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Background and aim: The Institute of Clinical Pharmacology at the TU Dresden offers a drug information service for patients, which seeks to provide independent and evidence-based information on all drug-related questions. The presented study analyzes whether increased information needs can be detected[for full text, please go to the a.m. URL], 16. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie

BACKGROUND: Diseases of the skin are important and often preventable conditions occurring among workers with dermal exposures to irritant and sensitizing agents. OBJECTIVE: We conducted this analysis to assess the associations between metalworking exposures and current and persistent skin symptoms among male and female participants in two population-based epidemiologic studies. METHODS: We pooled data from the European Community Respiratory Health Survey II (ECRHS II) and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults 2 (SAPALDIA 2), two prospective cohort studies in Europe. Each participant completed interviewer-administered questionnaires to provide information about symptoms and exposures related to selected occupations, including metalworking, during the follow-up periods. We assessed associations between skin symptoms and the frequency of metalworking exposures among 676 ECRHS II/SAPALDIA 2 respondents. RESULTS: Current skin symptoms were reported by 10% of metalworkers and were associated with frequent use, defined as four or more days per week, of oil-based metalworking fluids [prevalence ratio (PR): 1.76, 95% confidence interval (CI): 1.25-2.49)] and organic solvent/degreasing agents (PR: 2.06, 95% CI: 1.21-3.50). CONCLUSIONS: Skin symptom prevalence is associated with increasing frequency of oil-based metalworking fluid and degreasing agent use. Our findings justify assessing strategies for reducing the frequency of metal-related exposures.

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 1̊C 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 751 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.

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.

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. Copyright © 2008 by Lippincott Williams & Wilkins.

The short-term effects of nitrogen dioxide (NO2) on total, cardiovascular and respiratory mortality in 30 European cities participating in the Air Pollution on Health: a European Approach (APHEA)-2 project were investigated. The association was examined using hierarchical models implemented in two stages. In the first stage, data from each city were analysed separately, whereas in the second stage, the city-specific air pollution estimates were regressed on city-specific covariates to obtain overall estimates and to explore sources of possible heterogeneity. A significant association of NO2 with total, cardiovascular and respiratory mortality was found, with stronger effects on cause-specific mortality. There was evidence of confounding in respiratory mortality with black smoke and sulphur dioxide. The effect of NO2 on total and cardiovascular mortality was observed mainly in western and southern European cities, and was larger when smoking prevalence was lower and household gas consumption was higher. The effect of NO2 on respiratory mortality was higher in cities with a larger proportion of elderly persons in the population and higher levels of particulate matter with a 50% cut-off aerodynamic diameter of 10 mu m. The results of this large study are consistent with an independent effect of nitrogen dioxide on mortality, but the role of nitrogen dioxide as a surrogate of other unmeasured pollutants cannot be completely ruled out.

Several studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of theses studies linear nonthreshold relations were assumed. We investigated the exposure-response association between ambient particles and mortality in the 22 European cities participating in the APHEA (Air Pollution and Health - A European Approach) project, which is the largest available European database. We estimated the exposure-response curves using regression spline models with two knots and then combined the individual city estimates of the spline to get an overall exposure-response relationship. To further explore the heterogeneity in the observed city-specific exposure-response associations, we investigated several city descriptive variables as potential effect modifiers that could alter the shape of the curve. We conclude that the association between ambient particles and mortality in the cities included in the present analysis, and in the range of the pollutant common in all analyzed cities, could be adequately estimated using the linear model. Our results confirm those previously reported in Europe and the United States. The heterogeneity found in the different city-specific relations reflects real effect modification, which can be explained partly by factors characterizing the air pollution mix, climate, and the health of the population.

Background: Air pollution is associated with total mortality. This association may be confounded by uncontrolled time-varying risk factors such as influenza epidemics. Methods: We analyzed independent data on influenza epidemics from 7 European cities that also had data on mortality associated with particulates (PM10). We used 10 methods to control for epidemics (5 derived from influenza data and 5 from respiratory mortality series) and compared those results with analyses that did not control for these epidemics. Results: Adjustment for influenza epidemics increased the PM10 effect estimate in most cases (% change in the pooled regression coefficient: -1.9 to 38.9 for total mortality and 1.3 to 25.5 for cardiovascular mortality). A 10-mug/m(3) increase in PM10 concentrations (lag 0-1) was associated with a 0.48% (95% confidence interval = 0.27-0.70%) increase in daily mortality unadjusted for influenza epidemics, whereas under the various methods to control for epidemics the increase ranged from 0.45% (0.26-0.69%) to 0.67% (0.46-0.89%). The corresponding figures for cardiovascular mortality were 0.85% (0.53-1.18%) with no adjustment and from 0.86% (0.53-1.19%) to 1.06% (0.74-1.39%) with the methods of control. Conclusions: The association between air pollution and mortality is not weakened by control for influenza epidemic irrespective of the method used. To adjust for influenza epidemics, one can use methods based on respiratory mortality counts instead of counts of influenza cases if the latter are not available. However, adjustment for influenza by any method tested did not markedly alter the air pollution effect estimate.

Several recent studies have reported significant health effects of air pollution even at low levels of air pollutants. These studies have been criticized for the statistical methods and for inconsistency in results between cities. An important development in air pollution epidemiology has come from multicenter studies. Within the APHEA-2 project we have developed a statistical methodology to evaluate short-term health effects of air pollution using data from 30 cities across Europe. For the analysis, a hierarchical modelling approach was adopted and implemented in two stages: (a) data from each city were analyzed separately to allow for local differences, using generalized additive Poisson regression models; (b) city-specific effects estimates were regressed on city-specific covariates to obtain an overall estimate and to explore heterogeneity across cities. In order to illustrate our methodology we present results for PM10 effects. It was found that a 10 mug/m(3) increase in PM10 or NO2 concentrations is associated with a 0.67% (95% Cl: 0.50 to 0.90) and 0.33% (0.20 to 0.40) increase in total mortality, respectively. After mutual adjustment, the PM10 effect was reduced by 40% and that of NO2 by 20%, but both pooled estimates remained significant. Long-term mean NO2 concentrations act as an effect modifier for PM10 effects, even after adjustment for NO2 confounding effects. In the second stage we explored two different models for combining the adjusted for NO2, PM10 effects across cities: bivariate, which accounts for within-city correlation of PM10 and NO2; and univariate, which ignores this correlation. Both models gave broadly the same results. Copyright (C) 2004 John Wiley Sons, Ltd.

Background: Several recent studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of these studies linear non-threshold relations were assumed. Aims: To investigate the NO2 mortality dose-response association in nine cities participating in the APHEA-2 project using two different methods: the meta-smooth and the cubic spline method. Methods: The meta-smooth method developed by Schwartz and Zanobetti is based on combining individual city non-parametric smooth curves; the cubic spline method developed within the APHEA-2 project combines individual city estimates of cubic spline shaped dose-response relations. The metasmooth method is easier and faster to implement, but the cubic spline method is more flexible for further investigation of possible heterogeneity in the dose-response curves among cities. Results: In the range of the pollutant common to all cities the two methods gave similar and comparable curves. Using the cubic spline method it was found that smoking prevalence acts as an effect modifier with larger NO2 effects on mortality at lower smoking prevalence. Conclusions: The NO2-mortality association in the cities included in the present analysis, could be adequately estimated using the linear model. However, investigation of the city specific dose-response curves should precede the application of linear models.

Within the framework of the APHEA2 (Air Pollution on Health: a European Approach) project, the effects of ambient particles on mortality among persons greater than or equal to65 yrs were investigated. Daily measurements for particles with a 50%, cut-off aerodynamic diameter of 10 pm (PM10) and black smoke (BS), as well as the daily number of deaths among persons 65 yrs of age, from 29 European cities, have been collected. Data on other pollutants and meteorological variables, to adjust for confounding effects and data on city characteristics, to investigate potential effect modification, were also recorded. For individual city analysis, generalised additive models extending Poisson regression, using a locally weighted regression (LOESS) smoother to control for seasonal effects, were applied. To combine individual city results and explore effect modification, second stage regression models were applied. The per cent increase (95% confidence intervals), associated with a 10 mug.m(-3) increase in PM10, in the elderly daily number of deaths was 0.8%, (0.7-0.9%) and the corresponding number for BS was 0.6%, (0.5-0.8%). The effect size was modified by the long-term average levels of nitrogen dioxide (higher levels were associated with larger effects), temperature (larger effects were observed in warmer countries), and by the proportion of the elderly in each city (a larger proportion was associated with higher effects). These results indicate that ambient particles have effects on mortality among the elderly, with relative risks comparable or slightly higher than those observed for total mortality and similar effect modification patterns. The effects among the older persons are of particular importance, since the attributable number of events will be much larger, compared to the number of deaths among the younger population.

When striatal neurons are strongly activated they produce adenosine, which activates nearby adenosine A1 receptors (A1Rs) and adenosine A2A receptors (A2ARs). Although the effects of A1R or A2AR activation on neural activity in the striatum have been examined separately, the effects of coactivating both receptors has not been investigated. Using c-Fos immunohistochemistry as an indicator of neural activity, we examined the effects of coactivation of A1Rs and A2ARs on neural activity and their mechanism of interaction in the caudate-putamen, nucleus accumbens (NAc) and prefrontal cortex in rats. Administration of a motor-depressant dose of the A2AR agonist CGS 21680 (0.5 mg/kg i.p.) did not significantly induce c-fos expression in any of these brain regions. Administration of a motor-depressant dose of the A1R agonist CPA (0.3 mg/kg, i.p.) produced a small but significant induction of c-fos expression only in the shell of the NAc. Coadministration of CGS 21680 and CPA produced a synergistic induction of c-fos expression in the caudate-putamen, cingulate cortex, and especially the NAc. In the shell of the NAc administration of CPA significantly decreased extracellular dopamine levels measured by in vivo microdialysis and blocked CGS 21680-induced increases in dopamine levels. Because it has been previously shown that activation of dopamine D2 receptors (D2Rs) by endogenous dopamine blocks A2AR-mediated c-fos expression, it is hypothesized that the enabling role of A1Rs in A2AR-mediated striatal c-fos expression is related to the A1R-mediated inhibition of dopamine release. Eur J Neurosci

Background. Half of the dialysis population suffers from hyperphosphataemia, which is now recognized as a major factor of haemodialysis (HD) morbidity and mortality. Current control is focussed on reducing dietary phosphate intake and diminishing absorption using phosphate binders, whereas control and quantification of phosphate removal by HD is undervalued. The aim of this prospective study was to develop a simple, bedside formula to estimate dialytic phosphate removal in stable HD patients. Methods. This was a prospective, randomized trial. Phosphate and urea elimination were assessed in a representative group of patients at two dialysis centres using randomly different dialysers (1.3-2.4 m2). Quantification was performed by partial dialysate collection, concentration measurements in blood and effluent dialysate spot samples, and Kt/Vurea during standard high‐flux HD. Multiple linear regression analyses were used in 77% of all data sets to generate an equation to predict phosphate removal. The formula was validated in the remaining 23% of data sets, in the same group of patients using a large capillary filter, and in diabetic patients treated with a small dialyser at different blood flows (200, 250, and 300 ml/min). Results. A formula allowing quantification of phosphate removal within one HD session was developed in 18 of 74 patients during 41 treatments (137 out of 177 data sets) and was determined as: MPO4pred=0.1t −17+50cds60+11cb60, where t is treatment time in min, cds60 and cb60 are phosphate concentrations in dialysate and plasma measured 60 min into HD in mmol/l, and MPO4pred is estimated phosphate removed in mmol. The precision was remarkable (r2=0.92-0.94). The comparison of phosphate and Kt/Vurea showed a significant association (r2=0.28), albeit with remarkable scatter. Conclusions. We present the first approach to quantify phosphate removal during high‐flux HD by a bedside formula. Only 28% of the variation in phosphate removal was explained by Kt/Vurea. It appears that other factors not adequately accounted for by Kt/Vurea affect phosphate removal. Therefore, we propose an individual control and quantification of phosphate removal in HD

We present the results of the Air Pollution and Health: A European Approach (APHEA-2,) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 mum in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities’ pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 mug/m(3) increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 mug/m(3) in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.