Competing risks to breast cancer mortality in Catalonia

Background: Breast cancer mortality has experienced important changes over the last century. Breast cancer occurs in the presence of other competing risks which can influence breast cancer incidence and mortality trends. The aim of the present work is: 1) to assess the impact of breast cancer deaths among mortality from all causes in Catalonia (Spain), by age and birth cohort and 2) to estimate the risk of death from other causes than breast cancer, one of the inputs needed to model breast cancer mortality reduction due to screening or therapeutic interventions. Methods: The multi-decrement life table methodology was used. First, all-cause mortality probabilities were obtained by age and cohort. Then mortality probability for breast cancer was subtracted from the all-cause mortality probabilities to obtain cohort life tables for causes other than breast cancer. These life tables, on one hand, provide an estimate of the risk of dying from competing risks, and on the other hand, permit to assess the impact of breast cancer deaths on all-cause mortality using the ratio of the probability of death for causes other than breast cancer by the all-cause probability of death. Results: There was an increasing impact of breast cancer on mortality in the first part of the 20th century, with a peak for cohorts born in 1945–54 in the 40–49 age groups (for which approximately 24% of mortality was due to breast cancer). Even though for cohorts born after 1955 there was only information for women under 50, it is also important to note that the impact of breast cancer on all-cause mortality decreased for those cohorts. Conclusion: We have quantified the effect of removing breast cancer mortality in different age groups and birth cohorts. Our results are consistent with US findings. We also have obtained an estimate of the risk of dying from competing-causes mortality, which will be used in the assessment of the effect of mammography screening on breast cancer mortality in Catalonia.

Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.

Background In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]). We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis. Methods and Findings Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1þ2. Two studies were conducted: (1) a nested case-control study for studying biomarker associations with mortality, and (2) a study to compare DC and VS participants for biomarker changes. For (1), markers were determined at study entry and before death (latest level) for 85 deaths and for two controls (n¼170) matched on country, age, sex, and date of randomization. Odds ratios (ORs) were estimated with logistic regression. For each biomarker, each of the three upper quartiles was compared to the lowest quartile. For (2), the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following randomization. Higher levels of hsCRP, IL-6, and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality. Unadjusted ORs (highest versus lowest quartile) were 2.0 (95% confidence interval [CI], 1.0-4.1; p¼0.05), 8.3 (95% CI, 3.3-20.8; p , 0.0001), and 12.4 (95% CI, 4.2-37.0; p , 0.0001), respectively. Associations were significant after adjustment, when the DC and VS groups were analyzed separately, and when latest levels were assessed. IL-6 and D-dimer increased at 1 mo by 30% and 16% in the DC group and by 0% and 5% in the VS group (p , 0.0001 for treatment difference for both biomarkers); increases in the DC group were related to HIV-RNA levels at 1 mo (p , 0.0001). In an expanded case-control analysis (four controls per case), the OR (DC/VS) for mortality was reduced from 1.8 (95% CI, 1.1-3.1; p¼0.02) to 1.5 (95% CI, 0.8-2.8) and 1.4 (95% CI, 0.8-2.5) after adjustment for latest levels of IL-6 and D-dimer, respectively. Conclusions IL-6 and D-dimer were strongly related to all-cause mortality. Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels. Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation.

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported. Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death. Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coronary artery disease), diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to one year v longer duration treatment with dual antiplatelets. Conclusions: This meta-analysis offers evidence that compared with bare metal stents the use of cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes including cardiac survival, myocardial infarction, and overall stent thrombosis.

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported. Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death. Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coronary artery disease), diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to one year v longer duration treatment with dual antiplatelets. Conclusions: This meta-analysis offers evidence that compared with bare metal stents the use of cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes including cardiac survival, myocardial infarction, and overall stent thrombosis.

Health investment complementarities under competing risks

Applying the competing--risks model to multi--cause mortality,this paper provides a theoretical and empirical investigation of the positive complementarities that occur between disease--specific policy interventions. We argue that since an individual cannot die twice, competing risks imply that individuals will not waste resources on causes that are not the most immediate, but will make health investments so as to equalize cause--specific mortality. However, equal mortality risk from a variety of diseases does not imply that disease--specific public health interventions are a waste. Rather, a cause--specific intervention produces spillovers to other disease risks, so that the overall reduction in mortality will generally be larger than the direct effect measured on the targeted disease. The assumption that mortality from non--targeted diseases remains the same after a cause--specific intervention under--estimates the true effect of such programs, since the background mortality is also altered as a result of intervention. Analyzing data from one of the most important public health programs ever introduced, the Expanded Program on Immunization (EPI) of the United Nations, we find evidence for the existence of such complementarities, involving causes that are not biomedically, but behaviorally, linked.

Is the 23-valent pneumococcal polysaccharide vaccine useful in preventing community-acquired pneumonia?

Although bacteremic pneumococcal pneumonia is the most severe form of pneumonia, non-bacteremic forms are much more frequent. Laboratory methods for the diagnosis of nonbacteremic pneumococcal pneumonia have a low sensitivity and specificity, and therefore all-cause pneumonia has been proposed as a suitable outcome to evaluate vaccination effectiveness. This work reviews the epidemiology of community-acquired pneumonia (CAP) and evaluates the effectiveness of the 3-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing CAP requiring hospitalization in people aged ≥65 years. We performed a case-control study in patients aged ≥65 years admitted through the emergency department who presented with clinical signs and symptoms compatible with pneumonia. Weincluded 489 cases and 1,467 controls and it was obtained a vaccine efectiveness of 23.6 (0.9-41.0). Our results suggest that PPV-23 vaccination is effective and reduces hospital admissions due to pneumonia in the elderly, strengthening the rationale for vaccination programmes in this age group.

Is the 23-valent pneumococcal polysaccharide vaccine useful in preventing community-acquired pneumonia?

Although bacteremic pneumococcal pneumonia is the most severe form of pneumonia, non-bacteremic forms are much more frequent. Laboratory methods for the diagnosis of nonbacteremic pneumococcal pneumonia have a low sensitivity and specificity, and therefore all-cause pneumonia has been proposed as a suitable outcome to evaluate vaccination effectiveness. This work reviews the epidemiology of community-acquired pneumonia (CAP) and evaluates the effectiveness of the 3-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing CAP requiring hospitalization in people aged ≥65 years. We performed a case-control study in patients aged ≥65 years admitted through the emergency department who presented with clinical signs and symptoms compatible with pneumonia. Weincluded 489 cases and 1,467 controls and it was obtained a vaccine efectiveness of 23.6 (0.9-41.0). Our results suggest that PPV-23 vaccination is effective and reduces hospital admissions due to pneumonia in the elderly, strengthening the rationale for vaccination programmes in this age group.

Coherent forecasting of multiple-decrement life tables: a test using Japanese cause of death data

Planners in public and private institutions would like coherent forecasts of the components of age-specic mortality, such as causes of death. This has been di cult toachieve because the relative values of the forecast components often fail to behave ina way that is coherent with historical experience. In addition, when the group forecasts are combined the result is often incompatible with an all-groups forecast. It hasbeen shown that cause-specic mortality forecasts are pessimistic when compared withall-cause forecasts (Wilmoth, 1995). This paper abandons the conventional approachof using log mortality rates and forecasts the density of deaths in the life table. Sincethese values obey a unit sum constraint for both conventional single-decrement life tables (only one absorbing state) and multiple-decrement tables (more than one absorbingstate), they are intrinsically relative rather than absolute values across decrements aswell as ages. Using the methods of Compositional Data Analysis pioneered by Aitchison(1986), death densities are transformed into the real space so that the full range of multivariate statistics can be applied, then back-transformed to positive values so that theunit sum constraint is honoured. The structure of the best-known, single-decrementmortality-rate forecasting model, devised by Lee and Carter (1992), is expressed incompositional form and the results from the two models are compared. The compositional model is extended to a multiple-decrement form and used to forecast mortalityby cause of death for Japan

Old age mortality: a state of the art

This Phd research report aims to obtain a better understanding of the recent changes in mortality of the elderly population in developed countries. It’s essence will be a critical thinking, without performing empirical work, which means that the analysis and concepts of the actual demographic literature will form the main body of this work. There are two central questions: Which age and cause specific mortality trends caused these recent changes in the life expectancy?Did the increase in life expectancy of the elderly population accelerate, continue or decline in recent years?”

Health intervention and decline in infant mortality rates. Milk depots in Spain (1900-1936)

The role of public health has been a central topic on the classical debate about the historical mortality decline in Europe. One of these health initiatives were the Milk Depots. Spain set up those centres from the late 19th century until the beginning of the Civil War. The goal of this paper is to evaluate the effect of this health intervention on the infant mortality decline during this period. This study works out three kinds of sources: Statistical Yearbooks, Official documents and local records produced by the same Milk Depot. It analyses data available for all the country and one local case such as the Barcelona’s Milk Depot (1904-1935). The main methodological issue deals with the measurement of the effect of the Milk Depot activities on the pattern of changes of infant mortality. Results suggest that Milk Depots have a positive but quite moderate effect on the improving of overall levels of child survival.

Exploring the conditions for a mortality crisis: bringing context back into the debate

This study engages with the debate over the mortality crises in the former Soviet Union and Central and Eastern Europe by 1) considering at length and as complementary to each other the two most prominent explanations for the post-communist mortality crisis, stress and alcohol consumption; 2) emphasizing the importance of context by exploiting systematic similarities and differences across the region. Differential mortality trajectories reveal three country groups that cluster both spatially and in terms of economic transition experiences. The first group are the countries furthest west in which mortality rates increased minimally after the transition began. The second group experienced a severe increase in mortality rates in the early 1990s, but recovered previous levels within a few years. These countries are located peripherally to Russia and its nearest neighbours. The final group consists of countries that experienced two mortality increases or in which mortality levels had not recovered to pre-transition levels well into the 21st century. Cross-sectional time-series data analyses of men’s and women’s age and cause-specific death rates reveal that the clustering of these countries and their mortality trajectories can be partially explained by the economic context, which is argued to be linked to stress and alcohol consumption. Above and beyond many basic differences in the country groups that are held constant—including geographically and historically shared cultural, lifestyle and social characteristics—poor economic conditions account for a remarkably consistent share of excess age-specific and cause-specific deaths.

Monitoring mortality as an indicator of influenza in Catalonia, Spain.

This study aimed to investigate the behaviour of two indicators of influenza activity in the area of Barcelona and to evaluate the usefulness of modelling them to improve the detection of influenza epidemics. DESIGN: Descriptive time series study using the number of deaths due to all causes registered by funeral services and reported cases of influenza-like illness. The study concentrated on five influenza seasons, from week 45 of 1988 to week 44 of 1993. The weekly number of deaths and cases of influenza-like illness registered were processed using identification of a time series ARIMA model. SETTING: Six large towns in the Barcelona province which have more than 60,000 inhabitants and funeral services in all of them. MAIN RESULTS: For mortality, the proposed model was an autoregressive one of order 2 (ARIMA (2,0,0)) and for morbidity it was one of order 3 (ARIMA (3,0,0)). Finally, the two time series were analysed together to facilitate the detection of possible implications between them. The joint study of the two series shows that the mortality series can be modelled separately from the reported morbidity series, but the morbidity series is influenced as much by the number of previous cases of influenza reported as by the previous mortality registered. CONCLUSIONS: The model based on general mortality is useful for detecting epidemic activity of influenza. However, because there is not an absolute gold standard that allows definition of the beginning of the epidemic, the final decision of when it is considered an epidemic and control measures recommended should be taken after evaluating all the indicators included in the influenza surveillance programme.