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Abstract Background A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood–brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design Two centers will include a total of 600 smokers who are motivated to quit smoking. At week −2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention. Trial registration ClinicalTrials.gov: (NCT00995033)

Abstract. Tønnesen P, Tonstad S, Hjalmarson A, Lebargy F, van Spiegel PI, Hider A, Sweet R, Townsend J (Gentofte University Hospital, Gentofte, Denmark; Clinic for Preventive Medicine, Ullevål University Hospital, Oslo, Norway; Smoking Cessation Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden; Hospital Maison Blanche, Reims Cedex, France; Slotervaart Hospital, Amsterdam, The Netherlands; and GlaxoSmithKline Research and Development, Greenford, Middlesex, UK). A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation. J Intern Med 2003; 254: 184–192. Background. Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies. Objective. To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study. Methods. This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes. Results. Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89–4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29–3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%). Conclusion. Bupropion SR in... [ABSTRACT FROM AUTHOR]

The function of ammonia as tobacco additive is subject of scientific debate. It is argued that ammonia, by increasing the proportion of free nicotine, increases the absorption of nicotine in smokers. As a result of the addition of ammonia to cigarettes, smokers get exposed to higher internal nicotine doses and become more addicted to the product. On two occasions, the nicotine absorption in blood was measured after smoking a commercial cigarette of either brand 1 or brand 2, which differed 3.8-fold in ammonium salt content. Using a standardized smoking regime (six puffs, 30 s puff interval, 7 s breath hold before exhalation), 51 regular smokers smoked brand 1 (Caballero Smooth Flavor; 0.89 mg ammonium per gram tobacco) and brand 2 (Gauloise Brunes; 3.43 mg ammonium per gram tobacco). Puff volumes and cardiovascular parameters were monitored during and following smoking, respectively. Measurement of serum nicotine level in the blood samples collected over time following smoking of the two brands, showed that total amount of nicotine absorbed did not differ between the two brands. Present results demonstrate that smoking tobacco containing a higher amount of the tobacco additive ammonium does not increase the absorption of nicotine in the smoker's body., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aims: To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD)., Methods: Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study., Results: Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19)., Conclusions: After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.

Smoking is a major preventable health risk in western society. In the Netherlands, it is held responsible for 86 and 36% of annual mortality from lung cancer and cardiovascular disease, respectively. Nevertheless about 33% of Dutch people smoke. Only 2% of smokers quit successfully after being advised to stop once by a physician. Although the medical profession should play a leading role in campaigns to stop smoking, general practitioners advise only 10% of their smokers to quit. An overview was made of the various aids that can be used to support attempts to quit smoking. Three aids: supportive schedules, nicotine replacement and bupropion chloride had proven long-term effectiveness in up to 5-10, 3-13 and 11-15% of the subjects, respectively. In conclusion, supportive counselling combined with nicotine substitutes or bupropion chloride is the most worthwhile intervention to support quitting attempts. Wider application of this strategy is expected to have major implications on morbidity (50% myocardial infarct risk reduction) and mortality in the Netherlands.

Hyperventilation is considered an important factor in the development of somatic symptoms or even panic attacks, though its role has recently been disputed. Arguments are often based on findings from the so-called Hyperventilation Provocation Test (HVPT), which is a procedure consisting of voluntarily overbreathing. The HVPT has been widely used for diagnosing Hyperventilation Syndrome and for experimentally eliciting panic attacks. Almost no attention, however, has been paid to standardizing the test and determining critical values with respect to depth and duration of hyperventilation. In the present study, symptom development was examined in 16 healthy subjects who underwent four HVPTs that differed in depth of hyperventilation (end-tidal PCO2 < 2.4 kPa or < 1.9 kPa), as well as duration of hyperventilation (2 or 5 min). Both depth and duration appeared to have an independent effect on the development of symptoms. In the 5-min condition, symptoms appeared mainly within the first 3 min. To be sure that the HVPT is long enough and deep enough to elicit symptoms in most people, a minimum duration of 3 min is advised, with end-tidal PCO2 decreasing to at least 1.9 kPa or dropping well over 50% of baseline.

We report the unique occurrence of a unilateral sacroiliitis in a patient with active sarcoidosis accompanied by pulmonary tuberculosis. Convincing (clinical) evidence of sarcoidosis as the extremely rare cause of this articular involvement is presented. Discussion is focused on comparison of sarcoidosis and tuberculosis, particularly with respect to their articular involvement, and the literature of previously reported cases of sarcoid sacroiliitis is briefly reviewed.

Hyperventilation is considered an important factor in the production of a variety of somatic symptoms. This complex of symptoms is called the Hyperventilation Syndrome (HVS). Recognition of symptoms during the hyperventilation provocation test (HVPT) is a widely used criterion for diagnosing HVS. The validity of this criterion is tested in the present study. Twenty-three patients suspected of HVS performed a HVPT (hyperventilation during 3 min) and a mental load task (Stroop Color Word Test; CWT). It appeared that about the same number of patients (61%) recognized symptoms during the HVPT as during the CWT (52%), despite severe hypocapnia in the first test and normocapnia in the second. Reporting of symptoms was significantly related to psychological state and trait measures (SCL-90 and STAI scores) and unrelated to the degree of hypocapnia. These data have far reaching consequences, as they not only undermine the validity of the HVPT, but also question the tenability of the concept of HVS.