SETTING:SMIRA (Italian Study on Anti-Tuberculosis Drug Resistance) network, 46 major clinical units and 22 laboratories nationwide in Italy. OBJECTIVES:To determine the main features, adherence to WHO guidelines and the outcomes of multidrug-resistant tuberculosis (MDR-TB) patients enrolled from January 1995 to December 1999. DESIGN:Observational study, preceded by proficiency testing, according to WHO recommendations. Results were stratified by appropriate and inappropriate regimens (< three active drugs). Analysis of the outcomes was performed according to adequacy of treatment. Analysis of risk factors and factors predicting treatment outcomes was performed using univariate and multivariate analysis (level of significance P < 0.05). RESULTS:One hundred and twenty-seven MDR patients were diagnosed. The overall success rate was low (39%). Seventy per cent of cases were treated with at least three active drugs. Factors predicting treatment success were new MDR-TB cases (OR 3.45; 95% CI 1.22-9.78; P < 0.05) and treatment for > or = 12 months (OR 5.03; 95% CI 1.65-15. 31; P < 0.05). Immigration and HIV infection were the main risk factors among new MDR-TB cases. CONCLUSION:The best available treatment should be provided to all newly diagnosed MDR-TB patients, avoiding the use of poorly modified regimens. MDR-TB patients should be referred to highly specialised centres.

OBJECTIVE To determine specificity, sensitivity and predictive values of a rapid immunochromatographic assay (ICT tuberculosis) for the diagnosis of tuberculosis (TB) in an Italian clinical setting, and to identify tentative new guidance for the interpretation of test results. METHODS The ICT tuberculosis test is an immunochromatographic test based on the detection of IgG antibodies directed against five highly purified antigens secreted by Mycobacterium tuberculosis during active growth. Sera from 60 patients with active pulmonary (48 sputum smear-positive and six sputum smear-negative cases) and extrapulmonary (six cases) TB were obtained. Personal, anamnestic and clinical data were investigated and recorded for each patient. The control groups comprised 156 subjects: 40 healthy individuals, half of them Mycobacterium bovis BCG-vaccinated, and 116 patients with mycobacterial diseases other than TB (five cases), with nonmycobacterial lung diseases (30 cases), with nonmycobacterial nonlung diseases (30 cases), with nonmycobacterial diseases and rheumatoid factors positivity (30 cases), and with asymptomatic HIV infection (21 cases). For 21 individuals the test was simultaneously performed with both serum and whole blood sample. Each positive result of the ICT test was reported with regard to the number (1-4), position (A, B, C, D) and color intensity (+ to ++++) of the evidenced lines in order to assess the quality of the antibody response. RESULTS The overall sensitivity and specificity were 56.7% and 90.4%, respectively. The sensitivity for pulmonary TB patients was 61.1% (66.7% for smear-positive and 16.7% for smear-negative cases) and 16.7% for extrapulmonary TB patients. The difference between ICT results in pulmonary TB patients and control subjects was statistically significant (P < 0.0001). The analysis of the positive ICT tests revealed that samples with strong color intensity (>/=++) and specific antibodies bound to antigens immobilized on line D were significantly more frequent in TB patients than in controls (P = 0.001 and P= 0.027, respectively). ICT test results with the presence of at least three visible lines were more often observed in the TB patients than in controls, although not reaching statistical significance (P = 0.052). No difference was observed between the results of the ICT test performed both on serum and whole blood sample. CONCLUSIONS The ICT tuberculosis test was confirmed to be rapid and easy to perform without requiring special equipment, both on serum and whole blood sample. Our data, in accordance with those obtained in a previous study conducted in extra-European countries, confirmed higher sensitivities for the smear-positive TB patients than for the smear-negative TB patients, and for pulmonary TB patients than for the extrapulmonary TB patients. Data obtained on the quality of antibody response in the ICT positive samples, might be used to improve the performance of the test.

Microbiological findings at diagnosis and at the end of treatment are relevant for evaluating tuberculosis (TB) treatment programmes. The objectives of this study were to describe the microbiological findings at diagnosis and at the end of treatment in pulmonary and extrapulmonary TB patients treated under programme conditions in Italy. The study was a prospective monitoring activity based on the collection of standard recording and reporting forms from a representative sample of Italian TB Units. The forms with individual data were reviewed and analysed on a quarterly basis, 9 months after enrolment. The complete bacteriological profile of patients was analysed at diagnosis and at the completion of treatment. Individual data on 992 patients were analysed. At diagnosis 320 (32.2%) of cases were pulmonary sputum smear positive, 361 (36.4%) pulmonary smear negative or not done and 311 (33.4%) extrapulmonary; 424 (42.7%) of all TB cases were culture confirmed at diagnosis (368, 50.2%, of pulmonary cases); 575 (84.4%) of pulmonary cases had a culture done at diagnosis and 156 (22.9%) at the end of treatment (p < 0.001); 572 (84%) had a sputum smear done at diagnosis and 164 (24.1%) at the end of treatment (p < 0.001). Although the rate of bacteriologically confirmed cases is similar to that of other European countries, the bacteriological confirmation at diagnosis and, particularly, at the end of treatment, is sub-optimal. The importance of further disseminating national guidelines among physicians managing TB is emphasized, in order to achieve a higher proportion of TB cases bacteriologically confirmed at diagnosis and monitored at the end of treatment.

In Italy, no national data on tuberculosis (TB) treatment results were available. In 1995, the AIPO (Italian Association of Hospital Pneumologists) TB Study Group, in collaboration with the Istituto Superiore di Sanità (technical branch of the Ministry of Health), started a prospective monitoring activity based on World Health Organization (WHO) and International Union against Tuberculosis and Lung Disease (IUATLD) recommendations. Data were collected from a nationwide network of 41 TB units, managing a significant proportion of all TB cases notified in Italy each year. The aim of this study was to analyse the case findings and treatment results for the year 1995. Seven hundred and seventy eight TB cases were reported (59% males; 21% immigrants), 640 (82%) being new cases. Of these cases, 517 (66%) were pulmonary, 239 (31%) extrapulmonary and 22 (3%) both pulmonary and extrapulmonary. The main risk factors for TB were a history of recent contact and alcohol abuse among native Italians and human immunodeficiency virus-seropositive status among immigrants. The majority of immigrants were from Africa and South America, and had been in Italy > 24 months before diagnosis of TB. Thirty-seven per cent of patients had a positive direct sputum smear examination for alcohol acid-fast bacilli; 20% were resistant to any drug (monoresistance to isoniazid 3.5%; multidrug resistance 5.2%). In 95% of cases, the duration of treatment was < 12 months. The overall success rate (cured plus treatment completed) was 81.1%. A significantly higher percentage of deaths was found in native Italians (being age-related), whereas immigrants had a higher default rate.

In Italy no national data have been available on tuberculosis (TB) treatment results. In 1995 the AIPO (Italian Association of Hospital Pneumologists) TB Study Group, in collaboration with the Istituto Superiore di Sanità (technical branch of the Ministry of Health) started a prospective monitoring activity based on the recommendations of the World Health Organization and the International Union Against Tuberculosis and Lung Disease. The aim of this study was to analyse the case findings and treatment results during 1997. Data were collected from a representative network of TB units nation-wide, managing a significant proportion of all TB cases notified in Italy each year. A total of 715 TB cases were reported (56% males; 24% immigrants), of which 635 (89%) were new cases. Of these cases 493 (69%) were pulmonary, 187 (26%) extra-pulmonary cases and 35 (5%) both pulmonary and extrapulmonary. The main risk factors for TB were history of recent contact and diabetes among native Italians, human immunodeficiency virus-seropositive status and a history of recent contact among immigrants. The majority of immigrants came from Africa and Central and South America, and stayed in Italy for more than 24 months before the diagnosis of TB was made. Thirty-six per cent of patients had a positive direct sputum smear examination for alcohol acid-fast bacilli and 27% were resistant to any drug (monoresistance to isoniazid: 2.4%; multi-drug resistance: 7.5%). In 97% of cases the duration of treatment was < 12 months. The overall success rate (cured plus treatment completed) was 78.1%. A significantly higher percentage of deaths, which was age related, was found in native Italians, while immigrants had a higher default rate. In conclusion, case finding and treatment results in Italy in 1997 are similar to those described in 1995 and 1996.

Although in developing countries the treatment of tuberculosis (TB) cases is among the most cost-effective health interventions, few studies have evaluated the cost-effectiveness of TB control in low-prevalence countries. The aim of the present study was to carry out an economic analysis in Italy that takes into account both the perspective of the resource-allocating authority (i.e. the Ministry of Health) and the broader social perspective, including a cost description based on current outcomes applied to a representative sample of TB patients nationwide (admission and directly observed treatment (DOT) during the initial intensive phase of treatment); a cost-comparison analysis of two alternative programmes: current policy based on available data (scenario 1) and an hypothetical policy oriented more towards outpatient care (scenario 2) (both scenarios included the option of including or not including DOT outside hospital admission, and incentives) were compared in terms of cost per case treated successfully. Indirect costs (such as loss of productivity) were included in considerations of the broader social perspective. The study was designed as a prospective monitoring activity based on the supervised collection of forms from a representative sample of Italian TB units. Individual data were collected and analysed to obtain a complete economic profile of the patients enrolled and to evaluate the effectiveness of the intervention. A separate analysis was done for each scenario to determine the end-point at different levels of cure rate (50-90%). The mean length of treatment was 6.6 months (i.e. patients hospitalized during the intensive phase; length of stay was significantly higher in smear-positive patients and in human immunodeficiency virus (HIV) seropositive patients). Roughly six direct smear and culture examinations were performed during hospital admission and three during ambulatory treatment. The cost of a single bed day was US$186.90, whereas that of a single outpatient visit ranged, according to the different options, from US$2.50 to US$11. Scenario 2 was consistently less costly than scenario 1. The cost per case cured for smear-positive cases was US$16,703 in scenario 1 and US$5946 in scenario 2. The difference in cost between the cheapest option (no DOT) and the more expensive option (DOT, additional staff, incentives) ranged from US$1407 (scenario 1, smear-negative and extrapulmonary cases) to US$1814 (scenario 2, smear-positive cases). The additional cost to society including indirect costs ranged from US$1800 to US$4200. The possible savings at the national level were in the order of US$50 million per year. In conclusion, cost-comparison analysis showed that a relatively minor change in policy can result in significant savings and that the adoption of DOT will represent a relatively modest economic burden, although the real gain in effectiveness resulting from DOT in Italy requires further evaluation.

In Italy, no national data on tuberculosis (TB) treatment results were available. In 1995, the AIPO (Italian Association of Hospital Pneumologists) TB Study Group, in collaboration with the Istituto Superiore di Sanità (technical branch of the Ministry of Health), started a prospective monitoring activity based on World Health Organization (WHO) and International Union against Tuberculosis and Lung Disease (IUATLD) recommendations. Data were collected from a nationwide network of 41 TB units, managing a significant proportion of all the TB cases notified in Italy each year. The aim of this study was to analyse the case findings and treatment results for the year 1996. Eight hundred and thirty eight TB cases were reported (56% males; 26% immigrants), 708 (84%) being new cases. Of these cases, 565 (67%) were pulmonary, 235 (28%) extrapulmonary and 38 (5%) both pulmonary and extrapulmonary. The main risk factors for TB were a history of recent contact and diabetes among native Italians and recent contact and human immunodeficiency virus-seropositive status among immigrants. The majority of immigrants were from Africa and Asia, and had been in Italy > 24 months before diagnosis of TB. Thirty-six per cent of patients had a positive direct sputum smear examination for alcohol acid-fast bacilli; 37% were resistant to any drug (monoresistance to isoniazid 4.4%; multidrug resistance 10.4%). In 96% of cases, the duration of treatment was < 12 months. The overall success rate (cured plus treatment completed) was 84.1%. A significantly higher percentage of deaths was found in native Italians (being age-related), whereas immigrants had a higher default rate.

SETTING:A national survey including 203 pulmonary centres (PCs) (144 hospital PCs with beds dedicated to TB patients and 59 out-patient PCs) managing tuberculosis cases in Italy during 1995.OBJECTIVES:To evaluate: 1) hospitalisation practices (criteria for admission/discharge; duration of hospitalisation) as primary end-points; and 2) as secondary end-points the availability of beds, the preventive measures adopted to reduce the spread of infection, the sources of referral for hospitalisation and the procedures adopted to follow up TB patients after discharge.DESIGN:A 26-point questionnaire mailed to 203 PCs.RESULTS:Of 167 PCs that responded to the questionnaire (82.3%), 159 questionnaires were considered valid for the analysis (110 from hospitals PCs and 49 from out-patient PCs). The criteria adopted by PCs to admit TB patients were: all TB cases 47%, only smear-positive pulmonary TB 14%, TB cases with clinical problems 39%. Hospital PCs hospitalised significantly more cases of smear-negative, extra-pulmonary TB. On average 71.6% of all cases were hospitalised (88.2% by hospital and 28% by out-patient PCs). The median hospital stay was 34 days for sputum smear-positive, 20 for sputum smear-negative and 21.5 for extra-pulmonary TB cases. Sputum conversion was considered the mandatory criterion to allow discharge from 61% of hospital PCs.CONCLUSION:A switch from the present policy (majority of cases hospitalised for a long period) to an outpatient oriented policy needs the co-ordinated educational effort of scientific societies and health authorities.

The aim of the present multicentre, open, randomized, parallel group study was to evaluate the efficacy and safety of salmeterol versus theophylline in asthmatic patients. A total of 112 patients were randomized: 56 received inhaled salmeterol (50 micrograms twice daily) and 50 oral dose titrated theophylline twice daily. The study lasted 12 months. The efficacy of both drugs was evaluated for the first 3 months of the study and the safety for a further 9 months. Spirometric measurements were carried out for the total duration of the study. Salmeterol showed a greater and more significant efficacy than theophylline in reducing both day- and night-time symptoms (P < 0.001) and in reducing additional salbutamol requirement (P < 0.001). The subjective assessment of efficacy by physicians and patients was in favour of salmeterol from the first month of treatment (P < 0.001). Both drugs improved the quality of life as measured by the specific questionnaire 'Living with Asthma' with no significant differences. The total number of adverse events was slightly higher in the theophylline group compared with salmeterol (18 vs 9; P n.s.). Both salmeterol and theophylline increased morning and evening PEFR with no significant difference. FEV1 and FVC increased in both groups of patients; the difference between the effects of the two treatment was not statistically significant at 12 months. Our study suggests that salmeterol has higher efficacy and safety than theophylline in long-term treatment of asthmatic patients.

SETTING:Epidemiological data on the frequency of drug-resistant tuberculosis is not available in Italy. OBJECTIVES:Evaluation of the rate of multidrug-resistant tuberculosis in the Province of Florence, Italy. DESIGN:Retrospective analysis of all sensitivity tests performed with the Bactec method on initial mycobacterial isolates, from 1 January 1992 to 31 December 1995, in the Province of Florence. RESULTS:The following rates of resistance were found in the 433 samples tested: isoniazid + rifampicin 2.5%, at least one drug 13.8%, isoniazid 10.6%, rifampicin 3.6%, streptomycin 3.6%, pyrazinamide 1.7% and ethambutol 0.6%. Resistance was higher in foreign-born individuals from high prevalence countries than in the Italian-born population, whereas resistance to streptomycin was more frequent in the latter. The yearly rates of resistance showed no significant variation in the period examined. Clinical data were available in 231 patients: the rate of resistance to at least one drug and to isoniazid + rifampicin were 10.8% and 0%, respectively, in never treated patients, and 28.5% and 7.1%, respectively, in previously treated patients. CONCLUSION:These data show higher multidrug resistance rates than those found in other European countries such as England and Wales, France and Switzerland. This result suggests the need to establish official guidelines for the correct treatment of tuberculosis in Italy, in order to prevent the onset of drug resistance, and to establish a national surveillance system for mycobacterial resistance.

BACKGROUND:In recent years non-invasive ventilatory techniques have been used successfully in the treatment of acute on chronic respiratory failure (ACRF), but careful selection of patients is essential and a comatose state may represent an exclusion criterion. The aim of this retrospective and uncontrolled study was to evaluate whether a non-invasive ventilatory technique such as the iron lung could also be used successfully in patients with hypoxic hypercapnic coma, thus widening the range for application of non-invasive ventilatory techniques.METHODS:A series of 150 consecutive patients with ACRF and hypoxic hypercapnic coma admitted to our respiratory intensive care unit were evaluated retrospectively. The most common underlying condition was chronic obstructive pulmonary disease (79%). On admission a severe hypoxaemia (Pao2 5.81 (3.01) kPa) and hypercapnia (Paco2 14.88 (2.78) kPa) associated with a decompensated acidosis (pH 7.13 (0.13)) were present, the Glasgow coma score ranged from 3 to 8, and the mean APACHE II score was 31.6 (5.3). All patients underwent intermittent negative pressure ventilation with the iron lung. The study end point was based on a dichotomous classification of treatment failure (defined as death or need for endotracheal intubation) versus therapeutic success.RESULTS:There were 45 treatment failures (30%) and 36 deaths (24%). Nine patients (6%) required intubation because of lack of airway control. The median total duration of ventilation was 27 hours per patient (range 2-274). The 105 successfully treated cases recovered consciousness after a median of four hours (range 1-90) of continuous ventilatory treatment and were discharged after 12.1 (9.0) days.CONCLUSIONS:These results show that, in patients with acute on chronic respiratory failure and hypoxic hypercapnic coma, the iron lung resulted in a high rate of success. As this study has the typical limitations of all retrospective and uncontrolled studies, the results need to be formally confirmed by controlled prospective studies. Confirmation of these results could widen the range of application of non-invasive ventilatory techniques.

Noninvasive ventilatory supports are gaining a prominent position among ventilatory techniques aimed to improve ventilation in patients with acute-on-chronic respiratory failure (ACRF). It has not yet been established whether these techniques can be considered as a preventive measure to avoid the need for endotracheal intubation, or are really another means to provide full ventilatory support. At our respiratory intensive care unit (RICU), the ventilatory treatment of ACRF has, for many years, been based on a conservative method, which relies on the use of a body ventilator (iron lung) providing intermittent negative pressure ventilation (INPV). From 1975 to 1991, we treated ACRF in 2,116 patients with chronic obstructive pulmonary disease (COPD) and 604 patients with restrictive thoracopulmonary disease (RTD). Two thousand and eleven patients (95%) underwent INPV. The mortality rate during hospitalization was 9.9% for the patients as a whole (10% and 8.9% for COPD and RTD patients, respectively). The mean length of stay in the RICU was 10.5 +/- 9.5 days. Furthermore, we report the results of our previous studies which investigated how the iron lung works, and how it affected the short- and long-term prognosis of COPD patients in ACRF. Finally, in 180 patients, we report the effects of INPV provided by iron lung on the treatment of ACRF with hypoxic hypercapnic coma (HHC). INPV resulted in a significant improvement of arterial blood gas values and pH, associated with a progressive recovery of the level of consciousness. Only 13 patients needed intubation and 41 (23%) died during hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated retrospectively the effect of long-term oxygen therapy (LTOT) on the prognosis of 35 patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory insufficiency (group A) who were admitted to our respiratory intensive care unit from 1984 to 1986 for acute respiratory failure (ARF). All subjects were given intermittent negative pressure ventilation (INPV) by means of an iron lung to overcome the acute episode and were treated with LTOT after discharge. Forty-four patients with COPD who were treated with the same ventilatory method to overcome an acute disease exacerbation and who were not given LTOT were used as controls (group B). Both groups were followed up for at least 48 months. All relapses of ARF were treated by iron lung in both groups A and B. The overall survival was significantly better in group A than in group B (p = 0.05 by F test) indicating that LTOT improves survival in patients with COPD after a bout of ARF treated with mechanical ventilation. Therefore, combining INPV with LTOT for overcoming acute episodes and relapses of ARF appears to improve the prognosis of patients with COPD.