasing among women of reproductive age. The short- and long-term effects of these products on both mother and fetus are unknown. Because e-cigarettes are nicotine delivery systems, we sought to conduct a comprehensive review of the effects of nicotine on the fetus. In utero nicotine exposure in animal models is associated with adverse effects for the offspring lung, cardiovascular system and brain. In the lung, this included reduced surface area, weight, and volume, as well as emphysema-like lesions. In adulthood, exposed offspring demonstrate elevated blood pressure and increased perivascular adipose tissue. In the brain, exposure alters offspring serotonergic, dopaminergic, and norepinephrine networks, which in turn are associated with behavioral and cognitive impairments. We also review current data on the lack of efficacy of nicotine replacement therapy in pregnant women, and highlight different nicotine containing products such as snuff, snus, and hookah. We conclude that no amount of nicotine is known to be safe during pregnancy, and studies specifically addressing this risk are crucial and an imminent public health issue. © 2014 Wiley Periodicals, Inc.

Effects of combined nicotine and fluoxetine treatment on adult hippocampal neurogenesis and conditioned place preference.

PubMed

Faillace, M P; Zwiller, J; Bernabeu, R O

2015-08-06

Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal subarea. It is known to be induced by antidepressant treatment and reduced in response to nicotine administration. We checked here whether the antidepressant fluoxetine would inverse the decrease in hippocampal neurogenesis caused by nicotine. It is shown that repeated, but not a single injection of rats with fluoxetine was able to abolish the decrease in adult dentate cell proliferation produced by nicotine treatment. We measured the expression of several biochemical parameters known to be associated with neurogenesis in the dentate gyrus. Both drugs increased the expression of p75 neurotrophin receptor, which promotes proliferation and early maturation of dentate gyrus cells. Using the conditioned place preference (CPP) paradigm, we also gave both drugs in a context in which their rewarding properties could be measured. Fluoxetine produced a significant but less robust CPP than nicotine. A single injection of fluoxetine was found to reduce nicotine-induced CPP. Moreover, the rewarding properties of nicotine were completely abolished in response to repeated fluoxetine injections. Expression of nicotine-induced CPP was accompanied by an increase of phospho-CREB (cyclic AMP-responsive element-binding protein) and HDAC2 (histone deacetylase 2) expression in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to nicotine reward, depends on dentate gyrus neurogenesis. Since fluoxetine was able to disrupt the association between nicotine and the environment, this antidepressant may be tested as a treatment for nicotine addiction using cue exposure therapy. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Argon plasma coagulation of gastric inlet patches for the treatment of globus sensation: it is an effective therapy in the long term.

PubMed

Klare, P; Meining, A; von Delius, S; Wolf, P; Konukiewitz, B; Schmid, R M; Bajbouj, M

2013-01-01

To determine the long-term effect of argon plasma coagulation (APC) of gastric inlet patches in the cervical esophagus for patients suffering from globus sensation. We intended to follow up all patients between 2004 and 2011 (n = 49) who received argon plasma ablation of gastric inlet patches for globus sensation at our clinic. Symptoms were assessed by a visual analogue scale (VAS) in 31 of 49 patients. Follow-up endoscopy of the upper gastrointestinal tract was performed to confirm residual or relapsed cervical inlet patches. After a median period of 27 months, APC was assessed as a successful therapy in 23 of 31 patients (74%). VAS scores decreased significantly from 7.6 to 4.0 in the long term. Twenty-two of 31 patients were willing to undergo follow-up endoscopy. Endoscopy revealed recurrent/residual gastric inlet patches after APC in 11 of 22 cases. These patients suffered from a significant relapse of symptoms in the postinterventional period (p < 0.001). This retrospective study indicates that APC of gastric inlet patches for the treatment of globus sensation might be a sufficient therapy option. Recurrences or residual heterotopic gastric mucosa are possible and seem to be associated with a relapse of symptoms. Therefore, endoscopic follow-up and retreatment might be necessary if globus sensation is not sufficiently eliminated. © 2013 S. Karger AG, Basel.

A New Strategy for Smoking Cessation: Characterization of a Bacterial Enzyme for the Degradation of Nicotine.

PubMed

Xue, Song; Schlosburg, Joel E; Janda, Kim D

2015-08-19

Smoking is the leading cause of preventable diseases; thus, effective smoking cessation aids are crucial for reducing the prevalence of cigarette smoking and smoking-related illnesses. In our current campaign we offer a nicotine-degrading enzyme from Pseudomonas putida, NicA2, a flavin-containing protein. To explore its potential, a kinetic evaluation of the enzyme was conducted, which included determination of K(m), k(cat), buffer/serum half-life, and thermostability. Additionally, the catabolism profile of NicA2 was elucidated to assess the potential toxicity of the nicotine-derived products. In characterizing the enzyme, a favorable biochemical profile of the enzyme was discovered, making NicA2 a prospective therapeutic candidate. This approach provides a new avenue for the field of nicotine addiction therapy.

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio.

PubMed

Allenby, Cheyenne E; Boylan, Kelly A; Lerman, Caryn; Falcone, Mary

2016-09-01

Quitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and other biological and environmental factors such as estrogen levels, alcohol use, body mass index, or menthol exposure. Then, we highlight clinical trials that validate the NMR as a biomarker to predict therapeutic response to different pharmacotherapies for smoking cessation. Current evidence supports the use of nicotine replacement therapy for slow metabolizers, and non-nicotine treatments such as varenicline for normal metabolizers. Finally, we discuss future research directions to elucidate mechanisms underlying NMR associations with treatment response, and facilitate the implementation of the NMR as biomarker in clinical practice to guide smoking cessation.

Prefrontal gamma-aminobutyric acid type A receptor insertion controls cue-induced relapse to nicotine seeking.

PubMed

Lubbers, Bart R; van Mourik, Yvar; Schetters, Dustin; Smit, August B; De Vries, Taco J; Spijker, Sabine

2014-11-01

Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms underlying nicotine relapse, hampering development of more effective therapies. The objective of this study was to elucidate the role of medial prefrontal cortex (mPFC) glutamatergic and gamma-aminobutyric acid (GABA)ergic receptors in controlling relapse to nicotine seeking. Using an intravenous self-administration model, we studied glutamate and gamma-aminobutyric acid receptor regulation in the synaptic membrane fraction of the rat mPFC following extinction and cue-induced relapse to nicotine seeking. Subsequently, we locally intervened at the level of GABAergic signaling by using a mimetic peptide of the GABA receptor associated protein-interacting domain of GABA type A (GABAA) receptor subunit γ2 (TAT-GABAγ2) and muscimol, a GABAA receptor agonist. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors were not regulated after the 30-min relapse test. However, GABAA receptor subunits α1 and γ2 were upregulated, and interference with GABAA receptor insertion in the cell membrane using the TAT-GABAγ2 peptide in the dorsal mPFC, but not the ventral mPFC, significantly increased responding during relapse. Increasing GABAA transmission with muscimol in the dorsal and ventral mPFC attenuated relapse. These data indicate that cue-induced relapse entails a GABAergic plasticity mechanism that limits nicotine seeking by restoring inhibitory control in the dorsal mPFC. GABAA receptor-mediated neurotransmission in the dorsal mPFC constitutes a possible future therapeutic target for maintaining smoking abstinence. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Nicotine and Nicotine Abstinence Do Not Interfere with GABAA Receptor Neuroadaptations During Alcohol Abstinence.

PubMed

Hillmer, Ansel T; Kloczynski, Tracy; Sandiego, Christine M; Pittman, Brian; Anderson, Jon M; Labaree, David; Gao, Hong; Huang, Yiyun; Deluliis, Giuseppe; O'Malley, Stephanie S; Carson, Richard E; Cosgrove, Kelly P

2016-04-01

Alcohol dependence and tobacco smoking are highly comorbid, and treating both conditions simultaneously is controversial. Previously, we showed that tobacco smoking interferes with GABAA receptor neuroadaptations during alcohol withdrawal in humans, while this effect did not occur with continued nicotine use during alcohol abstinence in nonhuman primates. Here, we extend our previous work by measuring GABAA receptor availability with positron emission tomography (PET) during drug abstinence in nonhuman primates exposed to alcohol alone, nicotine and alcohol together, and alcohol abstinence with continued nicotine exposure. Twenty-four adolescent male rhesus macaques orally self-administered alcohol and nicotine, available separately in water and saccharin, over 20 weeks. The groups included alcohol alone (n = 8); nicotine and alcohol with simultaneous abstinence (n = 8); nicotine and alcohol with alcohol abstinence while nicotine was still available (n = 8); and a pilot group of animals consuming nicotine alone (n = 6). Animals were imaged with [(11)C]flumazenil PET to measure binding potential (BPND), an index of GABAA receptor availability. Imaging occurred at baseline (drug-naíve), and following alcohol and/or nicotine cessation at 1 day, 8 days, and 12 weeks of abstinence. Generalized linear mixed models were used to examine the time course of [(11)C]flumazenil BPND during alcohol abstinence across groups. Animals consumed 3.95 ± 1.22 g/kg/d alcohol and 55.4 ± 35.1 mg/kg/d nicotine. No significant group effects were observed in [(11)C]flumazenil BPND during alcohol abstinence; however, a main effect of time was detected. Post hoc analyses indicated that all groups abstaining from alcohol exhibited significantly increased GABAA receptor availability at 1 day and 8 days (but not 12 weeks) of abstinence relative to baseline, while no changes in [(11)C]flumazenil BPND during nicotine abstinence alone were observed. These data indicate that neither nicotine nor nicotine abstinence interferes with GABAA receptor neuroadaptations during alcohol withdrawal. This conclusion is consistent with our previous study and does not contradict the use of nicotine replacement therapies or non-nicotinic-acting pharmaceuticals to quit smoking during alcohol withdrawal from a GABAergic perspective. Copyright © 2016 by the Research Society on Alcoholism.

Anaesthetic modulation of nicotinic ion channel kinetics in bovine chromaffin cells.

PubMed Central

Charlesworth, P; Richards, C D

1995-01-01

1. We have investigated the action of the anaesthetics methoxyflurane, methohexitone and etomidate on the nicotinic acetylcholine receptor channel of bovine adrenal chromaffin cells using the whole cell patch clamp technique. 2. Spectral analysis of macroscopic currents evoked by 25 microM carbachol revealed that each of the agents tested reduced the lifetime of the channel open state in a dose-dependent manner. The whole cell current was inhibited in a concentration-dependent fashion by each agent. 3. Channel gating parameters were calculated from single channel studies and the results used to test models explaining the modulation of nicotinic acetylcholine receptor channels by anaesthetics. 4. Each of the agents studied reduced the mean channel open time in a concentration-dependent manner. Anaesthetic concentrations reducing mean open time by 50% were: 370 microM methoxyflurane, 30 microM methohexitone or 23 microM etomidate. 5. Methohexitone and etomidate produced an increase in the number of brief closures within bursts, while no such increase was observed with methoxyflurane. Despite these inter-burst gaps, mean burst length was reduced by each of the agents tested. 6. It is concluded that a simple sequential blocking model fails to account for the action of these anaesthetics. An extended model, in which blocked channels can close, may be applicable. PMID:7773553

Part-time vs. full-time occlusion for amblyopia: evidence for part-time patching.

PubMed

Matta, Noelle S; Silbert, David I

2013-01-01

Amblyopia is characterized by a decreased uncorrectable visual acuity in a structurally normal eye. Occlusion therapy has been used for years to improve acuity, and, traditionally, practitioners have utilized full-time patching. This article will explore more recent research looking at using part-time patching in the treatment of amblyopia.

How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes.

PubMed

Czoli, Christine D; Fong, Geoffrey T; Mays, Darren; Hammond, David

2017-03-01

To systematically review the literature regarding relative risk perceptions (RRPs) across non-combustible nicotine products. MEDLINE and PsycINFO databases were searched for articles published up to October 2014. Of the 5266 records identified, articles not published in English that did not quantitatively assess RRPs across categories of non-combustible nicotine products were excluded, yielding 55 records. One reviewer extracted measures and findings of RRPs for product comparisons of smokeless tobacco (SLT), e-cigarettes (ECs) and nicotine replacement therapy (NRT) to one another, and to combustible cigarettes (CCs). A total of 157 samples from 54 studies were included in the analyses. The accuracy of RRPs differed based on the products being compared: although the accuracy of RRPs was variable across studies, substantial proportions of respondents reported inaccurate beliefs about the relative harmfulness of SLT versus CCs, as well as of ECs versus NRT. In addition, in most studies, respondents did not know the relative harmfulness of SLT versus NRT. In contrast, respondents in many studies correctly perceived NRT and ECs as less harmful than CCs. Cigarette smokers and users of non-combustible nicotine products tended to correctly perceive the relative harmfulness of products more often than non-users. Measures used to assess RRPs varied across studies, with different approaches characterised by certain strengths and limitations. The highly variable and context-specific nature of non-combustible nicotine product RRPs have direct implications for researchers and present several challenges for policymakers working with modified risk products, including issues of measurement, health risk communication and behaviour change. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Alzheimer’s Disease and Its Treatment With a Novel Transdermal Patch Therapy: Survey of Caregiver Experiences

PubMed Central

Pepp, Mike

2012-01-01

Objective: To investigate experiences and perceptions of caregivers of patients with Alzheimer’s disease using transdermal patch therapy. Method: Assessment methods for the pilot study comprised an interview between the caregiver and a moderator, an interview between 1 moderator and 2 caregivers, or a video diary. The subsequent quantitative study involved a 45-minute telephone questionnaire. For both studies, participants were required to be the principal caregiver of a patient with Alzheimer’s disease who had been receiving transdermal patch therapy for at least 3 months. Their responses were grouped into the following 6 themes: interpersonal relationships, impact on caregivers, from symptoms to treatment, help and support for caregivers, daily routine, and caregiver experience with the patch. Results: Overall, 206 caregivers were enrolled from France, Germany, Greece, Spain, and the United States between July 2009 and January 2011 (pilot study: N = 56; quantitative study: N = 150). The studies revealed that caregivers of patients with Alzheimer’s disease experienced emotional and practical impacts, and many felt that they had not received sufficient information from health care providers about Alzheimer’s disease, treatment options, or available support. In the quantitative study, 47% of caregivers who had been caring for the patient prior to diagnosis (61% of total respondents) felt that there had been a delay in seeking medical advice, frequently due to slow onset of symptoms of Alzheimer’s disease. In both studies, patch therapy was considered more convenient and easier to administer than oral treatments. The practical and efficacy advantages of the patch often translated into emotional benefits. Conclusions: With recent data highlighting the importance of early initiation of symptomatic Alzheimer’s disease therapy and the importance of reaching an optimal therapeutic dose, reasons for delay in treatment initiation need to be explored. Information that patients and caregivers receive at the time of diagnosis may aid therapeutic decisions. PMID:23251856

Prevalence of NRT use and associated nicotine intake in smokers, recent ex-smokers and longer-term ex-smokers.

PubMed

Shahab, Lion; Beard, Emma; Brown, Jamie; West, Robert

2014-01-01

Nicotine replacement therapy (NRT) is used by smokers wanting to reduce their smoking and to quit. However, there are very little data on nicotine intake associated with NRT use in representative population samples. This study aimed to provide estimates for NRT use and associated nicotine exposure among smokers, recent and longer-term ex-smokers in England, a country with a permissive regulatory regime for nicotine substitution. In the Smoking Toolkit Study, a monthly series of representative household surveys of adults aged 16+ in England, current and recent ex-smokers who agreed to be re-contacted were followed up 6 months later and standard socio-demographic and smoking characteristics assessed (N = 5,467, response rate 25.1%). A random sub-sample (N = 1,614; 29.5%) also provided saliva, analysed for cotinine. The sample followed up was broadly representative of the original sample. At follow-up, 11.8% (95%CI 10.9-12.8, N = 565) of current smokers, 34.8% (95%CI 28.9-41.3, N = 77) of recent (≤ 3 months) ex-smokers, and 7.8% (95%CI 5.6-10.6, N = 36) of longer-term (> 3 months) ex-smokers reported using NRT. Smokers who used NRT had similar saliva cotinine concentrations to smokers who did not use NRT (mean ± sd  = 356.0 ± 198.6 ng/ml vs. 313.1 ± 178.4 ng/ml). Recent ex-smokers who used NRT had levels that were somewhat lower, but not significantly so, than current smokers (216.7 ± 179.3 ng/ml). Longer-term ex-smokers using NRT had still lower levels (157.3 ± 227.1 ng/ml), which differed significantly from smokers using NRT (p = 0.024). Concurrent use of nicotine replacement therapy while smoking is relatively uncommon and is not associated with higher levels of nicotine intake. Among ex-smokers, NRT use is common in the short but not longer-term and among longer-term users is associated with lower nicotine intake than in smokers.

Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT) - a study protocol.

PubMed

Klonizakis, Markos; Crank, Helen; Gumber, Anil; Brose, Leonie S

2017-04-04

The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or "e-") cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately) combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants' "quit date". Participants will be assessed at baseline, 3 days following their self-determined "quit date", at intervention end (3 months) and 6 months following their "quite date". Findings are expected to give an indication of the cardiovascular effects of e-cigarettes both in the short- and in the medium-term period, informing the general public, policy holders and researchers, helping to define the future role of e-cigarettes as a smoking cessation aid. Clinicaltrials.gov NCT03061253 . Registered 17th February 2017.

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
.

PubMed

Sukhija, Manpreet; Srivastava, Reena; Kaushik, Aditya

2018-03-01

Nicotine replacement therapy (NRT) increases the probability of smoking cessation. This study was conducted to determine if three prototype 4-mg nicotine lozenges produced locally in India were bioequivalent to a globally marketed reference product, Nicorette® 4-mg nicotine lozenge. Healthy adult smokers (N = 39) were treated with three prototype 4-mg nicotine lozenges in comparison with a reference 4-mg lozenge in this single-center, randomized, open-label, single-dose, 4-way crossover study. Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0-∞, time to maximal plasma concentration (tmax), half-life (T1/2), elimination rate constant (Kel), and safety of the prototype lozenges versus the reference lozenge were compared. Each prototype 4-mg nicotine lozenge was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0-∞. Although tmax; was significantly longer for prototype III, all four lozenges achieved maximum plasma nicotine concentrations at a median of 1.5 hours. The safety profiles of the three prototype 4-mg lozenges did not differ from that of the 4-mg reference product. Each prototype 4-mg nicotine lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in -vitro method deployed is not a firm predictor of pharmacokinetic behavior.
.

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

PubMed

Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2015-05-05

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

Metabotropic glutamate receptor 5 as a potential target for smoking cessation.

PubMed

Chiamulera, Cristiano; Marzo, Claudio Marcello; Balfour, David J K

2017-05-01

Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high, and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence, they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many "off-target" effects to be used clinically. However, newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence.

Slower nicotine metabolism among postmenopausal Polish smokers.

PubMed

Kosmider, Leon; Delijewski, Marcin; Koszowski, Bartosz; Sobczak, Andrzej; Benowitz, Neal L; Goniewicz, Maciej L

2018-06-01

A non-invasive phenotypic indicator of the rate of nicotine metabolism is nicotine metabolite ratio (NMR) defined as a ratio of two major metabolites of nicotine - trans-3'-hydroxycotinine/cotinine. The rate of nicotine metabolism has important clinical implications for the likelihood of successful quitting with nicotine replacement therapy (NRT). We conducted a study to measure NMR among Polish smokers. In a cross-sectional study of 180 daily cigarette smokers (42% men; average age 34.6±13.0), we collected spot urine samples and measured trans-3'-hydroxycotinine (3-HC) and cotinine levels with LC-MS/MS method. We calculated NMR (molar ratio) and analyzed variations in NMR among groups of smokers. In the whole study group, an average NMR was 4.8 (IQR 3.4-7.3). The group of women below 51 years had significantly greater NMR compared to the rest of the population (6.4; IQR 4.1-8.8 vs. 4.3; IQR 2.8-6.4). No differences were found among group ages of male smokers. This is a first study to describe variations in nicotine metabolism among Polish smokers. Our findings indicate that young women metabolize nicotine faster than the rest of population. This finding is consistent with the known effects of estrogen to induce CYP2A6 activity. Young women may require higher doses of NRT or non-nicotine medications for most effective smoking cessation treatment. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Effects of Transdermal Tulobuterol in Pediatric Asthma Patients on Long-Term Leukotriene Receptor Antagonist Therapy: Results of a Randomized, Open-Label, Multicenter Clinical Trial in Japanese Children Aged 4-12 Years.

PubMed

Katsunuma, Toshio; Fujisawa, Takao; Mizuho, Nagao; Akira, Akasawa; Nomura, Ichiro; Yamaoka, Akiko; Kondo, Hisashi; Masuda, Kei; Yamaguchi, Koichi; Terada, Akihiko; Ikeda, Masanori; Nishioka, Kenji; Adachi, Yuichi; Kurihara, Kazuyuki

2013-01-01

Few studies have examined the efficacy or safety of a transdermal β2 agonist as add-on medicationto long-term leukotriene receptor antagonist (LTRA) therapy in pediatric asthma patients. In this randomized, open-label, multicenter clinical trial, children aged 4-12 years on long-term LTRA therapy were treated with tulobuterol patches (1-2 mg daily) or oral sustained-release theophylline (usual dose, 4-5 mg_kg daily) for 4 weeks. LTRAs were continued throughout the trial. Outcomes included volume peak expiratory flow (% PEF), fractional exhaled nitric oxide (FeNO), clinical symptoms and adverse events. Thirty-three and 31 patients were treated with tulobuterol patches and theophylline, respectively. % PEF measured in the morning and before bedtime was significantly higher at all times in the treatment period compared with baseline in the tulobuterol patch group (p < 0.001), and was significantly higher in the tulobuterol patch group compared with the theophylline group. FeNO was similar and unchanged from baseline in both groups. There were no drug-related adverse events in either group. These results suggest that short-term use of a transdermal β2 agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy. © 2013 Japanese Society of Allergology.

Prevalence of Use of Electronic Nicotine Delivery Systems (ENDS) to Vape Recreational Drugs by Club Patrons in South London.

PubMed

Thurtle, Natalie; Abouchedid, Rachelle; Archer, John R H; Ho, James; Yamamoto, Takahiro; Dargan, Paul I; Wood, David M

2017-03-01

Electronic nicotine delivery systems (ENDS, often called e-cigarettes) are nicotine delivery devices that heat nicotine into vapour that is inhaled, a process called 'vaping'. Use eclipsed nicotine-replacement therapy (NRT) in 2014 but ENDS role in smoking cessation remains controversial. Safety has not been proven and there have been reports to US poison centres regarding potential ENDS-related nicotine toxicity. A further concern is use of ENDS to vape recreational drugs, but there is limited data to substantiate this. The aim of this study was to report on ENDS use to vape recreational drugs in patrons of a South London nightclub where high prevalence of recreational drug use has previously been shown. A convenience sample of 101 participants was surveyed in March 2015 as part of a larger survey on drug use. Individuals were asked if they used ENDS to vape nicotine and/or other substances (and if so which substances). Ninety (89.1 %) of respondents were male with median age of 28 years (IQR 23-34). Eighty (79.2 %) currently smoked cigarettes; 20 (19.8 %) currently used ENDS for nicotine. Six (5.9 %) reported using ENDS to take other substances: 2 for 'liquid cannabis' and 4 did not elaborate on the substance(s) used. Of these 6, 3 were using ENDS to vape nicotine and 3 had never used them for nicotine. 5.9 % of individuals in this sample reported using ENDS to vape substances other than nicotine. Further work is required in larger populations to determine how common this is, evaluate which agents are being vaped and to inform appropriate public education.

Silver acetate interactions with nicotine and non-nicotine smoke components.

PubMed

Rose, Jed E; Behm, Frédérique M; Murugesan, Thangaraju; McClernon, F Joseph

2010-12-01

Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Comparison of the reinforcing properties of nicotine and cigarette smoke extract in rats.

PubMed

Costello, Matthew R; Reynaga, Daisy D; Mojica, Celina Y; Zaveri, Nurulain T; Belluzzi, James D; Leslie, Frances M

2014-07-01

Tobacco dependence is difficult to treat, with the vast majority of those who try to quit relapsing within the first year. Improvements in smoking cessation therapies may be achieved by improving current preclinical research methods. However, most experimental tests in animals use nicotine alone, ignoring the 8000 other constituents found in tobacco smoke. To improve on this model, we have used self-administration to test the reinforcing properties of aqueous cigarette smoke extract (CSE) in rats, made by bubbling cigarette smoke through a saline solution. CSE is more potent than nicotine alone in both the acquisition and maintenance of self-administration, but did not exhibit higher progressive ratio responding. Mecamylamine and varenicline had similar potencies to block nicotine and CSE self-administration, indicating the involvement of nicotinic receptors in CSE reinforcement. Following extinction of responding, reinstatement was triggered by exposing animals to a pharmacological stressor, yohimbine (2.5 mg/kg, i.p.), alone and in combination with cues. Animals that self-administered CSE were significantly more sensitive to stress-induced reinstatement than those that self-administered nicotine. Ligand binding autoradiography studies showed nicotine and CSE to have similar affinities for different nicotinic receptor types. CSE significantly reduced MAO-A and MAO-B activities in vitro, whereas nicotine did not. Although CSE inhibition of MAO-A activity in vitro was found to be partially irreversible, irreversible inhibition was not observed in vivo. These experiments show that CSE is an effective reinforcer acting via nicotinic receptors. Furthermore, it better models MAO inhibition and is more sensitive to stress-induced reinstatement than nicotine alone, which is a potent trigger for relapse in smokers.

The effect of simultaneous exposure of HEMn-DP and HEMn-LP melanocytes to nicotine and UV-radiation on the cell viability and melanogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delijewski, Marcin; Wrześniok, Dorota; Beberok, Ar

Nicotine is a main compound of tobacco plants and may affect more than a billion people all over the world that are permanently exposed to nicotine from cigarettes, various forms of smoking cessation therapies, electronic cigarettes or second-hand smoke. It is known that nicotine forms complexes with melanin what may lead to accumulation of this alkaloid in tissues of living organisms containing the pigment. This may affect the viability of cells and process of melanin biosynthesis that takes place in melanocytes. Although UV radiation is known to be a particular inductor of melanin biosynthesis, its simultaneous effect with nicotine onmore » this process as well as the viability of human cells containing melanin have not been assessed so far. The aim of this study was to examine the simultaneous impact of nicotine and UV radiation on viability and melanogenesis in cultured normal human melanocytes dark (HEMn-DP) and light (HEMn-LP) pigmented. Nicotine together with UV radiation induced concentration-dependent loss in melanocytes viability. The higher cell loss was observed in dark pigmented melanocytes in comparison to light pigmented cells. Simultaneous exposure of cells to nicotine and UV radiation also caused changes in melanization process in both tested cell lines. The data suggest that simultaneous exposure of melanocytes to nicotine and UV radiation up-regulates melanogenesis and affects cell viability. Observed processes are more pronounced in dark pigmented cells. - Highlights: • Nicotine and UVA induced concentration-dependent loss in melanocytes viability. • Nicotine and UVA modulated melanization process in melanocytes. • Changes in viability and melanization were more pronounced in dark pigmented cells.« less

Nicotine-mediated improvement in L-dopa-induced dyskinesias in MPTP-lesioned monkeys is dependent on dopamine nerve terminal function.

PubMed

Quik, Maryka; Mallela, Archana; Chin, Matthew; McIntosh, J Michael; Perez, Xiomara A; Bordia, Tanuja

2013-02-01

L-dopa-induced dyskinesias (LIDs) are abnormal involuntary movements that develop with long term L-dopa therapy for Parkinson's disease. Studies show that nicotine administration reduced LIDs in several parkinsonian animal models. The present work was done to understand the factors that regulate the nicotine-mediated reduction in LIDs in MPTP-lesioned nonhuman primates. To approach this, we used two groups of monkeys, one with mild-moderate and the other with more severe parkinsonism rendered dyskinetic using L-dopa. In mild-moderately parkinsonian monkeys, nicotine pretreatment (300 μg/ml via drinking water) prevented the development of LIDs by ~75%. This improvement was maintained when the nicotine dose was lowered to 50 μg/ml but was lost with nicotine removal. Nicotine re-exposure again decreased LIDs. By contrast, nicotine treatment did not reduce LIDs in monkeys with more severe parkinsonism. We next determined how nicotine's ability to reduce LIDs correlated with lesion-induced changes in the striatal dopamine transporter and (3)H-dopamine release in these two groups of monkeys. The striatal dopamine transporter was reduced to 54% and 28% of control in mild-moderately and more severely parkinsonian monkeys, respectively. However, basal, K(+), α4β2* and α6β2* nAChR-evoked (3)H-dopamine release were near control levels in striatum of mild-moderately parkinsonian monkeys. By contrast, these same release measures were reduced to a significantly greater extent in striatum of more severely parkinsonian monkeys. Thus, nicotine best improves LIDs in lesioned monkeys in which striatal dopamine transmission is still relatively intact. These data suggest that nicotine treatment would most effectively reduce LIDs in patients with mild to moderate Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Ethnic differences in smoking rate, nicotine dependence, and cessation-related variables among adult smokers in Hawaii.

PubMed

Herzog, Thaddeus A; Pokhrel, Pallav

2012-12-01

This study tests hypotheses concerning ethnic disparities in daily cigarette smoking rates, nicotine dependence, cessation motivation, and knowledge and past use of cessation methods (e.g., counseling) and products (e.g., nicotine patch) in a multiethnic sample of smokers in Hawaii. Previous research has revealed significant differences in smoking prevalence among Native Hawaiians, Filipinos, Japanese, and Caucasians in Hawaii. However, no study has examined differences in dependence and cessation-related knowledge and practices among smokers representing these ethnic groups. Participants were recruited through newspaper advertisement as part of a larger smoking cessation intervention study. Participants (N = 919; M age = 45.6, SD = 12.7; 48 % women) eligible to participate provided self-report data through mail and telephone. Participants included 271 self-identified Native Hawaiians, 63 Filipinos, 316 Caucasians, 145 "East Asians" (e.g., Japanese, Chinese), and 124 "other" (e.g., Hispanic, African-American). Pair-wise comparisons of means, controlling for age, gender, income, education, and marital status, indicated that Native Hawaiian smokers reported significantly higher daily smoking rates and higher levels of nicotine dependence compared to East Asians. Native Hawaiian smokers reported significantly lower motivation to quit smoking than Caucasians. Further, Filipino and Native Hawaiian smokers reported lesser knowledge of cessation methods and products, and less frequent use of these methods and products than Caucasians. The results suggest that Native Hawaiian and Filipino smokers could be underserved with regard to receiving cessation-related advice, and may lack adequate access to smoking cessation products and services. In addition, cessation interventions tailored for Native Hawaiian smokers could benefit from a motivational enhancement component.

Developmental nicotine exposure affects larval brain size and the adult dopaminergic system of Drosophila melanogaster.

PubMed

Morris, Melanie; Shaw, Ariel; Lambert, Madison; Perry, Haley Halperin; Lowenstein, Eve; Valenzuela, David; Velazquez-Ulloa, Norma Andrea

2018-06-14

Pregnant women may be exposed to nicotine if they smoke or use tobacco products, nicotine replacement therapy, or via e-cigarettes. Prenatal nicotine exposure has been shown to have deleterious effects on the nervous system in mammals including changes in brain size and in the dopaminergic system. The genetic and molecular mechanisms for these changes are not well understood. A Drosophila melanogaster model for these effects of nicotine exposure could contribute to faster identification of genes and molecular pathways underlying these effects. The purpose of this study was to determine if developmental nicotine exposure affects the nervous system of Drosophila melanogaster, focusing on changes to brain size and the dopaminergic system at two developmental stages. We reared flies on control or nicotine food from egg to 3rd instar larvae or from egg to adult and determined effectiveness of the nicotine treatment. We used immunohistochemistry to visualize the whole brain and dopaminergic neurons, using tyrosine hydroxylase as the marker. We measured brain area, tyrosine hydroxylase fluorescence, and counted the number of dopaminergic neurons in brain clusters. We detected an increase in larval brain hemisphere area, a decrease in tyrosine hydroxylase fluorescence in adult central brains, and a decrease in the number of neurons in the PPM3 adult dopaminergic cluster. We tested involvement of Dα7, one of the nicotinic acetylcholine receptor subunits, and found it was involved in eclosion, as previously described, but not involved in brain size. We conclude that developmental nicotine exposure in Drosophila melanogaster affects brain size and the dopaminergic system. Prenatal nicotine exposure in mammals has also been shown to have effects on brain size and in the dopaminergic system. This study further establishes Drosophila melanogaster as model organism to study the effects of developmental nicotine exposure. The genetic and molecular tools available for Drosophila research will allow elucidation of the mechanisms underlying the effects of nicotine exposure during development.

[Continued Use of Rotigotine Transdermal Patches for Parkinson Disease].

PubMed

Yasutaka, Yuki; Fujioka, Shinsuke; Shibaguchi, Hirotomo; Imakyure, Osamu; Washiyama, Atsushi; Tsuboi, Yoshio; Futagami, Koujiro

2016-06-01

Transdermal patches containing rotigotine, a dopamine agonist (DA) for treatment of Parkinson disease, continuously exert stable effects when applied once daily. Therefore, they are expected to reduce the patient burdens due to complications such as wearing-off and dysphagia. However, dosing is occasionally reduced or discontinued after application because of several reasons such as skin reactions or unsatisfactory efficacy. To identify the risk factors involved in the reduced or discontinued use of rotigotine patches, a retrospective study was conducted with reference to the medical records of patients with Parkinson disease who received rotigotine patches in our hospital. 85 patients were involved in this study. Dosing of rotigotine was reduced or discontinued in 53 patients during the study period. The factors associated with charges in treatment included combination therapy with clonazepam and oral administration of another DA before the application of rotigotine. The reduction or discontinuation rate of rotigotine patches in patients who reduced the equivalent dose of DA on the introduction of rotigotine patches was 94.7%, showing a significantly higher rate compared with 61.3% in the increased dose group. To improve adherence to rotigotine patch therapy, physicians need to carefully consider concomitant drugs and total dose of DAs. (Received December 7, 2015; Accepted February 22, 2016; Published June 1, 2016).

Positive psychotherapy for smoking cessation enhanced with text messaging: Protocol for a randomized controlled trial.

PubMed

Kahler, Christopher W; Surace, Anthony; Rebecca, E F; Gordon, B A; Cioe, Patricia A; Spillane, Nichea S; Parks, Acacia; Bock, Beth C; Brown, Richard A

2018-06-21

Despite reductions in cigarette smoking in the U.S., improvements in the efficacy of smoking cessation treatments are needed, as rates of sustained abstinence remain disappointingly low. Both low positive affect and high negative affect contribute to smoking relapse and constitute viable targets for smoking cessation interventions. Although some clinical trials have evaluated interventions to address depression as a smoking relapse risk factor, very few have focused on positive affect. Recently, we developed and conducted a preliminary clinical trial of a smoking cessation treatment that targets positive affect and cognitions by incorporating interventions rooted in positive psychology. The current randomized controlled trial will expand upon this preliminary trial to test whether this positive psychology-informed approach results in higher smoking cessation rates compared to a time-matched standard smoking cessation treatment control. Three hundred and forty adult daily smokers will be randomly assigned to either positive psychotherapy for smoking cessation or standard behavioral smoking cessation counseling. Participants will meet weekly with a study counselor for 6 weeks and will receive transdermal nicotine patch and text messaging smoking cessation support. Additionally, text messaging in the positive psychotherapy condition will encourage engagement in positive psychology-specific strategies for boosting mood and staying smoke free. Smoking cessation outcomes will be measured at 12, 26, and 52 weeks following target quit date. Results from this study will provide evidence on whether incorporating positive psychology interventions into smoking cessation treatment can improve smoking cessation outcomes relative to standard behavioral counseling with nicotine patch and text messaging. Copyright © 2018. Published by Elsevier Inc.

Electronic cigarettes for smoking cessation and reduction.

PubMed

McRobbie, Hayden; Bullen, Chris; Hartmann-Boyce, Jamie; Hajek, Peter

2014-01-01

Electronic cigarettes (ECs) are electronic devices that heat a liquid - usually comprising propylene glycol and glycerol, with or without nicotine and flavours, stored in disposable or refillable cartridges or a reservoir - into an aerosol for inhalation. Since ECs appeared on the market in 2006 there has been a steady growth in sales. Smokers report using ECs to reduce risks of smoking, but some healthcare organisations have been reluctant to encourage smokers to switch to ECs, citing lack of evidence of efficacy and safety. Smokers, healthcare providers and regulators are interested to know if these devices can reduce the harms associated with smoking. In particular, healthcare providers have an urgent need to know what advice they should give to smokers enquiring about ECs. To examine the efficacy of ECs in helping people who smoke to achieve long-term abstinence; to examine the efficacy of ECs in helping people reduce cigarette consumption by at least 50% of baseline levels; and to assess the occurrence of adverse events associated with EC use. We searched the Cochrane Tobacco Addiction Groups Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two other databases for relevant records from 2004 to July 2014, together with reference checking and contact with study authors. We included randomized controlled trials (RCTs) in which current smokers (motivated or unmotivated to quit) were randomized to EC or a control condition, and which measured abstinence rates or changes in cigarette consumption at six months or longer. As the field of EC research is new, we also included cohort follow-up studies with at least six months follow-up. We included randomized cross-over trials and cohort follow-up studies that included at least one week of EC use for assessment of adverse events. One review author extracted data from the included studies and another checked them. Our main outcome measure was abstinence from smoking after at least six months follow-up, and we used the most rigorous definition available (continuous, biochemically validated, longest follow-up). For reduction we used a dichotomous approach (no change/reduction < 50% versus reduction by 50% or more of baseline cigarette consumption). We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for each study, and where appropriate we pooled data from these studies in meta-analyses. Our search identified almost 600 records, from which we include 29 representing 13 completed studies (two RCTs, 11 cohort). We identified nine ongoing trials. Two RCTs compared EC with placebo (non-nicotine) EC, with a combined sample size of 662 participants. One trial included minimal telephone support and one recruited smokers not intending to quit, and both used early EC models with low nicotine content. We judged the RCTs to be at low risk of bias, but under the GRADE system the overall quality of the evidence for our outcomes was rated 'low' or 'very low' because of imprecision due to the small number of trials. A 'low' grade means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. A 'very low' grade means we are very uncertain about the estimate. Participants using an EC were more likely to have abstained from smoking for at least six months compared with participants using placebo EC (RR 2.29, 95% CI 1.05 to 4.96; placebo 4% versus EC 9%; 2 studies; GRADE: low). The one study that compared EC to nicotine patch found no significant difference in six-month abstinence rates, but the confidence intervals do not rule out a clinically important difference (RR 1.26, 95% CI: 0.68 to 2.34; GRADE: very low). A higher number of people were able to reduce cigarette consumption by at least half with ECs compared with placebo ECs (RR 1.31, 95% CI 1.02 to 1.68, 2 studies; placebo: 27% versus EC: 36%; GRADE: low) and compared with patch (RR 1.41, 95% CI 1.20 to 1.67, 1 study; patch: 44% versus EC: 61%; GRADE: very low). Unlike smoking cessation outcomes, reduction results were not biochemically verified.None of the RCTs or cohort studies reported any serious adverse events (SAEs) that were considered to be plausibly related to EC use. One RCT provided data on the proportion of participants experiencing any adverse events. Although the proportion of participants in the study arms experiencing adverse events was similar, the confidence intervals are wide (ECs vs placebo EC RR 0.97, 95% CI 0.71 to 1.34; ECs vs patch RR 0.99, 95% CI 0.81 to 1.22). The other RCT reported no statistically significant difference in the frequency of AEs at three- or 12-month follow-up between the EC and placebo EC groups, and showed that in all groups the frequency of AEs (with the exception of throat irritation) decreased significantly over time. There is evidence from two trials that ECs help smokers to stop smoking long-term compared with placebo ECs. However, the small number of trials, low event rates and wide confidence intervals around the estimates mean that our confidence in the result is rated 'low' by GRADE standards. The lack of difference between the effect of ECs compared with nicotine patches found in one trial is uncertain for similar reasons. ECs appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo ECs and nicotine patches, but the above limitations also affect certainty in this finding. In addition, lack of biochemical assessment of the actual reduction in smoke intake further limits this evidence. No evidence emerged that short-term EC use is associated with health risk.

Nicotine replacement therapy, professional therapy, snuff use and tobacco smoking: a study of smoking cessation strategies in southern Sweden.

PubMed

Lindström, Martin

2007-12-01

The strategies used to support smoking cessation among quitters were investigated according to year of smoking cessation and sociodemographic characteristics. The 2004 public health survey in Skåne, Sweden, is a cross-sectional study. A total of 27,757 people aged 18-80 answered a postal questionnaire. The participation rate was 59%. Different strategies to support smoking cessation--that is, no therapy, nicotine replacement (NRT), professional therapy and snus (snuff) use, were investigated among quitters according to year of smoking cessation, and demographic and socioeconomic characteristics. 14.9% of the men and 18.1% of the women were daily smokers. The prevalence of daily snus use was 19.5% among men but only 2.3% among women. Stratifying the data according to year of smoking cessation (1938-2004) revealed a significant increase in active smoking cessation strategies such as NRT, professional therapy and snus use. NRT was more common among women (23.6%) than men (14.8%) among smokers who quit in 2000-4, but snus use was more common among men (30.4% versus 8.7%). No replacement or other therapy at all was significantly more common among women (63.6%) than men (52.1%). People aged 35-80 years used more nicotine replacement than people aged 18-34, while men aged 18-34 used snus to quit smoking significantly more than men aged 55-80. Snus is used commonly among men as a support for smoking cessation in Sweden. Women use pharmacological NRT to a greater extent, but this can probably not compensate for the much higher extent of snuff use as a cessation strategy among men.

Nicotine replacement therapy, professional therapy, snuff use and tobacco smoking: a study of smoking cessation strategies in southern Sweden

PubMed Central

Lindström, Martin

2007-01-01

Objectives The strategies used to support smoking cessation among quitters were investigated according to year of smoking cessation and sociodemographic characteristics. Methods The 2004 public health survey in Skåne, Sweden, is a cross‐sectional study. A total of 27 757 people aged 18–80 answered a postal questionnaire. The participation rate was 59%. Different strategies to support smoking cessation—that is, no therapy, nicotine replacement (NRT), professional therapy and snus (snuff) use, were investigated among quitters according to year of smoking cessation, and demographic and socioeconomic characteristics. Results 14.9% of the men and 18.1% of the women were daily smokers. The prevalence of daily snus use was 19.5% among men but only 2.3% among women. Stratifying the data according to year of smoking cessation (1938–2004) revealed a significant increase in active smoking cessation strategies such as NRT, professional therapy and snus use. NRT was more common among women (23.6%) than men (14.8%) among smokers who quit in 2000–4, but snus use was more common among men (30.4% versus 8.7%). No replacement or other therapy at all was significantly more common among women (63.6%) than men (52.1%). People aged 35–80 years used more nicotine replacement than people aged 18–34, while men aged 18–34 used snus to quit smoking significantly more than men aged 55–80. Conclusions Snus is used commonly among men as a support for smoking cessation in Sweden. Women use pharmacological NRT to a greater extent, but this can probably not compensate for the much higher extent of snuff use as a cessation strategy among men. PMID:18048619

Secretome analysis of human articular chondrocytes unravels catabolic effects of nicotine on the joint.

PubMed

Lourido, Lucía; Calamia, Valentina; Fernández-Puente, Patricia; Mateos, Jesús; Oreiro, Natividad; Blanco, Francisco J; Ruiz-Romero, Cristina

2016-06-01

Osteoarthritis (OA) is a degenerative joint pathology characterized by articular cartilage degradation that lacks from efficient therapy. Since previous epidemiological data show a high controversy regarding the role of smoking in OA, we aimed to evaluate the effects of nicotine (the most physiologically active compound of tobacco) on the joint. Secretome analyses, based on metabolic labeling followed by LC-MALDI-TOF/TOF analysis, were carried out using an in vitro model of articular inflammation (primary human articular chondrocytes treated with interleukin-1β), and also on osteoarthritic cells. ELISA and Western blot assays were performed to verify some of the results. Nineteen proteins were altered by nicotine in the model of articular inflammation, including several cytokines and proteases. We confirmed the increased secretion by nicotine of matrix metalloproteinase 1 and two proposed markers of OA, fibronectin, and chitinase 3-like protein 1. Finally, four components of the extracellular matrix of cartilage were decreased by nicotine in OA chondrocytes. Our data contribute to a better understanding of the molecular mechanisms that are modulated by nicotine in cartilage cells, suggesting a negative effect of this drug on the joint. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio

PubMed Central

Allenby, Cheyenne E.; Boylan, Kelly A.; Lerman, Caryn; Falcone, Mary

2017-01-01

Quitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and other biological and environmental factors such as estrogen levels, alcohol use, body mass index, or menthol exposure. Then, we highlight clinical trials that validate the NMR as a biomarker to predict therapeutic response to different pharmacotherapies for smoking cessation. Current evidence supports the use of nicotine replacement therapy for slow metabolizers, and non-nicotine treatments such as varenicline for normal metabolizers. Finally, we discuss future research directions to elucidate mechanisms underlying NMR associations with treatment response, and facilitate the implementation of the NMR as biomarker in clinical practice to guide smoking cessation. PMID:26872457

Thoracoscopic patch insulation to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy.

PubMed

Mediratta, Neeraj; Barker, Diane; McKevith, James; Davies, Peter; Belchambers, Sandra; Rao, Archana

2012-07-01

Cardiac resynchronization therapy is an established therapy for heart failure, improving quality of life and prognosis. Despite advances in technique, available leads and delivery systems, trans-venous left ventricular (LV) lead positioning remains dependent on the patient's underlying venous anatomy. The left phrenic nerve courses over the surface of the pericardium laterally and may be stimulated by the LV pacing lead, causing uncomfortable diaphragmatic twitch. This paper describes a video-assisted thoracoscopic (VATS) procedure to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy. Most current ways of avoiding phrenic stimulation involve either electronic reprogramming to distance the phrenic nerve from the stimulation circuit or repositioning the lead. We describe a case where the phrenic nerve was surgically insulated from the stimulating current by insinuating a patch of bovine pericardium between the epicardium and native pericardium of the heart thus completely resolving previously intolerable and incessant diaphragmatic twitch. The procedure was performed under general anaesthesia with single-lung ventilation and minimal use of neuromuscular blocking agents. Surgical patch insulation of the phrenic nerve was performed using minimally invasive VATS surgery, as a short-stay procedure, with no complications. No diaphragmatic twitch occurred post-surgery and the patient continued to gain symptomatic benefit from cardiac synchronization therapy (New York Heart Association Class III to II), enabling return to work. In cases where the trans-venous position of a LV lead is limited by troublesome phrenic nerve stimulation, thoracoscopic surgical patch insulation of the phrenic nerve could be considered to allow beneficial cardiac resynchronization therapy.

The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woynillowicz, Amanda K.; Raha, Sandeep; Nicholson, Catherine J.

The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normalmore » glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.« less

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice

PubMed Central

Lee, Bridgin G.; Anastasia, Agustin; Hempstead, Barbara L.; Lee, Francis S.

2015-01-01

Introduction: Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. Methods: This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNFMet/Met) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Results: Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNFMet/Met mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNFMet/Met mice; and (3) an increase in BDNF prodomain in BDNFMet/Met mice following nicotine withdrawal. Conclusions: Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNFMet/Met mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. PMID:25744957

Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors.

PubMed

Yohn, Nicole L; Turner, Jill R; Blendy, Julie A

2014-05-01

Although nicotine mediates its effects through several nicotinic acetylcholine receptor (nAChR) subtypes, it remains to be determined which nAChR subtypes directly mediate heightened anxiety during withdrawal. Relative success in abstinence has been found with the nAChR partial agonist varenicline (Chantix; Pfizer, Groton, CT); however, treatment with this drug fails to alleviate anxiety in individuals during nicotine withdrawal. Therefore, it is hypothesized that success can be found by the repurposing of other nAChR partial agonists for cessation therapies that target anxiety. It is noteworthy that the selective partial agonists for α4β2, ABT-089 [2-methyl-3-[2(S)-pyrrolidinylmethoxy]pyridine], and α7, ABT-107 [5-(6-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy] pyridazin-3-yl)-1H-indole] (AbbVie, North Chicago, IL), have not been evaluated as possible therapeutics for nicotine cessation. Therefore, we examined the effect of ABT-089 and ABT-107 on anxiety during withdrawal from nicotine in the novelty-induced hypophagia (NIH) paradigm. We found that short-term administration of ABT-089 and ABT-107 alleviate anxiety-like behavior during withdrawal from nicotine while long-term administration of ABT-089 but not ABT-107 reduces anxiety-like behavior during withdrawal. After behavioral testing, brains were harvested and β2-containing nAChRs were measured using [(3)H]epibaditine. ABT-089 and ABT-107 do not upregulate nAChRs, which is in contrast to the upregulation of nAChRs observed after nicotine. Furthermore, ABT-089 is anxiogenic in nicotine naive animals, suggesting that the effects on anxiety are specifically related to the nicotine-dependent state. Together, these studies identify additional nAChR partial agonists that may aid in the rational development of smoking cessation aids.

Counteracting desensitization of human α7-nicotinic acetylcholine receptors with bispyridinium compounds as an approach against organophosphorus poisoning.

PubMed

Scheffel, Corinna; Niessen, Karin V; Rappenglück, Sebastian; Wanner, Klaus T; Thiermann, Horst; Worek, Franz; Seeger, Thomas

2018-09-01

Irreversible inhibition of acetylcholinesterase (AChE) resulting in accumulation of acetylcholine and overstimulation of muscarinic and nicotinic receptors accounts for the acute toxicity of organophosphorus compounds (OP). Accordingly, the mainstay pharmacotherapy against poisoning by OP comprises the competitive muscarinic acetylcholine receptor antagonist atropine to treat muscarinic effects and, in addition, oximes to reactivate inhibited AChE. A therapeutic gap still remains in the treatment of desensitized nicotinic acetylcholine receptors following OP exposure. Hereby, nicotinic effects result in paralysis of the central and peripheral respiratory system if untreated. Thus, these receptors pose an essential target for therapeutic indication to address these life-threatening nicotinic symptoms of the cholinergic crisis. Identification of ligands regulating dynamic transitions between functional states by binding to modulatory sites appears to be a promising strategy for therapeutic intervention. In this patch clamp study, the ability of differently substituted bispyridinium non-oximes to "resensitize" i.e. to recover the activity of desensitized human homomeric α7-type nAChRs stably transfected in CHO cells was investigated and compared to the already described α7-specific positive allosteric modulator PNU-120596. The structures of these bispyridinium analogues were based on the lead structure of the tert-butyl-substituted bispyridinium propane MB327, which has been shown to have a positive therapeutic effect due to a non-competitive antagonistic action at muscle-type nAChRs in vivo and has been found to have a positive allosteric activity at neuronal receptors in vitro. Prior to test compounds, desensitization of hα7-nAChRs was verified by applying an excess of nicotine revealing activation at low, and desensitization at high concentrations. Thereby, desensitization could be reduced by modulation with PNU-120596. Desensitization was further verified by dose-response profiles of agonists, carbamoylcholine and epibatidine in the absence and presence of PNU-120596. Although less pronounced than PNU-120596 and the lead structure MB327, bispyridinium compounds, particularly those substituted at position 3 and 4, resensitized the nicotine desensitized hα7-nAChRs in a concentration-dependent manner and prolonged the mean channel open time. In summary, identification of more potent compounds able to restore nAChR function in OP intoxication is needed for development of a putative efficient antidote. Copyright © 2017 Elsevier B.V. All rights reserved.

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats.

PubMed

Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

2014-01-01

Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

A Link between Adolescent Nicotine Metabolism and Smoking Topography

PubMed Central

Moolchan, Eric T.; Parzynski, Craig S.; Jaszyna-Gasior, Maria; Collins, Charles C.; Leff, Michelle K.; Zimmerman, Debra L.

2009-01-01

Adult slow nicotine metabolizers have lower smoke exposure, carbon monoxide levels, and plasma nicotine levels than normal and fast metabolizers. Emerging evidence suggests nicotine metabolism influences smoking topography. This study investigated the association of nicotine metabolism (the ratio of plasma 3-hydroxycotinine to cotinine; 3OHCOT/COT) with smoking topography in adolescent smokers (N=85, 65% female, 68% European American, mean age 15.3 ± 1.2, mean cigarettes per day (CPD) 18.5 ± 8.5, mean Fagerström Test for Nicotine Dependence (FTND) 7.0 ± 1.2) presenting for a nicotine replacement therapy trial. Measures obtained included puff volume, inter-puff interval, number of puffs, puff duration, and puff velocity. Linear regression analysis controlling for hormonal contraception use showed that 3OHCOT/COT ratios predicted mean puff volume in the overall sample (t = 2.126, p = .037, adjusted R2 = .067). After gender stratification, faster metabolism predicted higher mean puff volume (t = 2.81, p = .009, adjusted R2 = .192) but fewer puffs (t = −3.160, p=0.004, adjusted R2 = .237) and lower mean puff duration (t = −2.06, p = .048, adjusted R2 = .101) among boys only, suggesting that as nicotine metabolism increases, puff volume increases but puffing frequency decreases. No significant relationships were found between nicotine metabolism and total puff volume, mean puff duration, inter-puff interval, or puff velocity. If confirmed in a broader sample of adolescent smokers, these findings suggest that, as among dependent adult smokers, rate of metabolism among adolescent boys is linked to select parameters of puffing behavior that may impact cessation ability. PMID:19423535

Postnatal Cardiovascular Consequences in the Offspring of Pregnant Rats Exposed to Smoking and Smoking Cessation Pharmacotherapies.

PubMed

Gopalakrishnan, Kathirvel; More, Amar S; Hankins, Gary D; Nanovskaya, Tatiana N; Kumar, Sathish

2017-06-01

Approximately 20% of pregnant women smoke despite intentions to quit. Smoking cessation drugs, such as nicotine replacement therapy (NRT) and bupropion, are recommended treatments. Adverse cardiovascular outcomes in offspring have raised concerns about NRT's safety during pregnancy. However, the effect of bupropion is unknown. Using a rat model, we determined whether NRT and bupropion interventions during pregnancy are safer than continued smoking on offspring's cardiovascular function. Male offspring of controls and dams exposed to cigarette smoke (1.6 packs/day, inhalation), nicotine (2 mg/kg/d subcutaneously), and bupropion (13 mg/kg twice daily orally) were assessed for fetoplacental weight, cardiac function, blood pressure, and vascular reactivity. Fetoplacental weights were decreased and spontaneous beating and intracellular calcium in neonatal cardiomyocytes were increased in smoking, nicotine, and bupropion offspring; however, these effects were more accentuated in smoking followed by nicotine and bupropion offspring. Increased heart rate and decreased cardiac output, stroke volume, and left ventricular percent posterior wall thickening were observed in smoking, nicotine, and bupropion offspring. The left ventricular mass was reduced in smoking and nicotine but not in bupropion offspring. Blood pressure was higher with decreased endothelium-dependent relaxation and exaggerated vascular contraction to angiotensin II in smoking and nicotine offspring, with more pronounced dysfunctions in smoking than nicotine offspring. Maternal bupropion did not impact offspring's blood pressure, endothelium-dependent relaxation, and vascular contraction. In conclusion, maternal nicotine intervention adversely affects offspring's cardiovascular outcomes, albeit less severely than continued smoking. However, bupropion causes cardiac derangement in offspring but does not adversely affect blood pressure and vascular function.

E-Cigarettes: The Science Behind the Smoke and Mirrors.

PubMed

Cobb, Nathan K; Sonti, Rajiv

2016-08-01

E-cigarettes are a diverse set of devices that are designed for pulmonary delivery of nicotine through an aerosol, usually consisting of propylene glycol, nicotine, and flavorings. The devices heat the nicotine solution using a battery-powered circuit and deliver the resulting vapor into the proximal airways and lung. Although the current devices on the market appear to be safer than smoking combusted tobacco, they have their own inherent risks, which remain poorly characterized due to widespread product variability. Despite rising use throughout the United States, predominantly by smokers, limited evidence exists for their efficacy in smoking cessation. Pending regulation by the FDA will enforce limited disclosures on the industry but will not directly impact safety or efficacy. Meanwhile, respiratory health practitioners will need to tailor their discussions with patients, taking into account the broad range of existing effective smoking cessation techniques, including pharmaceutical nicotine replacement therapy. Copyright © 2016 by Daedalus Enterprises.

Influence of chronic nicotine administration on cerebral type 1 cannabinoid receptor binding: an in vivo micro-PET study in the rat using [18F]MK-9470.

PubMed

Gérard, Nathalie; Ceccarini, Jenny; Bormans, Guy; Vanbilloen, Bert; Casteels, Cindy; Goffin, Karolien; Bosier, Barbara; Lambert, Didier M; Van Laere, Koen

2010-10-01

Several lines of evidence suggest a functional interaction between central nicotinic and endocannabinoid systems. Furthermore, type 1 cannabinoid receptor (CB1R) antagonism is evaluated as antismoking therapy, and nicotine usage can be an important confound in positron emission tomography (PET) imaging studies of the CB1R. We evaluated CB1R binding in the rat brain using the PET radioligand [(18)F]MK-9470 after chronic administration of nicotine. Twelve female Wistar rats were scanned at baseline and after chronic administration of either nicotine (1 mg/kg; 2 weeks daily intraperitoneal (IP)) or saline as control. In vivo micro-PET images of CB1R binding were anatomically standardized and analyzed by voxel-based statistical parametric mapping and a predefined volume-of-interest approach. We did not observe changes in [(18)F]MK-9470 binding (p (height) < 0.001 level; uncorrected) on a group basis in either condition. Only at a less stringent threshold of p (height) < 0.005 (uncorrected) was a modest increase observed in tracer binding in the cerebellum for nicotine (peak voxel value + 6.8%, p (cluster) = 0.002 corrected). In conclusion, chronic IP administration of nicotine does not produce major cerebral changes in CB1R binding of [(18)F]MK-9470 in the rat. These results also suggest that chronic nicotine usage is unlikely to interfere with human PET imaging using this radioligand.

Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers.

PubMed

Brossard, Patrick; Weitkunat, Rolf; Poux, Valerie; Lama, Nicola; Haziza, Christelle; Picavet, Patrick; Baker, Gizelle; Lüdicke, Frank

2017-10-01

Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence 4: Gum - THS (n = 9). Plasma nicotine concentrations were measured in 16 blood samples collected over 24 h after single use. Maximal nicotine concentration (C max ) and area under the curve from start of product use to time of last quantifiable concentration (AUC 0-last ) were similar between THS and CC in both studies, with ratios varying from 88 to 104% for C max and from 96 to 98% for AUC 0-last . Urge-to-smoke total scores were comparable between THS and CC. The THS nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to-smoke. This suggests that THS can satisfy smokers and be a viable alternative to cigarettes for adult smokers who want to continue using tobacco. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder

PubMed Central

Janes, Amy C; Pedrelli, Paola; Whitton, Alexis E; Pechtel, Pia; Douglas, Samuel; Martinson, Max A; Huz, Ilana; Fava, Maurizio; Pizzagalli, Diego A; Evins, A Eden

2015-01-01

Major depressive disorder (MDD) and nicotine dependence are highly comorbid, with studies showing that ~50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evidence indicates that individuals with rMDD show blunted responses to reward as measured by a probabilistic reward task (PRT), which assesses the ability to modify behavior as a function of reward history. Given nicotine's ability to enhance reward responsiveness, individuals with rMDD might smoke to address this persistent reward deficit. However, it is unclear whether smokers with rMDD show enhanced reward responsiveness relative to rMDD individuals who do not smoke. To test this hypothesis, we evaluated reward responsiveness on the PRT in four groups (N=198): individuals with and without rMDD who were or were not nicotine dependent. As hypothesized, rMDD nonsmokers had lower reward responsiveness relative to both control nonsmokers and rMDD smokers; conversely, smokers with rMDD showed behavioral patterns comparable to those without a history of depression. Given nicotine's ability to enhance reward sensitivity, it is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD. Therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD. PMID:25662839

Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring.

PubMed

Barra, Nicole G; Lisyansky, Maria; Vanduzer, Taylor A; Raha, Sandeep; Holloway, Alison C; Hardy, Daniel B

2017-12-01

Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also occur in the heart. At 3 months of age, nicotine-exposed offspring had 45% decreased PDI levels in the absence of endoplasmic reticulum stress. Given the association of PDI and superoxide dismutase enzymes, we further observed that antioxidant superoxide dismutase-2 levels were reduced by 32% in these offspring concomitant with a 26-49% decrease in mitochondrial complex proteins (I, II, IV and V) and tissue inhibitor of metalloproteinase-4, a critical matrix metalloprotease for cardiac contractility and health. Collectively, this study suggests that perinatal nicotine exposure decreases PDI, which can promote oxidative damage and mitochondrial damage, associated with a premature decline in cardiac function. Copyright © 2017 John Wiley & Sons, Ltd.

Sex differences in nicotine dependency and depressive tendency among smokers.

PubMed

Komiyama, Maki; Yamakage, Hajime; Satoh-Asahara, Noriko; Ozaki, Yuka; Morimoto, Tatsuya; Shimatsu, Akira; Takahashi, Yuko; Hasegawa, Koji

2018-06-09

Depressive tendency and nicotine dependency are factors related to the failure of smoking cessation. Women generally have a higher depressive tendency and difficulty in smoking cessation than men. However, the impact of sex differences on the relationship between nicotine dependency and depressive tendency remains unclear. We evaluated 727 patients (496 men and 231 women) who visited our outpatient clinic for smoking cessation therapy and compared various parameters measured between sexes during consultation. Age, duration of smoking, and daily cigarette consumption were significantly higher in men during the first visit. Women had significantly higher self-rating depression scale (SDS) scores and took significantly more antidepressant drugs than men. The SDS score significantly correlated with the Fagerström test for the nicotine dependence score and with daily cigarette consumption in women, but not in men. Thus, the present study demonstrates the differential relationship of depressive tendency with tobacco use or nicotine dependency in men and women, which might reflect sex differences in response to psychological stress. Copyright © 2018 Elsevier B.V. All rights reserved.

Randomized Controlled Trial of Group-Based Culturally Specific Cognitive Behavioral Therapy Among African American Smokers.

PubMed

Webb Hooper, Monica; Antoni, Michael H; Okuyemi, Kolawole; Dietz, Noella A; Resnicow, Ken

2017-03-01

This study tested the efficacy of group-based culturally specific cognitive behavioral therapy (CBT) for smoking cessation among low-income African Americans. Participants (N = 342; 63.8% male; M = 49.5 years old; M cigarettes per day = 18) were randomly assigned to eight sessions of group-based culturally specific or standard CBT, plus 8 weeks of transdermal nicotine patches. Biochemically verified 7-day point prevalence abstinence (ppa) was assessed at the end-of-therapy (ie, CBT) (EOT), and 3-, 6-, and 12-month follow-ups. Primary outcomes were the longitudinal intervention effect over the 12-month follow-up period, and 7-day ppa at the 6-month follow-up. Secondary outcomes included 7-day ppa at the EOT and 12-month follow-up, and intervention ratings. Generalized linear mixed modeling tested the longitudinal effect and logistic regression tested effects at specific timepoints. Generalized linear mixed modeling demonstrated a longitudinal effect of intervention condition. Specifically, 7-day ppa was two times (P = .02) greater following culturally specific CBT versus standard CBT when tested across all timepoints. Analyses by timepoint found no significant difference at 6 or 12 months, yet culturally specific CBT was efficacious at the EOT (62.5% vs. 51.5% abstinence, P = .05) and the 3-month follow-up (36.4% vs. 22.9% abstinence, P = .007). Finally, intervention ratings in both conditions were high, with no significant differences. Culturally specific CBT had a positive longitudinal effect on smoking cessation compared to a standard approach; however, the effects were driven by short-term successes. We recommend the use of group-based culturally specific CBT in this population when possible, and future research on methods to prevent long-term relapse. Culturally specific interventions are one approach to address smoking-related health disparities; however, evidence for their efficacy in African Americans is equivocal. Moreover, the methodological limitations of the existing literature preclude an answer to this fundamental question. We found a positive longitudinal effect of culturally specific CBT versus standard CBT for smoking cessation across the follow-up period. Analyses by assessment point revealed that the overall effect was driven by early successes. Best practices for treating tobacco use in this population should attend to ethnocultural factors, but when this is not possible, standard CBT is an alternative approach for facilitating long-term abstinence. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The science of tobacco addiction and cessation.

PubMed

2014-01-01

Over the past decade, researchers have found genetic variations that affect how nicotine, the main addictive component of tobacco, interacts with cells in the brain and how fast the body metabolizes it. Carrying a high-risk variant predicts a person's ability to snuff out their cigarettes for good. Genetic testing could help predict which smokers might benefit from nicotine replacement therapy or other prescription medications, much like sequencing of malignant tumors can point to the most effective cancer treatment.

Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

PubMed Central

Misra, Manoj; Leverette, Robert D.; Cooper, Bethany T.; Bennett, Melanee B.; Brown, Steven E.

2014-01-01

The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic. PMID:25361047

Treatment of complex regional pain syndrome type 1 in a pediatric patient using the lidocaine patch 5%: a case report☆

PubMed Central

Frost, Steven G

2003-01-01

Background Successful treatment of complex regional pain syndrome type 1 (CRPS-1) requires a coordinated, multidisciplinary approach. Physical rehabilitation is an important component of long-term treatment. Unfortunately, patients with significant allodynia or hyperalgesia characteristic of CRPS-1 often have difficulty progressing through a physical therapy (PT) regimen. In most adults with CRPS-1, the treatment of choice is PO opioids. Objective This article presents a case report of the use of the lidocaine patch 5%, a targeted peripheral analgesic, in a pediatric patient and its effects on reducing pain, improving the patient's overall attitude, and facilitating compliance with ongoing PT. Results A 10-year-old girl developed CRPS-1 after arthroscopic surgery for a sprained ankle. Attempts at PT were unsuccessful due to inadequate pain relief from various treatment modalities. Therapy with the lidocaine patch 5% was initiated and resulted in significant pain relief, improvements in the patient's attitude, and progress with PT. Conclusion This case report of a child with CRPS-1 showed that therapy with lidocaine patch 5% may be efficacious in treating children with pain resulting from CRPS-1, thereby increasing the success of PT. PMID:24944409

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

PubMed

Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

2015-12-01

Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation.

PubMed

Long, Cheng; Chen, Mei-Fang; Sarwinski, Susan J; Chen, Po-Yi; Si, Minliang; Hoffer, Barry J; Evans, M Steven; Lee, Tony J F

2006-07-01

We have proposed that activation of cerebral perivascular sympathetic alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) by nicotinic agonists releases norepinephrine, which then acts on parasympathetic nitrergic nerves, resulting in release of nitric oxide and vasodilation. Using patch-clamp electrophysiology, immunohistochemistry, and in vitro tissue bath myography, we tested this axo-axonal interaction hypothesis further by examining whether blocking norepinephrine reuptake enhanced alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation. The results indicated that choline- and nicotine-induced alpha7-nAChR-mediated nitrergic neurogenic relaxation in endothelium-denuded isolated porcine basilar artery rings was enhanced by desipramine and imipramine at lower concentrations (0.03-0.1 microM) but inhibited at higher concentrations (0.3-10 microM). In cultured superior cervical ganglion (SCG) neurons of the pig and rat, choline (0.1-30 mM)-evoked inward currents were reversibly blocked by 1-30 microM mecamylamine, 1-30 microM methyllycaconitine, 10-300 nM alpha-bungarotoxin, and 0.1-10 microM desipramine and imipramine, providing electrophysiological evidence for the presence of similar functional alpha7-nAChRs in cerebral perivascular sympathetic neurons of pigs and rats. In alpha7-nAChR-expressing Xenopus oocytes, choline-elicited inward currents were attenuated by alpha-bungarotoxin, imipramine, and desipramine. These monoamine uptake inhibitors appeared to directly block the alpha7-nAChR, resulting in diminished nicotinic agonist-induced cerebral nitrergic vasodilation. The enhanced nitrergic vasodilation by lower concentrations of monoamine uptake inhibitors is likely due to a greater effect on monoamine uptake than on alpha7-nAChR blockade. These results further support the hypothesis of axo-axonal interaction in nitrergic regulation of cerebral vascular tone.

Ethnic differences in smoking rate, nicotine dependence, and cessation-related variables among adult smokers in Hawaii

PubMed Central

Herzog, Thaddeus A; Pokhrel, Pallav

2012-01-01

This study tests hypotheses concerning ethnic disparities in daily cigarette smoking rates, nicotine dependence, cessation motivation, and knowledge and past use of cessation methods (e.g., counseling) and products (e.g., nicotine patch) in a multiethnic sample of smokers in Hawaii. Previous research has revealed significant differences in smoking prevalence among Native Hawaiians, Filipinos, Japanese, and Caucasians in Hawaii. However, no study has examined differences in dependence and cessation-related knowledge and practices among smokers representing these ethnic groups. Participants were recruited through newspaper advertisement as part of a larger smoking cessation intervention study. Participants (N=919; M age=45.6, SD=12.7; 48% Women) eligible to participate provided self-report data through mail and telephone. Participants included 271 self-identified Native Hawaiians, 63 Filipinos, 316 Caucasians, 145 “East Asians” (e.g., Japanese, Chinese), and 124 “Other” (e.g., Hispanic, African-American). Pair-wise comparisons of means, controlling for age, gender, income, education, and marital status, indicated that Native Hawaiian smokers reported significantly higher daily smoking rates and higher levels of nicotine dependence compared to East Asians. Native Hawaiian smokers reported significantly lower motivation to quit smoking than Caucasians. Further, Filipino and Native Hawaiian smokers reported lesser knowledge of cessation methods and products, and less frequent use of these methods and products than Caucasians. The results suggest that Native Hawaiian and Filipino smokers could be underserved with regard to receiving cessation-related advice, and may lack adequate access to smoking cessation products and services. In addition, cessation interventions tailored for Native Hawaiian smokers could benefit from a motivational enhancement component. PMID:22438074

Treating angina pectoris by acupuncture therapy.

PubMed

Xu, Lixian; Xu, Hao; Gao, Wei; Wang, Wei; Zhang, Hui; Lu, Dominic P

2013-01-01

Acupuncture therapy on PC 6 (Neiguan) has a therapeutic effect on cardiac and chest ailments including angina pectoris. Additional beneficial acupuncture points are PC 4 (Ximen), HT 7 (Shenmen point), PC 7 (Daling point), PC 5 (Jianshi point), PC 3 (Quze point), CV 17 (Danzhong point), CV 6 (Qihai point), BL 15 (Xinshu point), L 20 (Pishu point), BL 17 (Geshu point), BL23 (Shenshu point), BL18 (Ganshu point), HT 5 (Tongli point), and ST36 (Zusanli point). Acupuncture not only quickly relieve the symptoms of acute angina pectoris, but also improve nitroglycerine's therapeutic effects. Therefore, it is an efficient simple therapeutic method used for emergency and for regular angina treatment. Review of studies on acupuncture therapy has shown effectiveness were between 80% to 96.2% that are almost as effective as conventional drug regimen. When compared with conventional medical treatment, the acupuncture therapy shows the obvious advantage of lacking, adverse side effects commonly associated with the Western anti-anginal drugs such as 1) Nitroglycerine (headache--63% with nitroglycerine patch and 50% with spray; syncope--4%; and dizziness--8% with patch; hypotension--4% with patch; and increased angina 2% with patch). 2) Isosorbide mononitrate (dizziness--3 to 5%; nausea/vomiting--2 to 4% and other reactions including hypotension, and syncope even with small doses). 3) Propranolol (bradycardia, chest pain, hypotension, worsening of AV conduction disturbance, Raynaud's syndrome, mental depression, hyperglycemia, etc.). Many conventional anti-anginal medications cause inter-drug reactions with other medications the patients taking for other diseases. Whereas, acupuncture therapy does not pose such an interference with patient's medications. Nevertheless, surgery is still the treatment of choice when acupuncture or conventional drug therapy fails. Combination of conventional drug therapy and acupuncture would considerably decrease the frequency and the required dosage of drug taking, thereby decreasing the unpleasant side effects of the drug therapy.

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats

PubMed Central

Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

2014-01-01

Background: Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Materials and Methods: Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25th day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20th and 25th days. Results: The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). Conclusion: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols. PMID:25590029

The impact of anticipated and unanticipated smoking opportunities on cigarette smoking and nicotine lozenge responses.

PubMed

Schlagintweit, Hera E; Greer, Holly; Good, Kimberley P; Barrett, Sean P

2015-02-01

Perceptions regarding the availability of smoking opportunities are known to affect cigarette craving; however, whether they impact actual smoking or how smokers respond to acute nicotine replacement therapy (NRT) administration is not known. This study examined the impact of pharmacological and expectancy components of NRT administration on craving and smoking in smokers anticipating or not anticipating an imminent smoking opportunity. In total, 154 smokers (84 male) completed an experimental session in which instructions regarding the nicotine content of a lozenge (4 mg vs. no nicotine) and regarding the availability of a future smoking opportunity were manipulated. Cigarette craving was assessed before and after manipulations and lozenge administration. All participants were then allotted 1h to self-administer as many cigarette puffs as they wished. Unanticipated smoking opportunities reduced latency to self-administration (p<0.001), regardless of nicotine expectancy or pharmacology. When analyses included all participants, nicotine reduced intentions to smoke (p=0.016) and withdrawal-related craving (p=0.043) regardless of expectancy. Conversely, analyses using only "believers" of the nicotine content instructions revealed that nicotine expectancy reduced intentions to smoke (p=0.034) and withdrawal-related craving (p=0.047) regardless of actual nicotine administration. "Believers" also reported increased withdrawal-related craving when a smoking opportunity was perceived to be imminent (p=0.041). These effects were not significant when analyses included all participants. Findings suggest that unexpected smoking opportunities may be more appealing than expected ones regardless of perceived or actual acute NRT use. They also highlight the importance of reporting balanced placebo findings using all participants as well as "believers" only. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chronic nicotine inhibits the therapeutic effects of gemcitabine on pancreatic cancer in vitro and in mouse xenografts.

PubMed

Banerjee, Jheelam; Al-Wadei, Hussein A N; Schuller, Hildegard M

2013-03-01

Smoking is an established risk factor for pancreatic cancer and nicotine replacement therapy (NRT) often accompanies chemotherapy. The current study has tested the hypothesis that chronic exposure to low dose nicotine reduces the responsiveness of pancreatic cancer to the leading therapeutic for this cancer, gemcitabine. The effects of chronic nicotine (1 μm/L) on two pancreatic cancer cell lines in vitro and in a xenograft model were assessed by immunoassays, Western blots and cell proliferation assays. Exposure in vitro to nicotine for 7 days inhibited the gemcitabine-induced reduction in viable cells, gemcitabine-induced apoptosis as indicated by reduced expression of cleaved caspase-3 while inducing the phosphorylation of signalling proteins extracellular signal-regulated kinase (ERK), v-akt thymoma viral oncogene homolog (protein kinase B, AKT) and Src. Nicotine (1 μm/L) in the drinking water for 4 weeks significantly reduced the therapeutic response of mouse xenografts to gemcitabine while reducing the induction of cleaved caspase-3 and the inhibition of phosphorylated forms of multiple signalling proteins by gemcitabine in xenograft tissues. Our experimental data suggest that continued moderate smoking and NRT may negatively impact therapeutic outcomes of gemcitabine on pancreatic cancer and that clinical studies in cancer patients are now warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

Smokers' and ex-smokers' understanding of electronic cigarettes: a qualitative study.

PubMed

Rooke, Catriona; Cunningham-Burley, Sarah; Amos, Amanda

2016-04-01

To explore among a diverse range of smokers and recent ex-smokers, particularly those from disadvantaged groups, how nicotine-containing products, particularly electronic cigarettes (e-cigarettes), are understood and experienced. Qualitative study of 64 smokers and ex-smokers in Central Scotland. Twelve focus groups and 11 individual interviews were carried out with a range of purposively selected groups. Nicotine replacement therapies and e-cigarettes were regarded as being very different products. Nicotine replacement therapies were viewed as medical products for smokers who want to quit, while e-cigarettes emerged as an ambiguous product whose meanings are still being negotiated. Participants' attitudes and intentions about smoking and quitting were especially important in shaping their understanding of these products. Four main interpretations of e-cigarettes were identified: a more satisfying replacement for smoking, an ambiguous but potentially useful device, a less desirable cigarette and a threat to smoking cessation. The acceptability of continued nicotine addiction and the similarity of e-cigarettes to conventional cigarettes were central themes on which participants held conflicting views. There was considerable uncertainty among participants around the constituents and safety of e-cigarettes. Different groups of smokers bring diverse expectations, requirements and concerns to their evaluations and therefore to the potential use of nicotine-containing products. The ambiguity around e-cigarettes in public health debates and medical practice is reflected in the positions and concerns of smokers. There is a need for both clear, up-to-date trustworthy information about their benefits and risks, and stronger regulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Correlates of use of electronic cigarettes versus nicotine replacement therapy for help with smoking cessation.

PubMed

Pokhrel, Pallav; Little, Melissa A; Fagan, Pebbles; Kawamoto, Crissy T; Herzog, Thaddeus A

2014-12-01

Electronic- or e-cigarettes are nicotine-delivery devices commonly used by smokers to quit or reduce smoking. At present, not much is known about the characteristics of smokers who specifically try e-cigarettes to quit smoking compared to the nicotine replacement therapy (NRT) products approved by the U.S. Food and Drug Administration (FDA). Determining the characteristics of smokers who are likely to choose e-cigarettes as cessation aids would help develop strategies to impart valid information about e-cigarettes to such smokers as facts regarding the safety and utility of e-cigarettes emerge. This study is based on 834 daily smokers [mean age=45.8 (standard deviation=13)] from Hawaii. Demographic, smoking- and cessation-related variables were examined as correlates of ever use of e-cigarette only or any FDA-approved NRT product only or both as cessation aids. Results indicated that younger smokers, non-White smokers, and smokers reporting higher income, lower nicotine dependence, shorter smoking history, and higher lifetime quit attempts were more likely to have tried e-cigarettes but not NRT products for help with smoking cessation. Smokers who are attracted to use e-cigarettes but not FDA-approved NRT products may differ from smokers who are likely to have used NRT products but not e-cigarettes in terms of demographic (e.g., age, ethnicity) and smoking- or cessation-related characteristics (e.g., nicotine dependence, quit attempts). Given the lack of knowledge regarding the health effects of e-cigarettes and their efficacy as cessation aids, future research needs to continue characterizing smokers who are likely to use e-cigarettes for smoking cessation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of low-level laser therapy on the healing process of autogenous bone block grafts in the jaws of systemically nicotine-modified rats: A histomorphometric study.

PubMed

de Almeida, Juliano Milanezi; de Moraes, Ricardo Oliveira; Gusman, David Jonathan Rodrigues; Faleiros, Paula Lazilha; Nagata, Maria José Hitomi; Garcia, Valdir Gouveia; Theodoro, Letícia Helena; Bosco, Alvaro Francisco

2017-03-01

To analyze the influence of low-level laser therapy (LLLT) on the bone healing process of autogenous bone block grafts installed in nicotine systemically modified rats. Seventy-two rats (Wistar) were randomly assigned into 4 groups (n=18). SS-BG: saline application+bone graft. SS-BG/LLLT: saline application+bone graft+LLLT. NIC-BG: nicotine application+bone graft. NIC-BG/LLLT: nicotine application+bone graft+LLLT. After 30days of application of solutions, all animals received autogenous bone block graft in the jaw, with the donation from the parietal bone's calvarial area. Treatment with LLLT was in bed-graft interface, after accommodation of the graft. The animals in each group were sacrificed at 7, 14, and 28days after graft surgery. The histologic analyses of NIC-BG group depicted a delay of osteogenic activity in the recipient bed-graft interface and the irradiation of tissue with LLLT provided better bone healing. The histometric analysis revealed that SS-BG/LLLT and NIC-BG/LLLT groups showed increased bone formation compared to BG-SS and NIC-BG groups, after 14days (SS-BG 24.94%±13.06% versus SS-BG/LLLT 27.53%±19.07% and NIC-BG 14.27%±2.22% versus NIC-BG/LLLT 24.37%±11.93%) and 28days (SS-BG 50.31%±2.69% versus SS-BG/LLLT 58 19%±12.32% and NIC-BG 36.89%±8.40% versus NIC-BG/LLLT 45.81%±6.03%). Nicotine harms bone formation in the bed-graft interface and LLLT action can mitigate this. Copyright © 2016 Elsevier Ltd. All rights reserved.

Employment, gender, and smoking cessation outcomes in low-income smokers using nicotine replacement therapy.

PubMed

Burgess, Diana J; Fu, Steven S; Noorbaloochi, Siamak; Clothier, Barbara A; Ricards, Jennifer; Widome, Rachel; van Ryn, Michelle

2009-12-01

This study examines the presence and correlates of gender disparities in smoking cessation among lower income smokers prescribed nicotine replacement medication. We examined quit rates (7-day abstinence point prevalence) among a cohort of smokers who filled prescriptions for nicotine replacement (N = 1,782), using Minnesota Health Care Programs' (e.g., Medicaid) pharmacy claims databases (2005-2006) and mixed-mode survey protocols. A cohort of smokers who recently filled a prescription for nicotine replacement was stratified by race, and then subjects were selected by simple random sample from each race, oversampling the nonWhite groups (N = 1,782). The primary outcome was point prevalence of 7-day abstinence, and outcomes were assessed about 8 months after the nicotine replacement therapy (NRT) index prescription fill date using a mixed-mode survey protocol. Final interaction models were constructed using backward elimination. Abstinence rates were 11.4% among women and 19.2% among men (p = .02) and remained marginally significant after controlling for demographics, mental and physical health, period of cigarette abstinence, social environment, religious attendance, perceived stress, and NRT prescription type (p = .08). There was a significant Gender x Employment interaction (p = .02). Among men, quit rates were higher among the employed (26%) compared with the unemployed (16%); among women, quit rates were lower among those who were employed (8%) compared with those who were unemployed (14%). Results suggest the need for research on factors specific to women's work roles or workplaces that inhibit cessation as well as cessation programs tailored to low-income, employed female smokers. On-site workplace interventions and flexible counseling programs may be especially beneficial.

A retrospective analysis of the association between providing nicotine replacement therapy at admission and motivation to quit and nicotine withdrawal symptoms during an inpatient psychiatric hospitalization.

PubMed

Okoli, Chizimuzo T C; Al-Mrayat, Yazan D; Shelton, Charles I; Khara, Milan

2018-06-07

Psychiatric patients have high tobacco use prevalence, dependence, and withdrawal severity. A tobacco-free psychiatric hospitalization necessitates the management of nicotine withdrawal (NW) for tobacco using patients. NW management often requires the provision of approved nicotine replacement therapy (NRT) to patients, which may also motivate tobacco users towards cessation. However, few studies have examined the associations between providing NRT, motivation to quit, and NW among psychiatric patients. To examine the associations between providing NRT at admission and motivation to quit smoking and severity of NW symptoms. A retrospective review of the medical records of 255 tobacco using patients on whom NW was assessed during their hospital stay. The time when NRT was provided (i.e., at admission vs. not provided vs. on the unit), motivation to quit smoking, and 8-item Minnesota Nicotine Withdrawal Scale were assessed. The primary NW symptom was 'craving' (65.1%); reporting of 'anxiety' varied by psychiatric diagnosis. Providing NRT at admission was not associated with motivation to quit. Patients receiving NRT on the unit (i.e., delayed receipt) had significantly higher NW than those who received NRT at admission. In multivariate analyses, receiving NRT on the unit was significantly associated with greater NW severity (β = .19, p = .002). Among psychiatric patients, providing NRT at admission is associated with greater severity of NW. The provision of NRT for NW management may be considered as standard practice during tobacco-free psychiatric stays. Future studies may consider the effect of other tobacco treatment medications (such as varenicline, bupropion) on managing NW. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transdermal patches: history, development and pharmacology

PubMed Central

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

The current literature regarding the cardiovascular effects of electronic cigarettes.

PubMed

Nelluri, Bhargava; Murphy, Katie; Mookadam, Farouk; Mookadam, Martina

2016-03-01

Smoking is the leading cause of preventable morbidity and mortality globally. Electronic cigarettes are marketed both as nicotine substitutes and recreational devices. The popularity of electronic cigarettes has superseded other forms of nicotine replacement therapy. They are also popular in 'never smokers'. This review summarizes the available data regarding the cardiovascular effects of electronic cigarettes. The existing literature is limited and short term with a lack of high-quality studies and adequate follow-up. The available literature suggests that electronic cigarettes have sympathomimetic effects related to nicotine exposure, however, electronic cigarettes also contain other chemicals that require further investigation. Sparse data suggest vascular injury may be another concern. Further research is needed before broad recommendations can be made.

Anxiety and depressed mood decline following smoking abstinence in adult smokers with Attention Deficit Hyperactivity Disorder

PubMed Central

Covey, Lirio S.; Hu, Mei-Chen; Winhusen, Theresa; Lima, Jennifer; Berlin, Ivan; Nunes, Edward

2015-01-01

Introduction A preponderance of relevant research has indicated reduction in anxiety and depressive symptoms following smoking abstinence. This secondary analysis investigated whether the phenomenon extends to smokers with attention deficit hyperactivity disorder (ADHD). Methods The study setting was an 11-Week double-blind placebo-controlled randomized trial of osmotic release oral system methylphenidate (OROS-MPH) as a cessation aid when added to nicotine patch and counseling. Participants were 255 adult smokers with ADHD. The study outcomes are: anxiety (Beck Anxiety Inventory (BAI)) and depressed mood (Beck Depression Inventory II (BDI)) measured one Week and six Weeks after a target quit day (TQD). The main predictor is point - prevalence abstinence measured at Weeks 1 and 6 after TQD. Covariates are treatment (OROS-MPH vs placebo), past major depression, past anxiety disorder, number of cigarettes smoked daily, demographics (age, gender, education, marital status) and baseline scores on the BAI, BDI, and the DSM-IV ADHD Rating Scale. Results Abstinence was significantly associated with lower anxiety ratings throughout the post-quit period (p<0.001). Depressed mood was lower for abstainers than non-abstainers at Week 1 (p<0.05), but no longer at Week 6 (p=0.83). Treatment with OROS-MPH relative to placebo showed significant reductions at Week 6 after TQD for both anxiety (p<0.05) and depressed mood (p<0.001), but not at Week 1. Differential abstinence effects of gender were observed. Anxiety and depression ratings at baseline predicted increased ratings of corresponding measures during the post-quit period. Conclusion Stopping smoking yielded reductions in anxiety and depressed mood in smokers with ADHD treated with nicotine patch and counseling. Treatment with OROS-MPH yielded mood reductions in delayed manner. PMID:26272693

Immunotherapy for the treatment of drug abuse.

PubMed

Kosten, Thomas; Owens, S Michael

2005-10-01

Antibody therapy (as either active or passive immunization) is designed primarily to prevent drugs of abuse from entering the central nervous system (CNS). Antidrug antibodies reduce rush, euphoria, and drug distribution to the brain at doses that exceed the apparent binding capacity of the antibody. This is accomplished through a pharmacokinetic antagonism, which reduces the amount of drug in the brain, the rate of clearance across the blood-brain barrier, and the volume of drug distribution. Because the antibodies remain primarily in the circulatory system, they have no apparent central nervous system side effects. Active immunization with drug-protein conjugate vaccines has been tested for cocaine, heroin, methamphetamine, and nicotine in animal, with 1 cocaine and 3 nicotine vaccines in Phase 2 human trials. Passive immunization with high affinity monoclonal antibodies has been tested for cocaine, methamphetamine, nicotine, and phencyclidine (PCP) in preclinical animal models. Antibodies have 2 immediate clinical applications in drug abuse treatment: to treat drug overdose and to reduce relapse to drug use in addicted patients. The specificity of the therapies, the lack of addiction liability, minimal side effects, and long-lasting protection against drug use offer major therapeutic benefit over conventional small molecule agonists and antagonists. Immunotherapies can also be combined with other antiaddiction medications and enhance behavioral therapies. Current immunotherapies already show efficacy, but improved antigen design and antibody engineering promise highly specific and rapidly developed treatments for both existing and future addictions.

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Noelle; Department of Obstetrics and Gynecology, The University of Western Ontario; The Lawson Health Research Institute, The University of Western Ontario

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal daymore » 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced acetylation of histone H3 [K9,14]. • This provides a mechanism for developmental origins of health and disease (DOHaD)« less

Crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research.

PubMed

Wen, L; Yang, Z; Cui, W; Li, M D

2016-06-21

Cigarette smoking is a leading cause of preventable death throughout the world. Nicotine, the primary addictive compound in tobacco, plays a vital role in the initiation and maintenance of its use. Nicotine exerts its pharmacological roles through nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels consisting of five membrane-spanning subunits. Besides the CHRNA4, CHRNB2 and CHRNA5/A3/B4 cluster on chromosome 15, which has been investigated intensively, recent evidence from both genome-wide association studies and candidate gene-based association studies has revealed the crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence (ND). These studies demonstrate two distinct loci within this region. The first one is tagged by rs13277254, upstream of the CHRNB3 gene, and the other is tagged by rs4952, a coding single nucleotide polymorphism in exon 5 of that gene. Functional studies by genetic manipulation in mice have shown that α6*-nAChRs, located in the ventral tegmental area (VTA), are of great importance in controlling nicotine self-administration. However, when the α6 subunit is selectively re-expressed in the VTA of the α6(-/-) mouse by a lentiviral vector, the reinforcing property of nicotine is restored. To further determine the role of α6*-nAChRs in the process of nicotine-induced reward and withdrawal, genetic knock-in strains have been examined, which showed that replacement of Leu with Ser in the 9' residue in the M2 domain of α6 produces nicotine-hypersensitive mice (α6 L9'S) with enhanced dopamine release. Moreover, nicotine-induced upregulation may be another ingredient in the pathology of nicotine addiction although the effect of chronic nicotine exposure on the expression of α6-containing receptors is controversial. To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation therapies, we here present the most recent studies concerning the genetic effects of the CHRNB3-CHRNA6 gene cluster in ND.

Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

PubMed

Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

2017-04-01

Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine gums and lozenges. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Review article: Ulcerative colitis, smoking and nicotine therapy.

PubMed

Lunney, P C; Leong, R W L

2012-12-01

Smoking is the best-characterised environmental association of ulcerative colitis (UC). Smoking has been observed to exert protective effects on both the development and progression of UC. To examine the association between UC and smoking, possible pathogenic mechanisms and the potential of nicotine as a therapeutic agent in the treatment of UC. A literature search was conducted through MEDLINE, using the MeSH search terms 'ulcerative colitis' and 'smoking' or 'nicotine'. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. Ulcerative colitis is less prevalent in smokers. Current smokers with a prior diagnosis of UC are more likely to exhibit milder disease than ex-smokers and nonsmokers. There is conflicting evidence for smokers having reduced rates of hospitalisation, colectomy and need for oral corticosteroids and immunosuppressants to manage their disease. Multiple potential active mediators in smoke may be responsible for these clinical effects, including nicotine and carbon monoxide, but the precise mechanism remains unknown. Nicotine has demonstrated variable efficacy in the induction of remission in UC when compared to placebo and conventional medicines. Despite this, the high frequency of adverse events limits its clinical significance. Nicotine's application as a therapeutic treatment in ulcerative colitis is limited. Presently, it may be an option considered only in selected cases of acute ulcerative colitis refractory to conventional treatment options. This review also questions whether nicotine is the active component of smoking that modifies risk and inflammation in ulcerative colitis. © 2012 Blackwell Publishing Ltd.

A randomised, crossover study on an electronic vapour product, a nicotine inhalator and a conventional cigarette. Part B: Safety and subjective effects.

PubMed

Walele, Tanvir; Sharma, Girish; Savioz, Rebecca; Martin, Claire; Williams, Josie

2016-02-01

An Electronic Vapour Product (EVP) has been evaluated for short-term safety parameters and subjective effects in a 2-part study, in smokers. Part 1 compared the EVP with unflavoured (UF) and flavoured (FL) e-liquid at 2.0% nicotine to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette(®), 15 mg). Part 2 assessed the effect of increasing concentrations of nicotine in the e-liquid used with the EVP (0%, 0.4%, 0.9%, 2.0%). The study was designed as a randomised, controlled, crossover trial. Outcomes included adverse events (AEs), vital signs, exhaled carbon monoxide (CO), clinical laboratory parameters, smoking urges and withdrawal symptoms. In both study parts, only mild non-serious AEs were reported. No major differences were observed in AEs between the EVPs and Nicorette(®). Exhaled CO levels only increased for CC. All products appeared to decrease smoking urges and nicotine withdrawal symptom scores to a similar extent. The EVP had a similar short-term safety profile to Nicorette(®) and relieved smoking urges and nicotine withdrawal symptoms to a similar extent as Nicorette(®) and CC. Unlike nicotine replacement therapies, the EVP may offer an alternative for those finding it difficult to quit the behavioural and sensorial aspects of smoking. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Key issues surrounding the health impacts of electronic nicotine delivery systems (ENDS) and other sources of nicotine.

PubMed

Drope, Jeffrey; Cahn, Zachary; Kennedy, Rosemary; Liber, Alex C; Stoklosa, Michal; Henson, Rosemarie; Douglas, Clifford E; Drope, Jacqui

2017-11-01

Answer questions and earn CME/CNE Over the last decade, the use of electronic nicotine delivery systems (ENDS), including the electronic cigarette or e-cigarette, has grown rapidly. More youth now use ENDS than any tobacco product. This extensive research review shows that there are scientifically sound, sometimes competing arguments about ENDS that are not immediately and/or completely resolvable. However, the preponderance of the scientific evidence to date suggests that current-generation ENDS products are demonstrably less harmful than combustible tobacco products such as conventional cigarettes in several key ways, including by generating far lower levels of carcinogens and other toxic compounds than combustible products or those that contain tobacco. To place ENDS in context, the authors begin by reviewing the trends in use of major nicotine-containing products. Because nicotine is the common core-and highly addictive-constituent across all tobacco products, its toxicology is examined. With its long history as the only nicotine product widely accepted as being relatively safe, nicotine-replacement therapy (NRT) is also examined. A section is also included that examines snus, the most debated potential harm-reduction product before ENDS. Between discussions of NRT and snus, ENDS are extensively examined: what they are, knowledge about their level of "harm," their relationship to smoking cessation, the so-called gateway effect, and dual use/poly-use. CA Cancer J Clin 2017;67:449-471. © 2017 American Cancer Society. © 2017 American Cancer Society.

Evaluation of a water-soluble bioadhesive patch for photodynamic therapy of vulval lesions.

PubMed

McCarron, Paul A; Donnelly, Ryan F; Zawislak, Agnieszka; Woolfson, A David; Price, John H; McClelland, Raymond

2005-04-11

An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 Ncm(-2). Patient evaluation demonstrated comfort and firm attachment for up to 4h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

A Feasibility Study of Virtual Reality-Based Coping Skills Training for Nicotine Dependence

PubMed Central

Bordnick, Patrick S.; Traylor, Amy C.; Carter, Brian L.; Graap, Ken M.

2014-01-01

Objective Virtual reality (VR)-based cue reactivity has been successfully used for the assessment of drug craving. Going beyond assessment of cue reactivity, a novel VR-based treatment approach for smoking cessation was developed and tested for feasibility. Method In a randomized experiment, 10-week treatment feasibility trial, 46 nicotine-dependent adults, completed the10-week program. Virtual reality skills training (VRST) combined with nicotine replacement therapy (NRT) was compared to NRT alone. Participants were assessed for smoking behavior and coping skills during, at end of treatment, and at posttreatment follow-up. Results Smoking rates and craving for nicotine were significantly lower for the VRST group compared to NRT-only group at the end of treatment. Self-confidence and coping skills were also significantly higher for the VRST group, and number of cigarettes smoked was significantly lower, compared to the control group at follow-up. Conclusions Feasibility of VRST was supported in the current study. PMID:25484549

Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study.

PubMed

Kerr, A; McVey, J T; Wood, A M; Van Haren, Fmp

2016-11-01

Nicotine replacement therapy (NRT) is a common first-line treatment to prevent nicotine withdrawal in smokers. However, available literature reports conflicting results regarding its efficacy and safety in critically ill patients. The objective of this study was to evaluate the relationship between NRT in smokers in the intensive care unit (ICU) and outcomes. This case-control study was conducted in a university-affiliated tertiary hospital ICU. Over a period of five years, 126 active smokers who received transdermal NRT were matched to 126 active smokers who did not receive NRT. The groups were case-matched for sex, age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary outcome was administration of antipsychotic medication. Secondary outcomes included use of physical restraints, 30-day mortality, and ventilation requirements. Antipsychotic medication was prescribed in 43 (34.1%) patients who received NRT compared to 14 (11.1%) in controls ( P <0.01). Physical restraints were used in 37 (29.4%) patients who received NRT, compared to 12 (9.5%) of controls ( P <0.01). The 30-day mortality and number of patients intubated was not statistically different between groups. Average length of intubation time was greater in the NRT group (2.56 days; standard deviation 4.16) compared to the control group (1.44 days; standard deviation 2.68) ( P =0.012). The use of NRT to prevent nicotine withdrawal in ICU patients is associated with increased use of antipsychotic medication and physical restraint, and with prolonged mechanical ventilation.

Nicotine replacement therapy decision based on fuzzy multi-criteria analysis

NASA Astrophysics Data System (ADS)

Tarmudi, Zamali; Matmali, Norfazillah; Abdullah, Mohd Lazim

2017-08-01

It has been observed that Nicotine Replacement Therapy (NRT) is one of the alternatives to control and reduce smoking addiction among smokers. Since the decision to choose the best NRT alternative involves uncertainty, ambiguity factors and diverse input datasets, thus, this paper proposes a fuzzy multi-criteria analysis (FMA) to overcome these issues. It focuses on how the fuzzy approach can unify the diversity of datasets based on NRT's decision-making problem. The analysis done employed the advantage of the cost-benefit criterion to unify the mixture of dataset input. The performance matrix was utilised to derive the performance scores. An empirical example regarding the NRT's decision-making problem was employed to illustrate the proposed approach. Based on the calculations, this analytical approach was found to be highly beneficial in terms of usability. It was also very applicable and efficient in dealing with the mixture of input datasets. Hence, the decision-making process can easily be used by experts and patients who are interested to join the therapy/cessation program.

Anxiety and nicotine dependence: Emerging role of the habenulo-interpeduncular axis

PubMed Central

Molas, Susanna; DeGroot, Steven; Zhao-Shea, Rubing; Tapper, Andrew R.

2016-01-01

While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal. Insights into how this circuit inter-connects with regions more classically associated with anxiety and how chronic nicotine exposure induces neuroadaptations resulting in an anxiogenic state, may thereby provide novel strategies and molecular targets for therapies that facilitate smoking cessation, as well as, anxiety relief. PMID:27890353

KK-92A, a novel GABAB receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats.

PubMed

Li, Xia; Sturchler, Emmanuel; Kaczanowska, Katarzyna; Cameron, Michael; Finn, M G; Griffin, Patrick; McDonald, Patricia; Markou, Athina

2017-05-01

GABA B receptors (GABA B R) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABA B R positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABA B receptor agonists such as baclofen. The present study was aimed at developing novel, selective, and potent GABA B R PAMs with efficacy on abuse-related effects of nicotine. We synthetized ~100 analogs of BHF177, a GABA B R PAM that has been shown to inhibit nicotine taking and seeking, and tested their activity in multiple cell-based functional assays. Among these compounds, KK-92A displayed superior PAM properties at the GABA B R. Interestingly, our results revealed the existence of pathway-selective differential modulation of GABA B R signaling by the structurally related GABA B R allosteric modulators BHF177 and KK-92A. In vivo, similarly to BHF177, KK-92A inhibited intravenous nicotine self-administration under both fixed- and progressive-ratio schedules of reinforcement in rats. In contrast to BHF177, KK-92A had no effect on food self-administration. Furthermore, KK-92A decreased cue-induced nicotine-seeking behavior without affecting food seeking. These results indicate that KK-92A is a selective GABA B R PAM with efficacy in inhibition of the primary reinforcing and incentive motivational effects of nicotine, and attenuation of nicotine seeking, further confirming that GABA B R PAMs may be useful antismoking medications.

Nicotine induces self-renewal of pancreatic cancer stem cells via neurotransmitter-driven activation of sonic hedgehog signalling.

PubMed

Al-Wadei, Mohammed H; Banerjee, Jheelam; Al-Wadei, Hussein A N; Schuller, Hildegard M

2016-01-01

A small subpopulation of pancreatic cancer cells with characteristics of stem cells drive tumour initiation, progression and metastasis. A better understanding of the regulation of cancer stem cells may lead to more effective cancer prevention and therapy. We have shown that the proliferation and migration of pancreatic cancer cell lines is activated by the nicotinic receptor-mediated release of stress neurotransmitters, responses reversed by γ-aminobutyric acid (GABA). However, the observed cancer inhibiting effects of GABA will only succeed clinically if GABA inhibits pancreatic cancer stem cells (PCSCs) in addition to the more differentiated cancer cells that comprise the majority of cancer tissues and cell lines. Using PCSCs isolated from two pancreatic cancer patients by cell sorting and by spheroid formation assay from pancreatic cancer cell line Panc-1, we tested the hypothesis that nicotine induces the self-renewal of PCSCs. Nicotinic acetylcholine receptors (nAChRs) α3, α4, α5 and α7 were expressed and chronic exposure to nicotine increased the protein expression of these receptors. Immunoassays showed that PCSCs produced the stress neurotransmitters epinephrine and norepinephrine and the inhibitory neurotransmitter GABA. Chronic nicotine significantly increased the production of stress neurotransmitters and sonic hedgehog (SHH) while inducing Gli1 protein and decreasing GABA. GABA treatment inhibited the induction of SHH and Gli1. Spheroid formation and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assays showed significant nicotine-induced increases in self renewal and cell proliferation, responses blocked by GABA. Our data suggest that nicotine increases the SHH-mediated malignant potential of PCSCs and that GABA prevents these effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regular nicotine intake increased tooth movement velocity, osteoclastogenesis and orthodontically induced dental root resorptions in a rat model

PubMed Central

Kirschneck, Christian; Maurer, Michael; Wolf, Michael; Reicheneder, Claudia; Proff, Peter

2017-01-01

Orthodontic forces have been reported to significantly increase nicotine-induced periodontal bone loss. At present, however, it is unknown, which further (side) effects can be expected during orthodontic treatment at a nicotine exposure corresponding to that of an average European smoker. 63 male Fischer344 rats were randomized in three consecutive experiments of 21 animals each (A/B/C) to 3 experimental groups (7 rats, 1/2/3): (A) cone-beam-computed tomography (CBCT); (B) histology/serology; (C) reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR)/cotinine serology—(1) control; (2) orthodontic tooth movement (OTM) of the first and second upper left molar (NiTi closed coil spring, 0.25 N); (3) OTM with 1.89 mg·kg−1 per day s.c. of L(−)-nicotine. After 14 days of OTM, serum cotinine and IL-6 concentration as well as orthodontically induced inflammatory root resorption (OIIRR), osteoclast activity (histology), orthodontic tooth movement velocity (CBCT, within 14 and 28 days of OTM) and relative gene expression of known inflammatory and osteoclast markers were quantified in the dental-periodontal tissue (RT–qPCR). Animals exposed to nicotine showed significantly heightened serum cotinine and IL-6 levels corresponding to those of regular European smokers. Both the extent of root resorption, osteoclast activity, orthodontic tooth movement and gene expression of inflammatory and osteoclast markers were significantly increased compared to controls with and without OTM under the influence of nicotine. We conclude that apart from increased periodontal bone loss, a progression of dental root resorption and accelerated orthodontic tooth movement are to be anticipated during orthodontic therapy, if nicotine consumption is present. Thus patients should be informed about these risks and the necessity of nicotine abstinence during treatment. PMID:28960194

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate

PubMed Central

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2017-01-01

Background Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance, and a well validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Methods Sixty-nine treatment-seeking smokers (30 slow, 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once following 24 hours of smoking abstinence. Results In whole brain analysis, normal (compared to slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were even more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Conclusion Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. PMID:26805583

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

PubMed

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2016-08-01

Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Treatment-seeking smokers (N = 69; 30 slow metabolizers and 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once after 24 hours of smoking abstinence. In whole-brain analysis, normal (compared with slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Translational strategies for therapeutic development in nicotine addiction: rethinking the conventional bench to bedside approach.

PubMed

Le Foll, Bernard; Pushparaj, Abhiram; Pryslawsky, Yaroslaw; Forget, Benoit; Vemuri, Kiran; Makriyannis, Alexandros; Trigo, Jose M

2014-07-03

Tobacco produces an impressive burden of disease resulting in premature death in half of users. Despite effective smoking cessation medications (nicotine replacement therapies, bupropion and varenicline), there is a very high rate of relapse following quit attempts. The use of efficient strategies for the development of novel treatments is a necessity. A 'bench to bedside strategy' was initially used to develop cannabinoid CB1 receptor antagonists for the treatment of nicotine addiction. Unfortunately, after being tested on experimental animals, what seemed to be an interesting approach for the treatment of nicotine addiction resulted in serious unwanted side effects when tested in humans. Current research is focusing again on pre-clinical models in an effort to eliminate unwanted side effects while preserving the initially observed efficacy. A 'bed side to bench strategy' was used to study the role of the insula (part of the frontal cortex) in nicotine addiction. This line of research started based on clinical observations that patients suffering stroke-induced lesions to the insula showed a greater likelihood to report immediate smoking cessation without craving or relapse. Subsequently, animal models of addiction are used to explore the role of insula in addiction. Due to the inherent limitations existing in clinical versus preclinical studies, the possibility of close interaction between both models seems to be critical for the successful development of novel therapeutic strategies for nicotine dependence. © 2013.

Cholinergic left-right asymmetry in the habenulo-interpeduncular pathway.

PubMed

Hong, Elim; Santhakumar, Kirankumar; Akitake, Courtney A; Ahn, Sang Jung; Thisse, Christine; Thisse, Bernard; Wyart, Claire; Mangin, Jean-Marie; Halpern, Marnie E

2013-12-24

The habenulo-interpeduncular pathway, a highly conserved cholinergic system, has emerged as a valuable model to study left-right asymmetry in the brain. In larval zebrafish, the bilaterally paired dorsal habenular nuclei (dHb) exhibit prominent left-right differences in their organization, gene expression, and connectivity, but their cholinergic nature was unclear. Through the discovery of a duplicated cholinergic gene locus, we now show that choline acetyltransferase and vesicular acetylcholine transporter homologs are preferentially expressed in the right dHb of larval zebrafish. Genes encoding the nicotinic acetylcholine receptor subunits α2 and β4 are transcribed in the target interpeduncular nucleus (IPN), suggesting that the asymmetrical cholinergic pathway is functional. To confirm this, we activated channelrhodopsin-2 specifically in the larval dHb and performed whole-cell patch-clamp recording of IPN neurons. The response to optogenetic or electrical stimulation of the right dHb consisted of an initial fast glutamatergic excitatory postsynaptic current followed by a slow-rising cholinergic current. In adult zebrafish, the dHb are divided into discrete cholinergic and peptidergic subnuclei that differ in size between the left and right sides of the brain. After exposing adults to nicotine, fos expression was activated in subregions of the IPN enriched for specific nicotinic acetylcholine receptor subunits. Our studies of the newly identified cholinergic gene locus resolve the neurotransmitter identity of the zebrafish habenular nuclei and reveal functional asymmetry in a major cholinergic neuromodulatory pathway of the vertebrate brain.

Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents to midbrain dopamine cells.

PubMed

Lecca, Salvatore; Melis, Miriam; Luchicchi, Antonio; Ennas, Maria Grazia; Castelli, Maria Paola; Muntoni, Anna Lisa; Pistis, Marco

2011-02-01

Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains γ-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by α7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.

Tobacco and cognitive performance in schizophrenia patients: the design of the COGNICO study.

PubMed

Al-Halabí, Susana; Fernández-Artamendi, Sergio; Díaz-Mesa, Eva M; García-Álvarez, Leticia; Flórez, Gerardo; Martínez-Santamaría, Emilia; Arrojo, Manuel; Saiz, Pilar A; García-Portilla, M Paz; Bobes, Julio

2016-06-14

People with schizophrenia constitute a substantial part of the people who still smoke. Regarding cognitive performance, the self-medication hypothesis states that patients smoke to improve their cognitive deficits based on the stimulating effects of nicotine. The aim of this paper is to describe in detail the methodology used in the COGNICO study. A quasi-experimental, observational, prospective, multicenter study with follow-ups over 18 months was conducted in three cities in northern Spain (Oviedo, Ourense and Santiago de Compostela). A total of 81 outpatient smokers with schizophrenia were recruited with a mean age 43.35 years (SD = 8.83), 72.8% of them male. They were assigned to 3 groups: a) control group (smokers); b) patients who quit smoking using nicotine patches; c) patients who quit smoking with Varenicline. The MATRICS neuropsychological battery was applied as a primary measure. In addition, a comprehensive assessment of patients was performed, including the number of cigarettes per day, physical and psychological dependence on nicotine and CO expired. Clinical evaluation (PANSS, HDRS, CGI, C-SSRS), anthropometric measurements and vital signs assessment was also performed. The aim is to identify the relationship between the pattern of tobacco use and cognitive performance by comparing scores on the neuropsychological battery MATRICS during the follow-up periods (3, 6, 12 and 18months). The importance of this study lies in addressing a topical issue often ignored by clinicians: the unacceptably high rates of tobacco use in patients with severe mental disorders.

Comparison of NSAID patch given as monotherapy and NSAID patch in combination with transcutaneous electric nerve stimulation, a heating pad, or topical capsaicin in the treatment of patients with myofascial pain syndrome of the upper trapezius: a pilot study.

PubMed

Kim, Do-Hyeong; Yoon, Kyung Bong; Park, SangHa; Jin, Tae Eun; An, Yoo Jin; Schepis, Eric A; Yoon, Duck Mi

2014-12-01

This study compared the therapeutic effect of monotherapy with a nonsteroidal anti-inflammatory drug (NSAID) patch vs an NSAID patch combined with transcutaneous electric nerve stimulation (TENS), a heating pad, or topical capsaicin in the treatment of patients with myofascial pain syndrome (MPS) of the upper trapezius. A randomized, single-blind, controlled study of combination therapy for patients with MPS was performed. Ninety-nine patients were randomly assigned to one of four different self-management methods for treatment: NSAID patch (N = 25), NSAID patch + TENS (N = 24), NSAID patch + heating pad (N = 25), and NSAID patch + topical capsaicin (N = 25). The NSAID patch used in this study was a ketoprofen patch. All treatment groups were observed for 2 weeks, and the numeric rating scale (NRS) pain score, cervical active range of motion, pressure pain threshold, and Neck Disability Index were assessed. There was no significant difference between the NSAID patch alone group and the three combination therapy groups with respect to decrease in NRS score from baseline (day 0) to each period of observation. In covariate analysis, although there was no difference among the groups in most of the periods, the data at day 14 indicated a trend (P = 0.057). There were no significant differences in the other variables. We did not observe a statistical difference in improvements to the clinical variables among the four different methods. However, further studies regarding the effectiveness of a mixture of topical capsaicin and ketoprofen in patients with MPS should be considered. Wiley Periodicals, Inc.

Transdermal patches: history, development and pharmacology.

PubMed

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-05-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. © 2015 The British Pharmacological Society.

Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study.

PubMed

Shahab, Lion; Goniewicz, Maciej L; Blount, Benjamin C; Brown, Jamie; McNeill, Ann; Alwis, K Udeni; Feng, June; Wang, Lanqing; West, Robert

2017-03-21

Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential. To compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT. Cross-sectional study. United Kingdom. The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181). Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs). After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites. Cross-sectional design with self-selected sample. Former smokers with long-term e-cigarette-only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette-only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes. Cancer Research UK.

The rationale for intensity-modulated proton therapy in geometrically challenging cases

NASA Astrophysics Data System (ADS)

Safai, S.; Trofimov, A.; Adams, J. A.; Engelsman, M.; Bortfeld, T.

2013-09-01

Intensity-modulated proton therapy (IMPT) delivered with beam scanning is currently available at a limited number of proton centers. However, a simplified form of IMPT, the technique of field ‘patching’, has long been a standard practice in proton therapy centers. In field patching, different parts of the target volume are treated from different directions, i.e., a part of the tumor gets either full dose from a radiation field, or almost no dose. Thus, patching represents a form of binary intensity modulation. This study explores the limitations of the standard binary field patching technique, and evaluates possible dosimetric advantages of continuous dose modulations in IMPT. Specifics of the beam delivery technology, i.e., pencil beam scanning versus passive scattering and modulation, are not investigated. We have identified two geometries of target volumes and organs at risk (OAR) in which the use of field patching is severely challenged. We focused our investigations on two patient cases that exhibit these geometries: a paraspinal tumor case and a skull-base case. For those cases we performed treatment planning comparisons of three-dimensional conformal proton therapy (3DCPT) with field patching versus IMPT, using commercial and in-house software, respectively. We also analyzed the robustness of the resulting plans with respect to systematic setup errors of ±1 mm and range errors of ±2.5 mm. IMPT is able to better spare OAR while providing superior dose coverage for the challenging cases identified above. Both 3DCPT and IMPT are sensitive to setup errors and range uncertainties, with IMPT showing the largest effect. Nevertheless, when delivery uncertainties are taken into account IMPT plans remain superior regarding target coverage and OAR sparing. On the other hand, some clinical goals, such as the maximum dose to OAR, are more likely to be unmet with IMPT under large range errors. IMPT can potentially improve target coverage and OAR sparing in challenging cases, even when compared with the relatively complicated and time consuming field patching technique. While IMPT plans tend to be more sensitive to delivery uncertainties, their dosimetric advantage generally holds. Robust treatment planning techniques may further reduce the sensitivity of IMPT plans.

Nicotine Dependence and Cost-Effectiveness of Individualized Support for Smoking Cessation: Evidence from Practice at a Worksite in Japan

PubMed Central

Nakamura, Koshi; Sakurai, Masaru; Miura, Katsuyuki; Morikawa, Yuko; Nagasawa, Shin-ya; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Suwazono, Yasushi; Nakagawa, Hideaki

2013-01-01

Given the lack of economic studies evaluating the outcomes of smoking cessation programs from the viewpoint of program sponsors, we conducted a case study to provide relevant information for worksites. The present study was carried out between 2006 and 2008 at a manufacturing factory in the Toyama Prefecture of Japan and included subjects who voluntarily entered a smoking cessation program. The program included face-to-face counselling followed by weekly contact to provide encouragement over six months using e-mail or inter-office mail. Nicotine patches were available if required. All 151 participants stopped smoking immediately. Over the 24-month study period, self-report showed 49.7% abstained continuously from smoking. The rate of 24-month consecutive abstinence was higher in participants with lower Fagerström Test scores for Nicotine Dependence at baseline than in those with higher scores (63.6% for 0–2 points vs. 46.5% for 3–6 points vs. 43.8% for 7–10 points; chi-square test p = 0.19). A logistic regression model showed a significant linear trend for the association between the score and abstinence status after adjustment for possible confounding factors (p = 0.03). The crude incremental cost for one individual to successfully quit smoking due to the support program was ¥46,379 (i.e., ¥100 = $1.28, £0.83, or €1.03 at foreign exchange rates). The corresponding costs for the three categories of the Fagerström Test score for Nicotine Dependence were ¥31,953, ¥47,450 and ¥64,956, respectively. When a sensitivity analysis was conducted based on the 95% confidence interval of the success rate, the variance in the corresponding costs was ¥25,514–45,034 for 0–2 points, ¥38,344–61,824 for 3–6 points, and ¥45,698–108,260 for 7–10 points. The degree of nicotine dependence may therefore be an important determinant of the cost-effectiveness of smoking cessation programs. PMID:23383289

Nicotine dependence and cost-effectiveness of individualized support for smoking cessation: evidence from practice at a worksite in Japan.

PubMed

Nakamura, Koshi; Sakurai, Masaru; Miura, Katsuyuki; Morikawa, Yuko; Nagasawa, Shin-ya; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Suwazono, Yasushi; Nakagawa, Hideaki

2013-01-01

Given the lack of economic studies evaluating the outcomes of smoking cessation programs from the viewpoint of program sponsors, we conducted a case study to provide relevant information for worksites. The present study was carried out between 2006 and 2008 at a manufacturing factory in the Toyama Prefecture of Japan and included subjects who voluntarily entered a smoking cessation program. The program included face-to-face counselling followed by weekly contact to provide encouragement over six months using e-mail or inter-office mail. Nicotine patches were available if required. All 151 participants stopped smoking immediately. Over the 24-month study period, self-report showed 49.7% abstained continuously from smoking. The rate of 24-month consecutive abstinence was higher in participants with lower Fagerström Test scores for Nicotine Dependence at baseline than in those with higher scores (63.6% for 0-2 points vs. 46.5% for 3-6 points vs. 43.8% for 7-10 points; chi-square test p = 0.19). A logistic regression model showed a significant linear trend for the association between the score and abstinence status after adjustment for possible confounding factors (p = 0.03). The crude incremental cost for one individual to successfully quit smoking due to the support program was ¥46,379 (i.e., ¥100 = $1.28, £0.83, or €1.03 at foreign exchange rates). The corresponding costs for the three categories of the Fagerström Test score for Nicotine Dependence were ¥31,953, ¥47,450 and ¥64,956, respectively. When a sensitivity analysis was conducted based on the 95% confidence interval of the success rate, the variance in the corresponding costs was ¥25,514-45,034 for 0-2 points, ¥38,344-61,824 for 3-6 points, and ¥45,698-108,260 for 7-10 points. The degree of nicotine dependence may therefore be an important determinant of the cost-effectiveness of smoking cessation programs.

A localized flare of dermatitis may render patch tests uninterpretable in some patients with recently controlled widespread dermatitis.

PubMed

Magembe, Anna J; Davis, Mark D P; Richardson, Donna M

2009-01-01

Patch testing rarely is confounded by localized dermatitis induced in the area being tested (usually the back). Its occurrence renders the interpretation of patch tests impossible. To review our experience of the circumstances in which this phenomenon occurs during patch testing. We retrospectively reviewed patients with this phenomenon who underwent patch testing from January 1, 2002, through June 30, 2006. Of the 3,569 patients tested, 12 (0.34% [9 men and 3 women]) had development of this phenomenon. All patients previously had recent widespread dermatitis that was suppressed temporarily with topical corticosteroids and wet dressings at the time of patch testing. The period between control of the dermatitis and the initiation of patch testing was less than 1 week for all patients. Three patients (25%) had recently discontinued therapy with systemic corticosteroids (less than 1 week earlier). In patients with irritable skin either immediately after widespread dermatitis is controlled or after the cessation of systemic corticosteroid treatment, a flare of dermatitis induced by patch testing may render patch tests unreadable and therefore uninterpretable. To avoid this confounding occurrence, a waiting period between control of widespread dermatitis and initiation of patch testing is advised.

PATIENTS' KNOWLEDGE OF MEDICAL PATCHES IN HUNGARY.

PubMed

Somogyi, Orsolya; Zelko, Romana

2016-11-01

Transdermal therapy with medical patches is a simple possibility in home medication. As the correct use of patches has a decisive impact from the point of its modulator effect.A questionnaire survey was developed to explore level of patients' knowledge of the correct use of transdermal patches. A survey was administered in thirteen Hungarian community pharmacies from October of 2012 to May of 2015. Most of the participants, men and women over 18 years of age (n = 233), used major analgesic patches (fentanyl); the remainder were given nitroglycerin, NSAID analgesics patches during the survey. For the hypothesis testing it was assumed that men were more likely to use a razor for skin depilation before patch application than women as their denser pelage hinders patch adhesion. The hypothesis testing showed no significant gender difference in razor use (X² = 0.201; p = 0.654). Pharmacists should direct patients to avoid using soap for skin cleansing before patch application because only 22 percent of the participants always avoided its use. Since only 9 tests were flawless from 233 completed questionnaires. Many patients do not understand how to correctly apply a transdermal dosage patch. Pharmacists should teach their correct application based on results.

Conceptual obstacles to making use of four smoking-cessation strategies: What reasons do light smokers give for rejecting strategies?

PubMed Central

Ryan, Michael P; Hinojosa, Jennifer J

2015-01-01

Some smokers have safety and cost concerns about nicotine replacement therapy which discourage its use. We recruited 56 young adult light smokers to read detailed descriptions of a hybrid nicotine replacement therapy, a prescription drug treatment, scheduled reduced smoking, and a menu of self-help tactics. Participants listed five reasons smokers might reject each strategy. An emergent-category content analysis classified each response with a high degree of inter-rater reliability. Only one-third of 32 concerns were strategy-specific; the majority focused on the general difficulty of quitting. Most prevalent were “continued cravings,” “addiction too strong,” “takes too long,” and “won’t work.” These and other concerns reflect conceptual obstacles to be surmounted in smoking-cessation interventions. PMID:28070381

Modelling a budgetary impact analysis for funding drug-based smoking cessation therapies for patients with major depressive disorder in Spain.

PubMed

Rejas-Gutiérrez, J; Bruguera, E; Cedillo, S

2017-09-01

Smoking is associated with high healthcare resource utilisation and cost to society. Patients with major depressive disorder (MDD) exhibit high susceptibility to nicotine dependence. Varenicline, bupropion and nicotine replacement therapy are all indicated for smoking cessation; however funding by the Spanish national health system (SNHS) is limited. We modelled a budgetary impact analysis (BIA) to estimate the impact of the SNHS funding drug-based therapies for smoking cessation in smokers with MDD. The BIA compared the current unfunded scenario versus a funded scenario (varenicline, bupropion, nicotine replacement therapy combined with medical follow-up and counselling) using the Spanish SNHS and societal perspectives. The BIA design was a hybrid model using a decision tree algorithm (population size: smokers with MDD) and Markov chains (smoking cessation attempts) over a 5-year horizon. Smoking cessation drug efficacy was derived from clinical trials, and smoking cessation costs avoided were taken from an analysis of the Spanish National Health Survey. Results were shown as incremental cost savings. Scenarios and threshold univariate sensitivity analyses tested model robustness. The funded scenario resulted in an increase of 43,478 cessation attempts and 8930 fewer smokers after 5 years compared to the unfunded scenario. The cost of funding was €25.3 million and costs avoided were €26.5 million. There was a cumulative 5-year incremental cost saving of €1.2 million to Spanish society. Results were robust using alternative scenarios. Funding smoking cessation drugs in patients with MDD is of economic benefit to Spain and could produce net savings from the third year of implementation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reduced nicotine content cigarettes in smokers of low socioeconomic status: study protocol for a randomized control trial.

PubMed

Krebs, Nicolle M; Allen, Sophia I; Veldheer, Susan; Martinez, Diane J; Horn, Kimberly; Livelsberger, Craig; Modesto, Jennifer; Kuprewicz, Robin; Wilhelm, Ashley; Hrabovsky, Shari; Kazi, Abid; Fazzi, Alyse; Liao, Jason; Zhu, Junjia; Wasserman, Emily; Reilly, Samantha M; Reinhart, Lisa; Trushin, Neil; Moyer, Robinn E; Bascom, Rebecca; Foulds, Jonathan; Richie, John P; Muscat, Joshua E

2017-07-03

The Family Smoking Prevention and Tobacco Control Act gave the Food and Drug Administration jurisdiction over the regulation of all tobacco products, including their nicotine content. Under this act, a major strategy to reduce harm from cigarette tobacco is lowering the nicotine content without causing unintended adverse consequences. Initial research on reduced nicotine content (RNC) cigarettes has shown that smokers of these cigarettes gradually decrease their smoking frequency and biomarkers of exposure. The effectiveness of this strategy needs to be demonstrated in different populations whose response to RNC cigarettes might be substantially mediated by personal or environmental factors, such as low socioeconomic status (SES) populations. This study aims to evaluate the response to a reduced nicotine intervention in low SES smokers, as defined here as those with less than 16 years of education, by switching smokers from high nicotine commercial cigarettes to RNC cigarettes. Adults (N = 280) who have smoked five cigarettes or more per day for the past year, have not made a quit attempt in the prior month, are not planning to quit, and have less than 16 years of education are recruited into a two-arm, double-blinded randomized controlled trial. First, participants smoke their usual brand of cigarettes for 1 week and SPECTRUM research cigarettes containing a usual amount of nicotine for 2 weeks. During the experimental phase, participants are randomized to continue smoking SPECTRUM research cigarettes that contain either (1) usual nicotine content (UNC) (11.6 mg/cigarette) or (2) RNC (11.6 to 0.2 mg/cigarette) over 18 weeks. During the final phase of the study, all participants are offered the choice to quit smoking with nicotine replacement therapy, continue smoking the research cigarettes, or return to their usual brand of cigarettes. The primary outcomes of the study include retention rates and compliance with using only research cigarettes and no use of other nicotine-containing products. Secondary outcomes are tobacco smoke biomarkers, nicotine dependence measures, smoking topography, stress levels, and adverse health consequences. Results from this study will provide information on whether low SES smokers can maintain a course of progressive nicotine reduction without increases in incidence of adverse effects. ClinicalTrials.gov, NCT01928719 . Registered on 21 August 2013.

Anxiety and Nicotine Dependence: Emerging Role of the Habenulo-Interpeduncular Axis.

PubMed

Molas, Susanna; DeGroot, Steven R; Zhao-Shea, Rubing; Tapper, Andrew R

2017-02-01

While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal. Insights into how this circuit interconnects with regions more classically associated with anxiety, and how chronic nicotine exposure induces neuroadaptations resulting in an anxiogenic state, may thereby provide novel strategies and molecular targets for therapies that facilitate smoking cessation, as well as for anxiety relief. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute Nicotine Enhances Spontaneous Recovery of Contextual Fear and Changes "c-fos" Early Gene Expression in Infralimbic Cortex, Hippocampus, and Amygdala

ERIC Educational Resources Information Center

Kutlu, Munir G.; Tumolo, Jessica M.; Holliday, Erica; Garrett, Brendan; Gould, Thomas J.

2016-01-01

Exposure therapy, which focuses on extinguishing fear-triggering cues and contexts, is widely used to treat post-traumatic stress disorder (PTSD). Yet, PTSD patients who received successful exposure therapy are vulnerable to relapse of fear response after a period of time, a phenomenon known as spontaneous recovery (SR). Increasing evidence…

COPD flare-ups

MedlinePlus

... Stop smoking and avoid secondhand smoke. Avoiding smoke is the best way to slow down damage to your lungs. Ask your provider about stop-smoking programs and other options, such as nicotine-replacement therapy. Take your medicines as directed. Ask ...

Receptor May Underlie Gender Differences in Response to Smoking Cessation Therapy

MedlinePlus

... β 2 *-nAChRs comprise an excess. In previous studies, the Yale researchers linked heightened β 2 *-nAChR availability to ex-smokers’ nicotine craving and possibly other withdrawal symptoms ...

Achieving Smoking Cessation in Individuals with Schizophrenia: Special Considerations

PubMed Central

Cather, Corinne; Pachas, Gladys N.; Cieslak, Kristina M.; Evins, A. Eden

2017-01-01

Premature mortality due to cardiovascular disease in those with schizophrenia is the largest lifespan disparity in the US and is growing; adults in the US with schizophrenia die on average 28 years earlier than those in the general population. Smoking prevalence among individuals with schizophrenia is estimated to be from 64–79%. Smokers with schizophrenia have historically been excluded from most large nicotine-dependence treatment studies. Converging evidence, however, indicates that a majority of smokers with schizophrenia want to quit smoking and that available pharmacotherapeutic smoking cessation aids are well tolerated by this population of smokers and effective when combined with behavioral treatment. The aim of this review is to present updated evidence for safety and efficacy of smoking cessation interventions for those with schizophrenia spectrum illness. We also highlight implications of the very low abstinence rates for smokers with schizophrenia who receive placebo plus behavioral treatment in randomized trials and review treatment approaches to address the high rate of rapid relapse observed upon pharmacologic treatment discontinuation in this population. Recommendations for monitoring for treatment-emergent nicotine withdrawal symptoms, side effects and effects of cessation on antipsychotic medication are also provided. Smokers with schizophrenia spectrum disorders should be encouraged to quit smoking and should receive varenicline, bupropion with or without nicotine replacement therapy, or nicotine replacement therapy, all in combination with behavioral treatment for at least 12 weeks. Maintenance pharmacotherapy may reduce relapse and improve sustained abstinence rates. Controlled trials in smokers with schizophrenia consistently show no greater rate of neuropsychiatric adverse events with pharmacotherapeutic cessation aids than with placebo. PMID:28550660

Delay discounting rates: a strong prognostic indicator of smoking relapse.

PubMed

Sheffer, Christine E; Christensen, Darren R; Landes, Reid; Carter, Larry P; Jackson, Lisa; Bickel, Warren K

2014-11-01

Recent evidence suggests that several dimensions of impulsivity and locus of control are likely to be significant prognostic indicators of relapse. One-hundred and thirty-one treatment seeking smokers were enrolled in six weeks of multi-component cognitive-behavioral therapy with eight weeks of nicotine replacement therapy. Cox proportional hazard regressions were used to model days to relapse with each of the following: delay discounting of $100, delay discounting of $1000, six subscales of the Barratt Impulsiveness Scale (BIS), Rotter's Locus of Control (RLOC), Fagerstrom's Test for Nicotine Dependence (FTND), and the Perceived Stress Scale (PSS). Hazard ratios for a one standard deviation increase were estimated with 95% confidence intervals for each explanatory variable. Likelihood ratios were used to examine the level of association with days to relapse for different combinations of the explanatory variables while accounting for nicotine dependence and stress level. These analyses found that the $100 delay discounting rate had the strongest association with days to relapse. Further, when discounting rates were combined with the FTND and PSS, the associations remained significant. When the other measures were combined with the FTND and PSS, their associations with relapse non-significant. These findings indicate that delay discounting is independently associated with relapse and adds to what is already accounted for by nicotine dependence and stress level. They also signify that delay discounting is a productive new target for enhancing treatment for tobacco dependence. Consequently, adding an intervention designed to decrease discounting rates to a comprehensive treatment for tobacco dependence has the potential to decrease relapse rates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Outcomes of 3 hours part-time occlusion treatment combined with near activities among children with unilateral amblyopia.

PubMed

Alotaibi, Abdullah G; Fawazi, Samah M; Alenazy, Badriah R; Abu-Amero, Khaled K

2012-04-01

To evaluate the outcome of part-time occlusion therapy with or without near activities in monocular amblyopic patients. One hundred and thirty patients who prescribed daily occlusion therapy (part-time occlusion) were followed-up for a 12-week period. The study was carried out in the Pediatric Ophthalmology and Orthoptics Clinics of King Abdul-Aziz University Hospital, Riyadh, Saudi Arabia for the period from January to November 2010. Sixty-five patients were recommended to undertake the 3 hours of near visual activities (such as reading a book during patching) while the other 65 patients were not advised to do any near activity. Main outcome measures were best corrected visual acuity (VA) for both groups and line improvement. The total line of VA improved from baseline by an average of 6.7+/-2.37 line log MAR (logarithm of the minimum angle of resolution) units in the group of patching with near activities and by an average of 5.3+/- 2.04 line log MAR units in the group of patching without near activities. All type of amblyopia (strabismic, anisometropic, and mixed types of amblyopia) improved significantly after patching with near activities. Both moderate and severe amblyopia improved significantly in the group of near activities compared with the group without near activities. Performing near activities while patching in the treatment of anisometropic, stabismic, or combined amblyopia improves the VA outcome more than patching alone.

Comparison of the characteristics of long-term users of electronic cigarettes versus nicotine replacement therapy: A cross-sectional survey of English ex-smokers and current smokers.

PubMed

Nelson, Victoria A; Goniewicz, Maciej L; Beard, Emma; Brown, Jamie; Sheals, Kate; West, Robert; Shahab, Lion

2015-08-01

Electronic cigarettes (ECs) and nicotine replacement therapy (NRT) are non-combustible nicotine delivery devices being widely used as a partial or a complete long-term substitute for smoking. Little is known about the characteristics of long-term users, their smoking behaviour, attachment to smoking, experience of nicotine withdrawal symptoms, or their views on these devices. This study aimed to provide preliminary evidence on this and compare users of the different products. UK participants were recruited from four naturally occurring groups of long-term (≥6 months) users of either EC or NRT who had stopped or continued to smoke (N=36 per group, total N=144). Participants completed a questionnaire assessing socio-demographic and smoking characteristics, nicotine withdrawal symptoms, smoker identity and attitudes towards the products they were using. Adjusting for relevant confounders, EC use was associated with a stronger smoker identity (Wald X(2)(1)=3.9, p=0.048) and greater product endorsement (Wald X(2)(1)=4.6, p=0.024) than NRT use, irrespective of smoking status. Among ex-smokers, EC users reported less severe mood and physical symptoms (Wald X(2)(1)=6.1, p=0.014) and cravings (Wald X(2)(1)=8.5, p=0.003), higher perceived helpfulness of the product (Wald X(2)(1)=4.8, p=0.028) and lower intentions to stop using the product (Wald X(2)(1)=17.6, p<0.001) than NRT users. Compared with people who use NRT for at least 6 months, those who use EC over that time period appear to have a stronger smoker identity and like their products more. Among long-term users who have stopped smoking, ECs are perceived as more helpful than NRT, appear more effective in controlling withdrawal symptoms and continued use may be more likely. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Lipid-Altering Therapies and the Progression of Atherosclerotic Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wierzbicki, Anthony S.

2007-04-15

Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents,more » including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focused and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease.« less

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch

PubMed Central

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M. L.; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G.

2015-01-01

Introduction Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. Methods hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. Results SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Conclusions Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch. PMID:25993466

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch.

PubMed

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M L; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G

2015-01-01

Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch.

A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy

NASA Astrophysics Data System (ADS)

Lee, Hyunjae; Choi, Tae Kyu; Lee, Young Bum; Cho, Hye Rim; Ghaffari, Roozbeh; Wang, Liu; Choi, Hyung Jin; Chung, Taek Dong; Lu, Nanshu; Hyeon, Taeghwan; Choi, Seung Hong; Kim, Dae-Hyeong

2016-06-01

Owing to its high carrier mobility, conductivity, flexibility and optical transparency, graphene is a versatile material in micro- and macroelectronics. However, the low density of electrochemically active defects in graphene synthesized by chemical vapour deposition limits its application in biosensing. Here, we show that graphene doped with gold and combined with a gold mesh has improved electrochemical activity over bare graphene, sufficient to form a wearable patch for sweat-based diabetes monitoring and feedback therapy. The stretchable device features a serpentine bilayer of gold mesh and gold-doped graphene that forms an efficient electrochemical interface for the stable transfer of electrical signals. The patch consists of a heater, temperature, humidity, glucose and pH sensors and polymeric microneedles that can be thermally activated to deliver drugs transcutaneously. We show that the patch can be thermally actuated to deliver Metformin and reduce blood glucose levels in diabetic mice.

Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat.

PubMed

Zhang, X-L; Albers, K M; Gold, M S

2015-01-22

The goals of the present study were to determine (1) the properties of the nicotinic acetylcholine receptor (nAChR) currents in rat cutaneous dorsal root ganglion (DRG) neurons; (2) the impact of nAChR activation on the excitability of cutaneous DRG neurons; and (3) the impact of inflammation on the density and distribution of nAChR currents among cutaneous DRG neurons. Whole-cell patch-clamp techniques were used to study retrogradely labeled DRG neurons from naïve and complete Freund's adjuvant inflamed rats. Nicotine-evoked currents were detectable in ∼70% of the cutaneous DRG neurons, where only one of two current types, fast or slow currents based on rates of activation and inactivation, was present in each neuron. The biophysical and pharmacological properties of the fast current were consistent with nAChRs containing an α7 subunit while those of the slow current were consistent with nAChRs containing α3/β4 subunits. The majority of small diameter neurons with fast current were IB4- while the majority of small diameter neurons with slow current were IB4+. Preincubation with nicotine (1 μM) produced a transient (1 min) depolarization and increase in the excitability of neurons with fast current and a decrease in the amplitude of capsaicin-evoked current in neurons with slow current. Inflammation increased the current density of both slow and fast currents in small diameter neurons and increased the percentage of neurons with the fast current. With the relatively selective distribution of nAChR currents in putative nociceptive cutaneous DRG neurons, our results suggest that the role of these receptors in inflammatory hyperalgesia is likely to be complex and dependent on the concentration and timing of acetylcholine release in the periphery. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

The electronic cigarette. Official statement of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) on the efficacy, safety and regulation of electronic cigarettes.

PubMed

Jimenez Ruiz, Carlos A; Solano Reina, Segismundo; de Granda Orive, Jose Ignacio; Signes-Costa Minaya, Jaime; de Higes Martinez, Eva; Riesco Miranda, Juan Antonio; Altet Gómez, Neus; Lorza Blasco, Jose Javier; Barrueco Ferrero, Miguel; de Lucas Ramos, Pilar

2014-08-01

The electronic cigarette (EC) is a device formed by three basic elements: battery, atomizer and cartridge. When assembled, it looks like a cigarette. The cartridge contains different substances: propylene glycol, glycerine and, sometimes, nicotine. When the user "vapes", the battery is activated, the atomizer is heated and the liquid is drawn in and vaporized. The smoker inhales the mist produced. Various substances have been detected in this mist: formaldehyde, acetaldehyde and acrolein and some heavy metals. Although these are found in lower concentrations than in cigarettes, they may still be harmful for the human body. Several surveys show that 3-10% of smokers regularly use e-cigarettes. A randomized study has shown that the efficacy of e-cigarettes for helping smokers to quit is similar to nicotine patches. Nevertheless, the study has relevant methodological limitations and reliable conclusions cannot be deduced. This report sets down the Position Statement of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) on the efficacy and safety of e-cigarettes. This statement declares that e-cigarettes should be regulated as medicinal products. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Selective CRF2 receptor agonists ameliorate the anxiety- and depression-like state developed during chronic nicotine treatment and consequent acute withdrawal in mice.

PubMed

Bagosi, Zsolt; Palotai, Miklós; Simon, Balázs; Bokor, Péter; Buzás, András; Balangó, Beáta; Pintér, Dávid; Jászberényi, Miklós; Csabafi, Krisztina; Szabó, Gyula

2016-12-01

The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution. After 30min the mice were observed in an elevated plus-maze test or a forced swim test, for anxiety- and depression-like behavior. After 5min of testing, the plasma corticosterone concentration reflecting the activity of the hypothalamic-pituitary-adrenal (HPA) axis was also determined by a chemo-fluorescent method. Half of the animals were treated ICV and evaluated on the 8th day, the other half on the 9th day. On the 8th day, nicotine-treated mice presented signs of anxiolysis and depression, but no significant elevation of the plasma corticosterone concentration. On the 9th day, nicotine-treated mice exhibited signs of anxiety and depression and a significant increase of the plasma corticosterone levels. Central administration of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including the hyperactivity of the HPA axis, developed during acute withdrawal following chronic nicotine treatment. The present study suggests that selective CRF2 receptor agonists could be used as a therapy in nicotine addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

Bupropion-varenicline interactions and nicotine self-administration behavior in rats.

PubMed

Hall, Brandon J; Slade, Susan; Wells, Corinne; Rose, Jed E; Levin, Edward D

2015-03-01

Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness of a clinical practice change intervention in increasing the provision of nicotine dependence treatment in inpatient psychiatric facilities: an implementation trial.

PubMed

Wye, Paula M; Stockings, Emily A; Bowman, Jenny A; Oldmeadow, Chris; Wiggers, John H

2017-02-07

Despite clinical practice guidelines recommending the routine provision of nicotine dependence treatment to smokers in inpatient psychiatric facilities, the prevalence of such treatment provision is low. The aim of this study was to examine the effectiveness of a clinical practice change intervention in increasing clinician recorded provision of nicotine dependence treatment to patients in inpatient psychiatric facilities. We undertook an interrupted time series analysis of nicotine dependence treatment provision before, during and after a clinical practice change intervention to increase clinician recorded provision of nicotine dependence treatment for all hospital discharges (aged >18 years, N = 4175) over a 19 month period in two inpatient adult psychiatric facilities in New South Wales, Australia. The clinical practice change intervention comprised six key strategies: leadership and consensus, enabling systems and procedures, training and education, information and resources, audit and feedback and an on-site practice change support officer. Systematic medical record audit and segmented logistic regression was used to determine differences in proportions for each nicotine dependence treatment outcome measure between the 'pre', 'during' and 'post-intervention' periods. The prevalence of all five outcome measures increased significantly between the pre and post-intervention periods, including clinician recorded: assessment of patient smoking status (36.43 to 51.95%; adjusted odds ratio [AOR] = 2.39, 99% Confidence Interval [CI]: 1.23 to 4.66); assessment of patient nicotine dependence status (4.74 to 11.04%; AOR = 109.67, 99% CI: 35.35 to 340.22); provision of brief advice to quit (0.85 to 8.81%; AOR = 97.43, 99% CI: 31.03 to 306.30); provision of nicotine replacement therapy (8.06 to 26.25%; AOR = 19.59, 99% CI: 8.17 to 46.94); and provision of nicotine dependence treatment on discharge (8.82 to 13.45%, AOR = 12.36; 99% CI: 6.08 to 25.14). This is the first study to provide evidence that a clinical practice change intervention may increase clinician recorded provision of nicotine dependence treatment in inpatient psychiatric settings. The intervention offers a mechanism for psychiatric facilities to increase the provision of nicotine dependence treatment in accordance with clinical guidelines.

[Smoking cessation and pregnancy].

PubMed

Underner, M; Pourrat, O; Perriot, J; Peiffer, G; Jaafari, N

2017-10-01

Active and passive smoking during pregnancy induce several deleterious effects that may have a negative impact on pregnancy progress, fetus development and both mother and newborn health. Smoking cessation should be a rule for any woman as soon as the beginning of her pregnancy, or better in anticipation of a pregnancy when contraception is no more taken. Every caregiver must help every pregnant woman who smokes to quit smoking. Smoking cessation interventions in pregnant women must combine a psychological support (mainly with cognitive behavioral therapy) and nicotine replacement therapy, which can also be used during breast feeding. It is recommended to adjust the dosage of nicotine replacement therapy according to the symptoms of under or over dosage at the end of the first week of use. On the other hand, vareniclin and bupropion are contra-indicated during pregnancy or breast-feeding. Electronic cigarette is not advised during pregnancy. Prevention of smoking relapse in postpartum period is essential since a percentage as high as 50% of women having quit during their pregnancy resume smoking during the 6 months following delivery. Copyright © 2017. Published by Elsevier Masson SAS.

Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

PubMed

Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

2010-08-01

Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.

Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS).

PubMed

Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

2004-09-01

Amblyopia is the commonest visual disorder of childhood. Yet the contributions of the two principal treatments (spectacle wear and occlusion) to outcome are unknown. This study was undertaken to investigate the dose-response relationship of amblyopia therapy. The study comprised three distinct phases: baseline, in which repeat measures of visual function were undertaken to confirm the initial visual deficit; refractive adaptation: an 18-week period of spectacle wear with six weekly measurements of logarithm of the minimum angle of resolution (logMAR) visual acuity; occlusion: in which participants were prescribed 6 hours of "patching" per day. In the latter phase, occlusion was objectively monitored and logMAR visual acuity recorded at 2-week intervals until any observed gains had ceased. Data were obtained from 94 participants (mean age, 5.1 +/- 1.4 years) with amblyopia associated with strabismus (n = 34), anisometropia (n = 23), and both anisometropia and strabismus (n = 37). Eighty-six underwent refractive adaptation. Average concordance with patching was 48%. The relationship between logMAR visual acuity gain and total occlusion dose was monotonic and linear. Increasing dose rate beyond 2 h/d hastened the response but did not improve outcome. More than 80% of the improvement during occlusion occurred within 6 weeks. Treatment outcome was significantly better for children younger than 4 years (n = 17) than in those older than 6 years (n = 24; P = 0.0014). Continuous objective monitoring of the amount of patching therapy received has provided insight into the dose-response relationship of occlusion therapy for amblyopia. Patching is most effective within the first few weeks of treatment, even for those in receipt of a relatively small dose. Further studies are needed to elucidate the neural basis for the dose-response functions. Copyright Association for Research in Vision and Ophthalmology

Smoking cessation in primary care clinics.

PubMed

Sippel, J M; Osborne, M L; Bjornson, W; Goldberg, B; Buist, A S

1999-11-01

To document smoking cessation rates achieved by applying the 1996 Agency for Health Care Policy and Research (AHCPR) smoking cessation guidelines for primary care clinics, compare these quit rates with historical results, and determine if quit rates improve with an additional motivational intervention that includes education as well as spirometry and carbon monoxide measurements. Randomized clinical trial. Two university-affiliated community primary care clinics. Two hundred five smokers with routinely scheduled appointments. All smokers were given advice and support according to AHCPR guidelines. Half of the subjects received additional education with spirometry and carbon monoxide measurements. Quit rate was evaluated at 9-month follow-up. Eleven percent of smokers were sustained quitters at follow-up. Sustained quit rate was no different for intervention and control groups (9% vs 14%; [OR] 0.6; 95% [CI] 0.2, 1.4). Nicotine replacement therapy was strongly associated with sustained cessation (OR 6.7; 95% CI 2.3, 19.6). Subjects without insurance were the least likely to use nicotine replacement therapy ( p =.05). Historical data from previously published studies showed that 2% of smokers quit following physician advice, and additional support similar to AHCPR guidelines increased the quit rate to 5%. The sustained smoking cessation rate achieved by following AHCPR guidelines was 11% at 9 months, which compares favorably with historical results. Additional education with spirometry did not improve the quit rate. Nicotine replacement therapy was the strongest predictor of cessation, yet was used infrequently owing to cost. These findings support the use of AHCPR guidelines in primary care clinics, but do not support routine spirometry for motivating patients similar to those studied here.

Nicotine replacement therapy

MedlinePlus

... just starting to quit, chew 1 to 2 pieces each hour. DO NOT chew more than 20 pieces a day. Chew the gum slowly until it ... soft drinks, and acidic beverages before chewing a piece of gum. People who smoke more than 25 ...

A pliable electroporation patch (ep-Patch) for efficient delivery of nucleic acid molecules into animal tissues with irregular surface shapes.

PubMed

Wei, Zewen; Huang, Yuanyu; Zhao, Deyao; Hu, Zhiyuan; Li, Zhihong; Liang, Zicai

2015-01-05

Delivery of nucleic acids into animal tissues by electroporation is an appealing approach for various types of gene therapy, but efficiency of existing methodsis not satisfactory. Here we present the validation of novel electroporation patch (ep-Patch) for efficient delivery of DNA and siRNA into mouse tissues. Using micromachining technology, closely spaced gold electrodes were made on the pliable parylene substrate to form a patch-like electroporation metrics. It enabled large coverage of the target tissues and close surface contact between the tissues and electrodes, thus providing a uniform electric field to deliver nucleic acids into tissues, even beneath intact skin. Using this ep-Patch for efficiently delivery of both DNA and siRNA, non-invasive electroporation of healthy mouse muscle tissue was successfully achieved. Delivery of these nucleic acids was performed to intact tumors with satisfactory results. Silencing of tumor genes using the ep-Patch was also demonstrated on mice. This pliable electroporation patch method constitutes a novel way of in vivo delivery of siRNA and DNA to certain tissues or organs to circumvent the disadvantages of existing methodologies for in vivo delivery of nucleic acid molecules.

Occlusion-amblyopia following high dose oral levodopa combined with part time patching

PubMed Central

Kothari, Mihir

2014-01-01

Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa. PMID:23571255

Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

PubMed

Kothari, Mihir

2014-12-01

Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

Time-dependent morphological and biochemical changes following cutaneous thermal burn injury and their modulation by copper nicotinate complex: an animal model.

PubMed

Nassar, Muammar A Y; Eldien, Heba M Saad; Tawab, Hanem S Abdel; Saleem, Tahia H; Omar, Hossam M; Nassar, Ahmed Y; Hussein, Mahmoud Rezk Abdelwahed

2012-10-01

Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Effectiveness of 308-nm Excimer Laser Therapy in Treating Alopecia Areata, Determined by Examining the Treated Sides of Selected Alopecic Patches.

PubMed

Byun, Ji Won; Moon, Jong Hyuk; Bang, Chan Yl; Shin, Jeonghyun; Choi, Gwang Seong

2015-01-01

Some studies have reported the use of 308-nm excimer laser therapy for treating alopecia areata (AA); however, the effectiveness of this therapy on a theoretical basis has not yet been comparatively analyzed. To determine the therapeutic effect of excimer laser therapy on AA. One alopecic patch was divided into control and treated sides in 10 patients with AA. Then, 308-nm excimer laser therapy was administered twice a week for 12 weeks. Photograph and phototrichogram analyses were performed. Photographic assessments by both dermatologists and individuals of the general population showed objective improvements after excimer laser therapy. On the treated side, the hair count and hair diameter had statistically increased after treatment. However, only the hair diameter was found to be significantly high in the treated half when it was compared with the control side. The 308-nm excimer laser has a therapeutic effect on AA, which is proven by photograph and phototrichogram analysis by a side-by-side comparison. © 2015 S. Karger AG, Basel.

Behavioral Counseling and Pharmacotherapy Interventions for Tobacco Cessation in Adults, Including Pregnant Women: A Review of Reviews for the U.S. Preventive Services Task Force.

PubMed

Patnode, Carrie D; Henderson, Jillian T; Thompson, Jamie H; Senger, Caitlyn A; Fortmann, Stephen P; Whitlock, Evelyn P

2015-10-20

Tobacco use is the leading cause of preventable death in the United States. To review the effectiveness and safety of pharmacotherapy and behavioral interventions for tobacco cessation. 5 databases and 8 organizational Web sites were searched through 1 August 2014 for systematic reviews, and PubMed was searched through 1 March 2015 for trials on electronic nicotine delivery systems. Two reviewers examined 114 articles to identify English-language reviews that reported health, cessation, or adverse outcomes. One reviewer abstracted data from good- and fair-quality reviews, and a second checked for accuracy. 54 reviews were included. Behavioral interventions increased smoking cessation at 6 months or more (physician advice had a pooled risk ratio [RR] of 1.76 [95% CI, 1.58 to 1.96]). Nicotine replacement therapy (RR, 1.60 [CI, 1.53 to 1.68]), bupropion (RR, 1.62 [CI, 1.49 to 1.76]), and varenicline (RR, 2.27 [CI, 2.02 to 2.55]) were also effective for smoking cessation. Combined behavioral and pharmacotherapy interventions increased cessation by 82% compared with minimal intervention or usual care (RR, 1.82 [CI, 1.66 to 2.00]). None of the drugs were associated with major cardiovascular adverse events. Only 2 trials addressed efficacy of electronic cigarettes for smoking cessation and found no benefit. Among pregnant women, behavioral interventions benefited cessation and perinatal health; effects of nicotine replacement therapy were not significant. Evidence published after each review's last search date was not included. Behavioral and pharmacotherapy interventions improve rates of smoking cessation among the general adult population, alone or in combination. Data on the effectiveness and safety of electronic nicotine delivery systems are limited. Agency for Healthcare Research and Quality.

It is feasible and effective to help patients with severe mental disorders to quit smoking: An ecological pragmatic clinical trial with transdermal nicotine patches and varenicline.

PubMed

Garcia-Portilla, Maria P; Garcia-Alvarez, Leticia; Sarramea, Fernando; Galvan, Gonzalo; Diaz-Mesa, Eva; Bobes-Bascaran, Teresa; Al-Halabi, Susana; Elizagarate, Edorta; Iglesias, Celso; Saiz Martínez, Pilar A; Bobes, Julio

2016-10-01

Despite the proven association between smoking and high rates of medical morbidity and reduced life expectancy in people with severe mental disorders (SMD), their smoking rates do not decline as they do in the general population. We carried out a non-randomized, open-label, prospective, 9-month follow-up multicentre trial to investigate the clinical efficacy, safety and tolerability of a 12-week smoking cessation programme for patients with SMD in the community under real-world clinical conditions. Eighty-two adult outpatients with schizophrenic/bipolar disorder smoking ≥15 cigarettes/day were assigned by shared decision between doctors and patients to transdermal nicotine patches (TNP) [36(46.2%)] or varenicline [39(50%)]. Short-term efficacy: The 12-week 7-day smoking cessation (self-reported cigarettes/day=0 and breath carbon monoxide levels≤9ppm) prevalence was 49.3%, without statistically significant differences between medications (TNP 50.0% vs varenicline 48.6%, chi-square=0.015, p=1.000). Long-term efficacy: At weeks 24 and 36, 41.3 and 37.3% of patients were abstinent, with no statistically significant differences between treatments. Safety and Tolerability: no patients made suicide attempts/required hospitalization. There was no worsening on the psychometric scales. Patients significantly increased weight [TNP 1.1(2.8) vs varenicline 2.5(3.3), p=0.063], without significant changes in vital signs/laboratory results, except significant decreases in alkaline phosphatase and low-density lipoprotein-cholesterol levels in the varenicline group. Patients under varenicline more frequently presented nausea/vomiting (p<0.0005), patients under TNP experienced skin reactions more frequently (p=0.002). Three patients under varenicline had elevated liver enzymes. In conclusion, we have demonstrated that in real-world clinical settings it is feasible and safe to help patients with stabilized severe mental disorders to quit smoking. Copyright © 2016 Elsevier B.V. All rights reserved.

One year effectiveness of an individualised smoking cessation intervention at the workplace: a randomised controlled trial

PubMed Central

Rodriguez-Artalej..., F; Lafuente, U; Guallar-Castillon, P; Garteizaurrekoa, D.; Sainz, M; Diez, A; Foj, A; Banegas, J

2003-01-01

Aims: To assess the effectiveness of a smoking cessation intervention at the workplace. The intervention was adapted to smokers‘ tobacco dependence, and included minimal structured counselling at the first visit (5–8 minutes), nicotine patches for three months, and three sessions of counselling for reinforcement of abstinence (2–3 minutes) over a three month period. Methods: Open randomised trial with two groups: the intervention group, and the control group which was subjected to standard clinical practice, consisting of short (30 seconds to one minute) sporadic sessions of unstructured medical antismoking advice. The trial was carried out among 217 smokers of both sexes, aged 20–63 years, motivated to quit smoking and without contraindications for nicotine patches, who were employees at a public transport company and at two worksites of an electric company. The main outcome measure was self reported tobacco abstinence confirmed by carbon monoxide in expired air ≤10 ppm. Analysis was performed according to intention-to-treat. Results: The rate of continuous abstinence at 12 months was 20.2% for the intervention versus 8.7% for the control group (OR: 2.58; 95% CI: 1.13 to 5.90; p = 0.025). In subgroup analyses, effectiveness of the intervention did not vary substantially with age, tobacco dependence, number of cigarettes smoked per day, number of years of tobacco consumption, degree of desire to quit smoking, time spent with smokers, subjective health, and presence of tobacco related symptoms. Weight gain at 12 months was similar for both groups (1.69 kg in the intervention v 2.01 kg in the control group; p = 0.21). Conclusions: A simple and easily generalisable intervention at the workplace is effective to achieve long term smoking cessation. In a setting similar to ours, nine subjects would have to be treated for three months for one to achieve continuous abstinence for 12 months. PMID:12709522

Simultaneous multiplexed quantification of nicotine and its metabolites using surface enhanced Raman scattering.

PubMed

Alharbi, Omar; Xu, Yun; Goodacre, Royston

2014-10-07

The detection and quantification of xenobiotics and their metabolites in man is important for drug dosing, therapy and for substance abuse monitoring where longer-lived metabolic products from illicit materials can be assayed after the drug of abuse has been cleared from the system. Raman spectroscopy offers unique specificity for molecular characterization and this usually weak signal can be significantly enhanced using surface enhanced Raman scattering (SERS). We report here the novel development of SERS with chemometrics for the simultaneous analysis of the drug nicotine and its major xenometabolites cotinine and trans-3'-hydroxycotinine. Initial experiments optimized the SERS conditions and we found that when these three determinands were analysed individually that the maximum SERS signals were found at three different pH. These were pH 3 for nicotine and pH 10 and 11 for cotinine and trans-3'-hydroxycotinine, respectively. Tertiary mixtures containing nicotine, cotinine and trans-3'-hydroxycotinine were generated in the concentration range 10(-7)-10(-5) M and SERS spectra were collected at all three pH values. Chemometric analysis using kernel-partial least squares (K-PLS) and artificial neural networks (ANNs) were conducted and these models were validated using bootstrap resampling. All three analytes were accurately quantified with typical root mean squared error of prediction on the test set data being 5-9%; nicotine was most accurately predicted followed by cotinine and then trans-3'-hydroxycotinine. We believe that SERS is a powerful approach for the simultaneous analysis of multiple determinands without recourse to lengthy chromatography, as demonstrated here for the xenobiotic nicotine and its two major xenometabolites.

Decision-making deficits in patients diagnosed with disordered gambling using the Cambridge Gambling task: the effects of substance use disorder comorbidity.

PubMed

Zois, Evangelos; Kortlang, Noreen; Vollstädt-Klein, Sabine; Lemenager, Tagrid; Beutel, Martin; Mann, Karl; Fauth-Bühler, Mira

2014-07-01

Disordered gambling (DG) has often been associated with impaired decision-making abilities, suggesting a dysfunction in the ventromedial prefrontal cortex (vmPFC). To our knowledge, no previous study has accurately considered the effect of substance use disorder (SUD) comorbidity (including nicotine dependence) on decision-making impairments in DG. We employed the Cambridge Gambling Task (CGT) to assess a big cohort of patients diagnosed with DG (N = 80) against matched healthy controls (HCs) (N = 108). The cohort included DG patients with nicotine and alcohol dependence, alcohol dependence only and 12 "pure" nonsmokers with only DG diagnosis. Pure nonsmoking, nicotine dependent as well as alcoholic DGs with current nicotine dependence, demonstrated a decision making profile, characterized by poor decision-making abilities and failure to make right choices (rational), closely resembling that of patients with vmPFC damage. This suggests that DGs with and without SUD comorbidity are equally affected in that domain of decision making abilities. Additionally, gambling diagnosis combined with alcohol and nicotine dependence involves a group of gambling patients with a relatively riskier decision making profile, showing that these patients apart from making irrational decisions take also more risks. Our findings highlight the importance of accounting for SUD comorbidities with useful implications for future research and therapy. Limitations of the current investigation are discussed.

Decision-making deficits in patients diagnosed with disordered gambling using the Cambridge Gambling task: the effects of substance use disorder comorbidity

PubMed Central

Zois, Evangelos; Kortlang, Noreen; Vollstädt-Klein, Sabine; Lemenager, Tagrid; Beutel, Martin; Mann, Karl; Fauth-Bühler, Mira

2014-01-01

Background Disordered gambling (DG) has often been associated with impaired decision-making abilities, suggesting a dysfunction in the ventromedial prefrontal cortex (vmPFC). Aims To our knowledge, no previous study has accurately considered the effect of substance use disorder (SUD) comorbidity (including nicotine dependence) on decision-making impairments in DG. Methods and Materials We employed the Cambridge Gambling Task (CGT) to assess a big cohort of patients diagnosed with DG (N = 80) against matched healthy controls (HCs) (N = 108). The cohort included DG patients with nicotine and alcohol dependence, alcohol dependence only and 12 “pure” nonsmokers with only DG diagnosis. Results Pure nonsmoking, nicotine dependent as well as alcoholic DGs with current nicotine dependence, demonstrated a decision making profile, characterized by poor decision-making abilities and failure to make right choices (rational), closely resembling that of patients with vmPFC damage. Discussion This suggests that DGs with and without SUD comorbidity are equally affected in that domain of decision making abilities. Additionally, gambling diagnosis combined with alcohol and nicotine dependence involves a group of gambling patients with a relatively riskier decision making profile, showing that these patients apart from making irrational decisions take also more risks. Our findings highlight the importance of accounting for SUD comorbidities with useful implications for future research and therapy. Limitations of the current investigation are discussed. PMID:25161815

The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction.

PubMed

Selya, Arielle S; Dierker, Lisa; Rose, Jennifer S; Hedeker, Donald; Mermelstein, Robin J

2017-07-07

E-cigarettes (Electronic Nicotine Delivery Systems, or ENDS) are an increasingly popular tobacco product among youth. Some evidence suggests that e-cigarettes may be effective for harm reduction and smoking cessation, although these claims remain controversial. Little is known about how nicotine dependence may contribute to e-cigarettes' effectiveness in reducing or quitting conventional smoking. A cohort of young adults were surveyed over 4 years (approximately ages 19-23). Varying-coefficient models (VCMs) were used to examine the relationship between e-cigarette use and conventional smoking frequency, and how this relationship varies across users with different nicotine dependence levels. Lifetime, but not recent, e-cigarette use was associated with less frequent concurrent smoking of conventional cigarettes among those with high levels of nicotine dependence. However, nondependent e-cigarette users smoked conventional cigarettes slightly more frequently than those who had never used e-cigarettes. Nearly half of ever e-cigarette users reported using them to quit smoking at the last measurement wave. For those who used e-cigarettes in a cessation attempt, the frequency of e-cigarette use was not associated with reductions in future conventional smoking frequency. These findings offer possible support that e-cigarettes may act as a smoking reduction method among highly nicotine-dependent young adult cigarette smokers. However, the opposite was found in non-dependent smokers, suggesting that e-cigarette use should be discouraged among novice tobacco users. Additionally, although a substantial proportion of young adults used e-cigarettes to help them quit smoking, these self-initiated quit attempts with e-cigarettes were not associated with future smoking reduction or cessation. This study offers potential support for e-cigarettes as a smoking reduction tool among highly nicotine-dependent young adult conventional smokers, although the extent and nature of this remains unclear. The use of e-cigarettes as a quit aid was not associated with reductions in conventional smoking, consistent with most other quit aids in this sample except for nicotine replacement therapy, which was only effective for the most dependent smokers. Notably, these findings highlight the necessity of accounting for smokers' nicotine dependence levels when examining tobacco use patterns. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacological interventions for smoking cessation: an overview and network meta-analysis.

PubMed

Cahill, Kate; Stevens, Sarah; Perera, Rafael; Lancaster, Tim

2013-05-31

Smoking is the leading preventable cause of illness and premature death worldwide. Some medications have been proven to help people to quit, with three licensed for this purpose in Europe and the USA: nicotine replacement therapy (NRT), bupropion, and varenicline. Cytisine (a treatment pharmacologically similar to varenicline) is also licensed for use in Russia and some of the former socialist economy countries. Other therapies, including nortriptyline, have also been tested for effectiveness. How do NRT, bupropion and varenicline compare with placebo and with each other in achieving long-term abstinence (six months or longer)? How do the remaining treatments compare with placebo in achieving long-term abstinence? How do the risks of adverse and serious adverse events (SAEs) compare between the treatments, and are there instances where the harms may outweigh the benefits? The overview is restricted to Cochrane reviews, all of which include randomised trials. Participants are usually adult smokers, but we exclude reviews of smoking cessation for pregnant women and in particular disease groups or specific settings. We cover nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), nicotine receptor partial agonists (varenicline and cytisine), anxiolytics, selective type 1 cannabinoid receptor antagonists (rimonabant), clonidine, lobeline, dianicline, mecamylamine, Nicobrevin, opioid antagonists, nicotine vaccines, and silver acetate. Our outcome for benefit is continuous or prolonged abstinence at least six months from the start of treatment. Our outcome for harms is the incidence of serious adverse events associated with each of the treatments. We searched the Cochrane Database of Systematic Reviews (CDSR) in The Cochrane Library, for any reviews with 'smoking' in the title, abstract or keyword fields. The last search was conducted in November 2012. We assessed methodological quality using a revised version of the AMSTAR scale. For NRT, bupropion and varenicline we conducted network meta-analyses, comparing each with the others and with placebo for benefit, and varenicline and bupropion for risks of serious adverse events. We identified 12 treatment-specific reviews. The analyses covered 267 studies, involving 101,804 participants. Both NRT and bupropion were superior to placebo (odds ratios (OR) 1.84; 95% credible interval (CredI) 1.71 to 1.99, and 1.82; 95% CredI 1.60 to 2.06 respectively). Varenicline increased the odds of quitting compared with placebo (OR 2.88; 95% CredI 2.40 to 3.47). Head-to-head comparisons between bupropion and NRT showed equal efficacy (OR 0.99; 95% CredI 0.86 to 1.13). Varenicline was superior to single forms of NRT (OR 1.57; 95% CredI 1.29 to 1.91), and to bupropion (OR 1.59; 95% CredI 1.29 to 1.96). Varenicline was more effective than nicotine patch (OR 1.51; 95% CredI 1.22 to 1.87), than nicotine gum (OR 1.72; 95% CredI 1.38 to 2.13), and than 'other' NRT (inhaler, spray, tablets, lozenges; OR 1.42; 95% CredI 1.12 to 1.79), but was not more effective than combination NRT (OR 1.06; 95% CredI 0.75 to 1.48). Combination NRT also outperformed single formulations. The four categories of NRT performed similarly against each other, apart from 'other' NRT, which was marginally more effective than NRT gum (OR 1.21; 95% CredI 1.01 to 1.46). Cytisine (a nicotine receptor partial agonist) returned positive findings (risk ratio (RR) 3.98; 95% CI 2.01 to 7.87), without significant adverse events or SAEs. Across the 82 included and excluded bupropion trials, our estimate of six seizures in the bupropion arms versus none in the placebo arms was lower than the expected rate (1:1000), at about 1:1500. SAE meta-analysis of the bupropion studies demonstrated no excess of neuropsychiatric (RR 0.88; 95% CI 0.31 to 2.50) or cardiovascular events (RR 0.77; 95% CI 0.37 to 1.59). SAE meta-analysis of 14 varenicline trials found no difference between the varenicline and placebo arms (RR 1.06; 95% CI 0.72 to 1.55), and subgroup analyses detected no significant excess of neuropsychiatric events (RR 0.53; 95% CI 0.17 to 1.67), or of cardiac events (RR 1.26; 95% CI 0.62 to 2.56). Nortriptyline increased the chances of quitting (RR 2.03; 95% CI 1.48 to 2.78). Neither nortriptyline nor bupropion were shown to enhance the effect of NRT compared with NRT alone. Clonidine increased the chances of quitting (RR 1.63; 95% CI 1.22 to 2.18), but this was offset by a dose-dependent rise in adverse events. Mecamylamine in combination with NRT may increase the chances of quitting, but the current evidence is inconclusive. Other treatments failed to demonstrate a benefit compared with placebo. Nicotine vaccines are not yet licensed for use as an aid to smoking cessation or relapse prevention. Nicobrevin's UK license is now revoked, and the manufacturers of rimonabant, taranabant and dianicline are no longer supporting the development or testing of these treatments. NRT, bupropion, varenicline and cytisine have been shown to improve the chances of quitting. Combination NRT and varenicline are equally effective as quitting aids. Nortriptyline also improves the chances of quitting. On current evidence, none of the treatments appear to have an incidence of adverse events that would mitigate their use. Further research is warranted into the safety of varenicline and into cytisine's potential as an effective and affordable treatment, but not into the efficacy and safety of NRT.

Caregivers' and physicians' attitudes to rotigotine transdermal patch versus oral Parkinson's disease medication: an observational study.

PubMed

Sieb, Jörn Peter; Themann, Peter; Warnecke, Tobias; Lauterbach, Thomas; Berkels, Reinhard; Grieger, Frank; Lorenzl, Stefan

2015-05-01

To provide real-world data on caregiver and physician perceptions of the advantages and disadvantages of rotigotine transdermal patch (Neupro * ) versus oral Parkinson's Disease (PD) medication. Cross-sectional, non-interventional study in routine clinical practice in Germany (NCT01330290). Patients had PD with documented need for care, and had received rotigotine transdermal patch as add-on to oral PD treatment for ≥1 month. Caregivers/nurses and physicians assessed rotigotine transdermal patch versus oral PD medications using questionnaires. Specific questions regarding the possible benefits of transdermal application were asked and comprised questions on: swallowing dysfunction, nausea/vomiting, monitoring therapy, once daily application, application independently from meals, application to sleeping patients, caregiving efforts (caregivers only) and clinical aspects (physicians only). Each question was assessed on a 5 point scale ranging from -2 (major disadvantage) to 2 (major advantage) compared with oral treatment. Primary outcomes were mean total scores of all questions for caregivers/nurses and physicians who provided responses for ≥4 questions. As there are no validated tools to assess physician/caregiver preference in the PD setting, there is no reference against which the current findings can be compared; this study serves to pilot the questionnaires. Questionnaire responses from 128 caregivers/nurses and 41 physicians were documented for 147 patients. One hundred (68%) patients had a caregiving family member; 40 (27%) were cared for by a nurse. Mean PD duration was 8.2 (SD 6.3) years; 136 (93%) patients were taking levodopa. Mean total score of caregivers'/nurses' questionnaires was 1.32 (SD 0.67) and of physicians' questionnaires was 1.46 (0.32) indicating a perceived advantage of rotigotine transdermal patch over oral PD therapy. Mean scores for individual questions were in the range 1.03-1.54 for caregivers/nurses and 1.15-1.87 for physicians. When given a choice about rationale to prescribe, physicians cited pharmaceutical form (patch) in 139 (95%) cases and active agent (rotigotine) in 89 (61%) cases. Caregivers/nurses and physicians perceived advantages with rotigotine transdermal patch compared to an oral PD medication as add-on therapy in patients with PD; advantages were observed in aspects of medical treatment as well as in everyday situations of caregiving of PD patients.

Fast synaptic transmission mediated by α-bungarotoxin-sensitive nicotinic acetylcholine receptors in lamina X neurones of neonatal rat spinal cord

PubMed Central

Bradaïa, A; Trouslard, J

2002-01-01

Using patch clamp recordings on neonatal rat spinal cord slices, we have looked for the presence of α-bungarotoxin-sensitive nicotinic ACh receptors (nAChRs) on sympathetic preganglionic neurones (SPNs) surrounding the central canal of the spinal cord (lamina X) and examined whether they were implicated in a fast cholinergic synaptic transmission. SPNs were identified either by their morphology using biocytin in the recording electrode and/or by antidromic stimulation of the ventral rootlets. The selective α7-containing nAChR (α7*nAChR) agonist choline (10 mm) induced a fast, rapidly desensitizing inward current, which was fully blocked by α-bungarotoxin (α-BgT; 50 nm) and strychnine (1 μm), two antagonists of α7*nAChRs. The I-V relationship of the choline-induced current showed a strong inward-going rectification. Electrically evoked excitatory postsynaptic currents (eEPSCs) could be recorded. At -60 mV, eEPSCs peaked at -26.2 pA and decayed monoexponentially with a mean time constant of 8.5 ms. The current-voltage relationship for eEPSCs exhibited a strong inward rectification and a reversal potential close to 0 mV, compatible with a non-selective cationic current. The appearance of eEPSCs was entirely suppressed by the application of 100 μm ACh or nicotine. Choline (10 mm) and 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; 100 μm) both reduced the amplitude of eEPSCs, whereas cytisine (100 μm) had no effect. Strychnine (1 μm) and α-BgT (50 nm) both suppressed the eEPSCs. Blocking the P2X purinergic and 5-HT3 receptors had no effect on eEPSCs. DMPP induced four types of current, which differed in their onset and desensitization rate. The most frequently encountered responses were insensitive to the action of strychnine and α-BgT, and were reproduced by ACh and nicotine but not by cytisine. We conclude that SPNs of the lamina X express several classes of nAChRs and in particular α-BgT-sensitive nAChRs. This is the first demonstration in a mammalian spinal cord preparation of a fast cholinergic neurotransmission in which α-BgT-sensitive nicotinic receptors are involved. PMID:12411519

Clinical Application of Stem Cells in the Cardiovascular System

NASA Astrophysics Data System (ADS)

Stamm, Christof; Klose, Kristin; Choi, Yeong-Hoon

Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication of tissues and/or organs using scaffold material and viable cells - and "cell therapy" - the transplantation or manipulation of cells in diseased tissue in vivo. In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood vessels, heart valves, patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical applications of such vessels, valves and patches have been described, but information on systematic studies of the performance of such implants is not available, yet. Cell therapy for cardiovascular regeneration, however, has been performed in large series of patients, and numerous clinical studies have produced sometimes conflicting results. The purpose of this chapter is to summarize the clinical experience with cell therapy for diseases of the cardiovascular system, and to analyse possible factors that may influence its outcome.

The androgen-deficient aging male: current treatment options.

PubMed

Tenover, J Lisa

2003-01-01

All delivery forms of testosterone should be equally efficacious in treating the androgen-deficient aging male if adequate serum testosterone levels are obtained. The testosterone preparations available in North America include the oral undecanoate, injectable testosterone esters, the scrotal patch, the nonscrotal transdermal patch, and the transdermal gels. Selection of a specific testosterone preparation for replacement therapy depends on many factors, including the magnitude and pattern of serum testosterone levels produced, side effects of the particular formulation, reversibility if an adverse event should occur, convenience of use, cosmetic issues related to the preparation, and cost. In addition, potential adverse effects of testosterone therapy applicable to all forms of testosterone delivery, such as fluid retention, gynecomastia, polycythemia, worsening of sleep apnea, change in cardiovascular-disease risk, or alterations in prostate health, need to be considered both prior to therapy and during treatment monitoring.

Lidocaine patches reduce pain in trauma patients with rib fractures.

PubMed

Zink, Karen A; Mayberry, John C; Peck, Ellen G; Schreiber, Martin A

2011-04-01

Rib fracture pain is notoriously difficult to manage. The lidocaine patch is effective in other pain scenarios with an excellent safety profile. This study assesses the efficacy of lidocaine patches for treating rib fracture pain. A prospectively gathered cohort of patients with rib fracture was retrospectively analyzed for use of lidocaine patches. Patients treated with lidocaine patches were matched to control subjects treated without patches. Subjective pain reports and narcotic use before and after patch placement, or equivalent time points for control subjects, were gathered from the chart. All patients underwent long-term follow-up, including a McGill Pain Questionnaire (MPQ). Twenty-nine patients with lidocaine patches (LP) and 29 matched control subjects (C) were analyzed. During the 24 hours before patch placement, pain scores and narcotic use were similar (LP 5.3, C 4.6, P = 0.19 and LP 51, C 32 mg morphine, P = 0.17). In the 24 hours after patch placement, LP patients had a greater decrease in pain scores (LP 1.2, C 0.0, P = 0.01) with no change in narcotic use (LP -8.4, C 0.5-mg change in morphine, P = 0.25). At 60 days, LP patients had a lower MPQ pain score (LP 7.7, C 12.2, P < 0.01), although only one patient was still using a patch. There was no difference in time to return to baseline activity (LP 73, C 105 days, P = 0.16) and no adverse events. Lidocaine patches are a safe, effective adjunct for rib fracture pain. Lidocaine patches resulted in a sustained reduction in pain, outlasting the duration of therapy.

Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for research protocol standards definition and for public health authorities' regulation.

PubMed

Farsalinos, Konstantinos E; Romagna, Giorgio; Tsiapras, Dimitris; Kyrzopoulos, Stamatis; Voudris, Vassilis

2013-06-18

Although millions of people are using electronic cigarettes (ECs) and research on this topic has intensified in recent years, the pattern of EC use has not been systematically studied. Additionally, no comparative measure of exposure and nicotine delivery between EC and tobacco cigarette or nicotine replacement therapy (NRTs) has been established. This is important, especially in the context of the proposal for a new Tobacco Product Directive issued by the European Commission. A second generation EC device, consisting of a higher capacity battery and tank atomiser design compared to smaller cigarette-like batteries and cartomizers, and a 9 mg/mL nicotine-concentration liquid were used in this study. Eighty subjects were recruited; 45 experienced EC users and 35 smokers. EC users were video-recorded when using the device (ECIG group), while smokers were recorded when smoking (SM-S group) and when using the EC (SM-E group) in a randomized cross-over design. Puff, inhalation and exhalation duration were measured. Additionally, the amount of EC liquid consumed by experienced EC users was measured at 5 min (similar to the time needed to smoke one tobacco cigarette) and at 20 min (similar to the time needed for a nicotine inhaler to deliver 4 mg nicotine). Puff duration was significantly higher in ECIG (4.2 ± 0.7 s) compared to SM-S (2.1 ± 0.4 s) and SM-E (2.3 ± 0.5 s), while inhalation time was lower (1.3 ± 0.4, 2.1 ± 0.4 and 2.1 ± 0.4 respectively). No difference was observed in exhalation duration. EC users took 13 puffs and consumed 62 ± 16 mg liquid in 5 min; they took 43 puffs and consumed 219 ± 56 mg liquid in 20 min. Nicotine delivery was estimated at 0.46 ± 0.12 mg after 5 min and 1.63 ± 0.41 mg after 20 min of use. Therefore, 20.8 mg/mL and 23.8 mg/mL nicotine-containing liquids would deliver 1 mg of nicotine in 5 min and 4 mg nicotine in 20 min, respectively. Since the ISO method significantly underestimates nicotine delivery by tobacco cigarettes, it seems that liquids with even higher than 24 mg/mL nicotine concentration would be comparable to one tobacco cigarette. EC use topography is significantly different compared to smoking. Four-second puffs with 20-30 s interpuff interval should be used when assessing EC effects in laboratory experiments, provided that the equipment used does not get overheated. Based on the characteristics of the device used in this study, a 20 mg/mL nicotine concentration liquid would be needed in order to deliver nicotine at amounts similar to the maximum allowable content of one tobacco cigarette (as measured by the ISO 3308 method). The results of this study do not support the statement of the European Commission Tobacco Product Directive that liquids with nicotine concentration of 4 mg/mL are comparable to NRTs in the amount of nicotine delivered to the user.

Living cardiac patch: the elixir for cardiac regeneration.

PubMed

Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

2012-12-01

A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.

Optimal compliance for amblyopia therapy: occlusion with a translucent tape on the lens.

PubMed

Beneish, Raquel G; Polomeno, Robert C; Flanders, Michael E; Koenekoop, Robert K

2009-10-01

To demonstrate that optimal compliance to amblyopia therapy and a better visual outcome can be achieved by occluding the lens over the preferred eye with a translucent tape. Prospective study of amblyopic children. Eighty-four amblyopic children recruited from 2000 to 2006 at the Montreal Children's Vision Centre. A group of bilateral ametropes (mean age 3.8 years) were treated with glasses and occlusion of the sound eye with a translucent tape on the lens over the preferred eye, or an adhesive patch. The translucent tape reduced vision to hand motion at 0.3 m in the sound eye. Patients were divided into 2 groups depending on the treatment received. Group 1 (n = 36) was occluded with a translucent tape, and group 2 (n = 48) with a conventional adhesive patch, later replaced by the translucent tape. Twenty-five previously reported patients, treated with the conventional adhesive patch only, were used as controls (group 3). The mean amblyopic visual acuity was 20/100-2. Compliance was good in 36 patients (group 1), and was poor or deteriorated in 24/48 patients (group 2). Substituting the adhesive patch with a translucent tape permitted uninterrupted and prolonged occlusion, with a successful visual outcome. The amblyopic eye achieved a significantly better final vision (20/30+2; groups 1+2) than the controls (20/40+1; group 3) (p = 0.04). Sixty-four (76.19%) patients achieved >or=20/30. The translucent tape optimizes compliance and yields better vision by lengthening the duration of occlusion therapy and reducing the number of treatment failures due to noncompliance.

The Efficacy and Tolerability of the Clonidine Transdermal Patch in the Treatment for Children with Tic Disorders: A Prospective, Open, Single-Group, Self-Controlled Study.

PubMed

Song, Pan-Pan; Jiang, Li; Li, Xiu-Juan; Hong, Si-Qi; Li, Shuang-Zi; Hu, Yue

2017-01-01

To evaluate the efficacy and tolerability of a clonidine transdermal patch in the treatment of children with tic disorders (TD) and to establish a predictive model for patients. Forty-one patients who met the inclusion criteria entered into 12 weeks of prospective, open, single-group, self-controlled treatment with a clonidine transdermal patch. The Yale Global Tic Severity Scale (YGTSS) was employed before therapy (baseline) and at 4, 8, and 12 weeks after therapy. (1) The total effect rates of treatment with a clonidine transdermal patch were 29.27, 53.66, and 63.41% at 4, 8, and 12 weeks, respectively. Compared with the baseline, the differences were significant at three different observation periods. (2) Compared to the level of 25% reduction, there were significant decreases in the score-reducing rate of motor tic and total tic severities at 12 weeks. (3) If the disease course was ≤24 months and the motor tic score was <16 at the baseline, there was an effective rate of 100% for treatment with the clonidine transdermal patch. If the disease course was ≤24 months and the motor tic score was >16, there was an effective rate of 57.1%. If the disease course was >24 months and the clinical classification was chronic TD, there was an effective rate of 62.5%. If the disease course was >24 months and the clinical classification was Tourette's syndrome, 90% of the patients were invalid. (4) The main adverse events were rash, slight dizziness, and headache. (1) When patients were pretreated with a D2-dopamine receptor antagonist that was ineffective or not tolerated well, switching to a clonidine transdermal patch treatment was effective and safe. (2) A clonidine transdermal patch could be a first-line medication for mild and moderate TD cases that are characterized by motor tics.

Options for treating postherpetic neuralgia in the medically complicated patient

PubMed Central

Bruckenthal, Patricia; Barkin, Robert L

2013-01-01

Patients with postherpetic neuralgia (PHN) are often of advanced age or immunocompromised and likely to have ≥1 comorbid medical condition for which they receive ≥1 medication (polypharmacy). Comorbidities affecting renal or hepatic function can alter pharmacokinetics, thereby impacting the efficacy or tolerability of PHN analgesic therapies. Cardiovascular, cerebrovascular, or psychiatric comorbidities may increase patient vulnerability to potential adverse events associated with some PHN analgesic therapies. Because PHN is a localized condition, localized therapy with a topical analgesic (lidocaine patch 5% and capsaicin 8% patch or cream) may provide adequate efficacy while mitigating the risk of systemic adverse events compared with oral analgesics (eg, tricyclic antidepressants, anticonvulsants, opioids). However, combined therapy with a topical and an oral analgesic or with >1 oral analgesic may be needed for optimal pain management in some patients. This review summarizes how comorbidities and concomitant medications should be taken into account when selecting among available pharmacotherapies for PHN and provides recommendations for the selection of therapies that will provide analgesia while minimizing the risk of adverse events. PMID:23990726

A review of the effects of very low nicotine content cigarettes on behavioral and cognitive performance.

PubMed

Keith, Diana R; Kurti, Allison N; Davis, Danielle R; Zvorsky, Ivori A; Higgins, Stephen T

2017-11-01

The present systematic review examines whether very low nicotine content (VLNC) cigarettes ameliorate withdrawal-induced impairments in behavioral/cognitive performance. PubMed, PsycInfo, and Web of Science were searched for performance effects of VLNC cigarettes. For inclusion, reports had to be in English, published in a peer-reviewed journal through June 2017, examine VLNC cigarettes (<0.2mg nicotine yield), include ≥2hour smoking abstinence or reduced nicotine exposure, and examine performance. 19 of 1243 articles reviewed met inclusion criteria. Poorer performance after smoking VLNC versus normal nicotine content (NNC) cigarettes was observed across 7 of 10 domains, including reaction time (8/11), short-term memory (3/10), sustained attention (4/6), inhibitory control (1/4), long-term memory (3/3 studies), and response variability (2/2). In two studies, combining VLNC smoking with nicotine replacement therapy (NRT) resulted in performance that was comparable to performance after NNC smoking. VLNC versus NNC differences were not discerned in motor control/functioning (0/2), visuospatial processing (0/2), learning (0/1), or verbal fluency (0/1). Eleven of nineteen (58%) studies were rated of Good or Excellent quality. Overall, VLNC cigarettes may not fully ameliorate withdrawal-induced disruptions in performance, although this varies by domain, with the strongest evidence for reaction time. Importantly, combining VLNC cigarettes with NRT appears to ameliorate withdrawal that is not reduced by VLNC cigarettes alone. As only 19 studies were identified, many domains are under-investigated. A more thorough evaluation of the extent to which VLNC cigarettes affect withdrawal-impaired performance may be warranted. Copyright © 2017. Published by Elsevier Inc.

[Efficacy and security of electronic cigarette for tobacco harm reduction: Systematic review and meta-analysis].

PubMed

Vanderkam, Paul; Boussageon, Rémy; Underner, Michel; Langbourg, Nicolas; Brabant, Yann; Binder, Philippe; Freche, Bernard; Jaafari, Nematollah

2016-11-01

Smoking is the first cause of preventable death in France and in the world. Without help, it was shown that 80 % of smokers who try to quit smoking relapse after one month with a low long-term success rate. Smoking reduction can concern smokers who did not want to quit or failed in their attempt to weaning. The final aim is to increase attractiveness of drug therapies by developing new products, such as electronic cigarettes, that can compete cigarette without reproducing its harmful effects. Assess the capacity of electronic cigarettes to reduce or stop tobacco use among regular smokers. Consultations MEDLINE and COCHRANE databases. e-cigarette; electronic cigarettes; ENDD (electronic nicotine delivery system); ENDS (electronic nicotine delivery device); vaping were used. Randomized controlled trials (RCTs) comparing the electronic cigarette with nicotine versus placebo device. Two randomized controlled trials were included in the quantitative analysis. The nicotine electronic cigarette users have tobacco consumption significantly decreased compared to the placebo group (RR: 1.30, 95 % CI [1.02 to 1.66]) at 6 months. Smoking cessation rate at 3 months was greater with the electronic cigarette contains nicotine (RR: 2.55, 95 % CI [1.31 to 4.98]). The small number of RCTs included does not allow definitive conclusions about the effectiveness of electronic cigarettes, especially in the medium to long term. The use of electronic cigarette with nicotine decreases tobacco consumption among regular smokers. Further studies are needed to specify electronic cigarettes safety profile and its ability to cause a reduction in consumption and a long-term cessation in smokers. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Discontinuation of nicotine replacement therapy among smoking-cessation attempters.

PubMed

Burns, Emily K; Levinson, Arnold H

2008-03-01

Nicotine replacement therapy (NRT) doubles successful quitting, but more than half of NRT users do not comply with optimal treatment regimens. From the 2005 Colorado state tobacco survey, quit attempters who utilized NRT (N=366) were analyzed in spring 2007. Descriptive and regression analyses were used to examine reasons for discontinuing NRT, length of time on NRT, and quit intentions. The reasons for discontinuing NRT were resuming smoking (34%), side effects (17%), NRT not helping with quitting (14%), quitting smoking (10%), and cost (5%). Poverty, age, and non-Latino minority status were associated with reasons for discontinuation other than quitting smoking. Having side effects was associated with a short duration of NRT use and 95% lower odds of intending to quit in the next month. In the first population-level study examining reasons for discontinuing NRT, general-population smokers who initiate NRT use when attempting to quit are highly likely to discontinue NRT prematurely. Age and culturally-appropriate medication management interventions may increase NRT compliance and improve cessation outcomes.

Sex differences in availability of β2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers

PubMed Central

Cosgrove, Kelly P.; Esterlis, Irina; McKee, Sherry A.; Bois, Frederic; Seibyl, John P.; Mazure, Carolyn M.; Krishnan-Sarin, Suchitra; Staley, Julie K.; Picciotto, Marina R.; O’Malley, Stephanie S.

2012-01-01

Context Sex differences exist in the reinforcing effects of nicotine, smoking cessation rates, and in response to nicotine replacement therapies. Sex differences in availability of nicotinic acetylcholine receptors containing the β2 subunit (β2*-nAChRs) may underlie differential nicotine and tobacco smoking effects and related behaviors in women and men. Objective To examine β2*-nAChR availability between male and female smokers and nonsmokers. To determine relationships between β2*-nAChR availability and tobacco smoking characteristics and female sex steroid hormones. Design Male (n=26) and female (n=28) tobacco smokers participated in one [123I]5-IA-85380 ([123I]5-IA) single photon emission computed tomography (SPECT) scan at 7–9 days of abstinence. Age-matched male (n=26) and female (n=30) nonsmokers participated in a single [123I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. Setting Academic Imaging Center Participants Tobacco smokers (n=54) and age- and sex-matched nonsmokers (n=56). Main Outcome Measure [123I]5-IA SPECT images were converted to equilibrium distribution volumes and analyzed using regions-of-interest. Results β2*-nAChR availability was significantly higher in male smokers compared to male nonsmokers in striatum, cortex and cerebellum, but female smokers did not have higher β2*-nAChR availability than female nonsmokers in any region. In women, β2*-nAChR availability in the cortex and cerebellum was negatively and significantly correlated with progesterone level on the day of the scan. In female smokers, on the day of the scan, progesterone levels were positively and significantly correlated with depressive symptoms, craving for a cigarette, and nicotine withdrawal. Conclusions The regulatory effects of nicotine in the brain, i.e., tobacco-smoking induced upregulation of β2*-nAChRs, appear to be distinctly different between men and women, and female sex hormones likely play a role in this regulation. These findings suggest an underlying neurochemical mechanism for the reported behavioral sex differences. In order to treat female smokers more effectively, it is critical that non-nicotinic mediated medications are explored. PMID:22474108

[The evaluation of motivation and addiction to nicotine in smokers attempting to quit smoking].

PubMed

Szwed, Angelika

2012-01-01

Smoking cigarettes is a factor which increases the risk of developing many diseases, especially of the circulatory and respiratory systems. Quitting smoking is an essential element of prophylaxis and therapy. The effectiveness of treating the syndrome of nicotine addiction mostly depends on the motivation to give up the habit. The study aimed at evaluating the motivation and the strength of nicotine addiction as well as the factor which motivates smokers for giving up the habit. Sixty-two smokers were included in the study. There were 31 males and 31 females. The mean age of the study subjects was 47.26 ± 14.45. The study was performed using the author-made survey (including for example questions regarding sociodemographic data and motives for quitting smoking), Fagerström Tolerance Questionnaire (for analyzing degree of nicotine addiction) and Schneider Motivation Test (to evaluate the degree of motivation to quit smoking). Thirty-seven subjects out of the total number of 62 were the least addicted to nicotine. They were highly motivated to give up the habit of smoking. The mean value of motivation depended on the level of education of the subjects and was 7.71-8.50 scores. Health concerns were the reasons to make a decision to quit smoking for the majority of the subjects. Health concern is the most common reason for giving up the habit of smoking. The relationship between the motivation to quit smoking and the sex of the subjects was not observed.

Nicotine replacement prescribing trends in a large psychiatric hospital, before and after implementation of a hospital-wide smoking ban.

PubMed

Scharf, Deborah; Fabian, Tanya; Fichter-DeSando, Cecilia; Douaihy, Antoine

2011-06-01

We examined prescribing patterns for nicotine replacement therapies (NRTs) in a large psychiatric hospital, before and after the implementation of a smoking ban. We extracted 5 years of NRT utilization data from hospital pharmacy records. The ban went into effect on January 1, 2007. Data reflect NRT prescriptions from 2 years before and 3 years after the ban, and N = 30,908 total inpatient hospital admissions. The monthly rate of total NRT prescriptions increased after the ban from M = 254.25 (SD = 126.60) doses per month to M = 4,467.52 (SD = 1,785.87) doses per month (>1,700% increase, p < .0001). After the smoking ban, clinicians prescribed higher doses of transdermal (but not oral) NRT (Tukey, p < .0001). Comparisons of NRT prescribing across hospital units tentatively suggested that patients being treated on the substance use disorders unit were prescribed more doses of NRT, as well as higher doses of NRT compared with patients on other units. Analysis of trends over time showed no apparent downward trend for NRT usage during the 3 years following the smoking ban, suggesting that clinicians continued to treat nicotine dependence after smoking was restricted. Clinicians are more likely to identify and treat symptoms of nicotine withdrawal when smoking is restricted. Hospitals should consider monitoring prescriptions for NRT as part of their ongoing quality assurance practices so that patients receive aggressive treatment of nicotine withdrawal symptoms--an essential component of high-quality patient care.

High-dose transdermal nicotine replacement for tobacco cessation.

PubMed

Brokowski, Laurie; Chen, Jiahui; Tanner, Sara

2014-04-15

The safety and efficacy of high-dose transdermal nicotine-replacement therapy (NRT) for the treatment of tobacco-use cessation were reviewed. Transdermal nicotine doses of 7, 14, and 21 mg daily are approved by the Food and Drug Administration for use in tobacco cessation. However, studies have suggested that these doses are more adequate for people who smoke fewer than 20 cigarettes per day. A literature search was conducted to identify English-language studies that evaluated the use of transdermal nicotine doses of ≥42 mg daily. A total of 11 articles were identified, representing 10 separate trials. In terms of safety, the majority of the trials had no reports of serious adverse events related to transdermal NRT at doses of ≥42 mg daily. A dose-response relationship with adverse events occurred in most trials. In terms of efficacy, a numerically higher abstinence rate was achieved with high-dose transdermal NRT in all trials but 1. However, none of the studies showed significant differences in final abstinence rates at follow-up. Some reasons why statistical significance was not achieved in these trials may be related to the limitations of these trials, such as their small samples and the lack of a power calculation. A more robust trial is needed to support higher nicotine transdermal doses in tobacco cessation and to help elucidate which patient population would be most suitable for their use. The safety and efficacy of high-dose transdermal NRT for tobacco cessation have not been established in the medical literature.

Epidermal electronics for electromyography: An application to swallowing therapy.

PubMed

Constantinescu, Gabriela; Jeong, Jae-Woong; Li, Xinda; Scott, Dylan K; Jang, Kyung-In; Chung, Hyun-Joong; Rogers, John A; Rieger, Jana

2016-08-01

Head and neck cancer treatment alters the anatomy and physiology of patients. Resulting swallowing difficulties can lead to serious health concerns. Surface electromyography (sEMG) is used as an adjuvant to swallowing therapy exercises. sEMG signal collected from the area under the chin provides visual biofeedback from muscle contractions and is used to help patients perform exercises correctly. However, conventional sEMG adhesive pads are relatively thick and difficult to effectively adhere to a patient's altered chin anatomy, potentially leading to poor signal acquisition in this population. Here, the emerging technology of epidermal electronics is introduced, where ultra-thin geometry allows for close contouring of the chin. The two objectives of this study were to (1) assess the potential of epidermal electronics technology for use with swallowing therapy and (2) assess the significance of the reference electrode placement. This study showed comparative signals between the new epidermal sEMG patch and the conventional adhesive patches used by clinicians. Furthermore, an integrated reference yielded optimal signal for clinical use; this configuration was more robust to head movements than when an external reference was used. Improvements for future iterations of epidermal sEMG patches specific to day-to-day clinical use are suggested. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium.

PubMed

Li, Jun; Zhu, Kai; Yang, Shan; Wang, Yulin; Guo, Changfa; Yin, Kanhua; Wang, Chunsheng; Lai, Hao

2015-05-01

Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury. © 2015 by the Society for Experimental Biology and Medicine.

Therapeutic vaccines for substance dependence.

PubMed

Kosten, Thomas R; Biegel, Diane

2002-10-01

Several immunotherapies are under development for nicotine, cocaine and phencyclidine and a cocaine vaccine has started human trials. These therapies promise a new approach to diseases that have had limited treatment success and tremendous morbidity. Both the cocaine and nicotine addiction immunotherapies have reduced 'relapse' to drug use in animal model systems. To date, the active cocaine vaccine has few side effects and induces considerable antibody titers after active immunization in humans. Studies with the monoclonal phencyclidine immunotherapy provide intriguing evidence of sustained protection for months after single-dose administration. Other immunotherapy may include treatment of drug overdose, prevention of brain or cardiac toxicity and protection of a fetus during pregnancy in a drug abuser.

Understanding Food Allergies: How to Prevent Peanut Allergy and More

MedlinePlus

... slowly increasing amounts of the allergy-causing food. One recent study tried this approach for peanut-allergic preschool children. Almost 80% of ... to improve the safety and effectiveness of the approach. The therapy is also ... this type of therapy. One ongoing study is investigating using a skin patch ...

[Smoking cessation support among persons in situation of precariousness].

PubMed

Deschenau, A; Le Faou, A-L; Touzeau, D

2017-01-01

Underprivileged people smoke more frequently, present with a more severe smoking profile and stop less often than wealthier smokers. They can have difficulties to afford smoking cessation treatments as the French medical insurance coverage system requires smokers to pay it in advance with a later reimbursement. The objective of this study was to compare the characteristics, treatment plans and cessation rates of smokers from disadvantaged population in comparison with smokers in wealthier condition. Study population concerned smokers received for a first visit in the smoking cessation service at Georges-Pompidou European Hospital (Paris, France) in 2013. The EPICES score was used to define precariousness. The national file of smoking cessation consultation (CDT) was completed and the nicotine replacement therapy (NRT) prescriptions were detailed, as treatment could be given for free to precarious smokers on a weekly basis. Data were registered in CDTnet, the French national database of smoking cessation services. Precarious smokers (36.8%) presented with a more severe smoking profile and suffered more often from psychiatric disorders than wealthier smokers. They benefited most often from a combination NRT with patch and oral forms. The followed-up precarious smokers attended a greater number of consultations (4.7 against 3.4) and, if they were less often abstainers (22.2% against 41.3%), they were able to significantly reduce their consumption. Precarious smokers adhere to structured care with aid for access to TSN with a positive consequent impact on consumption. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The influence of smoking and cessation on the human reproductive hormonal balance.

PubMed

Jandíková, H; Dušková, M; Stárka, L

2017-09-26

Smoking is the most widespread substance dependence in the world. Nicotine and some other components of the cigarette smoke cause various endocrine imbalances, and have negative effects on pituitary, thyroid, adrenal, testicular and ovarian functions. Here, we examined studies that describe the influence of smoking and smoking cessation on the male and female reproductive systems. We also focused on studies providing an account of differences in cessation success rates between men and women. In men, the most common effects associated with smoking are erectile dysfunction and decreasing spermiogram quality. Several groups have studied the effects of cigarette smoking on testosterone levels in men. However, the results have been conflicting. In women, nicotine has an anti-estrogen effect and increases the ratio of androgens to estrogens throughout life. Beside nicotine, other cigarette toxins also cause dysregulation of reproductive and hormonal system, and essentially influence the probability of a successful pregnancy not only in cases of assisted reproduction but also in healthy women. Tobacco addiction is one of the forms of addiction that are generally thought to be different for men and for women. Women are less successful than men in quitting smoking, and nicotine replacement therapy is less effective in female smokers. We also summarize recent studies that have indicated possible reasons.

Characterization of Ryanodine Receptor Type 1 Single Channel Activity Using “On-Nucleus” Patch Clamp

PubMed Central

Wagner, Larry E.; Groom, Linda A.; Dirksen, Robert T.; Yule, David I.

2014-01-01

In this study, we provide the first description of the biophysical and pharmacological properties of ryanodine receptor type 1 (RyR1) expressed in a native membrane using the on-nucleus configuration of the patch clamp technique. A stable cell line expressing rabbit RyR1 was established (HEK-RyR1) using the FLP-in 293 cell system. In contrast to untransfected cells, RyR1 expression was readily demonstrated by immunoblotting and immunocytochemistry in HEK-RyR1 cells. In addition, the RyR1 agonists 4-CMC and caffeine activated Ca2+ release that was inhibited by high concentrations of ryanodine. On nucleus patch clamp was performed in nuclei prepared from HEK-RyR1 cells. Raising the [Ca2+] in the patch pipette resulted in the appearance of a large conductance cation channel with well resolved kinetics and the absence of prominent subconductance states. Current versus voltage relationships were ohmic and revealed a chord conductance of ~750 pS or 450 pS in symmetrical 250 mM KCl or CsCl, respectively. The channel activity was markedly enhanced by caffeine and exposure to ryanodine resulted in the appearance of a subconductance state with a conductance ~40 % of the full channel opening with a Po near unity. In total, these properties are entirely consistent with RyR1 channel activity. Exposure of RyR1 channels to cyclic ADP ribose (cADPr), nicotinic acid adenine dinucleotide phosphate (NAADP) or dantrolene did not alter the single channel activity stimulated by Ca2+, and thus, it is unlikely these molecules directly modulate RyR1 channel activity. In summary, we describe an experimental platform to monitor the single channel properties of RyR channels. We envision that this system will be influential in characterizing disease-associated RyR mutations and the molecular determinants of RyR channel modulation. PMID:24972488

Novel nitric oxide producing probiotic wound healing patch: preparation and in vivo analysis in a New Zealand white rabbit model of ischaemic and infected wounds.

PubMed

Jones, Mitchell; Ganopolsky, Jorge G; Labbé, Alain; Gilardino, Mirko; Wahl, Christopher; Martoni, Christopher; Prakash, Satya

2012-06-01

The treatment of chronic wounds poses a significant challenge for clinicians and patients alike. Here we report design and preclinical efficacy of a novel nitric oxide gas (gNO)-producing probiotic patch for wound healing. Specifically, a wound healing patch using lactic acid bacteria in an adhesive gas permeable membrane has been designed and investigated for treating ischaemic and infected full-thickness dermal wounds in a New Zealand white rabbit model for ischaemic wound healing. Kaplan-Meier survival curves showed increased wound closure with gNO-producing patch-treated wounds over 21 days of therapy (log-rank P = 0·0225 and Wilcoxon P = 0·0113). Cox proportional hazard regression showed that gNO-producing patch-treated wounds were 2·52 times more likely to close compared with control patches (hazard P = 0·0375, score P = 0·032 and likelihood ratio P = 0·0355), and histological analysis showed improved wound healing in gNO-producing patch-treated animals. This study may provide an effective, safe and less costly alternative for treating chronic wounds. © 2012 The Authors. © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Cardio-supportive devices (VRD & DCC device) and patches for advanced heart failure: A review, summary of state of the art and future directions.

PubMed

Naveed, Muhammad; Han, Lei; Khan, Ghulam Jilany; Yasmeen, Sufia; Mikrani, Reyaj; Abbas, Muhammad; Cunyu, Li; Xiaohui, Zhou

2018-06-01

Congestive heart failure (CHF) is a complicated pathophysiological syndrome, leading cause of hospitalization as well as mortalities in developed countries wherein an irregular function of the heart leads to the insufficient blood supply to the body organs. It is an accumulative slackening of various complications including myocardial infarction (MI), coronary heart disease (CAD), hypertension, valvular heart disease (VHD) and cardiomyopathy; its hallmarks include hypertrophy, increased interstitial fibrosis and loss of myocytes. The etiology of CHF is very complex and despite the rapid advancement in pharmacological and device-based interventional therapies still, a single therapy may not be sufficient to meet the demand for coping with the diseases. Total artificial hearts (TAH) and ventricular assist devices (VADs) have been widely used clinically to assist patients with severe HF. Unfortunately, direct contact between the patient's blood and device leads to thromboembolic events, and then coagulatory factors, as well as, infection contribute significantly to complicate the situation. There is no effective treatment of HF except cardiac transplantation, however, genetic variations, tissue mismatch; differences in certain immune response and socioeconomic crisis are an important concern with cardiac transplantation suggesting an alternate bridge to transplant (BTT) or destination therapies (DT). For these reasons, researchers have turned to mechanically driven compression devices, ventricular restraint devices (VRD) and heart patches. The ASD is a combination of all operational patches and cardiac support devices (CSD) by delivering biological agents and can restrain or compress the heart. Present study summarizes the accessible peer-reviewed literature focusing on the mechanism of Direct Cardiac Compression (DCC) devices, VRD and patches and their acquaintance to optimize the therapeutic efficacy in a synergistic way. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Weighted optimization of irradiance for photodynamic therapy of port wine stains

NASA Astrophysics Data System (ADS)

He, Linhuan; Zhou, Ya; Hu, Xiaoming

2016-10-01

Planning of irradiance distribution (PID) is one of the foremost factors for on-demand treatment of port wine stains (PWS) with photodynamic therapy (PDT). A weighted optimization method for PID was proposed according to the grading of PWS with a three dimensional digital illumination instrument. Firstly, the point clouds of lesions were filtered to remove the error or redundant points, the triangulation was carried out and the lesion was divided into small triangular patches. Secondly, the parameters such as area, normal vector and orthocenter for optimization of each triangular patch were calculated, and the weighted coefficients were determined by the erythema indexes and areas of patches. Then, the optimization initial point was calculated based on the normal vectors and orthocenters to optimize the light direction. In the end, the irradiation can be optimized according to cosine values of irradiance angles and weighted coefficients. Comparing the irradiance distribution before and after optimization, the proposed weighted optimization method can make the irradiance distribution match better with the characteristics of lesions, and has the potential to improve the therapeutic efficacy.

Expectancies for cigarettes, e-cigarettes, and nicotine replacement therapies among e-cigarette users (aka vapers).

PubMed

Harrell, Paul T; Marquinez, Nicole S; Correa, John B; Meltzer, Lauren R; Unrod, Marina; Sutton, Steven K; Simmons, Vani N; Brandon, Thomas H

2015-02-01

Use of e-cigarettes has been increasing exponentially, with the primary motivation reported as smoking cessation. To understand why smokers choose e-cigarettes as an alternative to cigarettes, as well as to US Food and Drug Administration (FDA)--approved nicotine replacement therapies (NRT), we compared outcome expectancies (beliefs about the results of drug use) for the three nicotine delivery systems among vapers, i.e., e-cigarette users, who were former smokers. Vapers (N = 1,434) completed an online survey assessing 14 expectancy domains as well as perceived cost and convenience. We focused on comparisons between e-cigarettes and cigarettes to determine the attraction of e-cigarettes as a smoking alternative and between e-cigarettes and NRT to determine perceived advantages of e-cigarettes over FDA-approved pharmacotherapy. Participants believed that e-cigarettes, in comparison to conventional cigarettes, had fewer health risks; caused less craving, withdrawal, addiction, and negative physical feelings; tasted better; and were more satisfying. In contrast, conventional cigarettes were perceived as better than e-cigarettes for reducing negative affect, controlling weight, providing stimulation, and reducing stress. E-cigarettes, compared to NRT, were perceived to be less risky, cost less, cause fewer negative physical feelings, taste better, provide more satisfaction, and be better at reducing craving, negative affect, and stress. Moderator analyses indicated history with ad libitum forms of NRT was associated with less positive NRT expectancies. The degree to which expectancies for e-cigarettes differed from expectancies for either tobacco cigarettes or NRT offers insight into the motivation of e-cigarette users and provides guidance for public health and clinical interventions to encourage smoking-related behavior change. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Inhibition of telomerase recruitment and cancer cell death.

PubMed

Nakashima, Mai; Nandakumar, Jayakrishnan; Sullivan, Kelly D; Espinosa, Joaquín M; Cech, Thomas R

2013-11-15

Continued proliferation of human cells requires maintenance of telomere length, usually accomplished by telomerase. Telomerase is recruited to chromosome ends by interaction with a patch of amino acids (the TEL patch, for TPP1 glutamate (E) and leucine (L)-rich patch) on the surface of telomere protein TPP1. In previous studies, interruption of this interaction by mutation prevented telomere extension in HeLa cells, but the cell culture continued to grow. We now show that the telomerase inhibitor BIBR1532 acts together with TEL patch mutations to inhibit the growth of HeLa cell lines and that apoptosis is a prominent mechanism of death of these cells. Survivor cells take over the population beginning around 40 days in culture. These cells no longer express the TEL patch mutant TPP1, apparently because of silencing of the expression cassette, a survival mechanism that would not be available to cancer cells. These results provide hope that inhibiting the binding of telomerase to the TEL patch of TPP1, perhaps together with a modest inhibition of the telomerase enzyme, could comprise an effective anticancer therapy for the ∼90% of human tumors that are telomerase-positive.

Acceptability of electronic cigarettes as an option to replace tobacco smoking for alcoholics admitted to hospital for detoxification.

PubMed

Truman, Penelope; Gilmour, Moira; Robinson, Geoffrey

2018-02-23

A feasibility/acceptability trial was undertaken at Ward 5, Kenepuru Hospital, Porirua, to ascertain whether electronic cigarettes (e-cigarettes) were a useful option to replace or reduce smoking in the detoxification ward. Two groups of patients were studied. Tobacco use and dependency data were collected for each. The first group was surveyed on the usefulness of standard nicotine replacement therapy (NRT). The second group were offered e-cigarettes with the option of standard NRT as well. All were asked to record their use of cigarettes, e-cigarettes and NRT during their stay on the ward, and to comment on their experiences. Outcomes monitored were self-reported use of NRT and of tobacco. Informal impressions of the nursing staff were also collected, where offered. For the e-cigarette group, a blood sample was taken on day 3 or 4 of their stay in hospital for nicotine/cotinine analysis, to confirm nicotine intake status. E-cigarettes were well tolerated as a form of nicotine replacement, eliciting positive comments, though they were not effective for all. The average reduction in median cigarettes per day was very similar between the group given standard NRT and the e-cigarette group, at 80% and 86% respectively. There were no adverse effects reported. The study showed that e-cigarettes were an acceptable form of nicotine replacement for these alcohol-dependent patients during their time in the ward. For heavily tobacco-dependent smokers, e-cigarettes may provide a useful aid to patient management within a hospital setting.

Conctact dermatitis: some important topics.

PubMed

Pigatto, P D

2015-11-01

Allergic contact dermatitis (ACD) is a type IV delayed hypersensitivity reaction. The gold standard for diagnosis is patch testing. The prevalence of positive patch tests in referred patients with suspected ACD ranges from 27 to 95.6%. The relationship between ACD and atopic dermatitis (AD) is complicated with conflicting reports of prevalence in the literature; however, in a patient with dermatitis not responding to traditional therapies, or with new areas of involvement, ACD should be considered as part of the work-up.

Perforated gastric ulcer--reappraisal of surgical options.

PubMed

Madiba, T E; Nair, R; Mulaudzi, T V; Thomson, S R

2005-08-01

The available operative procedures for perforated gastric ulcer are gastrectomy, ulcer excision and omental patch closure. This study analysed the outcome of these operative options in a single institution. Seventy-two patients (mean age 43 years, 62 males) with perforated gastric ulcers were managed by laparotomy. There were 34 lesser curve (incisural) and 38 antral ulcers. Partial gastrectomy was performed in 27 patients, ulcer excision in 27 and simple patch closure in 18. Two ulcers were malignant. The mortality rate was 18% (26% for gastrectomy, 19% for ulcer excision and 5% for patch closure). Shock on admission (p = 0.006) and Candida (p = 0.020) in the histological specimen were predictive of poor outcome. Hospital stay was similar in the 3 groups. Omental patch closure and ulcer excision are as effective as gastrectomy in the management of perforated gastric ulcer and merit consideration as first-line therapy in technically applicable cases.

Distress, race/ethnicity and smoking cessation in treatment-seekers: implications for disparity elimination.

PubMed

Webb Hooper, Monica; Kolar, Stephanie K

2015-09-01

Distress is a modifiable risk factor for smoking maintenance. This study aimed to assess racial/ethnic differences in distress pre- and post-cognitive-behavioral therapy (CBT) for smoking cessation, and relations with abstinence. Analyses of variance and logistic regressions were conducted. University-based smoking cessation laboratory in South Florida, USA. The sample comprised 234 treatment-seekers recruited from the community (18% white, 60% African American and 22% Hispanic). All participants received eight sessions of group CBT plus 8 weeks of transdermal nicotine patches (TNP). Demographics and smoking history [baseline], perceived stress and depressive symptoms [baseline and end of therapy (EOT)], carbon monoxide-verified 7-day point prevalence abstinence (p.p.a.) at EOT, 3 months post-CBT (primary outcome) and 6 months (self-report). Compared with whites, African Americans reported greater baseline perceived stress (P = 0.03) and depressive symptoms (P = 0.06); no EOT differences were found. African Americans (P < 0.001) and Hispanics (P < 0.01) reported greater perceived stress reduction, and African Americans reported greater reductions in depressive symptoms (P < 0.01). EOT-perceived stress (adjusted odds ratio (AOR) = 0.93 (0.89-0.98)) and depressive symptoms [AOR = 0.96 (0.93-0.99)] were associated inversely with 7-day p.p.a. at 3 months. Reductions in perceived stress [AOR = 0.93 (0.89-0.98)] and depressive symptoms at the EOT [AOR = 0.96 (0.93-0.99)] were associated with cessation, such that reduced distress increased the odds of abstinence. The interactions between race/ethnicity and distress on 7-day p.p.a. were not significant at any assessment point. Among smokers in Florida, USA, racial/ethnic differences in distress before starting cognitive-behavioral therapy for smoking cessation were eliminated at the end of treatment, driven by improvements among African Americans and Hispanics. High levels of distress were associated with reduced odds of abstinence through 6 months across racial/ethnic groups. © 2015 Society for the Study of Addiction.

Effect of rivastigmine or memantine add-on therapy is affected by butyrylcholinesterase genotype in patients with probable Alzheimer's disease.

PubMed

Han, Hyun Jeong; Kwon, Jay C; Kim, Jung Eun; Kim, Shin Gyeom; Park, Jong-Moo; Park, Kyung Won; Park, Key Chung; Park, Kee Hyung; Moon, So Young; Seo, Sang Won; Choi, Seong Hye; Cho, Soo-Jin

2015-01-01

The K variant of butyrylcholinesterase (BCHE-K) exhibits a reduced acetylcholine-hydrolyzing capacity; so the clinical response to rivastigmine may differ in Alzheimer's disease (AD) patients with the BCHE-K gene. To investigate the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine transdermal patch therapy in AD patients based on the BCHE-K gene. A total of 146 probable AD patients consented to genetic testing for butyrylcholinesterase and underwent the final efficacy evaluations. Responders were defined as patients with an equal or better score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at 16 weeks compared to their baseline score. BCHE-K carriers showed a lower responder rate on the ADAS-cog than non-carriers (38.2 vs. 61.7%, p = 0.02), and this trend was evident in AD patients with apolipoprotein E ε 4 (35 vs. 60.7%, p = 0.001). The presence of the BCHE-K allele predicted a worse response on the ADAS-cog (odds ratio 0.35, 95% confidence interval 0.14-0.87), after adjusting for demographic and baseline cognitive and functional variables. The BCHE-K genotype may be related to a poor cognitive response to rivastigmine patch or memantine add-on therapy, especially in the presence of apolipoprotein E ε 4.

E-cigarettes: an up to date review and discussion of the controversy.

PubMed

Sanford, Zachary; Goebel, Lynne

2014-01-01

Electronic cigarettes (e-cigarettes) present a novel method for nicotine delivery that is reportedly advantageous when compared to traditional cigarette usage. Manufacturers and consumers claim reduced chemical exposure, decreased symptom profiles, and efficacy in smoking reduction and cessation greater than conventional nicotine replacement therapies (NRT). However these products present new challenges and concerns to legislators, clinicians, and public health advocates. Questions of authority in state and federal legislation, establishing product quality control, assessing long-term studies on e-cigarettes and quantifying usefulness in harm reduction represent only a portion of the many unanswered topics being discussed. The purpose of this article is to assess the literature on e-cigarettes and establish perceptions and attitudes on this controversial subject.

Tobacco Cessation through Community Pharmacies: Knowledge, Attitudes, Practices and Perceived Barriers among Pharmacists in Penang

ERIC Educational Resources Information Center

Taha, Nur Akmar; Tee, Ooi Guat

2015-01-01

Objectives: Tobacco cessation is the primary goal of tobacco control measures. Community pharmacists are possible providers of tobacco cessation counselling due to their close contact with the public and the availability of non-prescription nicotine replacement therapies in pharmacies. However, community pharmacists often do not provide tobacco…

78 FR 277 - Food and Drug Administration Actions Related to Nicotine Replacement Therapies and Smoking...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-03

... Dependence; Public Hearing; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public hearing; Extension of comment period. SUMMARY: The Food and Drug Administration (FDA) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 15 [Docket No...

Galantamine Facilitates Acquisition of Hippocampus-Dependent Trace Eyeblink Conditioning in Aged Rabbits

ERIC Educational Resources Information Center

Weible, Aldis P.; Oh, M. Matthew; Lee, Grace; Disterhoft, John F.

2004-01-01

Cholinergic systems are critical to the neural mechanisms mediating learning. Reduced nicotinic cholinergic receptor (nAChR) binding is a hallmark of normal aging. These reductions are markedly more severe in some dementias, such as Alzheimer's disease. Pharmacological central nervous system therapies are a means to ameliorate the cognitive…

75 FR 53976 - Risks and Benefits of Long-Term Use of Nicotine Replacement Therapy Products; Public Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

...-0002, 301-796-3519, email: [email protected] ; or Dominic Chiapperino, Center for Drug Evaluation... Spring, MD 20993-0002, 301- 796-1183, email: [email protected] . Registration to Attend the... public hearing, please email your registration to [email protected] by October 5, 2010. Those...

Feasibility of a clinical trial of vision therapy for treatment of amblyopia.

PubMed

Lyon, Don W; Hopkins, Kristine; Chu, Raymond H; Tamkins, Susanna M; Cotter, Susan A; Melia, B Michele; Holmes, Jonathan M; Repka, Michael X; Wheeler, David T; Sala, Nicholas A; Dumas, Janette; Silbert, David I

2013-05-01

We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, aged 7 to less than 13 years, with amblyopia (20/40-20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis might be required to allow enrollment of a broader group of subjects.

Feasibility of a Clinical Trial of Vision Therapy for Treatment of Amblyopia

PubMed Central

Lyon, Don W.; Hopkins, Kristine; Chu, Raymond H.; Tamkins, Susanna M.; Cotter, Susan A.; Melia, B. Michele; Holmes, Jonathan M.; Repka, Michael X.; Wheeler, David T.; Sala, Nicholas A.; Dumas, Janette; Silbert, David I.

2013-01-01

Purpose We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. Methods A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, 7 to less than 13 years of age, with amblyopia (20/40–20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Results Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. Conclusions This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis, might be required to allow enrollment of a broader group of subjects. PMID:23563444

Seasonality in sales of nicotine replacement therapies: patterns and implications for tobacco control.

PubMed

Chandra, Siddharth; Gitchell, Joseph G; Shiffman, Saul

2011-05-01

Over the counter, nicotine replacement therapies (NRTs) are the most widely used smoking cessation treatment. This study sheds light on the seasonality of sales of NRT. A seasonal adjustment algorithm was applied to data on the sales of NRT products for 50 metro markets in the United States to test for and characterize seasonality in NRT sales. Granger's test was applied to the data to test whether changes in NRT sales systematically predicted changes in cigarette sales 1 month later. The results show (a) that sales of NRT products are seasonal, (b) that the seasonality pattern is the opposite of the seasonality pattern for cigarette sales, (c) that seasonally higher NRT sales in a given month tend to be followed by seasonally lower cigarette sales in the following month, and (d) that seasonally high months for NRT sales (January to March) correspond to seasonally low months for cigarette sales. NRT sales show a strong seasonality pattern that is the opposite of the seasonality pattern for cigarette sales. These patterns are indicative of seasonal variations in quitting behavior.

Looking for boomerang effects: a pre-post experimental study of the effects of exposure of youth to television advertising for nicotine replacement therapy and Zyban.

PubMed

Durkin, Sarah; Wakefield, Melanie; Spittal, Matt

2006-12-01

In the context of concerns about unintended "boomerang" influences of advertising, this study aimed to examine effects of nicotine replacement therapy (NRT) and Zyban advertising on youth perceptions of the ease of quitting, health risks of smoking and future intentions to smoke. 718 youth aged 14-16years were randomly allocated to view four television ads promoting either: NRT; Zyban; non-pharmaceutical cessation services (telephone Quitline); or non-cessation messages on sun protection. Questionnaire measures were administered before and after viewing ads. There were no effects of advertising exposure on perceived health effects of smoking or intentions to smoke. Compared with the sun protection ads, but not the Quitline ads, those exposed to NRT ads reported stronger perceptions about the ease of quitting, but non-susceptible non-smokers primarily drove this difference. This study suggests that exposure to NRT and Zyban advertising in an experimental context does not reliably influence youth smoking-related beliefs, especially those vulnerable to becoming regular smokers.

Applying a Social-Ecological Framework to Factors Related to Nicotine Replacement Therapy for Adolescent Smoking Cessation.

PubMed

King, Jessica L; Merten, Julie W; Wong, Tzu-Jung; Pomeranz, Jamie L

2018-06-01

This systematic review synthesizes factors related to nicotine replacement therapy (NRT) use among adolescents seeking to quit smoking, using the social-ecological model as a guiding framework. Searches of PubMED, ProQuest, EBSCOhost, and ERIC were conducted in July 2016. Original studies of cigarette smokers younger than 18 years that discussed NRT were included. Two reviewers individually extracted study purpose, sample, design, and results. Factors were categorized by social-ecological model level and summarized. A total of 103 907 articles were identified during initial search. After narrowing to peer-reviewed articles in English and eliminating reviews and adult-only studies, we reviewed 51 articles. These 51 articles identified factors from studies at each level of the social-ecological model: intrapersonal ( k = 20), interpersonal ( k = 2), organizational ( k = 7), community ( k = 11), and public policy ( k = 14). Findings provide insight into the applicability of NRT for adolescent smoking cessation, and factors by social-ecological model level highlight areas for additional research. Future adolescent NRT studies should assess factors at the interpersonal, organizational, and community levels, as well as the interactions between levels.

NAD+ and vitamin B3: from metabolism to therapies.

PubMed

Sauve, Anthony A

2008-03-01

The role of NAD(+) metabolism in health and disease is of increased interest as the use of niacin (nicotinic acid) has emerged as a major therapy for treatment of hyperlipidemias and with the recognition that nicotinamide can protect tissues and NAD(+) metabolism in a variety of disease states, including ischemia/reperfusion. In addition, a growing body of evidence supports the view that NAD(+) metabolism regulates important biological effects, including lifespan. NAD(+) exerts potent effects through the poly(ADP-ribose) polymerases, mono-ADP-ribosyltransferases, and the recently characterized sirtuin enzymes. These enzymes catalyze protein modifications, such as ADP-ribosylation and deacetylation, leading to changes in protein function. These enzymes regulate apoptosis, DNA repair, stress resistance, metabolism, and endocrine signaling, suggesting that these enzymes and/or NAD(+) metabolism could be targeted for therapeutic benefit. This review considers current knowledge of NAD(+) metabolism in humans and microbes, including new insights into mechanisms that regulate NAD(+) biosynthetic pathways, current use of nicotinamide and nicotinic acid as pharmacological agents, and opportunities for drug design that are directed at modulation of NAD(+) biosynthesis for treatment of human disorders and infections.

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial.

PubMed

Park, Kyung Won; Kim, Eun-Joo; Han, Hyun Jeong; Shim, Yong S; Kwon, Jae C; Ku, Bon D; Park, Kee Hyung; Yi, Hyon-Ah; Kim, Kwang K; Yang, Dong Won; Lee, Ho-Won; Kang, Heeyoung; Kwon, Oh Dae; Kim, SangYun; Lee, Jae-Hyeok; Chung, Eun Joo; Park, Sang-Won; Park, Mee Young; Yoon, Bora; Kim, Byeong C; Seo, Sang Won; Choi, Seong Hye

2017-01-01

Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. ClinicalTrials.gov NCT01380288.

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer’s dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial

PubMed Central

Kim, Eun-Joo; Han, Hyun Jeong; Shim, Yong S.; Kwon, Jae C.; Ku, Bon D.; Park, Kee Hyung; Yi, Hyon-Ah; Kim, Kwang K.; Yang, Dong Won; Lee, Ho-Won; Kang, Heeyoung; Kwon, Oh Dae; Kim, SangYun; Lee, Jae-Hyeok; Chung, Eun Joo; Park, Sang-Won; Park, Mee Young; Yoon, Bora; Kim, Byeong C.; Seo, Sang Won; Choi, Seong Hye

2017-01-01

Background and objective Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer’s disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Methods Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Results Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. Conclusions Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. Trial registration ClinicalTrials.gov NCT01380288 PMID:28786987

Randomised controlled trial evaluation of Tweet2Quit: a social network quit-smoking intervention.

PubMed

Pechmann, Cornelia; Delucchi, Kevin; Lakon, Cynthia M; Prochaska, Judith J

2017-03-01

We evaluated a novel Twitter-delivered intervention for smoking cessation, Tweet2Quit, which sends daily, automated communications to small, private, self-help groups to encourage high-quality, online, peer-to-peer discussions. A 2-group randomised controlled trial assessed the net benefit of adding a Tweet2Quit support group to a usual care control condition of nicotine patches and a cessation website. Participants were 160 smokers (4 cohorts of 40/cohort), aged 18-59 years, who intended to quit smoking, used Facebook daily, texted weekly, and had mobile phones with unlimited texting. All participants received 56 days of nicotine patches, emails with links to the smokefree.gov cessation website, and instructions to set a quit date within 7 days. Additionally, Tweet2Quit participants were enrolled in 20-person, 100-day Twitter groups, and received daily discussion topics via Twitter, and daily engagement feedback via text. The primary outcome was sustained abstinence at 7, 30 and 60 days post-quit date. Participants (mean age 35.7 years, 26.3% male, 31.2% college degree, 88.7% Caucasian) averaged 18.0 (SD=8.2) cigarettes per day and 16.8 (SD=9.8) years of smoking. Participants randomised to Tweet2Quit averaged 58.8 tweets/participant and the average tweeting duration was 47.4 days/participant. Tweet2Quit doubled sustained abstinence out to 60 days follow-up (40.0%, 26/65) versus control (20.0%, 14/70), OR=2.67, CI 1.19 to 5.99, p=0.017. Tweeting via phone predicted tweet volume, and tweet volume predicted sustained abstinence (p<0.001). The daily autocommunications caused tweeting spikes accounting for 24.0% of tweets. Tweet2Quit was engaging and doubled sustained abstinence. Its low cost and scalability makes it viable as a global cessation treatment. NCT01602536. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Reusable Floating-Electrode Sensor for Real-Time Electrophysiological Monitoring of Nonadherent Cells

NASA Astrophysics Data System (ADS)

Pham Ba, Viet Anh; Ta, Van-Thao; Park, Juhun; Park, Eun Jin; Hong, Seunghun

2015-03-01

We herein report the development of a reusable floating-electrode sensor (FES) based on aligned single-walled carbon nanotubes, which allowed quantitatively monitoring the electrophysiological responses from nonadherent cells. The FES was used to measure the real-time responses of normal lung cells and small-cell lung cancer (SCLC) cells to the addition of nicotine. The SCLC cells exhibited rather large electrophysiological responses to nicotine compared to normal cells, which was attributed to the overexpressed nicotinic acetylcholine receptors (nAChRs) in the SCLC cells. Importantly, using only a single device could measure repeatedly the responses of multiple individual cells to various drugs, enabling statistically meaningful measurements without errors from the device-to-device variations of the sensor characteristics. As results, that the treatment with drugs such as genistin or daidzein reduced Ca2+ influx in SCLC cells was found. Moreover, tamoxifen, has been known as an anti-estrogen compound, was found to only partly block the binding of daidzein to nAChRs. Our FES can be a promising tool for various biomedical applications such as drug screening and therapy monitoring.

Provision of smoking cessation support for pregnant women in England: results from an online survey of NHS stop smoking services for pregnant women

PubMed Central

2014-01-01

Background Smoking during pregnancy is a major public health concern and an NHS priority. In 2010, 26% of UK women smoked immediately before or during their pregnancy and 12% smoked continuously. Smoking cessation support is provided through free at the point of use Stop Smoking Services for Pregnant women (SSSP). However, to date, little is known of how these services provide support across England. The aim of this study was to describe the key elements of support provided through English SSSP. Methods SSSP managers were invited to participate in this survey by email. Data were then collected via an online questionnaire; one survey was completed for each SSSP. Up to four reminder emails were sent over a two month period. Results 86% (121 of 141) of services completed the survey. Responding services were, on average, larger than non-responding services in terms of the number of pregnant women setting quit dates and successfully quitting (p < 0.01). In line with the 2010 NICE guidelines, Stop Smoking in Pregnancy and following Childbirth, one in five SSSP identified pregnant smokers using carbon monoxide (CO) testing and refer via an opt-out pathway. All services offered nicotine replacement therapy (NRT) to pregnant women and 87% of services also offered dual therapy NRT, i.e. combination of a patch and short acting NRT product.. The 2010 NICE guidelines note that services should be flexible and client-centred. Consistent with this, SSSP offer pregnant women a range of support types (median 4) including couple/family, group (open or closed) or one-to-one. These are available in a number of locations (median 5), including in community venues, clinics and women’s homes. Conclusions English Stop Smoking Services offer behavioural support and pharmacotherapy to pregnant women motivated to quit smoking. Interventions provided are generally evidence-based and delivered in a variety of both social and health care settings. PMID:24593130

A Randomized Trial of Contingency Management for Smoking Cessation During Intensive Outpatient Alcohol Treatment.

PubMed

Cooney, Judith L; Cooper, Sharon; Grant, Christoffer; Sevarino, Kevin; Krishnan-Sarin, Suchitra; Gutierrez, Ian A; Cooney, Ned L

2017-01-01

This randomized clinical trial was designed to evaluate the efficacy of contingency management (CM) for smoking cessation for smokers with alcohol abuse or dependence delivered concurrently with intensive outpatient alcohol treatment. The study also explored the indirect effects of CM smoking treatment and smoking cessation on alcohol and drug use outcomes. Alcohol abuse/dependent smokers were randomized to cognitive behavioral therapy plus nicotine replacement therapy plus contingency management (CBT+NRT+CM) or to cognitive behavior therapy plus nicotine replacement therapy (CBT+NRT) delivered concurrent with a three-week intensive outpatient alcohol treatment program. Participants in the CBT+NRT+CM condition were significantly more likely to be cigarette abstinent at the end of treatment (χ 2 (1)=8.48, p=.004) with approximately double the carbon monoxide confirmed quit rate (60%) compared with the CBT+NRT condition (29%). At the one-month and six-month time-points there were nonsignificant differences in smoking abstinence outcomes by condition. Smoking treatment condition did not directly affect alcohol abstinence outcomes, but we observed an indirect effect of smoking treatment on alcohol and drug abstinence at one-month follow-up that was mediated by smoking cessation at the end of treatment. Adding CM to an evidence-based smoking cessation treatment that included medication and behavioral counseling doubled the quit rate at the end of treatment. This finding provides strong evidence for the efficacy of CM for helping alcohol dependent smokers reach the milestone of initial smoking abstinence. Published by Elsevier Inc.

Evaluation of a novel nicotine inhaler device: part 2--effect on craving and smoking urges.

PubMed

Moyses, Chris; Hearn, Alex; Redfern, Andrew

2015-01-01

Many smokers find currently available nicotine replacement therapies unsatisfactory. The pharmacokinetics of nicotine delivered via a novel inhaler device, and its effect on craving satiation and smoking urges, were compared with the Nicorette® Inhalator (10 mg). Results are reported for Parts B (N = 24) and D (N = 24) of a 4-part Phase I study. Participants (18-55 years, ≥ 10 cigarettes/day within 1 hr of waking, expired carbon monoxide >10 ppm on screening) received single doses of nicotine on consecutive days (0.45 and 0.67 mg [Part B] and 0.45 mg [Part D] via the novel device; 10 mg via Nicorette® [Parts B and D]). Venous pharmacokinetics, craving, and tolerability were assessed. In Part B, the novel device 0.45 and 0.67 mg produced significantly lower C max, AUClast, and AUCall than Nicorette® (all p ≤ .05), higher AUC0-10 and significantly shorter T max (18.7 and 19.2 min vs. 38.0 min, respectively, p ≤ .05). Craving score AUC was lower for the novel device 0.45 mg than for Nicorette® in Part B (1356.3 vs. 1566.3, p = .029) and approached statistical significance in Part D (1208.5 vs. 1402.3 [p = .059]). Mean craving scores were lower for the novel device 0.45 mg than Nicorette® at 7/8 postdose timepoints in Part B (p ≤ .05 at 180 and 240 min) and at all timepoints in Part D (p ≤ .05 at 2, 4, and 10 min). The novel device was at least as effective as the Nicorette® Inhalator (10mg) in relieving craving and smoking urges and was statistically superior at certain timepoints and in an overall craving AUC analysis, despite lower total nicotine exposure. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

Does smoking abstinence influence distress tolerance? An experimental study comparing the response to a breath-holding test of smokers under tobacco withdrawal and under nicotine replacement therapy.

PubMed

Cosci, Fiammetta; Anna Aldi, Giulia; Nardi, Antonio Egidio

2015-09-30

Distress tolerance has been operationalized as task persistence in stressful behavioral laboratory tasks. According to the distress tolerance perspective, how an individual responds to discomfort/distress predicts early smoking lapses. This theory seems weakly supported by experimental studies since they are limited in number, show inconsistent results, do not include control conditions. We tested the response to a stressful task in smokers under abstinence and under no abstinence to verify if tobacco abstinence reduces task persistence, thus distress tolerance. A placebo-controlled, double-blind, randomized, cross-over design was used. Twenty smokers underwent a breath holding test after the administration of nicotine on one test day and a placebo on another test day. Physiological and psychological variables were assessed at baseline and directly before and after each challenge. Abstinence induced a statistically significant shorter breath holding duration relative to the nicotine condition. No different response to the breath holding test was observed when nicotine and placebo conditions were compared. No response to the breath holding test was found when pre- and post-test values of heart rate, blood pressure, Visual Analogue Scale for fear or discomfort were compared. In brief, tobacco abstinence reduces breath holding duration but breath holding test does not influence discomfort. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Gender differences in satisfaction ratings for nicotine electronic cigarettes by first-time users.

PubMed

Grace, Randolph C; Kivell, Bronwyn M; Laugesen, Murray

2015-11-01

Nicotine electronic cigarettes (NECs) are becoming increasingly popular as a potentially safer alternative to tobacco but little is known regarding their subjective effects, including possible gender differences. Participants were New Zealand smokers with no intention to quit (N = 357) and whom had never used an NEC. During an interview in November-December 2012, participants sampled an NEC and rated it and their own-brand tobacco for satisfaction on a 10-point visual analogue scale. Participants were contacted again in February-March 2013 after a 10% increase in the tobacco excise tax on 1 January 2013. Overall participants rated NECs 83.3% as satisfying as own-brand tobacco. Females rated NECs more highly than males. Of those who agreed to be re-interviewed (n = 227), 37.8% said they had cut back or made a change in their smoking habit and 7% had quit in February-March 2013. NEC satisfaction ratings predicted changes in smoking habit and reductions in nicotine dependence after controlling for covariates including demographic variables, factory-made vs. roll-your-own tobacco preference, and addiction scores. Smokers' first impressions of NECs were very favourable, and were correlated with readiness to change after a tobacco tax increase. NECs appear to be particularly attractive for female smokers, and their use may help to improve the efficacy of nicotine replacement therapy for women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Competitive inhibition of the nondepolarizing muscle relaxant rocuronium on nicotinic acetylcholine receptor channels in the rat superior cervical ganglia.

PubMed

Zhang, Chengmi; Wang, Zhenmeng; Zhang, Jinmin; Qiu, Haibo; Sun, Yuming; Yang, Liqun; Wu, Feixiang; Zheng, Jijian; Yu, Weifeng

2014-05-01

A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.

Differences in cholinergic responses from outer hair cells of rat and guinea pig.

PubMed

Chen, C; LeBlanc, C; Bobbin, R P

1996-09-01

A cholinergic receptor on outer hair cells (OHC) in guinea pig cochlea induces a K+ current when it is activated by acetylcholine and suberyldicholine but not by nicotine or muscarine (Bobbin, 1995). This unusual receptor may contain an alpha 9-subunit. However, the pharmacology of the alpha 9-subunit cloned from rat and expressed in Xenopus oocytes does not completely match that obtained for the ACh receptor in guinea pig OHCs. The response to 1,1-dimethyl-4-phenylpiperazinium (DMPP) is large in guinea pig OHCs and small in oocytes containing receptors of the alpha 9-subunit. Therefore, we compared the effects of cholinergic receptor agonists in rat and guinea pig OHCs using the whole-cell variant of the patch-clamp technique. ACh caused the largest outward K+ current in OHCs from both rat and guinea pig. Carbachol- and suberyldicholine-induced responses were similar in magnitude in OHCs of rat and guinea pig. However, DMPP produced a small response in OHCs from rat and a large response in OHCs from guinea pig. At a concentration of 100 microM, muscarine, oxotremorine M, nicotine and cytisine induced little response in guinea pig OHCs and none in rat OHCs. Results suggest that the ACh receptor on rat OHCs is similar to the alpha 9-subunit-containing receptor expressed in oocytes but different from the ACh receptor on guinea pig OHCs.

Nicotinic acetylcholine receptors in porcine hypophyseal intermediate lobe cells.

PubMed Central

Zhang, Z W; Feltz, P

1990-01-01

1. Acetylcholine (ACh) was found to depolarize isolated porcine intermediate lobe cells maintained in primary cells culture. We investigated the ACh-induced responses in both whole-cell and cell-attached configurations of the patch-clamp technique. 2. From noise analysis of ACh-evoked whole-cell currents, we estimated an elementary conductance of 20 pS and a channel open duration of about 1.7 ms at -60 mV. From single-channel recordings, we obtained a slope conductance of 26 pS and a mean open time of 1.8 ms at membrane potentials between -60 and -80 mV. 3. ACh-evoked responses were blocked by d-tubocurarine (d-TC), hexamethonium and mecamylamine, but were insensitive to alpha-bungarotoxin. These characteristics define a neuronal type of nicotinic receptors. 4. The whole-cell current induced by ACh showed a strong inward rectification with no outward current being obtained. This phenomenon was observed when the intracellular ion is either sodium or caesium, and even when Ca2+ and Mg2+ were totally removed from the intracellular medium. 5. ACh-gated channels in intermediate lobe cells were cation selective and were permeable to Na+ and Cs+. In Ca2(+)-free extracellular solution, single-channel conductances were much larger (46 pS) than in the presence of 2 mM-Ca2+ (26 pS). 6. The possibility of an excitatory cholinergic control of intermediate lobe cells is discussed. PMID:1693685

Photodynamic therapy for the treatment of folliculitis decalvans.

PubMed

Castaño-Suárez, Esther; Romero-Maté, Alberto; Arias-Palomo, Dolores; Borbujo, Jesús

2012-04-01

Folliculitis decalvans is a chronic form of deep folliculitis that occurs on the scalp as patches of scarring alopecia at the expanding margins of which are follicular pustules. Treatment of folliculitis decalvans is extremely difficult with a resultant poor prognosis. Photodynamic therapy has been reported to be effective in disorders as acne or folliculitis. We report one patient with folliculitis decalvans who was successfully treated with photodynamic therapy. © 2012 John Wiley & Sons A/S.

Managing latex allergies at home

MedlinePlus

Latex products; Latex allergy; Latex sensitivity; Contact dermatitis - latex allergy ... Habif TP. Contact dermatitis and patch testing. In: Habif TP, ed. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 6th ed. ...