Overdiagnosis and overtreatment of breast cancer: Overdiagnosis in randomised controlled trials of breast cancer screening

Data from randomised controlled trials of mammographic screening can be used to determine the extent of any overdiagnosis, as soon as either a time equivalent to the lead-time has elapsed after the final screen, or the control arm has been offered screening. This paper reviews those randomised trials for which breast cancer incidence data are available. In recent trials in which the control group has not been offered screening, an excess incidence of breast cancer remains after many years of follow-up. In those trials in which the control arm has been offered screening, although there is a possible shift from invasive to in situ disease, there is no evidence of overdiagnosis as a result of incident screens

Evidence of space–time clustering of childhood acute lymphoblastic leukaemia in Sweden

We have examined 645 recorded cases of childhood acute lymphatic leukaemia (ALL) in Sweden during 1973–89 to identify space–time clustering by using the close-pair method of Knox. The records included date of birth and of diagnosis as well as addresses at birth and at diagnosis. There was a significant excess of case pairs close in date of birth and place of birth in the 5- to 15-year age group. © 1999 Cancer Research Campaig

Interpreting Posterior Relative Risk Estimates in Disease-Mapping Studies

There is currently much interest in conducting spatial analyses of health outcomes at the small-area scale. This requires sophisticated statistical techniques, usually involving Bayesian models, to smooth the underlying risk estimates because the data are typically sparse. However, questions have been raised about the performance of these models for recovering the “true” risk surface, about the influence of the prior structure specified, and about the amount of smoothing of the risks that is actually performed. We describe a comprehensive simulation study designed to address these questions. Our results show that Bayesian disease-mapping models are essentially conservative, with high specificity even in situations with very sparse data but low sensitivity if the raised-risk areas have only a moderate (< 2-fold) excess or are not based on substantial expected counts (> 50 per area). Semiparametric spatial mixture models typically produce less smoothing than their conditional autoregressive counterpart when there is sufficient information in the data (moderate-size expected count and/or high true excess risk). Sensitivity may be improved by exploiting the whole posterior distribution to try to detect true raised-risk areas rather than just reporting and mapping the mean posterior relative risk. For the widely used conditional autoregressive model, we show that a decision rule based on computing the probability that the relative risk is above 1 with a cutoff between 70 and 80% gives a specific rule with reasonable sensitivity for a range of scenarios having moderate expected counts (~ 20) and excess risks (~1.5- to 2-fold). Larger (3-fold) excess risks are detected almost certainly using this rule, even when based on small expected counts, although the mean of the posterior distribution is typically smoothed to about half the true value

Residential mobility and risk of childhood acute lymphoblastic leukaemia: an ecological study

We conducted an ecological analysis of childhood acute lymphoblastic leukaemia-incidence data from children ⩽5 years old during 1992–1998 from the Surveillance, Epidemiology, and End Results Program in 200 counties and Hawaii. The response variable was the count of cases in each county race–sex stratum, examined in relation to data from the United States Census and the United States Department of Agriculture. The final models for both sexes included race, proportion moved during 1985–1990, and proportion of households with income ⩾$5000 as potential predictors. Incidence was lower among black boys (rate ratio (RR)=0.5) and black girls (RR=0.4) than among other children of the same sex; no other significant racial differences were detected. Incidence was elevated among males (but not females) residing in counties where ⩾50$5000 (RR=1.5). These sex differences in risk factors were unexpected

Unraveling the Light-Activated Reaction Mechanism in a Catalytically Competent Key Intermediate of a Multifunctional Molecular Catalyst for Artificial Photosynthesis

Understanding photodriven multielectron reaction pathways requires the identification and spectroscopic characterization of intermediates and their excited-state dynamics, which is very challenging due to their short lifetimes. To the best of our knowledge, this manuscript reports for the first time on in situ spectroelectrochemistry as an alternative approach to study the excited-state properties of reactive intermediates of photocatalytic cycles. UV/Vis, resonance-Raman, and transient-absorption spectroscopy have been employed to characterize the catalytically competent intermediate [(tbbpy)2RuII(tpphz)RhICp*] of [(tbbpy)2Ru(tpphz)Rh(Cp*)Cl]Cl(PF6)2 (Ru(tpphz)RhCp*), a photocatalyst for the hydrogenation of nicotinamide (NAD-analogue) and proton reduction, generated by electrochemical and chemical reduction. Electronic transitions shifting electron density from the activated catalytic center to the bridging tpphz ligand significantly reduce the catalytic activity upon visible-light irradiation. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Urbanisation and incidence of acute lymphocytic leukaemia among United States children aged 0–4

Acute lymphocytic leukaemia (ALL) incidence among children under 5 years of age was examined, utilising data from 24 United States cancer registries. County-based incidence rates among white children were compared across four levels of urbanisation: large and small metropolitan counties, and adjacent and nonadjacent rural counties. In metropolitan areas, the incidence of ALL was lower among blacks (rate ratio (RR)=0.38, confidence interval (CI)=0.33–0.44) and among Asians/Pacific Islanders (RR=0.78, CI=0.63–0.97) than among whites. Among white children, the incidence of ALL decreased across the four strata of urbanisation, from 67 to 62 to 65 to 54 cases per million person-years at-risk (two-sided trend P=0.009), such that rates were significantly lower in the most remote rural counties than in the most populous metropolitan counties (RR=0.80, 95% CI=0.70–0.91)

Higher risk for acute childhood lymphoblastic leukaemia in Swedish population centres 1973-94

A population-based sample of acute childhood leukaemia cases in Sweden 1973–94 was analysed by a geographical information system (GIS) for spatial leukaemia distribution in relation to population density. The annual incidence rate for acute lymphoblastic leukaemia (ALL) was 3.6, and for acute non-lymphoblastic leukaemia (ANLL) 0.7, cases per 100 000 children. Incidence rates in population centres, constituting 1.3% of Sweden's land area and approximately 80% of the population, compared with the rest of Sweden showed a statistically significant excess of ALL [odds ratio (OR) 1.68; 95% confidence interval (CI) 1.44–1.95], but not ANLL (OR 1.13; 95% CI 0.98–1.32). An increasing trend, however not statistically significant, was found for ALL incidence with both increasing population density in parishes and increasing degree of urbanity in municipalities. These findings support the theories that some environmental factors associated with high population density, such as infectious agents, may be of aetiological importance for childhood acute lymphoblastic leukaemia. © 1999 Cancer Research Campaig

Population mixing, socioeconomic status and incidence of childhood acute lymphoblastic leukaemia in England and Wales: analysis by census ward

In this population-based study of acute lymphoblastic leukaemia (ALL) diagnosed among children aged under 15 years in England and Wales during 1986–1995, we analysed incidence at census ward level in relation to a range of variables from the 1991 census, which could be relevant to theories of infectious aetiology. ‘Population-mixing' measures, used as surrogates for quantity and diversity of infections entering the community, were calculated from census data on the origins and destinations of migrants in the year before the census. Incidence at ages 1–4 years tended independently to be higher in rural wards, to increase with the diversity of origin wards from which in-migrants had moved during the year before the census, and to be lower in the most deprived areas as categorised by the Carstairs index. This last association was much weaker when urban/rural status and in-migrants' diversity were allowed for. There was no evidence of association with population mixing or deprivation for ALL diagnosed at ages 0 or 5–14 years. The apparent specificity to the young childhood age group suggests that these associations are particularly marked for precursor B-cell ALL, with the disease more likely to occur when delayed exposure to infection leads to increased immunological stress, as predicted by Greaves. The association with diversity of incomers, especially in rural areas, is also consistent with the higher incidence of leukaemia predicted by Kinlen, where population mixing results in below average herd immunity to an infectious agent