High prevalence of non-alcoholic fatty liver disease and metabolic risk factors in Guatemala: A population-based study.

BACKGROUND: There are no data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in general population samples in Guatemala or in other Central American countries. The prevalence and distribution of NAFLD and its associated risk factors were evaluated in a population-based sample of adults in Guatemala. METHODS: Cross-sectional study of 411 men and women 40 years of age or older residing in urban and rural areas of Guatemala. Metabolic outcomes included obesity, central obesity, hypercholesterolemia, diabetes, and metabolic syndrome (MetS). Liver disease outcomes included elevated liver enzymes, elevated Fatty Liver Index (FLI), and elevated FIB-4 score. RESULTS: The overall prevalence of obesity, central obesity, diabetes, and MetS were 30.9, 74.3, 21.6, and 64.2%, respectively. The fully-adjusted prevalence ratios (95% CI) for obesity, central obesity, diabetes, and MetS comparing women to men were 2.83 (1.86-4.30), 1.72 (1.46-2.02), 1.18 (1.03-1.34), and 1.87 (1.53-2.29), respectively. The overall prevalence of elevated liver enzymes (ALT or AST), elevated FLI, and elevated FIB-4 scores were 38.4, 60.1, and 4.1%, respectively. The fully-adjusted prevalence ratios (95% CI) for elevated liver enzymes (either ALT or AST) and elevated FLI score comparing women to men were 2.99 (1.84-4.86) and 1.47 (1.18-1.84), respectively. CONCLUSIONS: The prevalence of metabolic abnormalities and liver outcomes in this general population study was very high. The prevalence of metabolic and liver abnormalities was particularly high among women, an observation that could explain the atypical 1:1 male to female ratio of liver cancer in Guatemala.

Lower-normal TSH is associated with better metabolic risk factors: A cross-sectional study on Spanish men.

BACKGROUND AND AIMS: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. METHODS AND RESULTS: We studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. CONCLUSIONS: TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.

Cardiovascular disease prevention in women: a rapidly evolving scenario.

The past decade has witnessed a long overdue recognition of the importance of CVD in women, accompanied by an increasing awareness of gender differences in risk factors, natural history, preventive strategies, treatment, and prognosis of CVD. Reflecting the disease burden and the specific aspects of CVD in women, the American Heart Association has developed women-specific evidence-based guidelines and consensus documents for CVD prevention. The most recent update of these guidelines, published in 2011, is a milestone in the field and shows the rapidly evolving scenario of CVD prevention in women. We discuss some novel aspects of the 2011 update. The new guidelines change the focus from evidence-based to effectiveness-based, with consideration of both benefits and harms/costs of preventive interventions. The guidelines also introduce "ideal cardiovascular health" as the lowest category of risk, which implies the need of communitywide preventive, educational and policy initiatives to promote healthy lifestyles in the general population. Furthermore, the guidelines emphasize long-term overall CVD risk rather than short-term coronary risk. We also address several barriers and open questions in the evaluation and implementation of these guidelines, including how to increase the small proportion of women with ideal cardiovascular health; how to increase implementation and compliance with the recommendations; how to provide effectiveness-based recommendations for lifetime prevention goals based on short-term trials; how to obtain the best possible evidence in women; how to identify subgroups of women with different cardiovascular risk profiles or who may require tailored preventive strategies; and how to adapt current guidelines to international settings, particularly to low- and middle-income countries.

The association of biomarkers of iron status with mortality in US adults.

BACKGROUND AND AIMS: Elevated iron biomarkers are associated with diabetes and other cardiometabolic abnormalities in the general population. It is unclear whether they are associated with an increased risk of all-cause or cause-specific mortality. The purpose of the current analysis was to evaluate the association of ferritin and transferrin saturation levels with all-cause, cardiovascular, and cancer mortality in the general US adult population. METHODS AND RESULTS: A prospective cohort study was conducted with 12,258 adults participating in the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of the US population. Study participants were recruited in 1988-1994 and followed through December 31, 2006 for all-cause, cardiovascular disease, and cancer mortality. The multivariable-adjusted hazard ratios (95% confidence interval) for all-cause mortality comparing the fourth versus the second quartiles of ferritin and transferrin saturation were 1.09 (0.82-1.44; p-trend across quartiles = 0.92) and 1.08 (0.82-1.43; p-trend across quartiles = 0.62), respectively, for men, 1.43 (0.63-3.23; p-trend across quartiles = 0.31) and 1.48 (0.70-3.11; p-trend across quartiles = 0.60), respectively, for premenopausal women, and 1.03 (0.79-1.34; p-trend across quartiles = 0.95) and 1.17 (0.92-1.49; p-trend across quartiles = 0.63), respectively, for postmenopausal women. Quartile of ferritin and transferrin saturation also showed no association between biomarkers of iron status and mortality. CONCLUSIONS: In a large nationally representative sample of US adults, within the spectrum of normal iron metabolism, ferritin and transferrin saturation were not associated with risk of mortality among people who were not taking iron supplements and did not have a baseline history of cardiovascular disease or cancer.

Structured management strategy based on the Gastro-oesophageal Reflux Disease (GERD) Questionnaire (GerdQ) vs. usual primary care for GERD: pooled analysis of five cluster-randomised European studies.

BACKGROUND: Response to treatment among primary care patients with gastro-oesophageal disease (GERD) is variable. AIM: The GERD Management Project (GMP) evaluated the effectiveness of a structured management approach to GERD vs. standard treatment (usual care). METHODS: Data from five cluster-randomised clinical trials in adult primary care patients with symptoms of GERD were pooled. The structured pathway was based on the self-administered GERD Questionnaire (GerdQ) and was compared with standard treatment. RESULTS: 1734 patients were enrolled (structured treatment, n=834; standard treatment, n=900). The difference in the mean GerdQ score change from baseline favoured the structured pathway (-0.61; 95% CI: -0.88, -0.34; p<0.001). The odds ratio for an indication for treatment revision at the end of follow-up (structured vs. standard treatment) was 0.39 (95% CI: 0.29, 0.52; p=0.001). CONCLUSIONS: Management of primary care patients with GERD can be improved by systematic stratification of patients using a patient management tool such as the GerdQ.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

Selenium status and cardiometabolic health: state of the evidence.

Use of selenium enriched foods, supplements and fertilizers has increased markedly in recent years in the US and other Western countries because of the perception that the anti-oxidant properties of selenium could potentially reduce the risk of cancer and other chronic diseases. However, concern has been raised recently about possible adverse cardiometabolic effects of high selenium exposure, including an increased risk of diabetes and hyperlipidemia with high selenium intake. Hence, from a public health perspective, the relationship between selenium status and cardiometabolic health should be clarified in order to help guide consumers in their choices of nutritional supplements and enriched food products. Additional experimental evidence is needed to provide new insights into the role of selenium and of specific selenoproteins in human biology, especially to clarify the underlying mechanisms linking selenium to chronic disease endpoints. Further epidemiological studies and randomized clinical trials across populations with different selenium status should be conducted to determine the causal effect of selenium on cardiovascular disease and risk factors. Nevertheless, at the present time the widespread use of selenium supplements or other strategies that artificially increase selenium status above the level required for optimal selenoprotein activity is not justified and should not be encouraged.

A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians.

OBJECTIVES: This study evaluated whether increased intake of fish oils (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary heart disease. BACKGROUND: Observational and clinical studies have suggested that increased intake of fish oils, as reflected in plasma levels of fish oils, may reduce the risk of myocardial infarction. METHODS: A nested case-control study was conducted among the 14,916 participants in the Physicians' Health Study with a sample of plasma before randomization. Each participant with myocardial infarction occurring during the first 5 years of follow-up was matched by smoking status and age with a randomly chosen control participant who had not developed coronary heart disease. RESULTS: Mean levels of fish oils (with 95% confidence interval [CI] for paired differences and p values) in case and control participants, expressed as percent of total fatty acids, were, for eicosapentaenoic acid, 0.26 versus 0.25 (95% CI -0.03 to 0.05, p = 0.70) in cholesterol esters and 0.56 versus 0.54 (95% CI -0.04 to 0.09, p = 0.44) in phospholipids, and for docosahexaenoic acid, 0.23 versus 0.24 (95% CI -0.07 to 0.04, p = 0.64) in cholesterol esters and 2.22 versus 2.14 (95% CI -0.10 to 0.27, p = 0.36) in phospholipids. Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infarction. CONCLUSIONS: These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infarction. However, the effect of very high levels of fish oils could not be evaluated.

Relationship between systemic markers of inflammation and serum beta-carotene levels.

BACKGROUND: Low serum levels of beta-carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, supplementation of the diet with beta-carotene either had no benefit or caused harm. This pattern of findings raises the possibility that confounding by other factors might explain the association between serum beta-carotene level and disease risk. METHODS: We used data from 14 470 current smokers, ex-smokers, and never smokers aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey to assess the relationship between serum beta-carotene and markers of inflammation (C-reactive protein and white blood cell count). RESULTS: After adjustment for beta-carotene intake and other factors, geometric mean levels of serum beta-carotene for individuals with undetectable (< 0.22 mg/dL), mildly elevated (0.22-0.99 mg/dL), and clinically elevated (> or =1.0 mg/dL) C-reactive protein levels were 18.0, 16.1, and 13.6 microg/dL, respectively, in never smokers; 18.1, 15.7, and 13.9 microg/dL in ex-smokers; and 11.3, 10.2, and 9.4 microg/dL in current smokers (P< .001 for all). In corresponding analyses, white blood cell count was also inversely related to serum beta-carotene concentration (P< .05 for all). CONCLUSIONS: The strong and inverse association of serum beta-carotene level with C-reactive protein level and white blood cell count suggests that the relationship between serum beta-carotene concentration and disease risk might be confounded by inflammation. More broadly, for beta-carotene and likely other nutrients, it seems unwise to interpret biomarker data as prima facie evidence of dietary intake without a more complete understanding of the physiologic processes that affect nutrient levels.

Age-period-cohort analysis of suicide mortality rates in Spain, 1959-1991.

BACKGROUND: Although there is evidence that suicide rates may be increasing in Spain, formal epidemiological studies have been limited to specific cities or counties. The objective of this study was to investigate nationwide trends in suicide mortality from 1959 to 1991 in Spain, with emphasis on age, period, and cohort effects. METHODS: Age- and sex-specific suicide mortality rates from 1959 until 1991 were obtained from official vital statistics tables from the Instituto Nacional de Estadística, the official registry of vital statistics in Spain. Poisson regression and graphical methods were used to model and estimate age, period and cohort effects. RESULTS: Suicide mortality rates increased with age, with a proportional increment for each decade of life of 45% (95% confidence interval: 45-46%). In both males and females, age-adjusted suicide mortality rates decreased from 1959 until the late 1970s and early 1980s. In 1982, trends started to increase, returning to the levels of 1959 in less than 6 years. Cohort effects were small for cohorts born prior to 1940. For cohorts born after 1950, suicide rates increased markedly. CONCLUSIONS: The increase in suicide mortality in younger cohorts and the high rates of suicide in the elderly demand further investigation to establish causal mechanisms and preventive strategies.

Previous disability as a predictor of outcome in a geriatric rehabilitation unit.

BACKGROUND: Functional status at admission has been shown consistently to predict rehabilitation results, but the impact of previous disability has been seldom considered. METHODS: A prospective follow-up study of elderly patients admitted to a geriatric rehabilitation unit in Madrid, Spain, was carried out. The study population comprised 135 subjects aged 65 years or older, who were consecutively admitted during a 7-month period. Outcome variables included the Barthel Index (BI) at discharge, the improvement in BI from admission to discharge, the achieved percentage of potential gain, and the efficiency of gains. Previous BI, admission BI, diagnosis, source (hospital/others), mental status, age, and gender were examined as explanatory variables. RESULTS: In multiple regression analysis, previous BI was the only significant independent predictor for all the outcome variables. For each 5-point increase in previous BI, the increase in BI at discharge was 1.7 (p = .007). Corresponding values for the achieved percentage of potential gain and for the efficiency of gains were 0.05 (p = .01) and 0.05 (p = .04), respectively. Except for the achieved percentage of potential gain, admission BI and source of referral were also independent significant predictors of outcome. CONCLUSIONS: Previous functional situation of elderly people is important to predict rehabilitation outcome, even after taking into account information on disability at admission. As a consequence, a measure of the achieved percentage of potential gain corrected by the preadmission functional status is proposed, especially in the case of elderly patients.

Cost-benefit analysis of Haemophilus influenzae type b vaccination in children in Spain.

OBJECTIVE: Invasive disease caused by Haemophilus influenzae type b (Hib), including meningitis, pneumonia, sepsis and epiglottitis, is associated with high mortality and serious neurological sequelae in children under 5 years of age. The availability of an efficacious vaccine suggests the need to perform an economic evaluation of its use. The objective of this study was to evaluate the costs and benefits of introducing a universal vaccination programme for children under 1 year of age in Spain. DESIGN & SETTING: A cost-benefit analysis (CBA) was conducted over a 5-year period from the societal perspective in the Spanish healthcare setting. Both direct and indirect costs were included in the analysis [using 1996 Spanish pesetas (Pta); Pta126.5 = $US1 in April 1996]. PATIENTS AND PARTICIPANTS: The target population used for cost and benefit estimation was the 384,883 Spaniards aged 1 year or less in the last Spanish Population and Housing Census of 1991. MAIN OUTCOME MEASURES AND RESULTS: The introduction of the universal Hib vaccination programme would imply vaccinating 346,395 children under 1 year of age, with a global expense of Pta2,444,855,910. For an average incidence of 15 cases of invasive disease per 100,000 children per year nationwide, the programme would prevent 219 cases of invasive disease and 8 deaths over a 5-year period, with a benefit of Pta2,182,868,907, a net benefit (i.e. benefit minus cost) of -Pta261,987,003, a benefit/cost ratio of 0.89 and a benefit per case prevented of -Pta1,196,288. Benefit/cost ratios above 1 would be obtained in the regions of highest incidence of invasive disease. CONCLUSION: The decision to implement a universal vaccination programme should not be based only on economic factors, but our results suggest that the economic returns of the programme for children under 1 year of age in Spain would be at least of a similar magnitude as its expenses.

Alcohol intake and risk of breast cancer: the euramic study.

To evaluate the association of alcohol intake with the risk of breast cancer in post-menopausal women, we analyzed the data from an international case-control study conducted in five European countries (FRG, Switzerland, Northern Ireland, the Netherlands and Spain). Information on alcohol intake was available in 315 cases and 364 controls. Medians for the tertiles of alcohol intake among current drinkers were 1.7, 6.0, and 20.0 g/day. Adjusted relative risks (and 95% confidence intervals) of breast cancer for each tertile of intake in current drinkers, compared to never drinkers, were 1.00 (0.60-1.67), 1.01 (0.60-1.73), and 1.18 (0.69-2.03). The adjusted relative risk for ex-drinkers was 1.73 (1.07-2.79). Among both current drinkers and ex-drinkers, the relative risk was higher for those with body mass index above the median compared to those with body mass index below the median. These results do not support a dose-response effect of alcohol on breast cancer risk, although consumption levels were too low to exclude increased risk with high regular intake. Further research is necessary to evaluate the risk of developing breast cancer among ex-drinkers and the potential interaction between body mass index and alcohol drinking.

[Methods of investigation in clinical cardiology. VIII. Meta-analysis and systematic reviews in cardiology]. / Métodos de investigación en cardiología clínica (VII). Metaanálisis y revisiones sistemáticas en cardiología.

Over the last 20 years, the development of meta-analysis has been aimed at obtaining objective synthesis of the available results on specific research questions. The main achievements of meta-analysis include the application of techniques to perform systematic literature searches and to obtain unbiased selection of studies, data extraction and pooled estimates of effect. This paper discusses the methodologic steps to follow when conducting a meta-analysis, with emphasis on study selections, data collection and statistical methods to combine the results from individual studies. We also present a set of guided questions as an aid to critically evaluate the conclusions of published meta-analyses. The application of meta-analytic techniques to cardiology is illustrated using a meta-analysis of the randomized controlled trials of angioplasty versus bypass surgery in the management of patients with ischemic heart disease.

[Meta-analysis: its role in clinical decision making in cardiology]. / Metaanálisis: su importancia en la toma de decisiones clínicas en cardiología.

Clinical decision-making in cardiology requires accurate estimates of the efficacy of diagnostic and therapeutic procedures. Defined as the quantitative integration of results from different studies on the same scientific question, meta-analyses are well-suited to summarize the evidence on the efficacy of clinical interventions. Meta-analyses aim at obtaining combined estimates of effect using all relevant information in a systematic fashion, complementing narrative reviews and expert committee reports. In this paper, the advantages and limitations of meta-analyses and their usefulness in clinical decision making in cardiology are illustrated using three recent examples in the literature--i.e., use of beta-blockers in secondary prevention of ischemic heart disease, intravenous streptokinase in acute myocardial infarction and fish intake in primary prevention of cardiovascular mortality. The steps to follow when conducting a meta-analysis are also discussed. Finally, a list of the most important meta-analyses in cardiology published to date is included for easy reference.

Determinants of p,p-dichlorodiphenyldichloroethane (DDE) concentration in adipose tissue in women from five European cities.

To identify the determinants of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE) in adipose tissue in subjects who participated in a cross-sectional study, we analyzed fatty acids, antioxidants, and p,p'-DDE in aspirates of adipose tissue of 328 postmenopausal women from 5 European countries. The overall mean of p,p'-DDE concentration was 1.66 microg/g of fatty acids (95% confidence interval = 1.46, 1.88). In a multiple-regression analysis, the main predictors of log10(p,p'DDE) were center of recruitment (p < .0001), adipose arachidic acid (p = .001), and adipose retinol (p = .04). These factors explained 14.9% of the overall variability of log10(p,p'-DDE). In our subjects, adipose tissue p,p'DDE concentrations were only weakly related with biomarkers reflecting intake of fish and other foods. This result is consistent with the notion that p,p'-DDE exists in different foods and, given the widespread contamination of the food chain, is relatively evenly distributed among foods.

[Nutrition surveys of Spanish school-age children: analysis of the period 1984-1994]. / Encuestas alimentarias en los niños españoles de edad escolar: análisis del período 1984-1994.

OBJECTIVE: To review available data on the usual dietary intake of school-age Spanish children, by analyzing the nutritional surveys carried out during the period 1984-1994. METHODS: Systematic and comprehensive search of surveys with dietary data in Spanish children aged 6 to 16 years collected during the period 1984-1994 and published after January 1997. The search of bibliographic databases (MEDLINE, IME, ISBN and Teseo), was completed with an extensive search of the gray literature and of unpublished studies through contact with public and private institutions which may fund such studies. The quality of the original surveys was assessed, and the data of the studies fulfilling pre-established quality requirements were summarized and tabulated. RESULTS: We located 65 nutritional surveys in children and adolescents performed between 1984 and 1994, which generated 91 documents. Most surveys (76.9%) were local, while 18.5% of them studied provinces or regions and 3.1% studied more than one region. Only 4 studies (6.2%) met the quality requirements, but the methods or the presentation of the results of these surveys were too heterogeneous. In spite of that, the available data tends to show a certain lack of balance of macronutrient intakes in relation to the usual dietary recommendations. CONCLUSIONS: Available data on nutritional intake of Spanish school-age children during 1984-1994 were too heterogeneous to be comparable, even if the analysis was restricted to high-quality surveys. Furthermore, there are no repeated surveys monitoring changes in intake in representative samples of children performed during the study period. This should be taken into account in future research endeavours which should contemplate a well defined sampling framework and the appropriate methodology to assure the proper interpretation of the eventual results.

DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study.

OBJECTIVE: To examine any possible links between exposure to DDE (1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene), the persistent metabolite of the pesticide dicophane (DDT), and breast cancer. DESIGN: Multicentre study of exposure to DDE by measurement of adipose tissue aspirated from the buttocks. Laboratory measurements were conducted in a single laboratory. Additional data on risk factors for breast cancer were obtained by standard questionnaires. SETTING: Centres in Germany, the Netherlands, Northern Ireland, Switzerland, and Spain. SUBJECTS: 265 postmenopausal women with breast cancer and 341 controls matched for age and centre. MAIN OUTCOME MEASURE: Adipose DDE concentrations. RESULTS: Women with breast cancer had adipose DDE concentrations 9.2% lower than control women. No increased risk of breast cancer was found at higher concentrations. The odds ratio of breast cancer, adjusted for age and centre, for the highest versus the lowest fourth of DDE distribution was 0.73 (95% confidence interval 0.44 to 1.21) and decreased to 0.48 (0.25 to 0.95; P for trend = 0.02) after adjustment for body mass index, age at first birth, and current alcohol drinking. Adjustment for other risk factors did not materially affect these estimates. CONCLUSIONS: The lower DDE concentrations observed among the women with breast cancer may be secondary to disease inception. This study does not support the hypothesis that DDE increases risk of breast cancer in postmenopausal women in Europe.

Meta-analysis: vitamin D and non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition. Emerging evidence suggests that vitamin D may play a role in the pathogenesis of NAFLD. AIM: To review systematically the association between vitamin D levels, measured as serum 25-hydroxy vitamin D [25(OH)D], and NAFLD. METHODS: We used PubMed and EMBASE databases to identify all studies that assessed the association between vitamin D and NAFLD up until 22 April 2013, without language restrictions. We included studies that compared vitamin D levels between NAFLD cases and controls and also those that compared the odds of vitamin D deficiency by NAFLD status. Pooled standardised differences and odds ratios were calculated using an inverse variance method. RESULTS: Seventeen cross-sectional and case-control studies have evaluated the association between vitamin D and NAFLD. NAFLD was diagnosed using biopsy (4 studies), ultrasound or CT (10 studies) and liver enzymes (3 studies). Nine studies provided data for a quantitative meta-analysis. Compared to controls, NAFLD patients had 0.36 ng/mL (95% CI: 0.32, 0.40 ng/mL) lower levels of 25(OH)D and were 1.26 times more likely to be vitamin D deficient (OR 1.26, 95% CI: 1.17, 1.35). CONCLUSIONS: NAFLD patients have decreased serum 25(OH)D concentrations, suggesting that vitamin D may play a role in the development of NAFLD. The directionality of this association cannot be determined from cross-sectional studies. Demonstration of a causal role of hypovitaminosis D in NAFLD development in future studies could have important therapeutic implications.