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J Wakefield

Publications and source records attributed to J Wakefield.

At least 19 recordsLinked to original sources
PubMed2007

The interpretation of exposure effect estimates in chronic air pollution studies.

In this article we consider the interpretation of regression parameters used to represent 'chronic' or 'long-term' air pollution exposure effects. Although scientific interest typically lies in understanding such effects at the level of the individual, studies have generally employed a semi-ecological design; outcomes and confounder information are collected on individuals while exposure is only available at the aggregate-or group-level. A precise interpretation of results from a semi-ecological design must take into account the aggregated nature, both spatial and temporal, of the exposure measure. The most common analysis approach for assessing chronic exposure effects has been within the Cox proportional hazards model framework; specific analyses are tailored to accommodate the shortcomings of the available exposure information. We revisit the underlying assumptions of the Cox model and discuss the implications of two common aspects of chronic effects studies: time-dependent exposures and time-varying effects. Focusing on the consequences of temporal aggregation of exposure, we show that an estimate obtained from a time-aggregated semi-ecological design can correspond to very different underlying time-varying exposure and risk scenarios. Further, distinguishing which of these is correct is not possible from the semi-ecological data alone. Our goal is to highlight some statistical issues faced by existing studies of chronic air pollution effects, and aid in the development and planning of future studies.

Air Pollution↗
PubMed2002

Cancer risks in populations living near landfill sites in Great Britain.

Previous studies have raised concerns about possible excess risks of bladder, brain and hepatobiliary cancers and leukaemias near landfill sites. Several cancers have been implicated, but no consistent pattern has emerged. We present a large nationwide analysis of selected cancers near landfill sites in Great Britain. The base population comprised people living within 2 km of 9565 (from a total of 19 196) landfill sites that were operational at some time from 1982 to 1997, with populations living more than 2 km from a landfill as reference. Risks of cancers at the above sites were computed with adjustment for age, sex, year of diagnosis, region and deprivation. National post-coded registers provided a total of 341 856 640 person-years for the adult cancer analyses and 113 631 443 person-years for childhood leukaemia. There were 89 786 cases of bladder cancer, 36 802 cases of brain cancer, 21 773 cases of hepatobiliary cancer, 37 812 cases of adult leukaemia and 3973 cases of childhood leukaemia. In spite of the very large scale of this national study, we found no excess risks of cancers of the bladder and brain, hepatobiliary cancer or leukaemia, in populations living within 2 km of landfill sites. The results were similar if the analysis were restricted to landfill sites licensed to carry special (hazardous) waste. Our results do not support suggestions of excess risks of cancer associated with landfill sites reported in other studies.

Child↗
PubMed2001

Risk of adverse birth outcomes in populations living near landfill sites.

OBJECTIVE: To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. DESIGN: Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. SETTING: Great Britain. SUBJECTS: Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). MAIN OUTCOME MEASURES: All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). RESULTS: For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. CONCLUSIONS: We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various possibilities.

Congenital Abnormalities↗
PubMed2001

Cumulative logit models for ordinal data: a case study involving allergic rhinitis severity scores.

Ordered categorical data arise in numerous settings, a common example being pain scores in analgesic trials. The modelling of such data is intrinsically more difficult than the modelling of continuous data due to the constraints on the underlying probabilities and the reduced amount of information that discrete outcomes contain. In this paper we discuss the class of cumulative logit models, which provide a natural framework for ordinal data analysis. We show how viewing the categorical outcome as the discretization of an underlying continuous response allows a natural interpretation of model parameters. We also show how covariates are incorporated into the model and how various types of correlation among repeated measures on the same individual may be accounted for. The models are illustrated using longitudinal allergy data consisting of sneezing scores measured on a four-point scale. Our approach throughout is Bayesian and we present a range of simple diagnostics to aid model building.

Antibodies, Monoclonal↗
PubMed2001

Spatial variation and temporal trends of testicular cancer in Great Britain.

Increases in testicular cancer incidence have been reported in several countries over a long period. Geographical variability has also been reported in some studies. We have investigated temporal trends and spatial variation of testicular cancer at ages 20-49 in Britain. Temporal trends in testicular cancer incidence were examined, 1974 to 1991 and in mortality, 1981-1997. Spatial variation in incidence was analysed across electoral wards, 1975 to 1991. We used Poisson regression to examine for regional and socio-economic effects and Bayesian mapping techniques to analyse small-area spatial variability. Incidence increased from 6.5 to 11.1 per 100 000 in men at ages 20-34, and from 5.6 to 9.7 per 100 000 in men at ages 35-49, while mortality declined by 50% in both age groups. Risks of testicular cancer varied across regional cancer registries, ranging from 0.79 (95% CI: 0.73-0.84) to 1.32 (95% CI: 1.25-1.38), and was higher in the most affluent compared with the most deprived areas. Analyses within 2 regions (one predominantly urban, the other predominantly rural) did not indicate any localized geographical clustering. The increasing incidence contrasted with a decreasing mortality over time in Great Britain, similar to that found in other countries. The higher risk in more affluent areas is not consistent with findings on social class at the individual level. The absence of any marked geographical variability at small area scale argues against a geographically varying environmental factor operating strongly in the aetiology of testicular cancer.

Adult↗
PubMed2001

Temperature, housing, deprivation and their relationship to excess winter mortality in Great Britain, 1986-1996.

OBJECTIVES: To examine the associations between temperature, housing, deprivation and excess winter mortality using census variables as proxies for housing conditions. DESIGN: Small area ecological study at electoral ward level. Setting Great Britain between 1986 and 1996. PARTICIPANTS: Men and women aged 65 and over. MAIN OUTCOME MEASURES: Deaths from all causes (International Classification of Diseases, Ninth Revision [ICD-9] codes 0-999), coronary heart disease (ICD-9 410-414), stroke (ICD-9 430-438) and respiratory diseases (ICD-9 460-519). Odds of death occurring in winter period of the four months December to March compared to the rest of the year. RESULTS: During the study period (excluding the influenza epidemic year of 1989/90), a total of 1,682,687 deaths occurred in winter and 2,825,223 deaths occurred during the rest of the year among people aged > or =65 (around 30,000 excess winter deaths per year). A trend of higher excess winter mortality with age was apparent across all disease categories (P < 0.01). There was a significant association between winter mortality and temperature with a 1.5% higher odds of dying in winter for every 1 degrees C reduction in 24-h mean winter temperature. The amount of rain, wind and hours of sunshine were inversely associated with excess winter mortality. Selected housing variables derived from the English House Condition Survey showed little agreement with census-derived variables at electoral ward level. For all-cause mortality there was little association between deprivation and excess winter mortality, although lack of central heating was associated with a higher risk of dying in winter (odds ratio [OR] = 1.016, 95% CI : 1.009-1.022). CONCLUSIONS: Excess winter mortality continues to be an important public health problem in Great Britain. There was a strong inverse association with temperature. Lack of central heating was associated with higher excess winter mortality. Further work is needed to disentangle the complex relationships between different indicators of housing quality and other measures of socioeconomic deprivation and their relationship to the high number of excess winter deaths in Great Britain.

Aged↗
PubMed2001

Errors-in-variables in joint population pharmacokinetic/pharmacodynamic modeling.

Pharmacokinetic (PK) models describe the relationship between the administered dose and the concentration of drug (and/or metabolite) in the blood as a function of time. Pharmacodynamic (PD) models describe the relationship between the concentration in the blood (or the dose) and the biologic response. Population PK/PD studies aim to determine the sources of variability in the observed concentrations/responses across groups of individuals. In this article, we consider the joint modeling of PK/PD data. The natural approach is to specify a joint model in which the concentration and response data are simultaneously modeled. Unfortunately, this approach may not be optimal if, due to sparsity of concentration data, an overly simple PK model is specified. As an alternative, we propose an errors-in-variables approach in which the observed-concentration data are assumed to be measured with error without reference to a specific PK model. We give an example of an analysis of PK/PD data obtained following administration of an anticoagulant drug. The study was originally carried out in order to make dosage recommendations. The prior for the distribution of the true concentrations, which may incorporate an individual's covariate information, is derived as a predictive distribution from an earlier study. The errors-in-variables approach is compared with the joint modeling approach and more naive methods in which the observed concentrations, or the separately modeled concentrations, are substituted into the response model. Throughout, a Bayesian approach is taken with implementation via Markov chain Monte Carlo methods.

Anticoagulants↗
PubMed2001

Proximity to coke works and hospital admissions for respiratory and cardiovascular disease in England and Wales.

BACKGROUND: The incidence of hospital admissions for respiratory and cardiovascular diseases in areas close to operating coke works in England and Wales was investigated. METHODS: A small area study using distance from source as a proxy for exposure was undertaken in subjects aged 65 or over and children under 5 years within 7.5 km of four coke works (1991 estimated populations 87 760 and 43 932, respectively). The main outcome measures were emergency hospital admissions in 1992/3-1994/5 with a primary diagnosis of coronary heart disease (ICD 410-414), stroke (ICD 431-438), all respiratory diseases (ICD 460-519), chronic obstructive pulmonary disease (ICD 491-492), and asthma (ICD 493) in those aged 65 or over, and all respiratory and asthma admissions in children under 5 years of age. RESULTS: At age 65 or over the combined estimate of relative risk with proximity to coke works (per km) ranged from 0.99 (95% CI 0.90 to 1.09) for chronic obstructive pulmonary disease to 1.03 (95% CI 0.94 to 1.13) for asthma. For children under 5 years the combined estimate of risk was 1.08 (95% CI 0.98 to 1.20) for all respiratory disease and 1.07 (95% CI 0.98 to 1.18) for asthma. There was evidence of significant heterogeneity in risk estimates between coke work groups, especially in children under 5 years (p<0.001 and p=0.004 for respiratory disease and asthma, respectively). For the Teesside coke works in North East England the relative risk with proximity (per km) was 1.09 (95% CI 1.06 to 1.12) for respiratory disease and 1.09 (95% CI 1.04 to 1.15) for asthma. CONCLUSIONS: No evidence overall was found for an association between hospital admissions and living near operational coke works in England and Wales. Trends of a higher risk of hospital admission for respiratory disease and asthma among children with proximity to the Teesside plant require further investigation.

Aged↗
PubMed2001

Environmental Florence Nightingales: nursing's new front line.

Nurses comprise the largest health professional group in terms of number, and they can be found in almost every health care setting, including homes, schools, work sites, and hospitals. To a large extent, nurses have always been aware of environmental factors when doing their job, but the definition of environmental health nursing is being expanded. Today, in addition to considering the possibility of environmental influences when taking patient health histories, evaluating symptoms, and conducting community assessments, nurses may change environmental conditions of affected individuals or populations through direct care, teaching, advocacy, and public policy initiatives. Nurses are helping patients evaluate the relative risks of various types of environmental exposures, such as lead. And they are also playing a key role in establishing a national tracking system of environmental health as well as in conducting patient research.

Education, Nursing↗
PubMed2000

Educating future physicians for Ontario: phase II.

In 1990, a collaborative project was launched to determine what the people of Ontario expect of their physicians and how the programs that prepare future physicians should be changed in response. The project, called Educating Future Physicians for Ontario (EFPO), brought together the five Ontario medical schools, the Council of Ontario Faculties of Medicine (COFM); a nonprofit, charitable organization, Associated Medical Services (AMS); and the Ontario Ministry of Health. The first phase ran for five years and was described in the November 1998 issue of Academic Medicine. After an external review, the project was continued for a second phase (EFPO II) for four more years until December 1998; that second phase is the topic of this article. EFPO II (1) focused more on residents' education; (2) emphasized four of the EFPO I-created physician roles in project activities; (3) maintained the province-wide, inter-institutional medical education framework of phase I, but fostered greater involvement of the seven sites (five medical schools and two regional health centers) in project activities; (4) stressed five project components (e.g., needs assessment and community partnerships) and worked for collaboration among components at all sites; (5) enhanced the original EFPO I Fellowship Program by adding residents and community fellows to the existing fellowships and by initiating leadership development activities, all of which bode well for the future leadership of medical education in Ontario. Students and residents played a vital role in EPFO II. Most of EFPO II's objectives were met, but the overall view of external reviewers was that the project was less successful than EFPO I. For example, the impact on clinical education, especially residency education, was less than anticipated. On the other hand, the project helped encourage the wide adoption of the eight physician roles that originated in EFPO I and advanced faculty development and assessment activities based on these roles. A third phase of EFPO concerning continuing medical education was planned, but support was not available. However, one of the funders will continue to support the successful fellowship and leadership program and the provincial education network for the next three years. Overall, the two phases of EFPO substantially modified medical education in Ontario to make it more responsive to evolving social needs.

Education, Medical↗
PubMed2000

The combination of population pharmacokinetic studies.

Pharmacokinetic data consist of drug concentrations with associated known sampling times and are collected following the administration of known dosage regimens. Population pharmacokinetic data consist of such data on a number of individuals, possibly along with individual-specific characteristics. During drug development, a number of population pharmacokinetic studies are typically carried out and the combination of such studies is of great importance for characterizing the drug and, in particular, for the design of future studies. In this paper, we describe a model that may be used to combine population pharmacokinetic data. The model is illustrated using six phase I studies of the antiasthmatic drug fluticasone propionate. Our approach is Bayesian and computation is carried out using Markov chain Monte Carlo. We provide a number of simplifications to the model that may be made in order to ease simulation from the posterior distribution.

Androstadienes↗
PubMed2000

Risk of mortality, cancer incidence, and stroke in a population potentially exposed to cadmium.

OBJECTIVES: To follow up mortality and cancer incidence in a cohort potentially exposed to cadmium and to perform a geographical (ecological) analysis to further assess the health effects of potential exposure to cadmium. METHODS: The English village of Shipham has very high concentrations of cadmium in the soil. A previous cohort study of residents of Shipham in 1939 showed overall mortality below that expected, but a 40% excess of mortality from stroke. This study extends the follow up of the cohort for mortality to 1997, and includes an analysis of cancer incidence from 1971 to 1992, and a geographical study of mortality and cancer incidence. Standardised mortality and incidence ratios (SMRs and SIRs) were estimated with regional reference rates. Comparisons were made with the nearby village of Hutton. RESULTS: All cause cohort mortality was lower than expected in both villages, although there was excess cancer incidence in both Shipham (SIR 167, 95% confidence interval (95% CI) 106 to 250) and Hutton (SIR 167, 95% CI 105 to 253). There was an excess of mortality from hypertension, cerebrovascular disease, and nephritis and nephrosis, of borderline significance, in Shipham (SMR 128, 95% CI 99 to 162). In the geographical study, all cause mortality in Shipham was also lower than expected (SMR 84, 95% CI 71 to 100). There was an excess in genitourinary cancers in both Shipham (SIR 160, 95% CI 107 to 239) and Hutton (SIR 153, 95% CI 122 to 192). CONCLUSION: No clear evidence of health effects from possible exposure to cadmium in Shipham was found despite the extremely high concentrations of cadmium in the soil.

Cadmium Poisoning↗