Impact of the use of small-area models on estimation of attributable mortality at a regional level.

The objective of this study is to assess the impact of applying prevalences derived from a small-area model at a regional level on smoking-attributable mortality (SAM). A prevalence-dependent method was used to estimate SAM. Prevalences of tobacco use were derived from a small-area model. SAM and population attributable fraction (PAF) estimates were compared against those calculated by pooling data from three national health surveys conducted in Spain (2011-2014-2017). We calculated the relative changes between the two estimates and assessed the width of the 95% CI of the PAF. Applying surveys-based prevalences, tobacco use was estimated to cause 53 825 (95% CI: 53 182-54 342) deaths in Spain in 2017, a figure 3.8% lower obtained with the small-area model prevalences. The lowest relative change was observed in the Castile-La Mancha region (1.1%) and the highest in Navarre (14.1%). The median relative change between regions was higher for women (26.1%), population aged ≥65 years (6.6%), and cardiometabolic diseases (9.0%). The differences between PAF by cause of death were never greater than 2%. Overall, the differences between estimates of SAM, PAF, and confidence interval width are small when using prevalences from both sources. Having these data available by region will allow decision-makers to implement smoking control measures based on more accurate data.

[Evolution of smoking prevalence in Spain and its 17 autonomous regions (1987-2020)]. / Evolución de la prevalencia de consumo de tabaco en España y sus 17 comunidades autónomas (1987-2020).

BACKGROUND AND OBJECTIVES: Continuous monitoring of smoking prevalence is essential to understand the evolution of the tobacco epidemic in a population. The objective of this study was to analyze the evolution of smoking prevalence in Spain and its 17 Autonomous Regions (ARs) in population ≥15 years during the period 1987-2020. METHODS: Tobacco consumption data were derived from the National Health Survey of Spain and the European Health Survey in Spain. A smoker was defined as a person who smoked at the time of the survey. The trend in prevalences by sex in Spain and its ARs was analyzed by applying joinpoint models. Age-standardized prevalences were calculated for Spain by applying the direct method. RESULTS: In Spain, the prevalence of consumption decreased 29 percentage points in men and 4.5 in women between 1987-2020. In men, the smoking prevalence decreased in all the ARs and the absolute change varied between -19.5% in the Balearic Islands and -33.9% in Andalusia. In women, the evolution of smoking prevalence differed between ARs. The absolute change varied between -15.4% in Basque Country and 0.5% in Andalusia. CONCLUSIONS: The number of men and women smokers has decreased in Spain between 1987-2020. Different patterns of evolution of the prevalence of consumption are observed among the ARs, especially among women. This reinforces the need for policies adapted to more local contexts and that take into account the gender perspective.

Small-area models to assess the geographical distribution of tobacco consumption by sex and age in Spain.

INTRODUCTION: Complete and accurate data on smoking prevalence at a local level would enable health authorities to plan context-dependent smoking interventions. However, national health surveys do not generally provide direct estimates of smoking prevalence by sex and age groups at the subnational level. This study uses a small-area model-based methodology to obtain precise estimations of smoking prevalence by sex, age group and region, from a population-based survey. METHODS: The areas targeted for analysis consisted of 180 groups based on a combination of sex, age group (15-34, 35-54, 55-64, 65-74, and ≥75 years), and Autonomous Region. Data on tobacco use came from the 2017 Spanish National Health Survey (2017 SNHS). In each of the 180 groups, we estimated the prevalence of smokers (S), ex-smokers (ExS) and never smokers (NS), as well as their coefficients of variation (CV), using a weighted ratio estimator (direct estimator) and a multinomial logistic model with random area effects. RESULTS: When smoking prevalence was estimated using the small-area model, the precision of direct estimates improved; the CV of S and ExS decreased on average by 26%, and those of NS by 25%. The range of S prevalence was 11-46% in men and 4-37% in women, excluding the group aged ≥75 years. CONCLUSIONS: This study proposes a methodology for obtaining reliable estimates of smoking prevalence in groups or areas not covered in the survey design. The model applied is a good alternative for enhancing the precision of estimates at a detailed level, at a much lower cost than that involved in conducting large-scale surveys. This method could be easily integrated into routine data processing of population health surveys. Having such estimates directly after completing a health survey would help characterize the tobacco epidemic and/or any other risk factor more precisely.

[Attributable mortality to tobacco consumption in Brazil, 1996-2019]. / Mortalidad atribuida al consumo de tabaco en Brasil, 1996-2019.

OBJECTIVE: To analyze the burden of tobacco consumption on mortality and years of life expectancy lost in population ≥35 years in Brazil in the period 1996-2019 and to identify trend changes in smoking-attributable mortality. METHOD: An independent prevalence method using the lung cancer mortality rate as a proxy for cumulative smoking risk was used to estimate smoking-attributable mortality. Smoking-attributable mortality is estimated from the lung cancer mortality rate and applying relative risks from 5 US cohorts. Smoking-attributable mortality, crude and standardized attributed mortality rates are presented overall, by sex, age and causes of death. Trend analysis was performed by applying joinpoint regression models. Years of life expectancy lost due to tobacco were calculated. RESULTS: Tobacco consumption caused 2,389,831 deaths in Brazil between 1996-2019. Cardiometabolic diseases were the leading cause of death in women throughout the period and in men until 2015. Since 2006, smoking-attributable mortality rates in men, regardless of age, show a decreasing trend while in females the evolution is different. The years of life expectancy lost show a slight decrease since the first triennia and are higher in men. CONCLUSIONS: In Brazil, the 8.5% of total mortality between 1996-2019 is attributed to tobacco consumption. It is important to monitor the burden of the tobacco consumption on mortality in order to strengthen or implement interventions against smoking in Brazil.

Mortality Attributable to Environmental Tobacco Smoke Exposure in Spain in 2020.

INTRODUCTION AND OBJECTIVES: Exposure to environmental tobacco smoke (ETS) is associated with increased mortality and morbidity. The objective of this study was to estimate the impact of ETS exposure in Spain on mortality in 2020 in the population aged 35 years and over. METHODS: A method of estimating attributable mortality (AM) based on the prevalence of ETS exposure was applied. Prevalence data were obtained from a representative study conducted in Spain and the relative risks were derived from a meta-analysis. AM point estimates are presented along with 95% confidence intervals (95% CI), calculated using a bootstrap naive procedure. AM, both overall and by smoking habit, was estimated for each combination of sex, age group, and cause of death (lung cancer and ischemic heart disease). A sensitivity analysis was performed. RESULTS: A total of 747 (95% CI 676-825) deaths were attributable to ETS exposure, of which 279 (95% CI 256-306) were caused by lung cancer, and 468 (95% CI 417-523) by ischemic heart disease. Three-quarters (75.1%) of AM occurred in men and 60.9% in non-smokers. When chronic obstructive pulmonary disease and cerebrovascular disease are included, the burden of AM is estimated at 2242 deaths. CONCLUSIONS: ETS exposure is associated with 1.5% of all deaths from lung cancer and ischemic heart disease in the population aged 35 and over. These data underline the need for health authorities to focus on reducing exposure to ETS in all settings and environments.

Trends in smoking-attributable mortality in Spain: 1990-2018.

BACKGROUND: This study sought to analyse the trend in smoking-attributable mortality (SAM) in Spain among the population aged ≥35 years across the period 1990-2018. METHODS: SAM was estimated by applying a prevalence-independent method, which uses lung cancer (LC) mortality as a proxy of tobacco consumption. We sourced observed mortality from the National Institute of Statistics (Spain), LC mortality rates in smokers and never smokers from the Cancer Prevention Study I-II, and relative risks from 5 US cohorts. Estimates of annual SAM by cause of death, sex and age are shown, along with crude and annual standardised SAM rates. The trend in standardised all-cause and LC rates was analysed using a joinpoint regression model. RESULTS: Tobacco caused 1 717 150 deaths in Spain in the period 1990-2018. Among men, cancers replaced cardiovascular diseases-diabetes mellitus (CVD-DM) as the leading group of tobacco-related cause of death in 1994. Among women, CVD-DM remained the leading cause of death throughout the period. Trend analysis of standardised SAM rates due to all causes and LC showed a decrease in men and an increase in women. CONCLUSIONS: The tobacco epidemic in Spain across the period 1990-2018 has had an important impact on mortality and has evolved differently in both genders. SAM is expected to increase dramatically in women in the coming years. SAM data highlight the importance of including a gender perspective in SAM analyses, in designing more effective and comprehensive public health interventions and in developing gender-specific tobacco control policies to curb tobacco consumption.

Methodological guidelines for the estimation of attributable mortality using a prevalence-based method: the STREAMS-P tool.

BACKGROUND: There is evidence of strong links between exposure to different risk factors and life-threatening diseases. Assessing the burden of a risk factor on the population's mortality due to a given disease provides a clear picture of these links. The estimation of attributable mortality to a risk factor is the most widely used procedure for doing this. Although different methods are available to estimate attributable mortality, the prevalence-based methodology is the most frequent. The main objective of this study is to develop guidelines and checklists to STrengthen the design and REporting of Attributable Mortality Studies using a Prevalence-based method (STREAMS-P) and also to assess the quality of an already published study which uses this methodology. METHODS: The design of the guideline and checklists has been done in two phases. A development phase, where we set recommendations based on the review of the literature, and a validation phase, where we validated our recommendations against other published studies that have estimated attributable mortality using a prevalence-based method. RESULTS: We have developed and tested a guideline that includes the information required to perform a prevalence-based attributable mortality study to a given risk factor; a checklist of aspects that should be present when a report or a paper on attributable mortality is written or interpreted and a checklist of quality control criteria for reports or papers estimating attributable mortality. CONCLUSION: To our knowledge, the STREAMS-P is the first set of criteria specifically created to assess the quality of such studies and it could be valuable for authors and readers interested in performing attributable mortality studies or interpreting their reliability.

Smoking-attributable mortality in the autonomous communities of Spain, 2017.

INTRODUCTION AND OBJECTIVES: To estimate smoking-attributable mortality (SAM) in the regions of Spain among people aged ≥ 35 years in 2017. METHODS: SAM was estimated using a prevalence dependent method based calculating the population attributable fraction. Observed mortality was derived from the National Statistics Institute. The prevalence of smoking by age and sex was based on the Spanish National Health Survey for 2011 and 2017 and the European Survey for 2014. Relative risks were reported from the follow-up of 5 North American cohorts. SAM and population attributable fraction were estimated for each region by age group, sex, and causes of death. Cause-specific and adjusted SAM rates were estimated. RESULTS: Smoking caused 53 825 deaths in the population aged ≥ 35 years (12.9% of all-cause mortality). SAM ranged from 10.8% of observed mortality in La Rioja to 15.3% in the Canary Islands. The differences remained after rates were adjusted by age. The highest adjusted SAM rates were observed in Extremadura in men and in the Canary Islands in women. Adjusted SAM rates in men were inversely correlated with those in women. The percentage of total SAM represented by cardiovascular diseases in each region ranged from 21.8% in Castile-La Mancha to 30.3% in Andalusia. CONCLUSIONS: The distribution of SAM differed among regions. Conducting a detailed region-by-region analysis provides relevant information for health policies aiming to curb the impact of smoking.

Smoking-attributable mortality in South America: A systematic review.

BACKGROUND: Dating from the 1920s and linked to the increase in mortality among smokers, tobacco has become one of the most studied health risk factors. Tobacco-use series, whether for the general population or for specific groups, are unavailable for most South American countries, something that hinders the characterisation of this risk factor. OBJECTIVES: To identify and analyse studies that estimate smoking-attributable mortality (SAM) in South America and provide an overview of the impact of smoking habit on mortality in the region. METHODS: Systematic review using PubMed, Embase, LILACS, Biblioteca Virtual en Salud, Google Scholar and Google, and including all papers published until June 2020 reporting studies in which SAM was estimated. RESULTS: The search yielded 140 papers, 17 of which fulfilled the inclusion criteria. There were SAM estimates for all South American countries, with Argentina having the most. The first estimate covered 1981 and the latest, 2013. The method most used was prevalence-based. Regardless of the country and point in time covered by the estimate, the highest figures were recorded for men in all cases. The burden of attributable vs observed mortality varied among countries, reaching a figure of 20.3% in Argentina in 1986. The highest SAM burden was registered for the group of cardiovascular diseases. CONCLUSIONS: SAM estimates are available for all South American countries but the respective study periods differ and the frequency of the estimates is unclear. For 4 countries, the only estimates available are drawn from reports, something that does not allow for a detailed assessment of the estimates obtained. To help with decision-making targeted at evaluating and enhancing the impact of smoking control policies, further studies are needed in order to update the impact of smoking on all countries across South America.

[Association between socioeconomic determinants and environmental tobacco smoke exposure in children]. / Asociación entre determinantes socioeconómicos y exposición al humo ambiental del tabaco en niños.

OBJECTIVE: To assess the association between exposure to environmental tobacco smoke (ETS) and different socioeconomic determinants among Spanish children. METHOD: We analyzed the data of 5495 children included in the 2011-2012 Spanish National Health Survey. We estimated the prevalence of exposure to ETS and adjusted logistic regression models to identify variables related to exposure to ETS: total exposure and exposure in the home in addition to ETS exposure in enclosed public places/transport. RESULTS: Total exposure to ETS among children aged 15 and younger was 11.8%, 11.5% of whom were exposed at home and 0.8% in enclosed public places/transport. The prevalence odds ratio (POR) of exposure at home increased with age (6-9 years: 2.19; 10-14 years: 2.28), in children with parents of low or medium education levels (1.97 and 1.29), of social class IV-VI (1.42), among those living in a household with a composition other than a "couple with children" (1.43), and in smaller-sized homes (1.39). Total exposure results were similar to home exposure results. CONCLUSION: The prevalence of ETS is higher among children younger than 15 years with a more difficult economic situation. These inequalities must be considered in the establishment and development of public health policies.

Smoking-Attributable mortality in Spain in 2016.

INTRODUCTION: Smoking-attributable mortality (SAM) is a valuable indicator that can be used to characterize the course and health burden of the smoking epidemic. The aim of this paper was to estimate SAM in Spain in 2016 in the population aged 35 and over, using the best available evidence. METHODS: A smoking prevalence-dependent analysis based on the estimation of population-attributable fractions was performed. Smoking prevalence (never, former, and current smokers) was calculated from a combination of the Spanish Health Survey (2016) and the European Health Survey (2014); the relative risk of death among current and former smokers was taken from the follow-up of various cohorts; and mortality rates were obtained from National Center for Statistics data. SAM estimates are presented globally, and by sex, age groups, and major disease categories: cancer, cardiometabolic diseases and respiratory diseases. RESULTS: In 2016, 56,124 deaths were attributed to tobacco consumption, 84% in men (47,000), and 50% in the population aged over 74 (27,795). Overall, 50% of SAM was due to cancer (28,281), 65% of which was lung cancer. One in 4 attributable deaths (13,849) occurred before the age of 65. CONCLUSIONS: One in 7 deaths in Spain in 2016 were attributable to smoking. This estimation of SAM clearly highlights the great impact of smoking on mortality in Spain, mainly due to lung cancer and chronic obstructive pulmonary disease.

Conflicts of interest in research on electronic cigarettes.

INTRODUCTION: The tobacco control community has raised some concerns about whether studies on electronic cigarettes (e-cigarettes) published in scientific journals hide conflicts of interest (COI) and whether such reports are biased. This study assessed potential COI in the e-cigarette scientific literature. METHODS: Cross-sectional study was conducted on e-cigarette publications indexed in PubMed up to August 2014. We extracted information about the authors (affiliations, location, etc.), publication characteristics (type, topic, subject, etc.), results and conclusions, presence of a COI statement, and funding by and/or financial ties to pharmaceutical, tobacco, and/or e-cigarette companies. An algorithm to determine the COI disclosure status was created based on the information in the publication. Prevalence ratios (PRs) and confidence intervals (CIs) were calculated to identify associations with COI disclosure, controlling for several independent variables. RESULTS: Of the 404 publications included in the analysis, 37.1% (n=150) had no COI disclosure statement, 38.6% declared no COI, 13.4% declared potential COI with pharmaceutical companies, 3.0% with tobacco companies, and 10.6% with e-cigarette companies. The conclusions in publications with COI, which were mainly tied to pharmaceutical companies, were more likely to be favourable to e-cigarette use (PR=2.23; 95% CI: 1.43-3.46). Publications that supported the use of e-cigarettes for both harm reduction (PR=1.81; 95%CI: 1.14-2.89) and smoking cessation (PR=2.02; 95% CI: 1.26-3.23) were more likely to have conclusions that were favourable to e-cigarettes. CONCLUSIONS: One-third of the publications reporting studies on e-cigarettes did not have a COI disclosure statement, and this proportion was even higher in news articles, editorials and other types of publications. Papers with conclusions that were favourable to e-cigarette use were more likely to have COI. Journal editors and reviewers should consider evaluating publications, including funding sources, to determine whether the results and conclusions may be biased.

Validity of self-reported exposure to second-hand smoke in hospitality venues.

The aim was to assess the validity of self-reported exposure to second-hand smoke (SHS) in 50 hospitality venues of Madrid (Spain) in 2010, taking as a reference vapour-phase nicotine measured by active sampling. The questions posed in the questionnaire permitted distinguishing between the different levels of SHS. However, the moderate relationship found (Spearman׳s correlation=0.387, p<0.001) suggests that intensity of exposure to SHS in hospitality venues, based solely on self-reported information, should be used with caution.

Variability in the correlation between nicotine and PM2.5 as airborne markers of second-hand smoke exposure.

The aim of this study was to assess the relationship between particulate matter of diameter≤2.5 µm (PM2.5) and airborne nicotine concentration as markers of second-hand smoke exposure with respect to the setting studied, the intensity of exposure, and the type of environment studied (indoors or outdoors). Data are derived from two independent studies that simultaneously measured PM2.5 and nicotine concentrations in the air as airborne markers of second-hand smoke exposure in public places and workplaces, including health care centres, bars, public administration offices, educational centres, and transportation. We obtained 213 simultaneous measures of airborne nicotine and PM2.5. Nicotine in the air was measured with active samplers containing a sodium bisulphate-treated filter that was analysed by gas chromatography/mass spectrometry. PM2.5 was measured with a SidePak AM510 Personal Aerosol Monitor. We calculated Spearman's rank correlation coefficient and its 95% confidence intervals (95% CI) between both measures for overall data and stratified by setting, type of environment (indoors/outdoors), and intensity of second-hand smoke exposure (low/high, according to the global median nicotine concentration). We also fitted generalized regression models to further explore these relationships. The median airborne nicotine concentration was 1.36 µg/m3, and the median PM2.5 concentration was 32.13 µg/m3. The overall correlation between both markers was high (Spearman's rank correlation coefficient=0.709; 95% CI: 0.635-0.770). Correlations were higher indoors (Spearman's rank correlation coefficient=0.739; 95% CI: 0.666-0.798) and in environments with high second-hand smoke exposure (Spearman's rank correlation coefficient=0.733; 95% CI: 0.631-0.810). The multivariate analysis adjusted for type of environment and intensity of second-hand smoke exposure confirmed a strong relationship (7.1% increase in geometric mean PM2.5 concentration per µg/m3 nicotine concentration), but only in indoor environments in a stratified analysis (6.7% increase; 95% CI: 4.3-9.1%). Although the overall correlation between airborne nicotine and PM2.5 is high, there is some variability regarding the type of environment and the intensity of second-hand smoke exposure. In the absence of other sources of combustion, air nicotine and PM2.5 measures can be used indoors, while PM2.5 should be used outdoors with caution.

Questionnaire-based second-hand smoke assessment in adults.

BACKGROUND: Numerous studies have assessed second-hand smoke (SHS) exposure but a gold standard remains to be established. This study aimed to review how SHS exposure has been assessed in adults in questionnaire-based epidemiological studies. METHODS: A literature search of original papers in English, French, Italian or Spanish published from January 2000 to May 2011 was performed using PubMed. The variables recorded for each study included target population, sample size, validation of the SHS questions, study design and phrasing of every question used to assess SHS exposure. For each item, information such as the setting where exposure was assessed or the indicator used to ascertain SHS exposure was extracted. RESULTS: We retrieved 977 articles, of which 335 matched the inclusion criteria. The main objective of 75.8% of the studies was to assess SHS exposure.The proportion of validated questions aiming to ascertain SHS exposure was 17.9%. Most studies collected data only for one (40.3%) or two settings (33.4%), most frequently the home (83.9%) and workplace (57%). The most commonly used indicator to ascertain exposure was the presence of smokers and 68.9% of the studies included an item to assess the intensity of SHS exposure. CONCLUSIONS: The variability in the indicators and items used to ascertain SHS exposure is very high, whereas the use of items derived from validated studies remains low. Identifying the diverse settings where SHS exposure may occur is essential to accurately assess exposure over time. A standard set of items to identify SHS exposure in distinct settings is needed.

Impact of the 2011 Spanish smoking ban in hospitality venues: indoor secondhand smoke exposure and influence of outdoor smoking.

INTRODUCTION: The Spanish tobacco control law of 2006 was modified in January 2011, banning smoking in all hospitality venues. The objective of the study was to assess the impact of the 2011 Spanish smoking ban on secondhand smoke (SHS) exposure in hospitality venues, and to analyze the potential impact of outdoor smokers close to entrances on indoor SHS levels after the law came into force. METHODS: Before-and-after evaluation study with repeated measures. The study was carried out in three regions of Spain (Catalonia, Galicia, and Madrid) and included a random sample of 178 hospitality venues. We measured vapor-phase nicotine and particulate matter 2.5 micrometers or less in diameter (PM2.5) as SHS markers at baseline (November-December 2010) and at follow-up (April-June 2011). We also recorded tobacco consumption variables such as the presence of butts, ashtrays, and smokers. In the posttest assessment, we also recorded the number of outdoor smokers close to the entrance. RESULTS: A total of 351 nicotine and 160 PM2.5 measurements were taken. Both nicotine and PM2.5 concentrations decreased by more than 90% (nicotine from 5.73 to 0.57 µg/m(3), PM2.5 from 233.38 to 18.82 µg/m(3)). After the law came into force, both nicotine and PM2.5 concentrations were significantly higher in venues with outdoor smokers close to the entrance than in those without outdoor smokers. All the observational tobacco consumption variables significantly decreased (p < .001). CONCLUSIONS: SHS exposure in hospitality venues dramatically decreased after the 2011 Spanish smoking ban. SHS from outdoor smokers close to entrances seems to drift inside venues. Smoking control legislation should consider outdoor restrictions to ensure complete protection against SHS.

[Estimation of environmental tobacco smoke exposure: review of questionnaires used in Spain]. / Estimación de la exposición al humo ambiental de tabaco: revisión de cuestionarios utilizados en España.

INTRODUCTION: In the last few years, health surveys and epidemiological studies on smoking have introduced questions on environmental tobacco smoke (ETS) exposure. However, a standardized questionnaire is lacking. METHODS: Between January and May 2008, we reviewed surveys containing items on ETS exposure carried out in Spain by public administrations, scientific societies and research institutes. The wording of the questions was reviewed and classified according to the study type, target population, geographical setting and place of exposure. RESULTS: We identified 27 surveys that included questions on passive smoking. Most were health surveys (81.5%) and were aimed at the general population (70.4%). The most frequent geographical setting consisted of autonomous regions (48.1%) and the most common place of exposure was the home (88.9%) DISCUSSION: The results show wide variability in the questions used. Questionnaire items on ETS exposure should be homogenized to allow comparison of the results of surveys.

[Lung cancer as an index of tobacco exposure: association with non-lung cancer mortality]. / El cáncer de pulmón como marcador de tabaquismo: relación con la mortalidad por cáncer no pulmonar.

OBJECTIVE: To assess the possible role of tobacco smoke in non-lung cancer (excluding stomach cancer) using changes in lung cancer mortality rates as a proxy for tobacco exposure. METHODS: A time series analysis of cancer mortality was performed to evaluate the possible association between changes in mortality rates for lung cancer and for non-lung, non-stomach cancer (NLNS) from 1970 to 2003 in Spanish males. To avoid problems with autocorrelation, Prais-Winsten regression was applied. RESULTS: Changes in NLNS cancer death rates showed a parallel trend with lung cancer death rates in the study period, with an adjusted slope of 1.07, 95% CI of 0.98-1.17, and R2 of 0.97. CONCLUSION: Variation in NLNS cancer death rates can be accurately modelled as a function of changes in lung cancer death rates for the study period, suggesting a possible association between tobacco exposure and NLNS cancers.

Methodologies used to estimate tobacco-attributable mortality: a review.

BACKGROUND: One of the most important measures for ascertaining the impact of tobacco on a population is the estimation of the mortality attributable to its use. To measure this, a number of indirect methods of quantification are available, yet there is no consensus as to which furnishes the best information. This study sought to provide a critical overview of the different methods of attribution of mortality due to tobacco consumption. METHOD: A search was made in the Medline database until March 2005 in order to obtain papers that addressed the methodology employed for attributing mortality to tobacco use. RESULTS: Of the total of 7 methods obtained, the most widely used were the prevalence methods, followed by the approach proposed by Peto et al, with the remainder being used in a minority of studies. CONCLUSION: Different methodologies are used to estimate tobacco attributable mortality, but their methodological foundations are quite similar in all. Mainly, they are based on the calculation of proportional attributable fractions. All methods show limitations of one type or another, sometimes common to all methods and sometimes specific.

25-Hydroxycholesterol has a dual effect on the proliferation of cultured rat astrocytes.

We examined the effects of 25-OH-cholesterol on the growth of cultured rat astrocytes in the presence of lipoprotein-deficient serum (LPDS). 25-OH-cholesterol at 0.5-8 microM induced an increase in DNA synthesis as measured by [3H]thymidine incorporation into DNA, staining the cells with crystal violet, or counting the number of cells in different phases of the cell cycle by flow cytometry; however, at higher doses, an inhibition of cell proliferation was produced. Similar dose-dependent effects were found in media containing albumin (alone or with added EGF, PDGF, IGF-I or insulin), fetal bovine serum (FBS), or cholesterol-enriched LPDS. Mevalonate, and partially 25-OH-cholesterol, reversed the decrease in cell viability caused by mevinolin (lovastatin). However, mevalonate did not have any effect on 25-OH-cholesterol-stimulated proliferation. Finally, in media with albumin alone or in the presence of fetal bovine serum, growth factors, insulin or forskolin, 25-OH-cholesterol did not affect the expression of either c-fos mRNA or c-fos protein, as measured by real-time quantitative PCR or by Western blot, respectively. These results suggest that 25-OH-cholesterol has a dual effect on the proliferation of cultured rat astrocytes through an AP-1-independent mechanism. This could be of interest for gaining a better knowledge of the pathophysiological processes occurring in these cells.