The Association Between Childhood Leukemia and Population Mixing: An Artifact of Focusing on Clusters?

BACKGROUND: Studies investigating the population-mixing hypothesis in childhood leukemia principally use two analytical approaches: (1) nonrandom selection of areas according to specific characteristics, followed by comparisons of their incidence of childhood leukemia with that expected based on the national average; and (2) regression analyses of region-wide data to identify characteristics associated with the incidence of childhood leukemia. These approaches have generated contradictory results. We compare these approaches using observed and simulated data. METHODS: We generated 10,000 simulated regions using the correlation structure and distributions from a United Kingdom dataset. We simulated cases using a Poisson distribution with the incidence rate set to the national average assuming the null hypothesis that only population size drives the number of cases. Selection of areas within each simulated region was based on characteristics considered responsible for elevated infection rates (population density and inward migration) and/or elevated leukemia rates. We calculated effect estimates for 10,000 simulations and compared results to corresponding observed data analyses. RESULTS: When the selection of areas for analysis is based on apparent clusters of childhood leukemia, biased assessments occur; the estimated 5-year incidence of childhood leukemia ranged between zero and eight per 10,000 children in contrast to the simulated two cases per 10,000 children, similar to the observed data. Performing analyses on region-wide data avoids these biases. CONCLUSIONS: Studies using nonrandom selection to investigate the association between childhood leukemia and population mixing are likely to have generated biased findings. Future studies can avoid such bias using a region-wide analytical strategy. See video abstract at, http://links.lww.com/EDE/B431.

No rise in incidence but geographical heterogeneity in the occurrence of primary biliary cirrhosis in North East England.

In this study, we examined temporal changes in the incidence of primary biliary cirrhosis (PBC) and investigated associations between PBC incidence and sociodemographic factors and spatial clustering. We included 982 patients aged ≥40 years from North East England with incident PBC diagnosed during 1987-2003. Age-standardized incidence rates with 95% confidence intervals were calculated. Negative binomial regression was used to analyze incidence and socioeconomic deprivation. Clustering analysis was performed using point process methods, testing the null hypothesis that disease risk does not vary spatially and that PBC cases occur independently. The age-standardized incidence rate was 53.50 per million persons per year (95% confidence interval: 48.65, 58.35) in 1987-1994 and 45.09 per million persons per year (95% confidence interval: 41.10, 49.07) in 1995-2003. Risk of PBC increased in areas with higher levels of socioeconomic deprivation (P = 0.035). More specifically, risk increased in areas with higher levels of overcrowded homes (P = 0.040), higher levels of households without cars (P < 0.001), and higher levels of non-owner-occupied homes (P < 0.001). Overall, there was evidence of spatial clustering (P = 0.001). The findings confirm that overall incidence of PBC did not rise over time, but sociodemographic variations suggest that certain aspects of deprivation are involved in its etiology.

Assessing asthma control in UK primary care: use of routinely collected prospective observational consultation data to determine appropriateness of a variety of control assessment models.

BACKGROUND: Assessing asthma control using standardised questionnaires is recommended as good clinical practice but there is little evidence validating their use within primary care. There is however, strong empirical evidence to indicate that age, weight, gender, smoking, symptom pattern, medication use, health service resource use, geographical location, deprivation, and organisational issues, are factors strongly associated with asthma control. A good control measure is therefore one whose variation is most explained by these factors. METHOD: Eight binary (Yes = poor control, No = good control) models of asthma control were constructed from a large UK primary care dataset: the Royal College of Physicians 3-Questions (RCP-3Qs); the Jones Morbidity Index; three composite measures; three single component models. Accounting for practice clustering of patients, we investigated the effects of each model for assessing control. The binary models were assessed for goodness-of-fit statistics using Pseudo R-squared and Akaikes Information Criteria (AIC), and for performance using Area Under the Receiver Operator Characteristic (AUROC). In addition, an expanded RCP-3Q control scale (0-9) was derived and assessed with linear modelling. The analysis identified which model was best explained by the independent variables and thus could be considered a good model of control assessment. RESULTS: 1,205 practices provided information on 64,929 patients aged 13+ years. The RCP-3Q model provided the best fit statistically, with a Pseudo R-squared of 18%, and an AUROC of 0.79. By contrast, the composite model based on the GINA definition of controlled asthma had a higher AIC, an AUROC of 0.72, and only 10% variability explained. In addition, although the Peak Expiratory Flow Rate (PEFR) model had the lowest AIC, it had an AUROC of 71% and only 6% of variability explained. However, compared with the RCP-3Qs binary model, the linear RCP-3Q Total Score Model (Scale 0-9), was found to be a more robust 'tool' for assessing asthma control with a lower AIC (28,6163) and an R-squared of 33%. CONCLUSION: In the absence of a gold standard for assessing asthma control in primary care, the results indicate that the RCP-3Qs is an effective control assessment tool but, for maximum effect, the expanded scoring model should be used.

The impact of New Labour's English health inequalities strategy on geographical inequalities in infant mortality: a time-trend analysis.

BACKGROUND: The English health inequalities strategy (1999-2010) aimed to reduce health inequalities between the most deprived local authorities and the rest of England. The multifaceted strategy included increased investment in healthcare, the early years, education and neighbourhood renewal. The objective of this study was to investigate whether the strategy was associated with a reduction in geographical inequalities in the infant mortality rate (IMR). METHODS: We used segmented regression analysis to measure inequalities in the IMR between the most deprived local authorities and the rest of England before, during and after the health inequalities strategy period. RESULTS: Before the strategy was implemented (1983-1998), absolute inequalities in the IMR increased between the most deprived local authorities and the rest of England at a rate of 0.034 annually (95% CI 0.001 to 0.067). Once the strategy had been implemented (1999-2010), absolute inequalities decreased at a rate of -0.116 annually (95% CI -0.178 to -0.053). After the strategy period ended (2011-2017), absolute inequalities increased at a rate of 0.042 annually (95% CI -0.042 to 0.125). Relative inequalities also marginally decreased during the strategy period. CONCLUSION: The English health inequalities strategy period was associated with a decline in geographical inequalities in the IMR. This research adds to the evidence base suggesting that the English health inequalities strategy was at least partially effective in reducing health inequalities, and that current austerity policies may undermine these gains.

Can changes in population mixing and socio-economic deprivation in Cumbria, England explain changes in cancer incidence around Sellafield?

Previously excesses in incident cases of leukaemia and non-Hodgkin lymphoma have been observed amongst young people born or resident in Seascale, Cumbria. These excesses have not been seen more recently. It is postulated that the former apparent increased risk was related to 'unusual population mixing', which is not present in recent years. This study investigated changes in measures of population mixing from 1951-2001. Comparisons were made between three specified areas. Area-based measures were calculated (migration, commuting, deprivation, population density). All areas have become more affluent, although Seascale was consistently the most affluent. Seascale has become less densely populated, with less migration into the ward and less diversity with respect to migrants' origin. There have been marked changes in patterns of population mixing throughout Cumbria. Lesser population mixing has been observed in Seascale in recent decades. Changes in pattern and nature of population mixing may explain the lack of recent excesses.

Socioeconomic patterning in the incidence and survival of teenage and young adult men aged between 15 and 24 years diagnosed with non-seminoma testicular cancer in northern england.

PURPOSE: Previous research from developed countries has shown a marked increase in the incidence of testicular cancer in the past 50 years. This has also been demonstrated in northern England, along with improving 5-year survival. The present study aims to determine if socioeconomic factors may play a role in both etiology and survival from non-seminoma testicular cancer. MATERIALS AND METHODS: We extracted all 214 cases of non-seminoma testicular cancer diagnosed in teenage and young adult men aged between 15 and 24 years during 1968 to 2006 from the Northern Region Young Persons' Malignant Disease Registry, which is a population-based specialist regional registry. Negative binomial regression was used to examine the relationship between incidence and both the Townsend deprivation score (and component variables) and small-area population density. Cox regression was used to analyze the relationship between survival and both deprivation and population density. RESULTS: Decreased incidence was associated with living in areas of higher household overcrowding for young adults aged between 20 and 24 years (relative risk per 1% increase in household overcrowding = 0.79; 95% CI: 0.66-0.94) but no association was detected for young people aged between 15 and 19 years. Community-level household unemployment was associated with worse survival (hazard ratio per 1% increase in household unemployment = 1.04; 95% CI: 1.00-1.08). CONCLUSIONS: This study has shown that increased risk of non-seminoma testicular cancer in teenage and young adult men may be associated with some aspect of more advantaged living. In contrast, greater deprivation is linked with worse survival prospects. The study was ecological by design and so these area-based results may not necessarily apply to individuals.

Socioeconomic patterning in the incidence and survival of children and young people diagnosed with malignant melanoma in northern England.

Previous studies have found marked increases in melanoma incidence. The increase among young people in northern England was especially apparent among females. However, overall 5-year survival has greatly improved. The present study aimed to determine whether socioeconomic factors may be involved in both etiology and survival. All 224 cases of malignant melanoma diagnosed in patients aged 10-24 years during 1968-2003 were extracted from a specialist population-based regional registry. Negative binomial regression was used to examine the relationship between incidence and area-based measures of socioeconomic deprivation and small-area population density. Cox regression was used to analyze the relationship between survival and deprivation and population density. There was significantly decreased risk associated with living in areas of higher unemployment (relative risk per 1% increase in unemployment=0.93; 95% confidence interval (CI) 0.90-0.96, P<0.001). Survival was better in less deprived areas (hazard ratio (HR) per tertile of household overcrowding=1.52; 95% CI 1.05-2.20; P=0.026), but this effect was reduced in the period 1986-2003 (HR=0.61; 95% CI 0.40-0.92; P=0.018). This study found that increased risk of melanoma was linked with some aspects of greater affluence. In contrast, worse survival was associated with living in a more deprived area.

The estimation of mortality for ethnic groups at local scale within the United Kingdom.

As an input to projections of sub-national populations by ethnicity, this paper develops the first estimates of the mortality risks experienced by the UK ethnic groups. Two estimates were developed using alternative methods. In the first, UK 2001 Census data on limiting long-term illness to predict mortality levels and regression equations between local Standardized Illness and Mortality Ratios for all ethnicities are assumed to apply to individual ethnic groups. In the second, the geographical distribution of ethnic groups by local areas is combined with local mortality for all ethnicities to estimate national mortality rates by ethnicity, which are then employed to estimate local ethnic mortality. A comparison of the two estimates indicates that the method based on illness rates produces more plausible outcomes. The local SMRs produced for each ethnic group were used to generate ethnic group life tables for 432 UK local authority areas in 2001, which included estimates of survivorship probabilities by single year of age, gender and ethnic group for each local area for use in a projection model.