Baseline patterns of adipose tissue fatty acids and long-term risk of breast cancer: a case-cohort study in the Danish cohort Diet, Cancer and Health.

BACKGROUND/OBJECTIVES: The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). SUBJECTS/METHODS: This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. RESULTS: After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER-, PR+ or PR- tumours. CONCLUSIONS: No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed.

Impact of bispectral index for monitoring propofol remifentanil anaesthesia. A randomised clinical trial.

BACKGROUND: Previous research has shown that the use of the bispectral index (BIS) monitor to measure the depth of anaesthesia reduces the amount of anaesthetics administered and the recovery time from general anaesthesia. The effect of BIS on recovery from anaesthesia and consumption of anaesthetics in a paediatric population receiving total intravenous anaesthesia (TIVA) with propofol and remifentanil has not been studied. METHODS: A single-blind, single-centre clinical trial. One hundred fifty-seven patients were enrolled. They were scheduled for ear, nose, and throat surgery and stratified according to age groups (1-3 years, 4-11 years, 12-17 years, 18-65 years) and type of operation, yielding a total of nine subgroups. Patients were randomly allocated to receive either a TIVA with propofol and remifentanil according to conventional clinical practice (control) or guided by BIS. Normalised propofol (µg/kg/min) and remifentanil (µg/kg/min) consumption and time to extubation (s) were the outcome measures. RESULTS: Children aged 1-3 years in the BIS group had a longer time to extubation compared with controls (P: 0.04). Patients aged 12-17 years in the BIS group received higher maintenance infusion rates of propofol compared with controls (P = 0.02). No significant difference for the outcome variables was evidenced in the other age groups. CONCLUSION: BIS monitoring for guidance of propofol-remifentanil anaesthesia does not result in reduced consumption of anaesthetics and does not reduce time to extubation in adult and children compared with conventional practice.

Poisson regression models outperform the geometrical model in estimating the peak-to-trough ratio of seasonal variation: a simulation study.

INTRODUCTION: Several statistical methods of assessing seasonal variation are available. Brookhart and Rothman [3] proposed a second-order moment-based estimator based on the geometrical model derived by Edwards [1], and reported that this estimator is superior in estimating the peak-to-trough ratio of seasonal variation compared with Edwards' estimator with respect to bias and mean squared error. Alternatively, seasonal variation may be modelled using a Poisson regression model, which provides flexibility in modelling the pattern of seasonal variation and adjustments for covariates. METHOD: Based on a Monte Carlo simulation study three estimators, one based on the geometrical model, and two based on log-linear Poisson regression models, were evaluated in regards to bias and standard deviation (SD). We evaluated the estimators on data simulated according to schemes varying in seasonal variation and presence of a secular trend. All methods and analyses in this paper are available in the R package Peak2Trough[13]. RESULTS: Applying a Poisson regression model resulted in lower absolute bias and SD for data simulated according to the corresponding model assumptions. Poisson regression models had lower bias and SD for data simulated to deviate from the corresponding model assumptions than the geometrical model. CONCLUSION: This simulation study encourages the use of Poisson regression models in estimating the peak-to-trough ratio of seasonal variation as opposed to the geometrical model.

Food intake of individuals with and without diabetes across different countries and ethnic groups.

BACKGROUND/OBJECTIVES: Given the importance of nutrition therapy in diabetes management, we hypothesized that food intake differs between individuals with and without diabetes. We investigated this hypothesis in two large prospective studies including different countries and ethnic groups. SUBJECTS/METHODS: Study populations were the European Prospective Investigation into Cancer and Nutrition Study (EPIC) and the Multiethnic Cohort Study (MEC). Dietary intake was assessed by food frequency questionnaires, and calibrated using 24h-recall information for the EPIC Study. Only confirmed self-reports of diabetes at cohort entry were included: 6192 diabetes patients in EPIC and 13 776 in the MEC. For the cross-sectional comparison of food intake and lifestyle variables at baseline, individuals with and without diabetes were matched 1:1 on sex, age in 5-year categories, body mass index in 2.5 kg/m(2) categories and country. RESULTS: Higher intake of soft drinks (by 13 and 44% in the EPIC and MEC), and lower consumption of sweets, juice, wine and beer (>10% difference) were observed in participants with diabetes compared with those without. Consumption of vegetables, fish and meat was slightly higher in individuals with diabetes in both studies, but the differences were <10%. Findings were more consistent across different ethnic groups than countries, but generally showed largely similar patterns. CONCLUSIONS: Although diabetes patients are expected to undergo nutritional education, we found only small differences in dietary behavior in comparison with cohort members without diabetes. These findings suggest that emphasis on education is needed to improve the current behaviors to assist in the prevention of complications.

Obesity and risk of subsequent hospitalisation with pneumonia.

Obesity may be associated with increased risk of pneumonia, but available data on this relationship are sparse and inconsistent. We followed a prospective cohort of 22,578 males and 25,973 females from the Danish Diet, Cancer and Health Study, aged 50-64 yrs and free from major chronic diseases at baseline (1993-1997), for first-time hospitalisation with pneumonia (median follow-up 12 yrs). Compared with males of normal weight, adjusted hazard ratios (HRs) for pneumonia were 1.4 (95% CI 1.2-1.7) for males with moderate obesity (body mass index (BMI) 30.0-34.9 kg·m⁻²), and 2.0 (95% CI 1.4-2.8) for males with severe obesity (BMI ≥ 35.0 kg·m⁻²), controlling for lifestyle and educational variables. Among females the associations were weaker, with adjusted HRs of 0.8 (95% CI 0.6-1.0) for moderate obesity, and 1.2 (95% CI 0.8-1.6) for severe obesity. Adjustment for major chronic diseases diagnosed during follow-up eliminated the associations between obesity and pneumonia risk. Obesity is associated with higher risk of hospitalisation with pneumonia among males but not among females, which is apparently explained by occurrence of other chronic diseases.

A bivariate measurement error model for nitrogen and potassium intakes to evaluate the performance of regression calibration in the European Prospective Investigation into Cancer and Nutrition study.

OBJECTIVES: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, the performance of 24-h dietary recall (24-HDR) measurements as reference measurements in a linear regression calibration model is evaluated critically at the individual (within-centre) and aggregate (between-centre) levels by using unbiased estimates of urinary measurements of nitrogen and potassium intakes. METHODS: Between 1995 and 1999, 1072 study subjects (59% women) from 12 EPIC centres volunteered to collect 24-h urine samples. Log-transformed questionnaire, 24-HDR and urinary measurements of nitrogen and potassium intakes were analysed in a multivariate measurement error model to estimate the validity of coefficients and error correlations in self-reported dietary measurements. In parallel, correlations between means of 24-HDR and urinary measurements were computed. Linear regression calibration models were used to estimate the regression dilution (attenuation) factors. RESULTS: After adjustment for sex, centre, age, body mass index and height, the validity coefficients for 24-HDRs were 0.285 (95% confidence interval: 0.194, 0.367) and 0.371 (0.291, 0.446) for nitrogen and potassium intakes, respectively. The attenuation factors estimated in a linear regression calibration model were 0.368 (0.228, 0.508) for nitrogen and 0.500 (0.361, 0.639) for potassium intakes; only the former was different from the estimate obtained using urinary measurements in the measurement error model. The aggregate-level correlation coefficients between means of urinary and 24-HDR measurements were 0.838 (0.637, 0.932) and 0.756 (0.481, 0.895) for nitrogen and potassium intakes, respectively. CONCLUSIONS: This study suggests that 24-HDRs can be used as reference measurements at the individual and aggregate levels for potassium intake, whereas, for nitrogen intake, good performance is observed for between-centre calibration, but some limitations are apparent at the individual level.

Smoking and venous thromboembolism: a Danish follow-up study.

BACKGROUND: Large-scale prospective studies are needed to assess whether smoking is associated with venous thromboembolism (VTE) (i.e. deep venous thrombosis and pulmonary embolism) independently of established risk factors. OBJECTIVE: To investigate the association between smoking and the risk of VTE among middle-aged men and women. METHODS: From 1993 to 1997, 27,178 men and 29,875 women, aged 50-64 years and born in Denmark, were recruited into the Danish prospective study 'Diet, Cancer and Health'. During follow-up, VTE cases were identified in the Danish National Patient Registry. Medical records were reviewed and only verified VTE cases were included in the study. Baseline data on smoking and potential confounders were included in gender stratified Cox proportional hazard models to asses the association between smoking and the risk of VTE. The analyses were adjusted for alcohol intake, body mass index, physical activity, and in women also for use of hormone replacement therapy. RESULTS: During follow-up, 641 incident cases of VTE were verified. We found a positive association between current smoking and VTE, with a hazard ratio of 1.52 (95% CI, 1.15-2.00) for smoking women and 1.32 (95% CI, 1.00-1.74) for smoking men, and a positive dose-response relationship. Former smokers had the same hazard as never smokers. CONCLUSIONS: Smoking was an independent risk factor for VTE among middle-aged men and women. Former smokers have the same risk of VTE as never smokers, indicating acute effects of smoking, and underscoring the potential benefits of smoking cessation.

Examining secular trends and seasonality in count data using dynamic generalized linear modelling: a new methodological approach illustrated with hospital discharge data on myocardial infarction.

Time series of incidence counts often show secular trends and seasonal patterns. We present a model for incidence counts capable of handling a possible gradual change in growth rates and seasonal patterns, serial correlation, and overdispersion. The model resembles an ordinary time series regression model for Poisson counts. It differs in allowing the regression coefficients to vary gradually over time in a random fashion. During the 1983-1999 period, 17,989 incidents of acute myocardial infarction were recorded in the Hospital Discharge Registry for the county of North Jutland, Denmark. Records were updated daily. A dynamic model with a seasonal pattern and an approximately linear trend was fitted to the data, and diagnostic plots indicated a good model fit. The analysis conducted with the dynamic model revealed peaks coinciding with above-average influenza A activity. On average the dynamic model estimated a higher peak-to-trough ratio than traditional models, and showed gradual changes in seasonal patterns. Analyses conducted with this model provide insights not available from more traditional approaches.

Magnitude of bacteraemia is a predictor of mortality during 1 year of follow-up.

We evaluated magnitude of bacteraemia as a predictor of mortality, comprising all adult patients with a first-time mono-microbial bacteraemia. The number of positive bottles [1 (reference), 2, or 3] in the first positive blood culture (BC) was an index of magnitude of bacteraemia. We used Cox's regression analysis to determine age and comorbidity adjusted risk of mortality at days 0-7, 8-30, and 31-365. Of 6406 patients, 31.1% had BC index 1 (BCI 1), 18.3% BCI 2, and 50.6% BCI 3. BCI 3 patients had increased risk of mortality for days 0-7 (1.30, 95% CI 1.10-1.55) and days 8-30 (1.37, 95% CI 1.12-1.68), but not thereafter. However, in surgical patients mortality increased only beyond day 7 (8-30 days: 2.04, 95% CI 1.25-3.33; 31-365 days: 1.27, 95% CI 0.98-1.65). Thus, high magnitude of bacteraemia predicted mortality during the first month with a shift towards long-term mortality in surgical patients.

Seasonal changes in climatic parameters and their relationship with the incidence of pneumococcal bacteraemia in Denmark.

The seasonal variation in the incidence of invasive pneumococcal disease is well recognized, but little is known about its relationship with actual changes in climatic parameters. In this 8-year longitudinal population-based study in Denmark, a harmonic sinusoidal regression model was used to examine whether preceding changes in climatic parameters corresponded with subsequent variations in the incidence of pneumococcal bacteraemia, independently of seasonal variation. The study shows that changes in temperature can be used to closely predict peaks in the incidence of pneumococcal bacteraemia with a time-lag of 16 days (95% CI 14-18 days), independently of a strong seasonal pattern.

Improved assay of cardiac troponin I is more sensitive than other assays of necrosis markers.

OBJECTIVE: Highly sensitive and specific assays of cardiac troponins I and T are the preferred biomarkers in diagnosing myocardial infarction (MI). Assays of cardiac troponin I (cTnI) have been improved with the addition of antibodies against the cTnI molecule and may have increased sensitivity. We hypothesized that a cTnI assay with modern antibody configuration will exhibit equal or better sensitivity in the setting of acute MI compared to cTnT and other markers of myocardial necrosis. MATERIAL AND METHODS: We investigated release kinetics of cTnI (Abbott ADV, Abbott Diagnostics), cTnT (Roche Diagnostics), CKMBmass, myoglobin and heart fatty acid binding protein (H-FABP) in 23 patients admitted with acute ST-segment elevation MI undergoing primary percutaneous coronary intervention. Calibrators for the Abbott ADV cTnI assay are traceable to the United States National Institute of Standards and Technology (NIST) reference material for cTnI. Eleven blood samples were drawn from each patient in the period from admission to 24 h. Biomarkers of necrosis showed marked increases in relative concentrations, especially within the first 2 h after admission. RESULTS: From 30 min after admission onwards, cTnI exhibited significantly higher relative concentrations compared to cTnT, CKMBmass, Myoglobin and H-FABP (p<0.05). CONCLUSIONS: The NIST standardized Abbott TnI ADV assay appears to be more sensitive than cTnT and other biomarkers in the early phase of MI.

Oxygenation and release of inflammatory mediators after off-pump compared with after on-pump coronary artery bypass surgery.

BACKGROUND: In a previous study, we showed that oxygenation was impaired for up to 5 day after conventional coronary artery bypass grafting (CABG). As cardiopulmonary bypass (CPB) may have a detrimental effect on pulmonary function, we hypothesized that coronary revascularization grafting without the use of CPB (OPCAB) would affect post-operative oxygenation and release of inflammatory mediators less compared with CABG. METHODS: Low-risk patients scheduled for elective coronary revascularization were randomly assigned to one of two groups (CABG, n = 17 or OPCAB, n = 18). Two parameters of oxygenation, shunt (%) and ventilation-perfusions mismatch, described as DeltaPO(2) (kPa), were estimated for up to 5 days post-operatively. Systemic release of interleukin (IL)-6, -8 and -10, C-reactive protein (CRP) and neutrophils were measured in peripheral blood samples for up to 3 days post-operatively. The lungs participation in the cytokine response was evaluated from mixed venous blood samples taken within the first 16 h post-operatively. RESULTS: OPCAB was followed by a higher shunt (P = 0.047), with no difference (P = 0.47) in the deterioration of DeltaPO(2) between the groups. OPCAB was followed by an attenuated systemic release of IL-8 (P = 0.041) and IL-10 (P = 0.006), while the release of IL-6 (P = 0.94), CRP (P = 0.121) and neutrophils (P = 0.078) did not differ between the groups. Indications of an uptake of cytokines in the lungs were found after OPCAB. CONCLUSIONS: When comparing OPCAB with CABG, oxygenation was more affected and only part of the systemic inflammatory response was attenuated.

Maternal glycated haemoglobin, pre-gestational weight, pregnancy weight gain and risk of large-for-gestational-age babies: a Danish cohort study of 209 singleton Type 1 diabetic pregnancies.

AIMS: To examine the association between maternal glycated haemoglobin in the second half of diabetic pregnancies and the relative risk of delivering large-for-gestational-age (LGA) babies, controlling for maternal body mass index (BMI) before pregnancy, weight gain, age, White class and smoking habits. METHODS: We identified all pregnant diabetic women in North Jutland County, Denmark from 1985 to 2003. Data on HbA(1c) values from the 20th gestational week to term were collected from medical records and the babies were classified as large, normal or small for gestational age. The association between glycated haemoglobin (HbA(1c)) and relative risk of delivering an LGA baby was quantified based on logistic regression models and stratified analysis controlling for the five covariates. RESULTS: We included 209 singleton pregnancies with assessable HbA(1c) values of which 59%[95% confidence interval (CI) 52-65%] terminated with an LGA baby. Increasing levels of HbA(1c), BMI and weight gain were all associated with increasing risk of delivering an LGA baby. Analyses stratified according to maternal BMI showed that the association between HbA(1c) and risk of delivering an LGA baby was restricted to pregnancies with pre-pregnancy BMI > 23 kg/m(2). We found no association between HbA(1c) and risk of delivering an LGA baby in pregnancies with lower BMI. CONCLUSION: The positive association between glycated haemoglobin and birth of an LGA baby seems to be restricted to women with BMI > 23 kg/m(2).

Severity of infection and seasonal variation of non-typhoid Salmonella occurrence in humans.

Non-typhoid Salmonella infections may present as severe gastroenteritis necessitating hospitalization and some patients become septic with bacteraemia. We hypothesized that the seasonal variation of non-typhoid Salmonella occurrence in humans diminishes with increased severity of infection. We examined the seasonal variation of non-typhoid Salmonella infections in three patient groups with differing severity of infection: outpatients treated for gastroenteritis (n=1490); in-patients treated for gastroenteritis (n=492); and in-patients treated for bacteraemia (n=113). The study was population-based and included all non-typhoid Salmonella patients in a Danish county from 1994 to 2003. A periodic regression model was used to compute the peak-to-trough ratio for the three patient groups. The peak-to-trough ratios were 4.3 [95% confidence interval (CI) 3.6-5.0] for outpatients with gastroenteritis, 3.2 (95% CI 2.4-4.2) for in-patients with gastroenteritis, and 1.6 (95% CI 1.0-2.8) for in-patients with bacteraemia. We conclude that the role of seasonal variation diminishes with increased severity of non-typhoid Salmonella infection.