Biomedical subjects
P Elliott
Publications and source records attributed to P Elliott.
A CRITICAL REVIEW OF THE PFANNENSTIEL INCISION IN OBSTETRICS AND GYNAECOLOGY.
Explore the source record for details and available documents.
THE RELATIONSHIP OF LIQUOR VOLUME AND PLACENTAL INSUFFICIENCY.
Explore the source record for details and available documents.
Hypertrophic cardiomyopathy.
Explore the source record for details and available documents.
Empirical Bayes estimation of small area prevalence of non-rare conditions.
Geographical studies are becoming increasingly common in epidemiology. The problems of small area investigations are well known, and several methods are available for the estimation and mapping of disease risk across small areas, with the emphasis mainly on applications concerning rare disease incidence or mortality. An empirical Bayes method is proposed for small area estimation of the prevalence of non-rare conditions, whose variability is binomial and cannot be approximated by a Poisson model. It is the direct equivalent of a semi-parametric non-iterative moment estimation method proposed in the Poisson case. As an example, the geographical distribution of the prevalence of respiratory symptoms in schoolchildren across 71 small areas in Huddersfield, Northern England is studied. Whereas random variability causes the crude area-specific prevalences to be unstable, the posterior estimates, corrected towards overall or local means, are capable of highlighting genuine extra-binomial variability. The method is very simple and can readily be applied to the study of a number of common conditions.
Use of Stone's method in studies of disease risk around point sources of environmental pollution.
The Small Area Health Statistics Unit is a national facility funded by the U.K. government for the analysis of disease risk around sources of environmental pollution. It holds cancer incidence (from 1974) and mortality data (from 1981) for Great Britain. Data retrieval is based on the postcode of residence, relating on average to 14 households. Population data for the calculation of disease rates and small area measures of socioeconomic deprivation are from census small area statistics for 1981 and 1991. Isotonic regression methods first described by Stone are used to test for declines in disease risk with distance from point sources of environmental pollution. This paper describes modifications of the method to include adjustments for socioeconomic confounding, a conditional approach to allow for generally elevated risks near the source, and methods to deal with pooling of data around a number of point sources. Examples from recent studies are given.
Issues in the statistical analysis of small area health data.
The availability of geographically indexed health and population data, with advances in computing, geographical information systems and statistical methodology, have opened the way for serious exploration of small area health statistics based on routine data. Such analyses may be used to address specific questions concerning health in relation to sources of pollution, to investigate clustering of disease or for hypothesis generation. We distinguish four types of analysis: disease mapping; geographic correlation studies; the assessment of risk in relation to a prespecified point or line source, and cluster detection and disease clustering. A general framework for the statistical analysis of small area studies will be considered. This framework assumes that populations at risk arise from inhomogeneous Poisson processes. Disease cases are then realizations of a thinned Poisson process where the risk of disease depends on the characteristics of the person, time and spatial location. Difficulties of analysis and interpretation due to data inaccuracies and aggregation will be addressed with particular reference to ecological bias and confounding. The use of errors-in-variables modelling in small area analyses will be discussed.
Statistical issues in the analysis of disease mapping data.
In this paper we discuss a number of issues that are pertinent to the analysis of disease mapping data. As an illustrative example we consider the mapping of larynx cancer across electoral wards in the North West Thames region of the U.K. Bayesian hierarchical models are now frequently employed to carry out such mapping. In a typical situation, a three-stage hierarchical model is specified in which the data are modelled as a function of area-specific relative risks at stage one; the collection of relative risks across the study region are modelled at stage two; and at stage three prior distributions are assigned to parameters of the stage two distribution. Such models allow area-specific disease relative risks to be 'smoothed' towards global and/or local mean levels across the study region. However, these models contain many structural and functional assumptions at different levels of the hierarchy; we aim to discuss some of these assumptions and illustrate their sensitivity. When relative risks are the endpoint of interest, it is common practice to assume that, for each of the age-sex strata of a particular area, there is a common multiplier (the relative risk) acting upon each of the stratum-specific risks in that area; we will examine this proportionality assumption. We also consider the choices of models and priors at stages two and three of the hierarchy, the effect of outlying areas, and an assessment of the level of smoothing that is being carried out. For inference, we concentrate on the description of the spatial variability in relative risks and on the association between the relative risks of larynx cancer and an area-level measure of socio-economic status.
Selective delivery of herpes virus vectors to experimental brain tumors using RMP-7.
RMP-7, a bradykinin analog, has been shown to selectively open the blood-tumor barrier for the delivery of chemotherapeutic drugs to brain tumors. In contrast to bradykinin, RMP-7 has no hypotensive effects and has been approved for human use. This study was initiated to determine whether RMP-7 would open the blood-tumor barrier to virus vectors encoding tumor-killing genes in an experimental model. The herpes virus vector used, hrR3, which encodes virus thymidine kinase gene and the lacZ reporter gene, is defective in a gene encoding ribonucleotide reductase, replicates selectively in dividing tumor cells and not in postmitotic neural cells. It was determined that an optimum dose of RMP-7 (1.5-3.0 microg/kg over 10-15 minutes) enhanced viral delivery to brain tumors in rats bearing intracranial 9 L gliosarcomas when infused through the carotid artery immediately prior to virus vector application. Maximum expression of the lacZ reporter gene occurred at 3 days after intracarotid infusion. By 8 days, transgene expression was largely confined to tumor foci away from the main tumor mass. Viral delivery was essentially specific to tumor cells, with little transgene expression elsewhere in the brain. Minimal uptake and pathology was noted in the kidney, spleen, and liver. These findings indicate that intracarotid delivery of RMP-7 can augment the selective delivery of virus vectors to brain tumors in an experimental rat model, with the potential for application to human brain tumors.
Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies.
We have reviewed the relevant issues in the exposure assessment of disinfection by-products (DBPs) of chlorination for epidemiological and health risk assessment. Various DBPs can be detected in drinking water and swimming pools, and the reported levels show a considerable range, but were generally below the current health standard for total trihalomethanes (TTHMs) (100 microg/l). Relatively little information is available on the correlation between the various DBPs in drinking water and in swimming pools. Chloroform was generally, but not always, the most predominant DBP. In epidemiological studies, TTHM levels have been used as an indicator for total DBP load, even though TTHM levels do not always correlate well with individual DPBs. Factors such as residence time, temperature, pH, organic content, including humic and fulvic acid and bromide levels affect the composition and levels of DBPs. Although there are biomarkers of DBPs, mainly for chloroform and more recently for the other volatile trihalomethanes (THMs) and the nonvolatile haloacetic acids (HAAs) such as trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA), they have not been used in epidemiological studies. The THMs have been measured in exhaled breath and serum, while the HAAs have been measured in urine. These biomarkers have been useful to estimate the actual uptake of the DBPs and the relative contribution of various exposure routes. Physiologically based pharmacokinetic (PBPK) models exist for, e.g. chloroform, but their main target organs are the kidney and liver and they have not been used in epidemiological studies. Tap water ingestion, showering, bathing, swimming, boiling water and dishwashing are all activities that have been associated with the uptake of DBPs, and considerable variation in these activities has been observed between people. No studies have reported on the correlation between human uptake of DBPs and water-zone mean estimates, but various studies found a good correlation between THM concentrations in exhaled breath and THM concentrations in water during showering and swimming. In general exposure assessment in epidemiological studies has been limited which complicates the interpretation. These findings have implications for epidemiological studies, particularly with reference to Berkson and classical error type models, study power, attenuation and precision of health-risk estimates and study efficiency. Recommendations are made for further areas of study.
Quantifying risk of death and disability associated with raised blood pressure.
Raised blood pressure is one of the most important underlying risk factors for morbidity and mortality in the world today, ranking alongside tobacco in estimates of the worldwide attributable burden of mortality. It is a major risk factor for coronary heart disease and the major risk factor for stroke. Taken together, the cardiovascular diseases are estimated to account for some 28% of all deaths in the world. Already many more of such deaths are occurring in the developing than the developed world, and this burden of disease is set to worsen as a result of demographic changes in the poorer countries, together with adoption of Western lifestyle. The development of unfavourable blood pressure patterns in populations is a key factor underlying this worldwide epidemic. Both primary prevention (for example through improved diet) and secondary prevention (through drug treatment and non-pharmacologic approaches) are needed.
Barking up the right tree.
Explore the source record for details and available documents.
Locality-based teaching.
Explore the source record for details and available documents.