Outcome of the treatment of culture negative tuberculosis (respiratory and non-respiratory): Blackburn 1996-2000.

OBJECTIVE: To determine the outcome of treating patients without culture confirmation of tuberculosis, with a regimen of two months of isoniazid, rifampicin, pyrazinamide and ethambutol followed by four months of isoniazid and rifampicin (2HRZE/4HR) in a setting with a rate of isoniazid resistance of 7.5% in culture confirmed cases. SETTING: Tuberculosis patients treated in the Blackburn, Hyndburn and Ribble Valley districts of the UK between 1996 and 2000 inclusive. METHODS: Patients from a detailed prospective clinical and epidemiological data base for all tuberculosis patients were studied for the years 1996-2000. RESULTS: One hundred and fourteen cases, all but two of Indian subcontinent ethnic origin, without culture confirmation had received 2HRZE/4HR. Twenty had pulmonary, 55 other respiratory and 39 non-respiratory tuberculosis. There was no bacteriologically confirmed relapse, 1 case was retreated as a clinical relapse. CONCLUSION: The treatment of tuberculosis cases without culture confirmation with a regimen of 2HRZE/4HR gives highly acceptable results. The clinical relapse rate was 0.85% (1/114), and the cure rate 99.15%.

Tuberculosis treatment outcome monitoring: Blackburn 1988-2000.

SETTING: All cases of tuberculosis in a high prevalence district (population 269,000) of England. OBJECTIVE: To analyse the tuberculosis programme outcome for confirmed pulmonary tuberculosis, and all other categories of cases for 1988-2000 inclusive. DESIGN: The outcome of all cases treated during the period 1988-2000 inclusive was assessed by agreed European outcome criteria, retrospectively for 1988-1998 and prospectively for 1999-2000. RESULTS: A total of 729 tuberculosis cases were notified, with 209 definite (culture-positive) pulmonary cases. Of the 205 definite pulmonary cases treated in life, 182 received self-administered treatment (SAT) and 23 directly observed treatment (DOT), with an 88% cure/completion rate and a 12% death rate. The relapse rate for SAT was 1/182 (0.5%) and 1/23 for DOT (4.3%). The cure/completion rate for all patients together was 94.3%, with a relapse rate of 0.8%. CONCLUSION: In this resource-rich setting, treatment largely by SAT, but carefully monitored, gives a very high cure/completion rate. Universal rather than selective DOT would make little additional impact on patient outcome. These outcomes are not likely to be reproducible, however, with SAT in a resource-poor setting.

Drug resistance trends in M. tuberculosis: Blackburn 1990-1999.

SETTING: Blackburn, United Kingdom. OBJECTIVE: To describe the drug resistance data for Mycobacterium tuberculosis in white and Indian Subcontinent (ISC) ethnic patients in a high prevalence district in the United Kingdom (UK) over a 10-year period. DESIGN: Data from a detailed prospective clinical and epidemiological database of all notified patients were examined for the years 1990-1999 inclusive. RESULTS: Primary isoniazid resistance was found in 17/229 (7.4%) of ISC and 3/67 (4.5%) of white isolates. There was no statistical difference in the rates of drug resistance in those of ISC ethnic origin, whether they were ISC or UK born and whether or not they had made return visits to the ISC. CONCLUSION: The rate of primary isoniazid resistance remains between 5-10% in ISC patients in Blackburn, showing no fall from previous surveys. The rate of drug resistance was not lower in those born in the UK, irrespective of whether return visits had been made to the ISC. These data will need to be further monitored.

Can a nine-month regimen be used to treat isoniazid resistant tuberculosis diagnosed after standard treatment is started?

OBJECTIVES: National tuberculosis treatment guidelines suggest a regimen of 2RZE/10RE for the treatment of isoniazid resistant organisms. A retrospective clinical study of all patients treated for non-MDR-TB isoniazid-resistant organisms was undertaken. METHODS: A continuous database of the patients treated between 1978-1999 inclusive was examined to determine the regimens used and the outcome of treatment for such patients. RESULTS: Thirty-seven patients were identified. Eighteen had regimens of greater than 9 months, 19 had regimens of 9 months or less. No relapses occurred in those cases treated with a regimen of 2RZE/7RE during 12 months' minimum follow-up. CONCLUSIONS: A regimen of 2RZE/7RE may be possible for the treatment of isoniazid-resistant organisms if given either under close supervision or as a formally supervised regimen. Larger clinical studies or a controlled clinical trial are needed to confirm these initial findings.

How frequently do endobronchial secondaries occur in an unselected series?

Isolated endobronchial secondaries are reported usually as single cases or in series from either specialist surgical or cancer units. The latter two are selected populations and are not a good guide to the true frequency of occurrence of such isolated endobronchial secondaries. The incidence of such endobronchial secondaries in a 15 yr prospective series is reported. Results of all fibre-optic bronchoscopies carried out in the Blackburn, Hyndburn and Ribble Valley districts from 1981 to 1995 together with histology were recorded prospectively throughout the period. These had been audited yearly throughout, the data were collated, and the individual records of cases of endobronchial secondaries examined. A total of 3353 bronchoscopies were carried out in the years 1981-1995 inclusive. Of these, 1391 had visible endobronchial abnormalities, from which 1059 had positive endobronchial histology. Sixteen of the 1059 (1.5%) were with endobronchial secondaries. Over the same period eight bronchial carcinoids (none biopsied, but later surgically resected) were encountered. Isolated endobronchial secondaries made up a higher proportion of endobronchial histology than expected at 1.5% and were twice as frequently found as bronchial carcinoids. The possibility of endobronchial secondaries should always be considered in those with a history of previous carcinomas at other sites.

Frequency and type of reactions to antituberculosis drugs: observations in routine treatment.

SETTING: United Kingdom, 1978-1992. OBJECTIVE: To assess the incidence and type of reactions to antituberculosis drugs in an unselected series of patients. DESIGN: All patients treated for tuberculosis had details of drug treatment, durations and side-effects requiring alteration of treatment available. The data was compiled retrospectively for 1978-1980 patients and prospectively thereafter. Analysis of drug reactions was by drug, total months drug use, by age, sex and ethnic group, and reaction type. RESULTS: Of 1317 patients 67 (5.1%) had 70 reactions to antituberculosis drugs requiring modification of treatment. The frequency of drug reactions increased from 2.3% at age 0-19 to 4.6% at age 20-39, 7.1% for age 40-59 and to 8.4% for those aged 60 and over. Females had significantly higher reactions rates than males. White patients had higher reaction rates than Pakistani and Indian patients, mainly due to the average age being greater. CONCLUSION: The drug reaction rate of 5.1% in this largely prospective study is lower than that reported in other unselected series in the UK and other countries.

Miliary tuberculosis in a high prevalence area of the U.K.: Blackburn 1978-1993.

Thirty-nine cases of military tuberculosis treated between 1978-1993 in a district with a high incidence of tuberculosis are reported. Twenty-eight patients were of Indian Subcontinent (ISC) ethnic origin, 10 patients were Caucasian and one patient was Chinese. Mortality at 10% in both Caucasian (chi2 4.94; 0.05 > P > 0.01) and ISC patients (chi2 10.22; 0.001 > P) were significantly lower than in a recently reported series from Edinburgh, as was the proportion of post mortem diagnoses of miliary tuberculosis (chi2 6.35; 0.02 > P > 0.01). Both the rate of miliary tuberculosis and the average age at diagnosis in Caucasian patients were lower than in the Edinburgh series suggesting that miliary tuberculosis could be under-diagnosed in the elderly Caucasian population in the Blackburn district. The better outcome of those diagnosed in life may be partly due to heightened awareness of tuberculosis locally and partly due to treatment by a centralized tuberculosis service.

Short-course chemotherapy for tuberculous pleural effusion and culture-negative pulmonary tuberculosis.

SETTING: Chest Clinics at Blackburn and Newham, UK. OBJECTIVE: To test the efficacy of a short-course regimen of 6 months rifampicin and isoniazid supplemented by 2 months initial pyrazinamide (2HRZ-4HR), in the treatment of smear and culture-negative pulmonary tuberculosis and tuberculous pleural effusion in routine clinical practice. DESIGN: The results of 152 patients with these forms of tuberculosis treated between 1981 and 1991 were analysed retrospectively. RESULTS: 127 patients, 65 with pleural effusion and 62 with culture-negative pulmonary tuberculosis, completed treatment as planned. 100 were followed up for a mean duration 20.5 months (range 4-72) for culture-negative disease and 14.6 months (range 3-46) for pleural effusion. There were no relapses, giving a relapse rate of 0% (95% confidence interval 0-3.62%). CONCLUSION: Unsupervised self-administered treatment with 2HRZ/4HR is a highly effective regimen for culture-negative pulmonary tuberculosis and tuberculous pleural effusion in service conditions.

First use of G-CSF in chlorpromazine-induced agranulocytosis: a report of two cases.

Chlorpromazine-induced agranulocytosis is an uncommon disorder associated with a high frequency of fatality. We describe two patients with chlorpromazine-induced granulocytosis in whom granulocyte colony stimulating factor (G-CSF) administration enhanced the speed of neutrophil recovery. No toxicity was noted with G-CSF and both patients made a successful recovery. We propose there is a role for such cytokine therapy in patients with life-threatening agranulocytosis in order to speed the recovery of neutrophils.

Short course chemotherapy for pulmonary tuberculosis.

A retrospective survey of the treatment of culture positive pulmonary tuberculosis with a standard 6-month course of unsupervised therapy, comprising rifampicin and isoniazid daily for 6 months with pyrazinamide for the first 8 weeks is reported. Of the 164 patients who commenced this regimen, 110 completed therapy as planned. There were five relapses, three of whom admitted significant non-compliance, giving a relapse rate of 4.59% (95% confidence interval, 1.49-10.7). The regimen gives satisfactory results in routine unsupervised treatment.

Etoposide compared with the combination of vincristine, doxorubicin, and cyclophosphamide in the treatment of small cell lung cancer.

One hundred and three patients with small cell lung carcinoma were stratified according to stage of disease (47 limited disease, 56 extensive disease) and then randomised to receive etoposide 300 mg/m2 alone for two days or a combination (VAC) of vincristine 1 mg/m2, doxorubicin (Adriamycin) 50 mg/m2, and cyclophosphamide 1000 mg/m2. The drugs were given at three week intervals. Patients were assessed after three cycles of treatment and continued with the same regimen if in complete remission and with the alternative regimen if in partial remission; they were withdrawn if the disease had progressed. Twenty four patients (23%) achieved complete remission and this occurred more often when patients were receiving VAC (19 of 82) than etoposide (5 of 75). There was no difference, however, in overall survival between those initially treated with etoposide and those having combination chemotherapy, whether for limited disease (both 8 months) or extensive disease (7 and 5.5 months). Toxicity was less with etoposide. Survival was disappointing, especially with limited disease, even in patients who showed a complete response to treatment.

Short-course antituberculous chemotherapy for pulmonary and pleural disease: 5 years' experience in clinical practice.

One hundred and twenty-four patients have been treated with 6-month regimens for pulmonary and pleural tuberculosis over 5 years; 118 patients have completed treatment as planned. No patient has relapsed of the 109 followed up for 15 months from the end of chemotherapy, or in the remaining nine patients still under observation. Significant drug side effects requiring alteration of treatment occurred in only three patients. Six-month regimens in routine practice are well tolerated and are highly effective.

Occupational asthma in a factory with a contaminated humidifier.

Thirty five printers who had work related wheeze, chest tightness, or breathlessness kept two hourly records of their peak expiratory flow for at least two weeks. They all worked in a factory supplied by air from contaminated humidifiers. The peak flow records showed consistent work related deterioration in 15 workers, nine of whom had a diurnal variation in peak flow exceeding 20%. Ten workers kept further records after the humidifiers had been cleaned, other work practices remaining unchanged. There was substantial improvement in all 10 workers, implying that material from the contaminated humidifier was the cause of the work related changes in peak flow. The patterns of work related changes in peak flow fell into four groups: falls maximal on the first work day, falls maximal midweek, falls equivalent each work day, and falls progressive throughout the working week. Three quarters of this last group had immediate prick test responses to humidifier antigen, which were negative in all the others with work related changes in peak flow. This suggests that the progressive daily deterioration pattern alone is due to an IgE mediated response to humidifier antigens. A large range of microorganisms was identified in the humidifiers. No single microorganism appeared to be the antigen responsible for the precipitating antibody seen in 75% of the study population.