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Background: An estimated 17.2% of patients continue to smoke following diagnosis of cardiovascular disease (CVD). To reduce the risk of further morbidity or mortality in cardiovascular patients, smoking cessation has been shown to reduce the risk of mortality by 36% and myocardial infarction by 32%. The objective of this study was to evaluate the long-term health and economic consequences of smoking cessation in patients with CVD. Design and methods: Results of a randomized clinical trial comparing varenicline plus counselling vs. placebo plus counselling were extrapolated using a Markov model to simulate the lifetime costs and health consequences of smoking cessation in patients with stable CVD. For the base case, we considered a payer's perspective including direct costs attributed to the healthcare provider, measuring cumulative life years (LY) and quality adjusted life (QALY) years as outcome measures. Secondary analyses were conducted from a societal perspective, evaluating lost productivity due to premature mortality. Sensitivity and subgroup analyses were also undertaken. Results were analysed for Belgium, Spain, Portugal, and Italy. Results: Varenicline plus counselling was associated with a gain in LY and QALY across all countries; relative to placebo plus counselling. From a payer's perspective, incremental cost effectiveness ratios were €6120 (Belgium), €5151 (Spain), €5357 (Portugal), and €5433 (Italy) per QALY gained. From a societal perspective, varenicline in addition to counselling was less costly than placebo and counselling in all cases. Sensitivity analyses showed little sensitivity in outcomes to model assumptions or uncertainty in model parameters. Conclusions: Varenicline in addition to counselling is cost-effective compared to placebo and counselling in smokers with CVD. © 2011 The European Society of Cardiology.

BACKGROUND: A review of the available scientific literature concerning forms of tobacco use other than regular cigarettes, cigars and pipes, the nature of such products, prevalence data and trends, health effects, regulatory issues and preventive measures. RESULTS: Narghile (water pipe), bidis, kreteks and other forms of oral tobacco are traditionally used in many low-income countries, and some of these are currently spreading to the Western countries. They are all linked to negative effects similar to, and often greater than, those associated with common cigarette smoking. Various potentially reduced exposure products (PREPs), including snus, targeted at smokers aware of the health risks of regular cigarettes, have recently been developed by the tobacco industry. Their pathogenic potential varies widely and is not fully known; it is in any case greater than that of pure nicotine forms (such as medicinal nicotine). Their use as cigarette substitutes should not be considered even by inveterate smokers who are unable or unwilling to quit nicotine before further independent evaluation and control. CONCLUSIONS: There is no such thing as a safe tobacco product. Like cigarettes, alternative forms of tobacco use need regulatory measures that are adapted to local situations and supplemented by preventive measures within the World Health Organization's Framework Convention for Tobacco Control.

OBJECTIVE: Examination of tobacco butts and its possible use in tobacco control. DESIGN: Macroscopic examination of cigarette butts collected outside or in dedicated smoking rooms of a smoke-free hospital. RESULTS: Of 925 butts, 3.8% were cigarillos, 11.1% cigarettes without filter, 57.7% ventilated filter cigarettes, 22.5% filter cigarettes without macroscopic ventilation and 4.9% undetermined. Thirty-six different cigarette brands were identified. A wide distribution of butt lengths (mean 32.1 mm, variation coefficient 28%), peripheral ovalisation of the filter in 83.9%, and extended browning of the mouth end of the filter in 48.6% were observed. Vent holes were macroscopically detectable in 70.5% and a sharp decrease in browning in 53.4% of the filter cigarettes. Most (94.7%) ventilation holes were located at > or =10 mm from the mouth end. CONCLUSIONS: In a smoke-free hospital, the use of tobacco products (mainly ventilated filter cigarettes) remains sizeable. Given the wide distribution of butt lengths, the number of cigarettes per day is a poor marker of toxin intake. Vent-hole localisation and signs of vent-blocking confirm the inadequacy of machine-measured smoke yields and the presence of compensatory smoking. More intensive individual cessation advice with pharmacological support is necessary. Examination of a smoker's own cigarette butts can be used as a tool for individual cessation advice.

Failure in smoking cessation is linked with behavioural factors and with nicotine dependence, due to the psychoactive effects of the drug, mainly on locus ceruleus and on mesolimbic dopaminergic system. Nicotine substitution partially controls the withdrawal syndrome, sometimes very intense in smokers with pharmacological dependence. After transdermal nicotine administration, nicotine blood levels are relatively low but steady; nicotine chewing gum can be used alone or in combination with transdermal administration. Both methods can double biologically controlled success rates. Risks are limited in comparison with those of continued smoking. Recent data from the literature allow a better understanding of indications and limits of the pharmacological approach to cessation, that should address smokers firmly decided to stop, and be completed by behavioural support, including changes in the way of life.

Background. We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months. Methods. HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months. The HIV-positive patients who had no evidence of tuberculosis were then randomly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months. We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months. Results. After six months, 260 of 335 HIV-seropositive and 186 of 188 HIV-seronegative participants could be evaluated, and their rates of treatment failure were similar: 3.8 and 2.7 percent, respectively. At 24 months, the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent, as compared with 9 percent among the HIV-seropositive patients who received placebo for the second 6 months (P<0.01). Extended treatment did not improve survival, however. Among the HIV-seronegative patients, 5.3 percent relapsed. Conclusions. Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited.

Failure in smoking cessation is linked with behavioural factors and with nicotine dependence, due to the psychoactive effects of the drug, mainly on locus ceruleus and on mesolimbic dopaminergic system. Nicotine substitution partially controls the withdrawal syndrome, sometimes very intense in smokers with pharmacological dependence. After transdermal nicotine administration, nicotine blood levels are relatively low bur steady, nicotine chewing gum can be used alone or in combination with transdermal administration Both methods can double biologically controlled success rates. Risks are limited in comparison with those of continued smoking. Recent data from the literature allow a better understanding of indications and limits of the pharmacological approach to cessation, that should address smokers firmly decided to stop, and be completed by behavioural support, including changes in the way of life.

IgA, IgG, and IgM antibodies to mycobacterial antigen A60 were measured by ELISA in blood, pleural fluid, and cerebrospinal fluid from 560 patients with pulmonary and/or extrapulmonary tuberculosis who were being treated at hospitals in northern China and from 734 uninfected controls. Among 529 healthy persons (most of whom had been vaccinated with bacille Calmette-Guérin [BCG] and 287 of whom were tuberculin-positive), the rate of false-positive results was negligible; this observation ruled out interference of remote BCG vaccination with A60 assays at the chosen cutoff level. Rates of positivity for IgM and IgG, respectively, were 80% and 36% among patients with active primary pulmonary tuberculosis, 31% and 88.5% among patients with active postprimary pulmonary tuberculosis, 0 and 41% among patients with inactive pulmonary tuberculosis, and 30%-61% and 69%-86% among patients with extrapulmonary tuberculosis. Paired samples of blood and pleural fluid from patients with pleurisy contained IgA antibody to A60 at equal titers; in contrast, most patients with tuberculous meningitis (100% of whom had a positive ELISA result) had higher levels of IgG antibody to A60 in cerebrospinal fluid than in blood--proof of intrathecal synthesis.

OBJECTIVE: A60 is a high molecular weight mycobacterial antigen complex. The detection of immunoglobulin (Ig) G antibodies to A60 has been advocated as a reasonably sensitive and specific test for active tuberculosis (TB). We aimed to compare the sensitivity of this test among HIV-seropositive and HIV-seronegative patients with pulmonary TB. METHODS: The presence and concentration of anti-A60 IgG antibodies was assessed by enzyme-linked immunosorbent assay in 208 HIV-seropositive and 91 HIV-seronegative Zaïrian patients with smear-positive pulmonary TB. The relationship between anti-A60 IgG levels and HIV serostatus, CD4+ lymphocyte counts, presence of clinical AIDS, and tuberculin skin test results was verified. RESULTS: Only 36.5% of the HIV-seropositive, compared with 69.2% of the HIV-seronegative patients had a positive anti-A60 IgG test (P < 0.00001). Among HIV-seropositive patients, anti-A60 IgG levels did not differ according to CD4+ lymphocyte counts, presence of clinical AIDS, or tuberculin skin test results. CONCLUSIONS: Among patients with pulmonary TB, the sensitivity of testing for anti-A60 IgG was much lower among HIV-seropositive than among HIV-seronegative patients, even from the early stages of HIV-related immunodeficiency. This limits the utility of anti-A60 IgG-antibody testing in the diagnosis of TB among HIV-infected patients.

Tuberculosis (TB) is the most common opportunistic infection in African patients who die from AIDS, yet the stage of immunodeficiency at which TB develops is uncertain. We studied the immune status of HIV-infected outpatients with pulmonary TB in relation to their clinical presentation in a cross-sectional study of 216 HIV-seropositive and 146 HIV-seronegative ambulatory incident cases of smear-positive and culture-positive pulmonary TB in Kinshasa, Zaire. HIV-seropositive and seronegative patients had median CD4 lymphocyte counts of 316.5/muL and 830.5/muL, respectively. Of the HIV-seropositive patients, 32 9% had less than 200 CD4 lymphocytes/muL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition ora modified version, was of similar limited use as a predictor of immunodeficiency. Among HIV-seropositive patients, oral candidosis, lymphopenia, a negative tuberculin purified protein derivative test, and cutaneous anergy were strongly associated with CD4 counts of less than 200/muL, and seemed to be better markers of immune dysfunction. We conclude that pulmonary TB develops across a broad spectrum of HIV-induced immunodeficiency and that a diagnosis of pulmonary TB is of limited use as a marker of stage of HIV disease in African HIV-infected outpatients.

Rates of infection with Mycobacterium tuberculosis were compared in Kinshasa, Zaire, in 521 household contacts of 74 human immunodeficiency virus type 1 (HIV-1)-seropositive index patients and in 692 household contacts of 95 HIV-1-seropositive index patients with sputum smear-positive pulmonary tuberculosis: No difference was noted between contacts of HIV-1-seropositive and -seronegative patients. The increasing prevalence of M. tuberculosis infection with increasing age was similar in household contacts of seropositive and seronegative patients; by age 16 years, 75% were purified protein derivative-positive. The similarly low rates of M. tuberculosis infection in household contacts of HIV-1-seropositive and -seronegative index patients with sputum smear-positive pulmonary tuberculosis indicates that HIV-1-seropositive patients with pulmonary tuberculosis are not more infectious than HIV-1-seronegative patients with pulmonary tuberculosis.

In the United States, it is estimated that the yearly incidence of lung cancer is about 150.000 with approximately 110.000 deaths from this disease. Lung cancer remains the number one cancer killer among males, accounting for 35% of cancer death. Among female, the incidence of lung cancer has recently surpassed that of all other cancers, included breast cancer and deaths of lung cancer in the female population accounts for 19% of the all cancer deaths. This evolution is clearly related to smoking habits (Spiro S.G., 1988). There are four major histological subtypes of lung cancer namely squamous cell carcinoma, adenocarcinoma, and large cell carcinoma (collectively referred to as non-small cell lung cancer), and small cell lung carcinoma (SCLC). SCLC accounts fro 25% of all new cases of lung cancer. Among the various histological types of lung cancer, SCLC is the most chemo- and radiosensitive. While the majority of patients will obtain an initial response to cytotoxic therapy, overall survival is poor and less than 5% of all patients will be cured. With the most effective treatment, the median survival time for SCLC patients ranges from 9 to 13 months. As in many other areas on oncology, our basic understanding of small cell lung cancer has increased over the past years and many data suggest that biological properties inherent within the tumor cells themselves may be of prognostic importance, including expression of genes or oncogenes. In the first chapter, we will discuss recently discovered biological properties of SCLC, including their first applications to the management of patients with the disease. This management will be the subject of the second chapter. Because it is well recognized that prognostic factors and stratification are crucial to compare the results of different studies, we will focus on these points before describing the up-to-date therapy of SCLC. As was pointed hereabove, patient’s survival is short and new studies are need, Thèse d'agrégation de l'enseignement supérieur (faculté de médecine) -- UCL, 1991

Carboplatin, a second generation platinum complex, is less nephrotoxic and emetogenic than its parent compound. We have tested the objective response to and the toxicity of the combination carboplatin 330 mg m-2 on day 1 with etoposide 120 mg m-2 on days 1, 3 and 5, administered every 3 weeks in histologically proven inoperable non-small-cell lung cancer (NSCLC) patients with a good performance status. Thirty-one patients entered the study; 29 were evaluable for response, 24 after 3 courses and 5 after 2 courses of chemotherapy. An overall response rate of 21% was found including zero complete response and 6 partial responses. In addition, 3 minor responses (10%), 12 stable diseases (38%), and 9 progressive diseases (39%) were observed. The median survival was 48 weeks, including 68 weeks for non-metastatic (M0) patients and 27 weeks for metastatic (M+) patients. This regimen was well tolerated. Gastrointestinal toxicity never exceeded WHO grade II and renal function remained in the normal range for all cases. Haematological toxicity was low in the majority of the cases; nevertheless it proved to be the dose limiting toxicity as illustrated by two grade III anemia, one grade III leucopenia, one grade III and one grade IV thrombocytopenia. Carboplatin-etoposide combination is not more active, but clearly much less toxic than cisplatin-etoposide in NSCLC.

In 43 cases of small cell carcinoma of the lung, a combined treatment has been initiated with three drugs (cyclophosphamide 750 mg/m2, adriamycin 50 mg/m2 and vincristine sulphate 1 or 2 mg total dosage), split-course-radiation therapy on the primary tumour (3500 rads) and prophylactic irradiation of the brain (2000 rads). The median survival of the 34 cases evaluable at day 50 attains 253 days. A more favourable evolution is observed for patients with a good response after therapy (median survival: 315 days) and for cases with limited disease (321 days) than for non-responders (median survival: 157 days) and for cases with extensive disease (median survival: 214 days). In spite of tumour site irradiation, prophylactic irradiation of CNS and chemotherapy, there were six local relapses, two CNS extensions and six metastatic relapses and only two autopsied cases without macroscopic evidence of relapse.

At present, the possibilities of pharmacological intervention in smoking cessation remain limited. Some products, like smoking deterrants, lobeline, amphetamine and sedatives, definitely seem to have been rejected. The efficiency of other drugs aiming to treat the withdrawal syndrome (e.g. clonidine) or to eradicate the smoking habit (e.g. mecamylamine) must still be confirmed in large controlled trials. The same is true of the "cigarette substitutes" which have appeared recently. The only effective substitute treatment currently available is nicotine, presented as nicotine gum; other modalities of administration of nicotine are in preparation. Even if it has not fulfilled all the expectations of its promoters and of the smokers who hoped for a panacea, nicotine gum, when administered to highly dependent smokers motivated to stop, with the appropriate technique, effects a moderate increase not only in the cessation rate but also in the long-term abstention rate, in so far as the necessary psychological support is provided, either by the physician in medical settings, or by other health professionals, in smoking-cessation clinics or in industrial and community settings. The addiction to psychoactive nicotine presents only one facet of the smoking process in chronic smokers. They must also be helped to face the behavioural components of their habits, so individualized counselling remains essential, in addition to the prescription of the gum, in order to achieve satisfactory rates of long-term smoking cessation.

In 36 severely hypoxaemic patients (arterial oxygen tension (PaO2) less than 7.3 kPa or 55 mmHg), candidates for long-term oxygen therapy, we compared the effectiveness of three oxygen-delivery systems, the standard nasal prongs, a so-called oxygen-conserving reservoir device ("Oxymizer Pendant") and the reference pharyngeal catheter, at a preset flow rate of 2 l.min-1. After 30 min, the conserving device (OX) was at least as efficient as the pharyngeal catheter (PC) and did significantly better than the nasal prongs (NP), the mean increments in PaO2 and arterial oxygen saturation (SaO2) being, respectively, 1.1 kPa (8.1 mmHg) and 1.3% higher with OX than with NP. Twenty patients did not reach the target level of 8.6 kPa (65 mmHg) PaO2 with the nasal prongs, but the reservoir cannula allowed nine of these "refractory" patients to hit this therapeutic goal, a result indicating a clear trend towards improved immediate oxygen response. Although initially designed to spare gas, we suggest that a reservoir cannula could serve another purpose, namely to optimize oxygenation in patients treated by an oxygen concentrator. Indeed, since the oxygen flow rate cannot be reliably increased over 3 l.min-1 with the available oxygen concentrators, the reservoir device could be more effective in some selected patients whose hypoxaemia cannot be adequately corrected by standard nasal prongs.

The bronchodilating effect of Duovent (0.2 mg fenoterol +0.8 mg ipratropium bromide) was compared with that of each of its components at the same doses. Twenty patients were included in the trial. Maximum expiratory flow-volume curves with air and helium-oxygen, intrathoracic gas volume and airway conductance were used for assessing the bronchomotor tone before and 15, 30, 60, 240 and 360 min after drug administration. All the drugs showed a significant bronchodilating effect. No differences between Duovent and fenoterol or ipratropium bromide were observed except a slight but statistically significant greater decrease of ITGV with Duovent. When expressing the data as percentage variation of the initial values, Duovent induced a better effect than the other drugs. The evaluation of density dependence was highly disappointing, and no conclusion can be drawn.

In order to assess the dose/response ratio of two different doses of theophylline, the effects of two periods of 4-day treatment with 300 and 450 mg sustained release anhydrous theophylline (Theodur, Astra, Sweden) b.i.d. in 16 in-patients with reversible chronic obstructive lung disease in a stable state were investigated in a double-blind randomized crossover study. On the 4th day in each treatment period, ventilatory function parameters (FEV1, FVC, PEFR, MEF25, MEF50), theophylline serum concentration and blood gases were measured. Asthma symptoms, beta 2-adrenergic aerosol use significantly different from its value before treatment: the mean FEV1 increase during the 300-mg period reached 12% and during the 450-mg period 15%. The mean difference in theophylline serum concentration between the periods of 300 and 450 mg reached approximately 2 micrograms/ml, but a significant difference could not be demonstrated between both treatment periods, neither in the mean ventilatory parameters, nor in the patients preference. In spite of the use of a sustained release preparation, variations of serum levels of theophylline were observed individually throughout a 12-hour observation period: the extent of those variations differs from one patient to another.