Michela Baccini

Heat effects on mortality in 15 European cities

BACKGROUND Higher incidence rates of childhood cancer and particularly leukemia have been observed in regions with higher radon levels, but case-control studies have given inconsistent results. We tested the hypothesis that domestic radon exposure increases the risk for childhood cancer. METHODS We identified 2400 incident cases of leukemia, central nervous system tumor, and malignant lymphoma diagnosed in children between 1968 and 1994 in the Danish Cancer Registry. Control children (n = 6697) were selected from the Danish Central Population Registry. Radon levels in residences of children and the cumulated exposure of each child were calculated as the product of exposure level and time, for each address occupied during childhood. RESULTS Cumulative radon exposure was associated with risk for acute lymphoblastic leukemia (ALL), with rate ratios of 1.21 (95% confidence interval = 0.98-1.49) for levels of 0.26 to 0.89 x 10(3) Bq/m3-years and 1.63 (1.05-2.53) for exposure to >0.89 x 10(3) Bq/m3-years, when compared with <0.26 x 10(3) Bq/m3-years. A linear dose-response analysis showed a 56% increase in the rate of ALL per 10(3) Bq/m3-years increase in exposure. The association with ALL persisted in sensitivity analyses and after adjustment for potential confounders. No association was found with the other types of childhood cancer. CONCLUSIONS This study suggests that domestic radon exposure increases the risk for ALL during childhood but not for other childhood cancers.Background: Epidemiologic studies show that high temperatures are related to mortality, but little is known about the exposure-response function and the lagged effect of heat. We report the associations between daily maximum apparent temperature and daily deaths during the warm season in 15 European cities. Methods: The city-specific analyses were based on generalized estimating equations and the city-specific results were combined in a Bayesian random effects meta-analysis. We specified distributed lag models in studying the delayed effect of exposure. Time-varying coefficient models were used to check the assumption of a constant heat effect over the warm season. Results: The city-specific exposure-response functions have a V shape, with a change-point that varied among cities. The meta-analytic estimate of the threshold was 29.4°C for Mediterranean cities and 23.3°C for north-continental cities. The estimated overall change in all natural mortality associated with a 1°C increase in maximum apparent temperature above the city-specific threshold was 3.12% (95% credibility interval = 0.60% to 5.72%) in the Mediterranean region and 1.84% (0.06% to 3.64%) in the north-continental region. Stronger associations were found between heat and mortality from respiratory diseases, and with mortality in the elderly. Conclusions: There is an important mortality effect of heat across Europe. The effect is evident from June through August; it is limited to the first week following temperature excess, with evidence of mortality displacement. There is some suggestion of a higher effect of early season exposures. Acclimatization and individual susceptibility need further investigation as possible explanations for the observed heterogeneity among cities.

Effects of Cold Weather on Mortality: Results From 15 European Cities Within the PHEWE Project

Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.

High temperature and hospitalizations for cardiovascular and respiratory causes in 12 European cities.

RATIONALE Episode analyses of heat waves have documented a comparatively higher impact on mortality than on morbidity (hospital admissions) in European cities. The evidence from daily time series studies is scarce and inconsistent. OBJECTIVES To evaluate the impact of high environmental temperatures on hospital admissions during April to September in 12 European cities participating in the Assessment and Prevention of Acute Health Effects of Weather Conditions in Europe (PHEWE) project. METHODS For each city, time series analysis was used to model the relationship between maximum apparent temperature (lag 0-3 days) and daily hospital admissions for cardiovascular, cerebrovascular, and respiratory causes by age (all ages, 65-74 age group, and 75+ age group), and the city-specific estimates were pooled for two geographical groupings of cities. MEASUREMENTS AND MAIN RESULTS For respiratory admissions, there was a positive association that was heterogeneous between cities. For a 1 degrees C increase in maximum apparent temperature above a threshold, respiratory admissions increased by +4.5% (95% confidence interval, 1.9-7.3) and +3.1% (95% confidence interval, 0.8-5.5) in the 75+ age group in Mediterranean and North-Continental cities, respectively. In contrast, the association between temperature and cardiovascular and cerebrovascular admissions tended to be negative and did not reach statistical significance. CONCLUSIONS High temperatures have a specific impact on respiratory admissions, particularly in the elderly population, but the underlying mechanisms are poorly understood. Why high temperature increases cardiovascular mortality but not cardiovascular admissions is also unclear. The impact of extreme heat events on respiratory admissions is expected to increase in European cities as a result of global warming and progressive population aging.

Impact of high temperatures on mortality: is there an added heat wave effect?

Background: Mortality during sustained periods of hot weather is generally regarded as being in excess of what would be predicted from smooth temperature-mortality gradients estimated using standard time-series regression models. However, the evidence for an effect of continuous days of exceptional heat (“heat wave effect”) is indirect. In addition, because some interventions may be triggered only during forecasted heat waves, it would be helpful to know what fraction of all heat-related deaths falls during these specific periods and what fraction occurs throughout the remainder of the summer. Methods: Extended time-series data sets of daily mortality counts in 3 major European cities (London, 28 years of data; Budapest, 31 years; Milan, 18 years) were examined in relation to hot weather using a generalized estimating equations approach. We modeled temperature and specific heat wave terms using a variety of specifications. Results: With a linear effect of same-day temperature above an identified threshold, an additional “heat wave” effect of 5.5% was observed in London (95% confidence interval = 2.2 to 8.9), 9.3% in Budapest (5.8 to 13.0), and 15.2% in Milan (5.7 to 22.5). Heat wave effects were reduced slightly when we relaxed the linear assumption and these effects were reduced substantially when temperature was modeled as an average value of lags 0 to 2 days. In London, fewer than half of all heat-related deaths could be attributed to identified heat wave periods. In Milan and Budapest, the fraction was less than one fifth. Conclusions: Heat wave effects were apparent in simple time-series models but were reduced in multilag nonlinear models and small when compared with the overall summertime mortality burden of heat. Reduction of the overall heat burden requires preventive measures in addition to those that target warnings and responses uniquely to heat waves.

Impact of heat on mortality in 15 European cities: attributable deaths under different weather scenarios

Background High ambient summer temperatures have been shown to influence daily mortality in cities across Europe. Quantification of the population mortality burden attributable to heat is crucial to the development of adaptive approaches. The impact of summer heat on mortality for 15 European cities during the 1990s was evaluated, under hypothetical temperature scenarios warmer and cooler than the mean and under future scenarios derived from the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios (SRES). Methods A Monte Carlo approach was used to estimate the number of deaths attributable to heat for each city. These estimates rely on the results of a Bayesian random-effects meta-analysis that combines city-specific heat-mortality functions. Results The number of heat-attributable deaths per summer ranged from 0 in Dublin to 423 in Paris. The mean attributable fraction of deaths was around 2%. The highest impact was in three Mediterranean cities (Barcelona, Rome and Valencia) and in two continental cities (Paris and Budapest). The largest impact was on persons over 75 years; however, in some cities, important proportions of heat-attributable deaths were also found for younger adults. Heat-attributable deaths markedly increased under warming scenarios. The impact under SRES scenarios was slightly lower or comparable to the impact during the observed hottest year. Conclusions Current high summer ambient temperatures have an important impact on European population health. This impact is expected to increase in the future, according to the projected increase of mean ambient temperatures and frequency, intensity and duration of heat waves.

Meta-analysis of the Italian Studies of Short-term Effects of Air Pollution (MISA), 1990–1999

Abstract A meta-analysis of short-term effects of air pollution on health in eight Italian cities from 1990 to 1999 is presented. Death certificates and hospital admission data as well as daily concentrations of pollutants were collected. The same generalized linear model adjusted for age, day of the week, holidays, influenza epidemics, meteorological. variables, and seasonality pattern was fitted to the city data. City-specific model selection was not done. In the meta-analysis, for each outcome, the city-specific estimates for each pollutant were combined using fixed and random-effects models. Hierarchical Bayesian models were use to investigate the effects of PM10 in detail. Each, pollutant (SO2, NO2, CO, PM10, O3) was significantly associated with mortality for natural causes. The effect of PM10 on mortality was greater during the warm season and for elderly. A north-south gradient in risk was observed for total natural mortality. The excess risks on hospital admission were modified by deprivation score and by the NO2/PM10 ratio. Results add evidence for an association between air pollution and early mortality or morbidity and support the hypothesis of a synergism between meteorological variables and air pollution.

Clearance of leukaemic blasts from peripheral blood during standard induction treatment predicts the bone marrow response in acute myeloid leukaemia : a pilot study

Although several parameters are useful for risk stratification of patients with acute myeloid leukaemia (AML), there are no firm criteria for predicting response to induction treatment of individual patients. Daily flow cytometry (FC) analysis, carried out during induction treatment in 30 AML patients, showed that the clearance of blasts from peripheral blood (PBC) correlated closely with response, as assessed by bone marrow FC on day 14, and by morphologic analysis at haematopoietic recovery. Therefore, a major treatment outcome can be predicted very early in AML patients, thus providing an opportunity for tailoring treatment modalities from the outset.

Biases induced by pooling samples in microarray experiments

MOTIVATION If there is insufficient RNA from the tissues under investigation from one organism, then it is common practice to pool RNA. An important question is to determine whether pooling introduces biases, which can lead to inaccurate results. In this article, we describe two biases related to pooling, from a theoretical as well as a practical point of view. RESULTS We model and quantify the respective parts of the pooling bias due to the log transform as well as the bias due to biological averaging of the samples. We also evaluate the impact of the bias on the statistical differential analysis of Affymetrix data.

Analysis of Gene Expression Profiles Reveals Novel Correlations With the Clinical Course of Colorectal Cancer

In order to discover potential markers of prognosis in colorectal cancer (CRC) we have determined gene expression profiles, using cDNA microarrays in CRC samples obtained from 19 patients in Dukes stages C and D, with favorable clinical course (Dukes C patients, survival >5 years after surgery, group A, n=7) or unfavorable clinical course (Dukes stage C and D patients, survival <5 years after surgery, group B, n=12). Gene expression was measured in RNA from each tumor, using a pool of equal amounts of RNA from all tumors as a reference. To identify and rank differentially expressed genes we used three different analytical methods: (i) Significance Analysis of Microarrays (SAM), (ii) Coxs Proportional Hazard Model, and (iii) Trend Filter (a mathematical method for the assessment of numerical trends). The level of expression of a gene in an individual tumor was regarded as of interest when that gene was identified as differentially expressed by at least two of these three methods. By these stringent criteria we identified eight genes (ITGB2, MRPS11, NPR1, TXNL2, PHF10, PRSS8, KCNK3, JAK3) that were correlated with prolonged survival after surgery. Pathway analysis showed that patients with favorable prognosis had several activated metabolic pathways (carbon metabolism, transcription, amino acid and nitrogen metabolism, signaling and fibroblast growth factor receptor pathways). To further validate individual gene expression findings, the RNA level of each gene identified as a marker with microarrays was measured by real-time RT-PCR in CRC samples from an independent group of 55 patients. In this set of patients the Cox Proportional Hazard Model analysis demonstrated a significant association between increased patient survival and low expression of ITGB2 (p = 0.011) and NPR1 (p = 0.023) genes.

Impact of Summer Heat on Urban Population Mortality in Europe during the 1990s: An Evaluation of Years of Life Lost Adjusted for Harvesting

Background Efforts to prevent and respond to heat-related illness would benefit by quantifying the impact of summer heat on acute population mortality. We estimated years of life lost due to heat in 14 European cities during the 1990s accounting for harvesting. Methods We combined the number of deaths attributable to heat estimated by the PHEWE project with life expectancy derived from population life tables. The degree of harvesting was quantified by comparing the cumulative effect of heat up to lagged day 30 with the immediate effect of heat, by geographical region and age. Next, an evaluation of years of life lost adjusted for harvesting was obtained. Results Without accounting for harvesting, we estimated more than 23,000 years of life lost per year, 55% of which was among individuals younger than 75. When 30 day mortality displacement was taken into account, the overall impact reduced on average by 75%. Harvesting was more pronounced in North-continental cities than in Mediterranean cities and was stronger among young people than among elderly. Conclusions High ambient temperatures during summer were responsible for many deaths in European cities during the 1990s, but a large percentage of these deaths likely involved frail persons whose demise was only briefly hastened by heat exposure. Differences in harvesting across regions and classes of age could reflect different proportions of frail individuals in the population or could be indicative of heterogeneous dynamics underlying the entry and exit of individuals from the high-risk pool which is subject to mortality displacement.