Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study.

Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. Design Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Participants 109 118 men and 254 870 women, mainly aged 37-70. Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. Results If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women. Conclusions In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.

Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). Design Nested case–control study. Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.

Area deprivation and mortality in the provincial capital cities of Andalusia and Catalonia (Spain)

Objective: To study the linkage between material deprivation and mortality from all causes, for men and women separately, in the capital cities of the provinces in Andalusia and Catalonia (Spain). Methods: A small-area ecological study was devised using the census section as the unit for analysis. 188 983 Deaths occurring in the capital cities of the Andalusian provinces and 109 478 deaths recorded in the Catalan capital cities were examined. Principal components factorial analysis was used to devise a material deprivation index comprising the percentage of manual labourers, unemployment and illiteracy. A hierarchical Bayesian model was used to study the relationship between mortality and area deprivation. Main results: In most cities, results show an increased male mortality risk in the most deprived areas in relation to the least depressed. In Andalusia, the relative risks between the highest and lowest deprivation decile ranged from 1.24 (Malaga) to 1.40 (Granada), with 95% credibility intervals showing a significant excess risk. In Catalonia, relative risks ranged between 1.08 (Girona) and 1.50 (Tarragona). No evidence was found for an excess of female mortality in most deprived areas in either of the autonomous communities. Conclusions: Within cities, gender-related differences were revealed when deprivation was correlated geographically with mortality rates. These differences were found from an ecological perspective. Further research is needed in order to validate these results from an individual approach. The idea to be analysed is to identify those factors that explain these differences at an individual level.

Parental occupational exposure to organic solvents and anencephaly in Mexico

Objective: To assess the relationship between parental occupational exposure to organic solvents, and the risk of anencephaly in Mexico. Methods: A case-control study was conducted based on the registers of the Epidemiological Surveillance System for Neural Tube Defects in Mexico; 151 cases of anencephaly of ≥20 weeks’ gestation were included. A control, born alive and without any apparent congenital malformations at birth, was selected for each case in the same maternity service in which the case was born. Information on occupational exposures, lifestyle habits, reproductive history, use of medicines, supplementation with multivitamins and folic acid, was obtained by a general questionnaire; a food frequency questionnaire was also applied to obtain information of daily intake of folate and other B vitamins. Occupational exposure to organic solvents was based on job title as a proxy for exposure and analysed considering two critical periods around conception. Results: In logistic regression analysis, the odds of having a child with anencephaly was higher if the mother or the father was occupationally exposed to organic solvents during the periconceptional period, or when both parents or at least one of them were occupationally exposed during this period with an adjusted odds ratio of 2.97 (95% CI 1.36 to 6.52). Conclusions: The results support the hypothesis that both maternal and paternal occupational exposure to organic solvents can increase the probability of having a child with anencephaly.

Identifying pesticide use patterns among flower growers to assess occupational exposure to mixtures

Objectives Exposure assessment to a single pesticide does not capture the complexity of the occupational exposure. Recently, pesticide use patterns analysis has emerged as an alternative to study these exposures. The aim of this study is to identify the pesticide use pattern among flower growers in Mexico participating in the study on the endocrine and reproductive effects associated with pesticide exposure. Methods A cross-sectional study was carried out to gather retrospective information on pesticide use applying a questionnaire to the person in charge of the participating flower growing farms. Information about seasonal frequency of pesticide use (rainy and dry) for the years 2004 and 2005 was obtained. Principal components analysis was performed. Results Complete information was obtained for 88 farms and 23 pesticides were included in the analysis. Six principal components were selected, which explained more than 70% of the data variability. The identified pesticide use patterns during both years were: 1. fungicides benomyl, carbendazim, thiophanate and metalaxyl (both seasons), including triadimephon during the rainy season, chlorotalonyl and insecticide permethrin during the dry season; 2. insecticides oxamyl, biphenthrin and fungicide iprodione (both seasons), including insecticide methomyl during the dry season; 3. fungicide mancozeb and herbicide glyphosate (only during the rainy season); 4. insecticides metamidophos and parathion (both seasons); 5. insecticides omethoate and methomyl (only rainy season); and 6. insecticides abamectin and carbofuran (only dry season). Some pesticides do not show a clear pattern of seasonal use during the studied years. Conclusions The principal component analysis is useful to summarise a large set of exposure variables into smaller groups of exposure patterns, identifying the mixtures of pesticides in the occupational environment that may have an interactive effect on a particular health effect.

Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Objective. To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. Design Nested case-control study. Setting. The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. Participants: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls. Main outcome measures. Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. Results. 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); ≥100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

Alcohol intake and the risk of coronary heart disease in the Spanish EPIC

Background: The association between alcohol consumption and coronary heart disease (CHD) has been widely studied. Most of these studies have concluded that moderate alcohol intake reduces the risk of CHD. There are numerous discussions regarding whether this association is causal or biased. The objective of this paper is to analyse the association between alcohol intake and CHD risk in the Spanish cohort of the European Prospective Investigation into Cancer (EPIC). Methods: Participants from the EPIC Spanish cohort were included (15 630 men and 25 808 women). The median follow-up period was 10 years. Ethanol intake was calculated using a validated dietary history questionnaire. Participants with a definite CHD event were considered cases. A Cox regression model adjusted for relevant co-variables and stratified by age was produced. Separate models were carried out for men and women. Results: The crude CHD incidence rate was 300.6/100 000 person-years for men and 47.9/100 000 person-years for women. Moderate, high and very high consumption was associated with a reduced risk of CHD in men: hazard ratio 0.90 (95% CI 0.56 to 1.44) for former drinkers, 0.65 (95% CI 0.41 to 1.04) for low, 0.49 (95% CI 0.32 to 0.76) for moderate, 0.46 (95% CI 0.30 to 0.71) for high and 0.50 (95% CI 0.29 to 0.85) for very high consumers. A negative association was found in women, with p values above 0.05 in all categories. Conclusions: Alcohol intake in men aged 29–69 years was associated with a more than 30% lower CHD incidence. This study is based on a large prospective cohort study and is free of the abstainer error.

Necrotising pneumonia due to influenza A (H1N1) and community-acquired methicillin-resistant Staphylococcus aureus clone USA300: successful management of the first documented paediatric case.

Necrotising pneumonia in young, previously healthy patients due to Panton–Valentine leucocidin (PVL) producing Staphylococcus aureus has been increasingly recognised. PVL pneumonia is often associated with influenza co-infection and high mortality. This case report describes the successful management of the first documented paediatric case of a previous healthy adolescent who developed necrotising pneumonia due to community-acquired methicillin-resistant (CA-MRSA) clone USA300 with pandemic influenza A (H1N1) co-infection, and highlights the importance of early recognition and initiation of appropriate therapy for this potentially fatal co-infection. PCR remains the gold standard to diagnose pandemic H1N1 since it may not be detected by rapid antigen tests. Bacterial necrotising pneumonia should be suspected in those presenting with worsening flu-like symptoms and clinical and/or radiological evidence of PVL infection (multifocal infiltrates, effusion and cavitation). These patients may benefit from the administration of toxin neutralising agents. In light of the current H1N1 pandemic, healthcare professionals will be increasingly confronted with this clinical scenario.

Eosinophil cationic protein is not only a distinctive eosinophil protein

We read with interest the article by Qiu et al (Thorax 2007;62:475–82). In this paper, neutrophils and eosinophils were identified using mouse anti-human neutrophil elastase and anti-eosinophil cationic protein (ECP), both monoclonal antibodies (mAbs). mAbs against ECP have been used to detect total eosinophils, but immunostaining techniques evidenced that the number of ECP+ cells was higher than the number of eosinophils.1 Recent studies show that ECP is not only a distinctive eosinophil protein, but has been found in neutrophils.1–3

Ki-67 MIB1 labelling index and the prognosis of primary TaT1 urothelial cell carcinoma of the bladder.

Aims: To evaluate whether ki-67 labelling index (LI) has independent prognostic value for survival of patients with bladder urothelial tumours graded according to the 2004 World Health Organisation classification. Methods: Ki-67 LI was evaluated in 164 cases using the grid counting method. Non-invasive (stage Ta) tumours were: papilloma (n = 5), papillary urothelial neoplasia of low malignant potential (PUNLMP; n = 26), and low (LG; n = 34) or high grade (HG; n = 15) papillary urothelial carcinoma. Early invasive (stage T1) tumours were: LG (n = 58) and HG (n = 26) carcinoma. Statistical analysis included Fisher and x2 tests, and mean comparisons by ANOVA and t test. Univariate and multivariate survival analyses were performed according to the Kaplan–Meier method with log rank test and Cox’s proportional hazard method. Results: Mean ki-67 LI increased from papilloma to PUNLMP, LG, and HG in stage Ta (p,0.0001) and from LG to HG in stage T1 (p = 0.013) tumours. High tumour proliferation (.13%) was related to greater tumour size (p = 0.036), recurrence (p = 0.036), progression (p = 0.035), survival (p = 0.054), and high p53 accumulation (p = 0.015). Ki-67 LI and tumour size were independent predictors of disease free survival (DFS), but only ki-67 LI was related to progression free survival (PFS). Cancer specific overall survival (OS) was related to ki-67 LI, tumour size, and p27kip1 downregulation. Ki-67 LI was the main independent predictor of DFS (p = 0.0005), PFS (p = 0.0162), and cancer specific OS (p = 00195). Conclusion: Tumour proliferation measured by Ki-67 LI is related to tumour recurrence, stage progression, and is an independent predictor of DFS, PFS, and cancer specific OS in TaT1 bladder urothelial cell carcinoma.

‘No olvides, hay esperanza’, lema del día mundial del alzheimer 2009

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

The Endocannabinoid System as Pharmacological Target Derived from Its CNS Role in Energy Homeostasis and Reward. Applications in Eating Disorders and Addiction

The endocannabinoid system (ECS) has been implicated in many physiological functions, including the regulation of appetite, food intake and energy balance, a crucial involvement in brain reward systems and a role in psychophysiological homeostasis (anxiety and stress responses). We first introduce this important regulatory system and chronicle what is known concerning the signal transduction pathways activated upon the binding of endogenous cannabinoid ligands to the Gi/0-coupled CB1 cannabinoid receptor, as well as its interactions with other hormones and neuromodulators which can modify endocannabinoid signaling in the brain. Anorexia nervosa (AN) and bulimia nervosa (BN) are severe and disabling psychiatric disorders, characterized by profound eating and weight alterations and body image disturbances. Since endocannabinoids modulate eating behavior, it is plausible that endocannabinoid genes may contribute to the biological vulnerability to these diseases. We present and discuss data suggesting an impaired endocannabinoid signaling in these eating disorders, including association of endocannabinoid components gene polymorphisms and altered CB1-receptor expression in AN and BN. Then we discuss recent findings that may provide new avenues for the identification of therapeutic strategies based on the endocannabinod system. In relation with its implications as a reward-related system, the endocannabinoid system is not only a target for cannabis but it also shows interactions with other drugs of abuse. On the other hand, there may be also a possibility to point to the ECS as a potential target for treatment of drug-abuse and addiction. Within this framework we will focus on enzymatic machinery involved in endocannabinoid inactivation (notably fatty acid amide hydrolase or FAAH) as a particularly interesting potential target. Since a deregulated endocannabinoid system may be also related to depression, anxiety and pain symptomatology accompanying drug-withdrawal states, this is an area of relevance to also explore adjuvant treatments for improving these adverse emotional reactions.

Colorectal cancer survival in the USA and Europe: a CONCORD high-resolution study.

OBJECTIVES: To assess the extent to which stage at diagnosis and adherence to treatment guidelines may explain the persistent differences in colorectal cancer survival between the USA and Europe. DESIGN: A high-resolution study using detailed clinical data on Dukes' stage, diagnostic procedures, treatment and follow-up, collected directly from medical records by trained abstractors under a single protocol, with standardised quality control and central statistical analysis. SETTING AND PARTICIPANTS: 21 population-based registries in seven US states and nine European countries provided data for random samples comprising 12 523 adults (15-99 years) diagnosed with colorectal cancer during 1996-1998. OUTCOME MEASURES: Logistic regression models were used to compare adherence to 'standard care' in the USA and Europe. Net survival and excess risk of death were estimated with flexible parametric models. RESULTS: The proportion of Dukes' A and B tumours was similar in the USA and Europe, while that of Dukes' C was more frequent in the USA (38% vs 21%) and of Dukes' D more frequent in Europe (22% vs 10%). Resection with curative intent was more frequent in the USA (85% vs 75%). Elderly patients (75-99 years) were 70-90% less likely to receive radiotherapy and chemotherapy. Age-standardised 5-year net survival was similar in the USA (58%) and Northern and Western Europe (54-56%) and lowest in Eastern Europe (42%). The mean excess hazard up to 5 years after diagnosis was highest in Eastern Europe, especially among elderly patients and those with Dukes' D tumours. CONCLUSIONS: The wide differences in colorectal cancer survival between Europe and the USA in the late 1990s are probably attributable to earlier stage and more extensive use of surgery and adjuvant treatment in the USA. Elderly patients with colorectal cancer received surgery, chemotherapy or radiotherapy less often than younger patients, despite evidence that they could also have benefited.