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OBJECTIVE: To evaluate the cost-effectiveness of an extended (12+12 weeks) course of varenicline plus brief counselling compared with the currently reimbursed smoking cessation interventions (in combination with brief counselling) in Belgium, from a public payer perspective. METHODS: The previously published version of the BENESCO model which included the extended course of varenicline was updated with recent publically available demographic and cost data from Belgium. RESULTS: The extended course of varenicline plus brief counselling has an incremental cost per quality adjusted life year gained of 1101€ compared with a nonextended 12-week course of varenicline (plus brief counselling). The extended course of varenicline dominates all other comparators in this analysis. CONCLUSIONS: The extended course of varenicline (12 weeks followed by 12 weeks maintenance therapy in successful quitters) plus brief counselling is a highly cost-effective alternative to a non-extended (12 weeks only) course of varenicline plus brief counselling. This strategy dominates the other alternative smoking cessation interventions currently reimbursed in Belgium.

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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.

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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.

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Many barriers must be tackled for controlling the tobacco epidemic responsible for completely preventable mortality. Tobacco addiction is presently considered as the central element in smoking. The mechanisms of action of drugs of abuse (including nicotine) and the current techniques for their study in animals and in humans are briefly reviewed. Cigarettes are manipulated by the tobacco industry to increase the level of dependence. The transnational tobacco companies use a global tactic to expand their sales, particularly in the third world, so that the mean world cigarette consumption per adult remains unchanged at approximately 1500 per year. Nevertheless, it is hoped that control of the epidemic will be gained in the 21st century, since the awareness of tobacco risks and costs is increasing, an antismoking climate is developing and the tobacco lobby has lost its credibility. On the other hand, improved behavioural and pharmacological methods increase the cessation rate. Health professionals are progressively more involved in the smoking cessation problems, while international control measures are applied by the European Commission. The World Health Organization is preparing a "Framework Convention on Tobacco Control" with binding mechanisms for governments. A larger involvement of the community is needed to promote an international policy based on health values, rather than on trade considerations, and addressing the specific problems of the third world. Nevertheless, since a latency of approximately 30 yrs exists between the increase in tobacco consumption in a population and the rise in tobacco mortality, past trends in consumption will continue to influence health status during the next 30 yrs. Present, urgently needed, radical health measures are expected to have their major impact only after that period.

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This report relates to the 1,667 responses to a selfadministered mail-back questionnaire sent by BELTA to a sample of 4,643 physicians (17.3% current smokers) who are in professional contact with patients (response rate: 35.9%). Links between active smoking and disease are considered as well-demonstrated by 98.8% physicians and for passive smoking by 85.3%, for foetal consequences of smoking during pregnancy by 96.4%. Nicotine dependence is admitted by 83.3%. Interaction of smoking with drug metabolism is insufficiently known. Modulation of the specific approach of smoking cessation, according to the various stages of the cessation cycle, to the level of nicotine dependence and to the psychological status of the smoker is not sufficiently perceived by the physicians. Patient's smoking status is systematically determined by less than half the physicians, of whom nearly 90% claim to inform their smoking patients on smoking-related risks, and 84.2% to tackle the problem of cessation. The intervention is mostly limited to a firm advice, completed by nicotine replacement for a maximum of 50% of smokers (especially gum and patch). Referral to specialized structures is unfrequent (between 10 and 20%). Follow up after cessation is clearly deficient. In this retrospective study of their activity patterns, physicians' reports may reflect their intentions rather than their actual practices. We conclude that smoking issues and cessation techniques should be more intensively taught both at graduate and postgraduate levels, in order to obtain a more active behaviour of health professionals against smoking.

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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.

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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.

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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.

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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.

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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/microL and 830.5/microL, respectively. Of the HIV-seropositive patients, 32.9% had less than 200 CD4 lymphocytes/microL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition or a 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/microL, 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.

PIP: Between March 1989 and September 1991, physicians compared CD4 lymphocyte counts of 216 HIV-seropositive patients whose sputum smears tested positive for pulmonary tuberculosis (TB) with those of 146 HIV- negative patients who also tested positive for TB at a TB screening center in Kinshasa, Zaire. The researchers wanted to investigate the immune status of HIV-infected outpatients with pulmonary TB in relation to clinical criteria. HIV seropositive patients had much lower CD4 lymphocyte counts than did HIV seronegative patients (total CD4 count, 316.5/mcl vs. 830.5/mcl; CD4 count, 13% vs. 36%; p .001). 90.4% of HIV-positive patients had CD4 counts 800 compared with 48% of HIV- negative patients. 32.9% of HIV-positive patients had CD4 counts 200 while just 1.4% of HIV-negative patients did. As CD4 counts fell, weight loss, diarrhea during the previous month, past or present herpes zoster, and oral candidosis occurred more frequently (p = .004 for oral candidosis and p = .02 for the rest). Negative purified protein derivative RT23 (PPD) tests and cutaneous anergy occurred more often as immunodeficiency rose (p .001). Increased immunosuppression was also characterized by no detectable cavitation on chest radiography, anemia, and low total lymphocyte counts (p = .02 for absence of cavitation and p .001 for the others). These results suggested that pulmonary TB occurred along the continuum of immunodeficiency as defined by CD4 counts. Thus, it is not likely to be a marker of the severity of HIV infection. Instead weight loss, diarrhea during the previous month, past or present herpes zoster, oral candidosis, negative PPD test and cutaneous anergy, absence of detectable cavitation on chest radiography, anemia, and low total lymphocyte appeared to be better markers of the severity of HIV-related immunodeficiency.

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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-seronegative [corrected] 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.

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To evaluate their treatment outcomes 170 human immunodeficiency virus (HIV) seropositive and 597 HIV seronegative patients with active pulmonary tuberculosis (TB) treated for 1 yr with "standard" chemotherapy, including streptomycin, isoniazid, and, in most cases, thiacetazone, were traced at completion of therapy. All 582 survivors were invited for reevaluation, and 385 patients, of whom 82 (21.3%) were HIV seropositive, were evaluated. Of those, 325 consenting patients, of whom 67 (20.6%) were HIV seropositive, were followed for 12 months. One year after TB had been diagnosed 47 (31.3%) of the 150 HIV seropositive and 22 (4.4%) of the 501 HIV seronegative patients traced had died (p = 10(-6]. During the subsequent year the mortality of 67 HIV seropositive patients (26.3/100 patient-years) was higher than that of the 303 HIV seronegative patients (2.2/100 patients-years, p = 10(-6]. HIV seropositive patients had a higher overall TB therapy failure rate 24 months after the diagnosis of TB than did HIV seronegative patients (21.1/100 patient-years versus 8.1/100 patient-years, p = 0.002), mainly because their relapse rate of pulmonary TB (18.1/100 patient-years) was higher than that of HIV seronegative patients (6.0/100 patient-years, p = 0.03). Given their higher relapse rate after 1 yr of "standard" chemotherapy, the public health impact of routine maintenance therapy in HIV seropositive patients with pulmonary TB who complete such therapy should be assessed in comparison to the introduction of rifampicin-based short-course antituberculosis chemotherapy in developing countries.

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An ELISA method for detecting serum antibodies against A60, an antigen prepared from the cytoplasm of Mycobacterium bovis BCG, has been applied to 385 subjects, namely 197 controls (neonates, healthy adults, and tuberculin negative, nontuberculous patients), and 188 subjects at various stages of tuberculous infection and disease. Most IgM determinations gave negative results. While the neonates and normal adults had titers of IgG anti-A60 antibodies below the cut off value, wide variations in antibody titers were observed among the various types of subjects infected by M. tuberculosis. The results obtained with nontuberculous subjects were: 100% negative IgG in neonates and healthy adult individuals and 6.4% "false positive" cases among 124 non-tuberculous patients. The percentage of serologically positive cases of tuberculosis was: 5.9% in latent active primary forms, 42.8% in patent active primary forms, and 82.8% in active postprimary forms. Tuberculous infections had a positively rate of 14.7%, while inactive postprimary tuberculosis had a positivity rate of 50%. The results obtained with A60 can favourably be compared with other serum ELISA tests for tuberculous antibodies against purified or semipurified mycobacterial antigens. Anti-A60 ELISA IgG antibody test can be useful to monitor the kinetics of humoral immunological response during tuberculous infection, disease and chemotherapy. A positive IgG ELISA test may support the diagnosis of active tuberculous disease.

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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.

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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.

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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.

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