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Biomedical subjects

J Peto

Publications and source records attributed to J Peto.

At least 109 records · Page 6Linked to original sources
PubMed1978

The hygiene standard for chrysotile asbestos.

Previous studies, including the analysis on which the current 2 fibres/cm3 hygiene standard is based, may have underestimated the risk of morbidity or mortality following exposure to low levels of asbestos dust. Accurate dose-response data at levels below 2 fibres/cm3 are unlikely to be available for the foreseeable future, and the biologically plausible assumption that excess cancer mortality is approximately proportional to dust level should be provisionally accepted. It may be reasonable, however, to postulate a safe threshold for mortality from asbestosis. If excess mortality from asbestos-related disease is proportional to dust level for each cause, approximately 10% of male asbestos workers might, under certain assumptions, eventually die of asbestos-induced disease after 50 years' exposure at 2 fibres/cm3. Peritoneal mesothelioma is usually due to crocidolite (blue asbestos) or other amphiboles, but exposure to chrysotile (white asbestos) alone may lead to a substantial risk of pleural mesothelioma. These predictions are based on rather small numbers in a single factory, and further studies in other working environments are required. Fibre counts based on optical microscopy are likely to be less relevant than total counts by electron microscopy, and excess mortality is virtually confined to men first exposed more than 20 years ago, when little or no accurate data on dust levels were collected.

Asbestos↗
PubMed1977

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.

Drug Evaluation↗
PubMed1977

Analysis of treatment of childhood leukaemia. V. Advantage of reduced chemotherapy during and immediately after cranial irradiation.

This paper compares anti-leukaemic efficiency with toxicity to the patient of chemotherapy during and immediately after central nervous system irradiation. The drug regimen consisted of daily mercaptopurine (MP) and weekly methotrexate (MTX) at the maximum tolerated dose. Of 140 patients with acute lymphoblastic leukaemia allocated to receive this drug regimen during and after cranial irradiation, 8 died in complete remission within 6 months of the end of irradiation. Details of the nature of these deaths are given. This result led the Working Party to modify the chemotherapy scheduled for this stage in treatment. The modified chemotherapy consisted of MP at reduced dosage before and during cranial irradiation and omission of MP and MTX for 3 weeks after irradiation, during which time daily prednisolone with 2 doses of vincristine were substituted. Following that, the treatment reverted to the original schedule of daily MP and weekly MTX at maximum tolerated dose. Of 109 patients allocated to this modified regimen only one died in remission within 24 weeks after cranial irradiation. Analysis of the anti-leukaemic effect of the modified regimen showed that up to 600 days it was at least as effective as the original more intensive regimen. We conclude that there is a definite advantage in keeping chemotherapy to a minimum during and immediately following cranial prophylactic irradiation.

Brain↗
PubMed1977

A mortality study among workers in an English asbestos factory.

The previous report on this cohort study of workers in an asbestos textile factory (Knox et al., 1968) showed little evidence of increased mortality among workers who had entered the factory after the implementation in 1932 of the first Asbestos Industry Regulation (1931) but observed that no firm conclusions could be drawn, as little carcinogenic effect would be expected for 20 years after first exposure. A further 8 1/2 years of follow-up has revealed some asbestos-related disease in this latter group, although very much less than for employees first exposed before 1933. Among the 963 workers first exposed in 1933 or later, mortality was increased for carcinoma of the bronchus (31 deaths; 19-3 expected for all lung cancers) and non-malignant respiratory disease (35 deaths, 25-0 expected), and a further 5 deaths were attributed to pleural mesothelioma.

Adult↗
PubMed1976

An assessment of the carcinogenicity of isoniazid in patients with pulmonary tuberculosis.

In an assessment of the carcinogenicity of isoniazid, 3,842 adult tuberculous patients admitted to 2 sanatoria in the period 1950 to 1957 (that is, in the years immediately before and after the introduction of isoniazid) have been followed up for a mean period of over 19 years. Their mortality has been compared with that expected during the same calendar period in a general population group in England and Wales with the same age and sex distribution. The relative risk of death (the observed divided by the expected number of deaths) from all malignant neoplasms in patients first starting chemotherapy in 1950 to 1952, before the general introduction of isoniazid, was 0.8 for those who received isoniazid at some time, compared with 0.5 for those who never received it; for those first starting chemotherapy in 1953 to 1957, after the general introduction of the drug, the respective risks were 1.4 and 1.8. The relative risk of death from malignant neoplasms was 2.1 in the first 4 years after starting the treatment with isoniazid; this high relative risk is unlikely to be attributable to isoniazid and largely disappears subsequently, for in successive 4-year periods it was 1.3, 0.9, 1.2 and 1.4. The relative risks of death from all malignant neoplasms for patients receiving a total dosage of less than 50, 50-99, 100-199 and 200 g or more were 1.5, 1.5, 1.0 and 1.3, respectively. For patients receiving a maximum daily dose of less than 250 g the relative risk was 1.3, and for those receiving 250 g or more it was 1.2. There was a curious and unexplained difference in the mortality from malignant neoplasms in patients first starting chemotherapy in 1950 to 1952 (relative risk 0.6) and those first starting in 1953 to 1957 (relative risk 1.5). This is being studied further. This study has provided no evidence of a carcinogenic effect of isoniazid in a period of follow-up averaging nearly 20 years. The follow-up is being continued.

Adolescent↗
PubMed1976

Tuberculosis in Scotland: a national sample survey (1968-70). 2. A two-year follow-up of newly-diagnosed respiratory tuberculosis notified in 1968.

The methods and results of therapy during a two-year period of follow-up have been studied in a 50% random sample of the newly notified cases of pulmonary tuberculosis in Scotland for the year 1968. Of the 770 patients, 1.9% died of active tuberculosis, 2.6% were bacteriological failures, the regimen was changed for initial drug resistance in 0.9% and for drug toxicity in 2.6%. Default from chemotherapy in the first year occurred in 8.1% of patients, 4.7% absconding permanently. The bacteriological failure rate in the 372 positive cases was 7.3%. A further 20 patients were diagnosed at necropsy, 16 having died of the disease. Eighty-seven per cent of 372 initially positive patients were in hospital for an average of 18.0 weeks and 65% of 309 initially negative patients for an average of 11.0 weeks. Eighty per cent of the positive patients received streptomycin plus PAS plus isoniazid and a further 10% PAS plus isoniazid, the porportions for the negative patients being 57% and 35%. Side effects occurred in 53% of the patients on the triple regimen and 43% of those on PAS plus isoniazid. The mean duration of chemotherapy for the bacteriologically positive patients was 22.2 months and for those negative 19.1 months, the duration of the initial streptomycin supplement being 4.4 months and 3.4 months, respectively. Corticosteroids were given to 58 (8%) of the 770 patients. Only 6 (0.8%) had surgery for their tuberculosis. Forty-one per cent of the positive patients were off work for more than 6 months and 19% of the negative patients, and 18% and 8% never returned to work. In the two-year period an average of 12.5 radiographs were taken per patient and 10.8 bacteriological specimens were examined for tubercle bacilli. The number of clinic attendances in a full out-patient year averaged 4.2. Urine tests for antituberculosis drugs (invariably PAS) were performed in only 6 of 25 Burghs and 5 of 14 Counties, and were done infrequently in them. A continuous evaluation procedure for tuberculosis therapy programmes is recommended.

Adrenal Cortex Hormones↗
PubMed1976

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design.

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

Clinical Trials as Topic↗
PubMed1975

Treatment of inoperable carcinoma of bronchus.

A randomised prospective trial comparing "no immediate treatment" with single and multiple agent chemotherapy in 188 patients with inoperable carcinoma of the bronchus is reported. No immediate treatment proved a significantly better policy both for patients' survival and for quality of remaining life.

Adenocarcinoma↗
PubMed1975

Pulmonary tuberculosis in Scotland: a national sample survey and follow-up (1968-70). 1. The characteristics of the cases notified in 1968.

A survey has been undertaken of a 50 per cent random sample of 865 patients notified as having pulmonary tuberculosis in 1968 in Scotland. The estimated notification rate for the total population was 33.3 per 100,000. The highest rate for males was 89.8 for those aged 55 or more and for females 29.5 for those aged 25 to 54. The rates for bacteriologically confirmed cases were 51.6 and 16.0, respectively, for these two groups. An independent radiological assessor reported the characteristic appearances of active tuberculosis in 50 per cent of the chest radiographs. Nearly half the patients were referred by general practitioners and 20 per cent were hospital inpatients when diagnosed. Contacts and mass radiography services produced many fewer cases and the proportion of infectious cases in these groups was low. The notification procedure is discussed and it is suggested that as progress towards eradication is made notification information is inadequate, and that standardised supplementary information on severity of disease and infectiousness should be collected, annually or periodically.

Adolescent↗
PubMed1975

Systolic blood pressure variation during the first 6 days of life.

1. Systolic blood pressure was measured by a Doppler ultrasound technique in twenty normal babies on 6 successive days after the day of delivery. In three babies blood pressure was recorded every 15 min for 24 h. 2. Systolic blood pressure during the first 6 days of life was 95 (SEM = 2) mmHg. 3. Systolic blood pressure increased on average by 2 mmHg/day, but increased most between the second and third days of life. 4. Systolic blood pressure was 11 mmHg higher when awake than when the babies were asleep. 5. There was marked within-baby variation in the systolic blood pressure of neonates, which could not be accounted for by age or recognizable changes in level in consciousness.

Age Factors↗