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J F Bithell

Publications and source records attributed to J F Bithell.

At least 19 recordsLinked to original sources

Childhood leukaemia clustering--fact or artefact?

There is a general belief that the clustering of childhood leukaemia is a widespread phenomenon and that it provides evidence for appreciable environmental influence on the incidence of the disease. We discuss this issue critically, identifying different kinds of clustering and their possible aetiological mechanisms and examining some analyses of British data. We argue that, in some cases, analyses have been used which lead to dubious conclusions, and that, allowing for multiple testing and anecdotal reporting, the total evidence for clustering is at best weak.

Bias↗

Uranium-235 and childhood leukaemia around Greenham Common airfield.

There has been considerable publicity recently concerning the possible release of enriched uranium from the Greenham Common USAF base near Newbury in Berkshire. Evidence for the release relies on an internal report of the Atomic Weapons Research Establishment at Aldermaston, the authors of which postulated that it resulted from a fire in 1958 involving a B47 bomber standing on the runway. Their report contained a much publicised contour map of excess 235U levels estimated from the ratio of 235U to 238U in 26 evergreen leaf samples examined. The current concern of the inhabitants of Newbury centres mostly on the incidence of leukaemia, which was known beforehand to be slightly elevated in parts of West Berkshire, at least for young children. A number of cases have received considerable press publicity, with suggestions that their homes are located close to the base or the flight-path. The reports are, however, anecdotal and are not based on a complete register of cases. We have examined the evidence for this putative association by re-analysing the uranium data and determining the spatial relationship to the base of cases of childhood leukaemia diagnosed in the years 1966-87. We conclude that, although the excess uranium found has a non-random distribution, it does not support the pattern depicted by the contours and bears no relation to the incidence of childhood leukaemia for the period we examined. In any case, the increase in level of environmental radiation as a result of the putative release must be very small and is at variance with the reporting in some of the national press.

Child↗

Apparent association between benzene and childhood leukaemia: methodological doubts concerning a report by Knox.

A recent study by Knox concludes that cases and "clusters" of two or more cases of childhood leukaemia and non-Hodgkin's lymphoma occur closer to many kinds of industrial installation than to supposedly comparable control locations. It is argued that these findings could be largely or entirely artefactual, the apparent differences arising out of the inappropriateness of the control data. Knox used randomly selected postcode units as controls, a procedure that leads to the comparison of individuals located in areas with typically quite different population densities from those for the cases. The resulting potential for bias is explored and the arguments are exemplified by analysing household data based on postcodes.

Benzene↗

Controlling for socioeconomic confounding using regression methods.

STUDY OBJECTIVE: To describe the advantages of using Poisson regression methods as an alternative to standardisation when computing expected numbers of disease occurrences adjusted for possible confounding factors. The problem of assessing the adequacy of model fit when the expectations are small is addressed by analytical calculations and by simulation. The method is illustrated with data from the national register of childhood tumours. DESIGN: The tumour data are recorded in a national register. SETTING: England, Scotland, and Wales. SUBJECTS: The cases considered are all children registered with leukaemia or non-Hodgkin lymphoma under the age of 15 years between 1966-87. MAIN RESULTS: The methods show a significant variation of leukaemia incidence in relation to the Register General's standard region and a negative association with socioeconomic deprivation, as measured by the Townsend index. After allowing for these variables, the incidence seems to be reasonably homogeneous throughout the population, in the sense that the residual deviance does not seem to be much larger than would be expected by chance. CONCLUSIONS: The methods described have major advantages over standardisation in controlling for confounding, both in terms of flexibility of factor selection and assessment and also in the ability to determine whether there is residual variability of incidence after allowing for these factors.

Child, Preschool↗

Estimation of relative risk functions.

The risk associated with different levels of a quantitative factor X is often measured relative to the level corresponding to X = 0. There are situations, however, where there is no natural zero for X, for example where the risk factor is the age of an individual. In this case it is more natural to measure risk relative to an overall average for the study population. To use the whole population in this way also raises the possibility of regarding X as truly continuous, rather than as a grouped variable. This gives rise to the concept of a relative risk function. Methods for estimating such functions are discussed, concentrating for the most part on the discrete case. The extension to higher dimensions permits the investigation of joint effects of several factors, while the problem of controlling for confounding variables can be handled by fitting multiplicative risk models. Relating the latter to the log-linear model permits the estimation of adjusted relative risk functions. The method is illustrated using data on childhood cancer. The continuous case can in principle be handled in a similar way using density estimation techniques.

Epidemiologic Methods↗

An application of density estimation to geographical epidemiology.

A relative risk function over a geographical region is defined and it is shown that it can be estimated effectively using kernel density estimation separately for the spatial distribution of disease cases and for a sample of controls. This procedure is demonstrated using data on childhood leukaemia in the vicinity of the Sellafield nuclear reprocessing plant in Cumbria, U.K. Various modifications to the method are proposed, including the use of an adaptive kernel. The final plot demonstrates a sharp peak at Sellafield and a reasonably smooth surface over the rest of the region, despite the small number of cases in the series.

Child↗

On statistical methods for analysing the geographical distribution of cancer cases near nuclear installations.

There is great public concern, often based on anecdotal reports, about risks from ionising radiation. Recent interest has been directed at an excess of leukaemia cases in the locality of civil nuclear installations at Sellafield and Sizewell, and epidemiologists have a duty to pursue such information vigorously. This paper sets out to show that the epidemiological methods most commonly used can be improved upon. When analysing geographical data it is necessary to consider location. The most obvious quantification of location is ranked distance, though other measures which may be more meaningful in relation to aetiology may be substituted. A test based on distance ranks, the "Poisson maximum test", depends on the maximum of observed relative risk in regions of increasing size, but with significance level adjusted for selection. Applying this test to data from Sellafield and Sizewell shows that the excess of leukaemia incidence observed at Seascale, near Sellafield, is not an artefact due to data selection by region, and that the excess probably results from a genuine, if as yet unidentified cause (there being little evidence of any other locational association once the Seascale cases have been removed). So far as Sizewell is concerned, geographical proximity to the nuclear power station does not seem particularly important.

Cluster Analysis↗

A new calculation of the carcinogenic risk of obstetric X-raying.

The association between obstetric X-raying and childhood cancer was first identified by the Oxford Survey of Childhood Cancers in 1956. The present re-analysis exploits the case-control matching of the study while incorporating the effects of important risk determinants, notably year of birth, trimester of exposure and number of films exposed. The decline in risk over time is closely mirrored by the estimated decline in dose per film and, by constraining these two relationships to be parallel, time-invariant estimates of the extra risk per mGy are obtained. For example, it is now estimated that irradiating 10(6) foetuses with 1 mGy of X-rays would, in the absence of other causes of death, yield 175 extra cases of cancer and leukaemia in the first 15 years of life.

Adolescent↗

Relationship between lower oesophageal contractility, clinical signs and halothane concentration during general anaesthesia and surgery in man.

The effects of a range of concentrations of halothane upon lower oesophageal contractility (LOC) and on defined clinical signs has been studied in patients undergoing surgery. Changes in clinical signs were assigned a numerical value by means of a scoring system. One hundred and eighty-one sets of measurements were made in 46 patients exposed to concentrations of halothane between 2.0 and 0.5 minimum alveolar concentration (MAC). The results were examined to identify relationships between (i) the clinical signs and alveolar halothane concentration, (ii) the clinical signs and LOC and (iii) the changes in LOC and alveolar concentration; significant correlations were found between these variables. Decreasing alveolar halothane concentration was associated with an increase in LOC and these increases in LOC were also associated with increases in the clinical score.

Adult↗

Pre-natal irradiation and childhood malignancy: a review of British data from the Oxford Survey.

This paper reviews data relating to obstetric radiography from the Oxford Survey of Childhood Cancers, i.e. for deaths in Britain from 1953 to 1967. Some 8513 cases were traced and used in the analyses, together with an equal number of matched controls. The relative risk estimate (1-47 overall) does not vary significantly between different tumour groups, for different ages at death, nor between sexes. Other epidemiological factors-sibship position, maternal age, social class, region of residence and maternal morbidity-are analysed and show varying degrees of association, but not sufficient to "explain" the observed risk in terms of a selection effect. The dependence of the risk on the number of films exposed is highly significant and adequately described by a linear relationship. The timing of and reason for the exposure are also examined. Analysis of the risk by year of birth shows a pattern of steadily declining risk for both solid and haematopoietic tumours; this may be partly attributable to lower radiation doses per film exposed but is also due to the smaller numbers of films used. A consequence may well be that the risk-always of small clinical significance-would become virtually undetectable in future investigations.

Adolescent↗

Association between malignant disease in children and maternal virus infections.

The possibility of an association between virus infections during pregnancy and subsequent malignant disease in the child has been investigated using retrospective data from the Oxford Survey of Childhood Cancers. Such an association appears to exist for influenza, chickenpox, and possibly rubella. For influenza and rubella the estimated risk is small; the data do not permit an estimate to be made directly in the case of chickenpox. It is suggested that there may be a specific association between maternal chickenpox and tumours of the nervous system.It is important to emphasize that, even if the relative risk associated with these viruses is fairly large, the number of cases of childhood cancer and leukaemia actually attributable to them is probably very small.

Chickenpox↗

A classification of disease mapping methods.

This paper considers the underlying principles of depicting disease incidence on geographical maps and uses them to attempt a comparative classification of methods. After a discussion of the possibilities for incorporating time, we consider projection methods, some of which have been used to portray information in a manner supposed to be independent of population density. We then distinguish between non-parametric and model-based methods, including models for areal data using Bayesian ideas. Data in point form are also discussed and it is argued that the relative risk function provides a fundamental model useful for assessing different methods as a whole, some of which are known to be flawed and many of which are untested as regards their statistical properties.

Bayes Theorem↗