[Show abstract][Hide abstract] ABSTRACT: The current deconstruction of paradoxes is one among several signs that a profound renewal of methods for clinical and epidemiological research is taking place; perhaps for some basic life sciences as well. The new methodological approaches have already deconstructed and explained long puzzling apparent paradoxes, including the (non-existent) benefits of obesity in diabetics, or of smoking in low birth weight. Achievements of the new methods also comprise the elucidation of the causal structure of long-disputed and highly complex questions, as Berkson's bias and Simpson's paradox, and clarifying reasons for deep controversies, as those on estrogens and endometrial cancer, or on adverse effects of hormone replacement therapy. These are signs that the new methods can go deeper and beyond the methods in current use. A major example of a highly relevant idea is: when we condition on a common effect of a pair of variables, then a spurious association between such pair is likely. The implications of these ideas are potentially vast. A substantial number of apparent paradoxes may simply be the result of collider biases, a source of selection bias that is common not just in epidemiologic research, but in many types of research in the health, life, and social sciences. The new approaches develop a new framework of concepts and methods, as collider, instrumental variables, d-separation, backdoor path and, notably, Directed Acyclic Graphs (DAGs). The current theoretical and methodological renewal-or, perhaps, "revolution"-may be changing deeply how clinical and epidemiological research is conceived and performed, how we assess the validity and relevance of findings, and how causal inferences are made. Clinical and basic researchers, among others, should get acquainted with DAGs and related concepts.
European Journal of Epidemiology 07/2015; DOI:10.1007/s10654-015-0068-8 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long-term exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity and mortality but little is known about the role of the chemical composition of PM. This study examined the association of residential long-term exposure to PM components with incident coronary events.
Eleven cohorts from Finland, Sweden, Denmark, Germany, and Italy participated in this analysis. 5,157 incident coronary events were identified within 100,166 persons followed on average for 11.5 years. Long-term residential concentrations of PM < 10 μm (PM10), PM < 2.5 μm (PM2.5), and a priori selected constituents (copper, iron, nickel, potassium, silicon, sulfur, vanadium, and zinc) were estimated with land-use regression models. We used Cox proportional hazard models adjusted for a common set of confounders to estimate cohort-specific component effects with and without including PM mass, and random effects meta-analyses to pool cohort-specific results.
A 100 ng/m³ increase in PM10 K and a 50 ng/m³ increase in PM2.5 K were associated with a 6% (hazard ratio and 95% confidence interval: 1.06 [1.01, 1.12]) and 18% (1.18 [1.06, 1.32]) increase in coronary events. Estimates for PM10 Si and PM2.5 Fe were also elevated. All other PM constituents indicated a positive association with coronary events. When additionally adjusting for PM mass, the estimates decreased except for K.
This multicenter study of 11 European cohorts pointed to an association between long-term exposure to PM constituents and coronary events, especially for indicators of road dust.
[Show abstract][Hide abstract] ABSTRACT: The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style (espresso and mocha) coffee consumption and CHD risk.
We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids.
After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87-1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and 1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend <0.001) compared to reference (<1 cup/day). Plasma triglycerides, and total, LDL and HDL cholesterol did not vary significantly (ANOVA) with coffee consumption.
Consumption of over 2 cups/day of Italian-style coffee is associated with increased CHD risk, but coffee consumption was not associated with plasma lipid changes, so the adverse effect of consumption appears unrelated to lipid profile.
PLoS ONE 05/2015; 10(5):e0126550. DOI:10.1371/journal.pone.0126550 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients.
The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.
The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models.
Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
BMC Medicine 05/2015; 13(1):107. DOI:10.1186/s12916-015-0332-5 · 7.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62–0.99), 0.82 (0.64–1.04), 0.70 (0.55–0.90), 0.91 (0.63–1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.
International Journal of Cancer 04/2015; DOI:10.1002/ijc.29559. · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear.
We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures.
This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures.
Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity.
The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
American Journal of Clinical Nutrition 03/2015; 101(3):613-21. DOI:10.3945/ajcn.114.100065 · 6.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.
The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.
We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.
The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
Environmental Health Perspectives 02/2015; DOI:10.1289/ehp.1409149 · 7.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality.
Our aim was to study the association between natural cause mortality and long-term exposure to elemental components of particulate matter.
Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of Copper (Cu), Iron (Fe), Potassium (K), Nickel (Ni), Sulfur (S), Silicon (Si), Vanadium (V) and Zinc (Zn) within PM size fractions <2.5 µm (PM2.5) and <10 µm (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis.
The total study population consisted of 291,816 participants, of which 25,466 died from a natural cause during follow-up (average time of follow-up 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 S (1.14; 95% CI: 1.06, 1.23 per 200 ng/m(3)). In a two-pollutant model, the association with PM2.5 S was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced.
Long-term exposure to PM2.5 S was associated with natural cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
Environmental Health Perspectives 02/2015; DOI:10.1289/ehp.1408095 · 7.98 Impact Factor