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Background Missing data are common in end-of-life care studies, but there is still relatively little exploration of which is the best method to deal with them, and, in particular, if the missing at random (MAR) assumption is valid or missing not at random (MNAR) mechanisms should be assumed. In this paper we investigated this issue through a sensitivity analysis within the ACTION study, a multicenter cluster randomized controlled trial testing advance care planning in patients with advanced lung or colorectal cancer. Methods Multiple imputation procedures under MAR and MNAR assumptions were implemented. Possible violation of the MAR assumption was addressed with reference to variables measuring quality of life and symptoms. The MNAR model assumed that patients with worse health were more likely to have missing questionnaires, making a distinction between single missing items, which were assumed to satisfy the MAR assumption, and missing values due to completely missing questionnaire for which a MNAR mechanism was hypothesized. We explored the sensitivity to possible departures from MAR on gender differences between key indicators and on simple correlations. Results Up to 39% of follow-up data were missing. Results under MAR reflected that missingness was related to poorer health status. Correlations between variables, although very small, changed according to the imputation method, as well as the differences in scores by gender, indicating a certain sensitivity of the results to the violation of the MAR assumption. Conclusions The findings confirmed the importance of undertaking this kind of analysis in end-of-life care studies.

Acknowledgments This project is funded by the Nutrigenomics Organisation, EC funded Network of Excellence, grant nr.FOOD- 2004-506360.

OBJECTIVES: To evaluate whether a training intervention can improve the ability of geriatricians to recognize depression in older persons. DESIGN: Multicenter, cluster randomized clinical trial. SETTING: Fourteen geriatric outpatient clinics in Italy, each representing the unit of randomization. PARTICIPANTS: After training, a total of 1,914 outpatients aged 65 years and older in both arms, not on antidepressant at entry, were blindly evaluated by the clinic geriatrician, in charge of routine clinical management, and by a field researcher, who formally diagnosed depression by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), taken as the criterion standard. INTERVENTION: After randomization, geriatricians belonging to the intervention arm were assigned to receive a residential 3-day educational program on depression. Those in the control arm received a generic course on disease management in elderly people. MEASUREMENTS: Sensitivity and specificity of the diagnosis of depression made by geriatricians, compared with the DSM-IV diagnosis. RESULTS: Sensitivity and specificity were significantly higher in trained than in untrained geriatricians (49 vs 35% and 91 vs 88%, respectively; P=.002 in marginal regression models). Effectiveness of training was confirmed, adjusting for age, sex, and cognitive performance (P=.02). CONCLUSION: The ability of geriatricians to diagnose depression in older outpatients can be improved with a specific training intervention. Improvement of diagnostic performance might translate into more-appropriate clinical management.

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.

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.

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°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. © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

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.