Factors Associated with Underreporting of Adverse Drug Reactions by Health Care Professionals: A Systematic Review Update.

INTRODUCTION: Underreporting is a major limitation of the voluntary reporting system of adverse drug reactions (ADRs). A 2009 systematic review showed the knowledge and attitudes of health professionals were strongly related with underreporting of ADRs. OBJECTIVE: Our aim was to update our previous systematic review to determine factors (sociodemographic, knowledge and attitudes) associated with the underreporting of ADRs by healthcare professionals. METHODS: We searched the MEDLINE and EMBASE databases for studies published between 2007 and 2021 that met the following inclusion criteria: (1) published in English, French, Portuguese or Spanish; (2) involving health professionals; and (3) the goal was to evaluate factors associated with underreporting of ADRs through spontaneous reporting. RESULTS: Overall, 65 papers were included. While health professional sociodemographic characteristics did not influence underreporting, knowledge and attitudes continue to show a significant effect: (1) ignorance (only serious ADRs need to be reported) in 86.2%; (2) lethargy (procrastination, lack of interest, and other excuses) in 84.6%; (3) complacency (the belief that only well tolerated drugs are allowed on the market) in 46.2%; (4) diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 44.6%; and (5) insecurity (it is nearly impossible to determine whether or not a drug is responsible for a specific adverse reaction) in 33.8%, and the absence of feedback in 9.2%. In this review, the non-obligation to reporting and confidentiality emerge as new reasons for underreporting. CONCLUSIONS: Attitudes regarding the reporting of adverse reactions continue to be the main determinants of underreporting. Even though these are potentially modifiable factors through educational interventions, minimal changes have been observed since 2009. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42021227944.

Temperature-related effects on respiratory medical prescriptions in Spain.

BACKGROUND: The increased risk of mortality during periods of high and low temperatures has been well established. However, most of the studies used daily counts of deaths or hospitalisations as health outcomes, although they are the ones at the top of the health impact pyramid reflecting only a limited proportion of patients with the most severe cases. OBJECTIVES: This study evaluates the relationship between short-term exposure to the daily mean temperature and medication prescribed for the respiratory system in five Spanish cities. METHODS: We fitted time series regression models to cause-specific medical prescriptions, including different respiratory subgroups and age groups. We included a distributed lag non-linear model with lags up to 14 days for daily mean temperature. City-specific associations were summarised as overall-cumulative exposure-response curves. RESULTS: We found a positive association between cause-specific medical prescriptions and daily mean temperature with a non-linear inverted J- or V-shaped relationship in most cities. Between 0.3% and 0.6% of all respiratory prescriptions were attributed to cold for Madrid, Zaragoza and Pamplona, while in cities with only cold effects the attributable fractions were estimated as 19.2% for Murcia and 13.5% for Santander. Heat effects in Madrid, Zaragoza and Pamplona showed higher fractions between 8.7% and 17.2%. The estimated costs are in general higher for heat effects, showing annual values ranging between €191,905 and €311,076 for heat per 100,000 persons. CONCLUSIONS: This study provides novel evidence of the effects of the thermal environment on the prescription of medication for respiratory disorders in Spain, showing that low and high temperatures lead to an increase in the number of such prescriptions. The consumption of medication can reflect exposure to the environment with a lesser degree of severity in terms of morbidity.

La ruleta rusa de los análisis estadísticos de estudios clínicos. Una reflexión para lectores y autores / The Russian Roulette of Statistical Analysis in Clinical Trials. Some Considerations for Readers and Authors

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Heat wave intensity and daily mortality in four of the largest cities of Spain.

In the current context of climate change, heat waves have become a significant problem for human health. This study assesses the effects of heat wave intensity on mortality (natural, respiratory and cardiovascular causes) in four of the largest cities of Spain (Barcelona, Bilbao, Madrid and Seville) during the period between 1990 and 2014. To model the heat wave severity the Excess Heat Factor (EHF) was used. The EHF is a two-component index. The first is the comparison of the three-day average daily mean temperature with the 95th percentile. The second component is a measure of the temperatures reached during the three-day period compared with the recent past (the previous 30 days). The city-specific exposure-response curves showed a non-linear J-shaped relationship between mortality and the EHF. Overall city-specific mortality risk estimates in natural causes for 1st vs. 99th percentile increases range from the highest mortality risk with 2.73 (95% CI: 2.34-3.18) in Seville to a risk of 1.78 (95% CI: 1.62-1.97) and 1.78 (95% CI: 1.45-2.19) in Barcelona and Bilbao, respectively. When we compare our results with risk estimates for the analyzed Spanish cities in other studies, the heat wave related mortality risks seem to be clearly higher. Furthermore, it has been demonstrated that different heat wave days of the same event do not present the same degree of severity/intensity. Thus, the intensity of a heat wave is an important mortality risk indicator during heat wave days. Due to the low number of studies on the EHF as a heat wave intensity indicator and heat-related mortality and morbidity, further research is required to validate its application in other geographic areas and focus populations.

Short-term effects of heat and cold on respiratory drug use. A time-series epidemiological study in A Coruña, Spain.

The consumption of medication, especially over-the-counter drugs, can reflect environmental exposure with a lesser degree of severity in terms of morbidity. The non-linear effects of maximum and minimum apparent temperature on respiratory drug sales in A Coruña from 2006 to 2010 were examined using a distributed lag nonlinear model. In particular, low apparent temperatures proved to be associated with increased sales of respiratory drugs. The strongest consistent risk estimates were found for minimum apparent temperatures in respiratory drug sales with an increase of 33.4% (95% CI, 12.5%-58.0%) when the temperature changed from 2.8°C to -1.4 °C. These findings may serve to guide the planning of public health interventions to predict and manage the health effects of exposure to the thermal environment for lower degrees of morbidity. More precisely, significant increases in the use of measured over-the-counter medication could be used to identify and anticipate influenza outbreaks due to a more sensitive degree of the data source.

Knowledge, attitudes, perceptions and habits towards antibiotics dispensed without medical prescription: a qualitative study of Spanish pharmacists.

OBJECTIVE: To investigate community pharmacists' knowledge, attitudes, perceptions and habits with regard to antibiotic dispensing without medical prescription in Spain. METHODS: A qualitative research using focus group method (FG) in Galicia (north-west Spain). FG sessions were conducted in the presence of a moderator. A topic script was developed to lead the discussions, which were audiorecorded to facilitate data interpretation and transcription. Proceedings were transcribed by an independent researcher and interpreted by two researchers working independently. We used the Grounded Theory approach. SETTING: Community pharmacies in Galicia, region Norwest of Spain. PARTICIPANTS: Thirty pharmacists agreed to participate in the study, and a total of five FG sessions were conducted with 2-11 pharmacists. We sought to ensure a high degree of heterogeneity in the composition of the groups to improve our study's external validity. Pharmacists' participation had no gender or age restrictions, and an effort was made to form FGs with pharmacists who were both owners and non-owners, provided in all cases that they were Official Colleges of Pharmacists-registered community pharmacists. For the purpose of conducting FG discussions, the basic methodological principle of allowing groups to attain their 'own structural identity' was applied. MAIN OUTCOME MEASUREMENTS: Community pharmacists' habits and knowledge with regard to antibiotics and identification of the attitudes and/or factors that influence antibiotic dispensing without medical prescription. RESULTS: Pharmacists attributed the problem of antibiotics dispensed without medical prescription and its relationship to antibiotic resistance to the following attitudes: external responsibility (doctors, dentists and the National Health Service (NHS)); acquiescence; indifference and lack of continuing education. CONCLUSIONS: Despite being a problem, antibiotic dispensing without a medical prescription is still a common practice in community pharmacies in Galicia, Spain. This practice is attributed to acquiescence, indifference and lack of continuing education. The problem of resistance was ascribed to external responsibility, including that of patients, physicians, dentists and the NHS.

Trends in socioeconomic inequalities in mortality in small areas of 33 Spanish cities.

BACKGROUND: In Spain, several ecological studies have analyzed trends in socioeconomic inequalities in mortality from all causes in urban areas over time. However, the results of these studies are quite heterogeneous finding, in general, that inequalities decreased, or remained stable. Therefore, the objectives of this study are: (1) to identify trends in geographical inequalities in all-cause mortality in the census tracts of 33 Spanish cities between the two periods 1996-1998 and 2005-2007; (2) to analyse trends in the relationship between these geographical inequalities and socioeconomic deprivation; and (3) to obtain an overall measure which summarises the relationship found in each one of the cities and to analyse its variation over time. METHODS: Ecological study of trends with 2 cross-sectional cuts, corresponding to two periods of analysis: 1996-1998 and 2005-2007. Units of analysis were census tracts of the 33 Spanish cities. A deprivation index calculated for each census tracts in all cities was included as a covariate. A Bayesian hierarchical model was used to estimate smoothed Standardized Mortality Ratios (sSMR) by each census tract and period. The geographical distribution of these sSMR was represented using maps of septiles. In addition, two different Bayesian hierarchical models were used to measure the association between all-cause mortality and the deprivation index in each city and period, and by sex: (1) including the association as a fixed effect for each city; (2) including the association as random effects. In both models the data spatial structure can be controlled within each city. The association in each city was measured using relative risks (RR) and their 95 % credible intervals (95 % CI). RESULTS: For most cities and in both sexes, mortality rates decline over time. For women, the mortality and deprivation patterns are similar in the first period, while in the second they are different for most cities. For men, RRs remain stable over time in 29 cities, in 3 diminish and in 1 increase. For women, in 30 cities, a non-significant change over time in RR is observed. However, in 4 cities RR diminishes. In overall terms, inequalities decrease (with a probability of 0.9) in both men (RR = 1.13, 95 % CI = 1.12-1.15 in the 1st period; RR = 1.11, 95 % CI = 1.09-1.13 in the 2nd period) and women (RR = 1.07, 95 % CI = 1.05-1.08 in the 1st period; RR = 1.04, 95 % CI = 1.02-1.06 in the 2nd period). CONCLUSIONS: In the future, it is important to conduct further trend studies, allowing to monitoring trends in socioeconomic inequalities in mortality and to identify (among other things) temporal factors that may influence these inequalities.

Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis.

BACKGROUND: The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. METHODS: A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. RESULTS: Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer's disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer's disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. CONCLUSIONS: This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered.

Respiratory and mental health effects of wildfires: an ecological study in Galician municipalities (north-west Spain).

BACKGROUND: During the summer of 2006, a wave of wildfires struck Galicia (north-west Spain), giving rise to a disaster situation in which a great deal of the territory was destroyed. Unlike other occasions, the wildfires in this case also threatened farms, houses and even human lives, with the result that the perception of disaster and helplessness was the most acute experienced in recent years. This study sought to analyse the respiratory and mental health effects of the August-2006 fires, using consumption of anxiolytics-hypnotics and drugs for obstructive airway diseases as indicators. METHODS: We conducted an analytical, ecological geographical- and temporal-cluster study, using municipality-month as the study unit. The independent variable was exposure to wildfires in August 2006, with municipalities thus being classified into the following three categories: no exposure; medium exposure; and high exposure. Dependent variables were: (1) anxiolytics-hypnotics; and (2) drugs for obstructive airway diseases consumption. These variables were calculated for the two 12-month periods before and after August 2006. Additive models for time series were used for statistical analysis purposes. RESULTS: The results revealed a higher consumption of drugs for obstructive airway diseases among pensioners during the months following the wildfires, in municipalities affected versus those unaffected by fire. In terms of consumption of anxiolytics-hypnotics, the results showed a significant increase among men among men overall -pensioners and non-pensioners- in fire-affected municipalities. CONCLUSIONS: Our study indicates that wildfires have a significant effect on population health. The coherence of these results suggests that drug utilisation research is a useful tool for studying morbidity associated with environmental incidents.

Case-crossover analysis of air pollution health effects: a systematic review of methodology and application.

BACKGROUND: Case-crossover is one of the most used designs for analyzing the health-related effects of air pollution. Nevertheless, no one has reviewed its application and methodology in this context. OBJECTIVE: We conducted a systematic review of case-crossover (CCO) designs used to study the relationship between air pollution and morbidity and mortality, from the standpoint of methodology and application. DATA SOURCES AND EXTRACTION: A search was made of the MEDLINE and EMBASE databases.Reports were classified as methodologic or applied. From the latter, the following information was extracted: author, study location, year, type of population (general or patients), dependent variable(s), independent variable(s), type of CCO design, and whether effect modification was analyzed for variables at the individual level. DATA SYNTHESIS: The review covered 105 reports that fulfilled the inclusion criteria. Of these, 24 addressed methodological aspects, and the remainder involved the design's application. In the methodological reports, the designs that yielded the best results in simulation were symmetric bidirectional CCO and time-stratified CCO. Furthermore, we observed an increase across time in the use of certain CCO designs, mainly symmetric bidirectional and time-stratified CCO. The dependent variables most frequently analyzed were those relating to hospital morbidity; the pollutants most often studied were those linked to particulate matter. Among the CCO-application reports, 13.6% studied effect modification for variables at the individual level. CONCLUSIONS: The use of CCO designs has undergone considerable growth; the most widely used designs were those that yielded better results in simulation studies: symmetric bidirectional and time-stratified CCO. However, the advantages of CCO as a method of analysis of variables at the individual level are put to little use.

[Case-crossover design: Basic essentials and applications]. / Fundamentos y aplicaciones del diseño de casos cruzados.

Case-crossover analysis is an observational epidemiological design that was proposed by Maclure in 1991 to assess whether a given intermittent or unusual exposure may have triggered an immediate short-term, acute event. The present article outlines the basics of case-crossover designs, as well as their applications and limitations. The case-crossover design is based on exclusively selecting case subjects. To calculate relative risk, exposure during the period of time prior to the event (case period) is compared against the same subject's exposure during one or more control periods. This method is only appropriate when the exposures are transient in time and have acute short-term effects. For exposures in which there is no trend, a unidirectional approach is the most frequent and consists of selecting one or more control periods prior to the case period. When the exposure displays a time trend (e.g., air pollution), a unidirectional approach will yield biased estimates, and therefore bidirectional case-crossover designs are used, which select control time intervals preceding and subsequent to that of the event. The case-crossover design is being increasingly used across a wide range of fields, including factors triggering traffic, occupational and domestic accidents and acute myocardial infarction, and those involved in air pollution and health and pharmacoepidemiology, among others. Insofar as data-analysis is concerned, case-crossover designs can generally be regarded as matched case-control studies and consequently conditional logistic regression can be applied. Lastly, this study analyzes practical examples of distinct applications of the case-crossover design.

Fundamentos y aplicaciones del diseño de casos cruzados / Case-crossover design: Basic essentials and applications

El diseño de casos cruzados es un diseño epidemiológico observacional propuesto por Maclure en 1991 para valorar si alguna exposición intermitente o inusual ha desencadenado un evento agudo a muy corto plazo. En este trabajo se presentan los fundamentos de los diseños de casos cruzados, con sus aplicaciones y limitaciones. El diseño de casos cruzados se basa en seleccionar sólo sujetos caso. Para calcular el riesgo relativo se compara la exposición durante el periodo de tiempo previo al evento (periodo caso) con la exposición del mismo sujeto en uno o varios periodos control. Este método únicamente es adecuado cuando las exposiciones son cambiantes en el tiempo, con efectos a corto plazo, y el efecto es agudo. Para exposiciones en que no existe tendencia, el planteamiento unidireccional es el más frecuente, y consiste en seleccionar uno o varios periodos control previos al momento caso. Cuando la exposición tiene una tendencia temporal (por ejemplo las de contaminación atmosférica), el planteamiento unidireccional proporciona estimaciones sesgadas, por lo que se utilizan diseños de casos cruzados bidireccionales, que seleccionan periodos de tiempo control anteriores y posteriores al del evento. Es un método que cuenta con una creciente utilización en amplios campos: desencadenantes de accidentes de tráfico, laborales y domésticos, o de infarto agudo de miocardio, contaminación atmosférica y salud, farmacoepidemiología, etc. Para el análisis de datos, generalmente se pueden considerar los diseños de casos cruzados como estudios de casos y controles emparejados, por lo que se aplica regresión logística condicional. Finalmente, en este trabajo se analizan ejemplos prácticos de diferentes aplicaciones del diseño de casos cruzados (AU)

Case-crossover analysis is an observational epidemiological design that was proposed by Maclure in 1991 to assess whether a given intermittent or unusual exposure may have triggered an immediate short-term, acute event. The present article outlines the basics of case-crossover designs, as well as their applications and limitations. The case-crossover design is based on exclusively selecting case subjects. To calculate relative risk, exposure during the period of time prior to the event (case period) is compared against the same subject's exposure during one or more control periods. This method is only appropriate when the exposures are transient in time and have acute short-term effects. For exposures in which there is no trend, a unidirectional approach is the most frequent and consists of selecting one or more control periods prior to the case period. When the exposure displays a time trend (e.g., air pollution), a unidirectional approach will yield biased estimates, and therefore bidirectional case-crossover designs are used, which select control time intervals preceding and subsequent to that of the event. The case-crossover design is being increasingly used across a wide range of fields, including factors triggering traffic, occupational and domestic accidents and acute myocardial infarction, and those involved in air pollution and health and pharmacoepidemiology, among others. Insofar as data-analysis is concerned, case-crossover designs can generally be regarded as matched case-control studies and consequently conditional logistic regression can be applied. Lastly, this study analyzes practical examples of distinct applications of the case-crossover design (AU)

[The EMECAS Project: Spanish multicentre study on short-term health effects of air pollution]. / El proyecto EMECAS: protocolo del estudio multicéntrico en España de los efectos a corto plazo de la contaminación atmosférica sobre la salud.

UNLABELLED: The EMECAM Project demonstrated the short-term effect of air pollution on the death rate in 14 cities in Spain throughout the 1990-1995 period. The Spanish Multicentre Study on Health Effects of Air Pollution (EMECAS) is broadening these objectives by incorporating more recent data, information on hospital disease admissions and totaling 16 Spanish cities. This is an ecological time series study in which the response variables are the daily deaths and the emergency hospitalizations due to circulatory system diseases and respiratory diseases among the residents in each city. Pollutants analyses: suspended particles, SO2, NO2, CO and O3. Control variables: meteorological, calendar, seasonality and influenza trend and incidence. STATISTICAL ANALYSIS: estimate of the association in each city by means of the construction of generalized additive Poisson regression models and metanalysis for obtaining combined estimators. The EMECAS Project began with the creation of three working groups (Exposure, Epidemiology and Analysis Methodology) which defined the protocol. The average levels of pollutants were below those established under the current regulations for sulfur dioxide, carbon monoxide and ozone. The NO2 and PM10 values were around those established under the regulations (40 mg/m3). This is the first study of the relationship between air pollution and disease rate among one group of Spanish cities. The pollution levels studied are moderate for some pollutants, although for others, especially NO2 and particles, these levels could entail a problem with regard to complying with the regulations in force.

El Proyecto EMECAS: protocolo del estudio multicéntrico en España de los efectos a corto plazo de la contaminación atmosférica sobre la salud / The EMECAS project: spanish multicentre study on short-term health effects of air pollution

El proyecto EMECAM constató el efecto a corto plazo de la contaminación atmosférica sobre la mortalidad en 14 ciudades españolasentre 1990 y 1995. El Estudio Multicéntrico Español de Contaminación Atmosférica y Salud (EMECAS) amplía estos objetivosincorporando al análisis datos de morbilidad hospitalaria, utilizainformación más reciente y suma un total de 16 ciudades. Se trata deun estudio ecológico de series temporales, siendo las variables respuestalas defunciones diarias y los ingresos hospitalarios urgentespor enfermedades del aparato circulatorio y enfermedades respiratoriasen los residentes de cada ciudad. Contaminantes analizados: partículas en suspensión, SO2, NO2, CO y O3. Variables de control:meteorológicas, de calendario, estacionalidad y tendencia e incidenciade gripe. Análisis estadístico: estimación de la asociación en cadaciudad mediante la construcción de modelos de regresión de Poissonaditivos generalizados, y meta-análisis para la obtención de estimadoresconjuntos. Los niveles medios de contaminantes se situaronpor debajo de los establecidos por la normativa actual para el dióxidode azufre, el monóxido de carbono y el ozono. Los valores de NO2y PM10 se situaron alrededor de los establecidos en la normativa (40mg/m3). Se trata del primer estudio de la relación entre contaminación atmosférica y morbilidad en un conjunto de ciudades españolas.Los niveles de contaminantes estudiados son moderados para algunoscontaminantes, aunque en otros, especialmente NO2 y partículas,podrían representar un problema para el cumplimiento de la normativavigente

The EMECAM Project demonstrated the short-term effect of airpollution on the death rate in 14 cities in Spain throughout the 1990-1995 period. The Spanish Multicentre Study on Health Effects of AirPollution (EMECAS) is broadening these objectives by incorporatingmore recent data, information on hospital disease admissionsand totaling 16 Spanish cities. This is an ecological time series studyin which the response variables are the daily deaths and the emergencyhospitalizations due to circulatory system diseases and respiratorydiseases among the residents in each city. Pollutants analyses:suspended particles, SO2, NO2, CO and O3. Control variables:meteorological, calendar, seasonality and influenza trend and incidence.Statistical analysis: estimate of the association in each city bymeans of the construction of generalized additive Poisson regressionmodels and metanalysis for obtaining combined estimators. TheEMECAS Project began with the creation of three working groups(Exposure, Epidemiology and Analysis Methodology) which definedthe protocol. The average levels of pollutants were below thoseestablished under the current regulations for sulfur dioxide, carbonmonoxide and ozone. The NO2 and PM10 values were around thoseestablished under the regulations (40 mg/m3). This is the first studyof the relationship between air pollution and disease rate among onegroup of Spanish cities. The pollution levels studied are moderate forsome pollutants, although for others, especially NO2 and particles,these levels could entail a problem with regard to complying with theregulations in force

Analysis of case-crossover designs using longitudinal approaches: a simulation study.

BACKGROUND: Application of case-crossover designs provides an alternative to time-series analysis for analyzing the health-related effects of air pollution. Although some case-crossover studies can control for trend and seasonality by design, to date they have been analyzed as matched case-control studies. Such analyses may exhibit biases and a lower statistical efficiency than traditional time series analyzed with Poisson. METHODS: In this article, case-crossover studies are treated as cohort studies in which each subject is observed for a short period of time before and/or after the event, thus making possible analyzing with Andersen-Gill and generalized linear mixed models. We conducted a simulation study to compare the behavior of these models applied to case-crossover designs with time series analyzed with Poisson and with case-crossover analyzed by conditional logistic regression. To this end, we created a random variable that follows a Poisson distribution of low (2/day) and high mean events (22/day). This variable is a function of an unobserved confounding variable (that introduces trend and seasonality) and data on small particulate matter (PM10) from Barcelona. In addition, scenarios were created to assess the effect on exposure exerted by autocorrelation and the magnitude of the pollutant coefficient. RESULTS: The full semisymmetric design analyzed with generalized linear mixed models yields good coverage and a high statistical power for air-pollution effect magnitudes close to the real values but shows bias for high effect magnitudes. This bias seems to be attributable to autocorrelation in the exposure variable. CONCLUSIONS: Longitudinal approaches applied to case-crossover designs may prove useful for analyzing the acute effects of environmental exposures.

[Short-term relationship between air pollution and mortality in 13 Spanish cities]. / Relación a corto plazo de la contaminación atmosférica y la mortalidad en 13 ciudades españolas.

BACKGROUND AND OBJECTIVE: EMECAM is a collaborative project that seeks to evaluate the short-term effects of air pollution on mortality in Spain. MATERIAL AND METHOD: We collected data for air pollutants (particles and gases), daily mortality (total except external, cardiovascular and respiratory causes) and co-variables (temperature, humidity, influenza and calendar variables) in 13 Spanish cities. The magnitude of the association in every city was estimated using GAM under a Poisson distribution. Combined estimates for each cause and pollutant were obtained under 'fixed effects' and 'random effects'models. RESULTS: An increase of 10 (g/m3 in the levels of the average of the concurrent and one day lag for black smoke was associated with a 0.8% (CI: 0.4-1.1) increase in mortality. The same increase in the concentration of SO2 was associated with a 0.5% (CI: 0.1-1.0) increase in daily deaths, and a 0.6% (CI: 0.3-0.8) increase in the case of NO2. An increase of 1 mg/m3 in the levels of CO was associated with an increase of 1.5% (CI: 0.5-2.6) in daily deaths. CONCLUSIONS: There is a short-term association between increases of daily levels of air pollutants and the number of daily deaths in Spanish cities.

Relación a corto plazo de la contaminación atmosférica y la mortalidad en 13 ciudades españolas / Short-term relationship between air pollution and mortality in 13 Spanish cities

FUNDAMENTO Y OBJETIVO: EMECAM es un proyecto multicéntrico cuyo objetivo es evaluar la asociación a corto plazo de la contaminación sobre la salud en España. MATERIAL Y MÉTODO: Se obtuvieron los datos sobre contaminación atmosférica (partículas en suspensión y gases), mortalidad (todas las causas excluidas las externas, causas respiratorias y causas del aparato circulatorio) y de covariables para el control de la confusión (temperatura, humedad, gripe, variables de calendario) en 13 ciudades españolas. Los estimadores locales de los efectos de los contaminantes, obtenidos a partir de modelos autorregresivos generalizados aditivos de Poisson, se combinaron mediante modelos de efectos fijos y, cuando existía heterogeneidad, modelos de efectos aleatorios. Se construyeron todos los modelos con uno y con dos contaminantes simultáneamente. RESULTADOS: Un aumento de 10 µg/m3 en el promedio de las concentraciones del día simultáneo y el día anterior de humos negros se asoció con un incremento del 0,8 por ciento (intervalo de confianza [IC] del 95 por ciento, 0,4-1,1) de la mortalidad total. El mismo incremento de dióxido de azufre y de dióxido de nitrógeno se asoció con incrementos del 0,5 por ciento (IC del 95 por ciento, 0,1-1,0) y del 0,6 por ciento (IC del 95 por ciento: 0,3-0,8) de la mortalidad, respectivamente. Un aumento de 1 mg/m3 en los valores de monóxido de carbono se asoció con un incremento del 1,5 por ciento (IC del 95 por ciento, 0,5-2,6) en las defunciones diarias. Los coeficientes obtenidos para los grupos de causas específicas fueron, en general, de mayor magnitud. En los modelos de dos contaminantes las partículas y el monóxido de carbono fueron los contaminantes que mostraron mayor robustez en los estimadores. CONCLUSIONES: Los incrementos diarios en las concentraciones de contaminantes atmosféricos se asocian, a corto plazo, con un aumento en el número de defunciones en las ciudades españolas (AU)