An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study.

BACKGROUND: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. METHODS: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202,206 women in the European Prospective Investigation into Cancer and Nutrition study. RESULTS: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. CONCLUSION: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.

Intake of total omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study.

BACKGROUND AND AIMS: The evidence about the benefits of omega-3 fatty acid intake on coronary heart disease (CHD) is not consistent. We thus aimed to assess the relation between dietary intake of total omega-3 fatty acids (from plant and marine foods) and marine polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS AND RESULTS: The analysis included 41,091 men and women aged 20-69 years, recruited from 1992 to 1996 and followed-up until December 2004. Omega-3 fatty acid intake was estimated from a validated dietary questionnaire. Only participants with definite incident CHD event were considered as cases. Cox regression models were used to assess the association between the intake of total omega-3 fatty acids, EPA or DHA and CHD. A total of 609 participants (79% men) had a definite CHD event. Mean intakes of total omega-3 fatty acids, EPA and DHA were very similar in the cases and in the cohort, both in men and women. In the multivariate adjusted model, omega-3 fatty acids, EPA and DHA were not related to incident CHD in either men or women. The hazard ratios (HR) for omega-3 were 1.23 in men (95% CI 0.94-15.9, p = 0.20); and 0.77 in women (95% CI 0.46-1.30, p = 0.76). CONCLUSION: In the Spanish EPIC cohort, with a relatively high intake of fish, no association was found between EPA, DHA and total omega-3 fatty acid intake and risk of CHD.

Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition.

Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79-0.97 and 0.76; 95% CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded.

Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project.

BACKGROUND: In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. METHODS: In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). RESULTS: By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). CONCLUSIONS: Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

Associations among musculoskeletal impairments, depression, body image and fatigue in breast cancer survivors within the first year after treatment.

The aim of the current study was to investigate the relationship between pressure pain thresholds, shoulder movement, mood state, pain perception, muscle endurance, quality of life and fatigue in breast cancer survivors (BCS). Fifty-nine BCS reporting fatigue were examined at 6 months post-treatment. Women completed the Piper Fatigue Scale, the Breast Cancer-Specific Quality of Life Questionnaire, the Profile of Mood State, and neck-shoulder visual analogue scale. Additionally, shoulder flexion range of motion, the McQuade test (trunk flexor endurance) and pressure pain thresholds over the C5-C6 joint, the deltoid muscle, the second metacarpal and tibialis anterior muscle were assessed. Fatigue was greater in those patients with higher depression (r= 0.45, P < 0.05), higher shoulder pain (r= 0.39, P < 0.05), higher neck pain (r= 0.46, P < 0.01), lower body image (r=-0.34, P < 0.05) and reduced shoulder movement (r=-0.32, P < 0.05). Regression analyses demonstrated that depression, cervical pain intensity, body image and shoulder mobility were associated with fatigue (r= 0.55, P < 0.001). A psychological state characterised with higher depression and reduced body image and a physical impairment with higher cervical pain intensity and reduced shoulder mobility confirm multidimensional character of fatigue in BCS.

[Factors associated with prehospital delay in men and women with acute coronary syndrome]. / Factores asociados a la demora prehospitalaria en hombresy mujeres con síndrome coronario agudo.

OBJECTIVE: To identify factors associated with prehospital delay in people who have had an acute coronary syndrome. METHODS: Using a survey we studied patients admitted due to acute coronary syndrome in the 33 Andalusian public hospitals, obtaining information about different types of variables: socio-demographic, contextual,clinical, perception, action, and transportation.Multivariate logistic regression models were applied to calculate the odds ratios for the delay. RESULTS: Of the 1,416 patients studied, more than half had a delay of more than an hour. This is associated to distance to the hospital and means of transport: when the event occurs in the same city,using the patient's own means of transport increases the delay, odds ratio = 1.51 (1.02 to 2.23); if the distance is 1 to 25 kilometers from the hospital,there is no difference between the patient's own means of transport and an ambulance, odds ratio =1.41 and odds ratio =1.43 respectively; and when the distance exceeds 25 kilometers transport by ambulance means more delay, odds ratio = 3.13 and odds ratio = 2.20 respectively. Also, typical symptoms reduce delay amongst men but increase amongst women. Also, not caring and waiting for the resolution of symptoms, seeking health care other than a hospital or emergency services, previous clinical history, being away from home, and having an income under 1,500 euros, all increase delay. Respiratory symptoms reduce delay. CONCLUSIONS: Prehospital delay times do not meet health recommendations. The physical and social environment,in addition to clinical, perceptual and attitudinal factors, are associated with this delay.

Relationship between QT Interval Length and Arterial Stiffness in Systemic Lupus Erythematosus (SLE): A Cross-Sectional Case-Control Study.

INTRODUCTION AND OBJECTIVES: The QT interval on the electrocardiogram has been shown to be longer in patients with systemic lupus erythematosus (SLE) compared to that of the general population. The clinical significance of this finding is unknown. The aim of this study was to assess the relationship between QT interval and subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. MATERIAL AND METHODS: 93 patients with SLE and 109 healthy women with similar basal characteristics were studied. All patients underwent a 12- lead electrocardiogram, and corrected QT interval (QTc) was measured using the Bazett's formula. The presence of atherosclerosis was evaluated by carotid-femoral pulse-wave velocity. RESULTS: Clinical basal characteristics were similar in both groups. QTc interval was 415 ± 21.4 milliseconds in all patients, and 407 ± 19.1 milliseconds in the control group (p = 0.007). There was a positive correlation between QTc interval and carotid-femoral pulse-wave velocity (r = 0.235; p = 0.02) in patients with SLE. This association was independent of hypertension and age in a multivariate analysis. CONCLUSION: QTc interval measured by electrocardiogram is prolonged in SLE patients; it is related to subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. This measure may help stratify risk in routine clinical practice and select the patients that might benefit from a more aggressive therapy in the prevention of cardiovascular events.

Preoperative use of statins does not improve outcomes and development of acute renal failure after cardiac surgery. A propensity score analysis of ARIAM-Andalucía database.

BACKGROUND: Statin use prior to cardiac surgery has been reported to improve outcomes in the postoperative period because of other effects apart from decreasing lipid levels. Objective of the study was to analyse mortality and acute renal failure (ARF) during the cardiac surgery postoperative period in patients treated with or without statins. METHODS: This prospective cohort study comprised adult patients who underwent cardiac surgery at 11 institutions in the Andalusian community from March 2008 to July 2012 included in the ARIAM adult cardiac surgery project. We performed a first analysis in the whole cohort and in a second analysis statin users prior to surgery were pair matched with non-users according to their propensity score based on demographics, comorbidities, medication and surgical data. We analysed differences in outcomes, ARF, need for renal replacement therapy (RRT) and a composite end point with mortality or major morbidity in both groups. RESULTS: The study included 7276 patients, of whom 3749 were treated with statins. Overall, hospital mortality was 10.1%, 10.5% developed ARF and 2.5% required RRT. In the whole non-matched cohort, statins were associated with lower hospital mortality (OR 0.79; 95% CI, 0.67-0.93) and less ARF (OR 0.79; 95% CI, 0.68-0.93). However, after propensity score analysis in the matched cohort of 3056 patients (1528 in each group), statin use was not consistently associated with less ARF (OR 0.94; 95% CI, 0.74-1.19), hospital mortality (OR 0.83; 95% CI, 0.68-1.1) or composite outcome (OR 0.857; 95% CI, 0.723-1.015). CONCLUSION: Despite better outcomes for the statin users in the whole cohort, the matched analysis showed that statin use before cardiac surgery was not associated with a lower risk of ARF. Nor was presurgery statin use associated with lower hospital mortality.

Correlation of histologic grade and lymph node status with some histopathologic discriminants in breast cancer.

In fifty non selected ductal carcinomas of the breast we found that a marked tumoral inflammatory infiltrate (P less than 0.025), perinodal tumoral infiltrate (P less than 0.01), sinus catarrh (P less than 0.05), follicular hyperplasia (P less than 0.025), mixed pattern in lymph nodes (P less than 0.01) and with 54 years of age or younger (P less than 0.01) correlated significantly with lymph node metastases and/or high histologic grade. On the contrary, elastosis (P less than 0.05), scanty or absent inflammatory infiltrate (P less than 0.01), sinus histiocytosis (P less than 0.001) and endothelial hyperplasia were statistically related to low histologic grade and/or lack of metastases. Elastosis is considered a defensive host response. Groups of lymphocytes in the perinodal fat is usually found in metastasized lymph nodes and may indicate metastasis should be sought in a lymph node which otherwise seems to be tumor-free.

Breast tumors: immunoglobulins in axillary lymph nodes.

The immunohistochemical determination of immunoglobulins IgA, IgG and IgM in axillary lymph nodes from 50 unselected breast ductal carcinomas disclosed that lymph nodes with IgG-positive lymphoid follicles and/or metastasized lymph nodes with IgM-positive lymphoid cells are statistically related to breast tumors with a high histologic grade and more than 3 lymph node metastases.

[Multilevel models or the importance of ranking]. / Los modelos multinivel o la importancia de la jerarquía.

Many researchers in Public Health have data bases with a hierarchical structure. The studied patients (level 1) can be nested in groups, i.e., district, doctor, hospital, etc. (level 2). It is possible that patients in the same group be similar, so traditional regression models can not be used because the hypothesis of independent observations is not satisfied. A Multilevel Analysis, using hierarchical models, can be a solution for this problem; these models take into account the distribution of the data at different levels to estimate two types of variability: one due to individuals in the study and another due to the groups in which patients are nested. These types of models were applied in education in the last decade, however they have been recently applied in Health Research. This paper is a review about multilevel analysis. A discussion about hierarchichal models versus traditional regression models is presented and some applications in Epidemiology and Health Research are showed.

[Prognostic value of the degree of differentiation and the peri-tumor lymphoid infiltration in epidermoid carcinoma of the larynx]. / Valor pronóstico del grado de diferenciación y el infiltrado linfoide peritumoral en el carcinoma epidermoide de laringe.

By multiple linear regression the authors show a closed relationship between survival and conventional anatomopathologic data as grade of differentiation and of lymphoid infiltration of the primary tumor. This retrospective pathological study showed that various degrees of squamous cell differentiation may be recognized for malignant laryngeal lesions and that such distinction may be of prognostic significance.

Compliance with dietary and nutrient recommendations in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada cohort at recruitment.

BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk.

[Analysis of the epidemiological characteristics and prognostic factors in probable or confirmed invasive meningococcal disease in a cohort of adolescents and adults during an epidemic outbreak]. / Análisis de las características epidemiológicas y de los factores pronósticos en la enfermedad meningocócica invasiva probable o confirmada en una cohorte de adolescentes y adultos durante un brote epidémico.

OBJECTIVE: To describe the profile of people suffering Invasive Meningococcal Disease in Andalusia and the Canary Islands, and identify the risk factors for death. MATERIAL AND METHODS: A retrospective study was designed, recruiting cases from week 41 of 1995 to week 40 2000. Cases were probable or definite, and were extracted from the databases of the hospital by examining diagnosis at discharge or death. RESULTS: 167 cases were identified, with a mortality rate of 7.2%. Mean age was 28.88 years, this being greater in those who died (p = 0.041). There was no previous contact with the Health System before the diagnosis in 56.3% of the cases, this being associated with death (p = 0.017). The more frequent reason for contact was a low level of consciousness, and it was the only one associated to death (p = 0.036). Pharyngotonsilitis was associated with a lower incidence of death. About 24% of patients received antibiotics as out-patients and their use was associated to a lower incidence of death (p = 0.07). Temperature over 40 degrees C (p = 0.003) and heart rate lower than 60 beats per minute (p < 0.0005) were associated with death. Leucocytes in peripheral blood less than 4.500 cells/ microliter, or platelets less than 100.000 cells/microliter were associated with a greater proportion of deaths. In Cerebrospinal fluid, less than 5 leucocytes per microliter, or proteins less than 50 mg/dl were associated with more deaths. Neisseria meningitidis B was isolated in 47 patients (28.1%), and C in 77 cases (46.1%). Sepsis was significantly associated with death (p < 0.0005). CONCLUSIONS: The absence of previous contacts with the Health System reveals an abrupt onset of Meningococcal disease, with less inflammatory response and very severe. Out of hospital antibiotic treatment and pharyngoamygdalitis are associated with a better prognosis.

Predictors of concentrations of hexachlorobenzene in human adipose tissue: a multivariate analysis by gender in Southern Spain.

Hexachlorobenzene (HCB) was measured in adipose tissue intraoperatively collected from 387 subjects over 16 years old undergoing surgery in two hospitals in Granada (Southern Spain). HCB was quantified in 90.7% of subjects. The concentrations and frequencies of HCB were similar to those reported in adipose tissue samples in other recent European studies. Exposure patterns differed between females and males: higher HCB concentrations were found in females than in males (geometric mean 18.3 vs. 6.8 ng/g, p<0.001). The relationship between HCB concentrations and exposure risk factors was assessed by multivariate analysis stratifying by gender. In men, HCB concentrations were predicted (r(2)=0.45) by age, body mass index (BMI), place of residence, smoking, consumption of fish, chicken and cheese, occupation related to agriculture, and family involvement in construction activities. In women, HCB concentrations were predicted (r(2)=0.50) by age, BMI, consumption of milk and cheese, and occupation related to industry. The finding that women had three-fold higher levels of HCB than the men deserves further investigation.

[Reliability assessment of the EUROTEST]. / Evaluación de la fiabilidad del EUROTEST.

INTRODUCTION: The EUROTEST is a valid and useful instrument for detecting cognitive impairment and dementia. Our aim was to assess the test-retest reliability (TRTR) and the inter-rater reliability (IRR) of this instrument. METHODS: We assessed the TRTR by means of a cross-sectional repeated measures design in 30 subjects with no cognitive impairment. The IRR was determined through the blind assessment of 10 test administrations by 20 independent observers. In both instances we calculated the intra-class correlation coefficient and we compared those coefficients with the ones of the semantic Verbal Fluency Test (sVFT) obtained with the same samples and procedures. RESULTS: There were not significant differences concerning the characteristics of the subjects included in this study and those of previous studies on the EUROTEST. The EUROTEST showed a significantly higher TRTR (0.94 [95% CI: 0.87-0.97]) than the sVFT (0.51 [95% CI: 0.17- 0.74]), but there was not significant difference in IRR between the EUROTEST (0.91 [95% CI: 0.82-0.97]) and the sVFT (0.96 [95% CI: 0.91-0.99]). CONCLUSIONS: The EUROTEST shows high TRTR and IRR; therefore, this instrument is appropriate for the longitudinal assessment of subjects with dementia and their response to treatment.

[Serum levels of testosterone, follicie-stimulating hormone and luteinizing hormone in normal human males (author's transl)]. / Concentraciones de testosterona, hormona folículo estimulante y hormona luteinizante en suero humano normal.

The serum levels of testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have been measured in healthy man of different ages to stablish their normal values in the population of Granada. The serum levels of testosterone, FSH and LH have been compared to each other in each age group. No clear relation between these hormones was found at any age.

Effects of depot testosterone administration on serum levels of testosterone, FSH, LH and prolactin.

The effects of the administration of testosterone on plasma testosterone (T), estradiol (E), FSH, LH and prolactin (PRL) were tested in a group of men, aged over sixty. Blood samples were collected on the 2nd, 4th, 7th and 15th day afterr the administration of testosterone propionate (TP) (n = 28 men) and testosterone propionate with testosterone enantate (TP + TE) (n = 21 men). After the administration of TP + TE plasma T increased on days 2-4, returned to the normal basal level on the 7th day, and rose again on the 15th day. With the TP preparation the levels of testosterone remained elevated during the first seven days and returned to the basal values by the 15th day. The FSH and LH were suppressed during the first seven days after the injection of both TP and TP + TE preparations. On the 15th day gonadotropins were suppressed only by the administration of TP. The plasma concentration of E behaved like that of T. We found a significant increase in the PRL levels on the 4th day after treatment with 100 mg of the two preparations. Moreover, we found that PRL basal values were significantly higher in those subjects whose T basal values were low.