Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery.

BACKGROUND: Omega-3 fatty acids (n-3 FAs) may have beneficial clinical effects, and n-3 FA supplements may improve outcome after surgery. METHODS: In a randomized double-blind placebo-controlled trial in single centre, patients referred for elective colorectal cancer surgery received either an n-3 FA-enriched oral nutritional supplement (ONS) (Supportan, 200 ml twice daily) providing 2.0 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA) per day, or a standard isocaloric and isonitrogenous ONS, for 7 days before and 7 days after surgery. The primary endpoint was infectious and non-infectious complications within 30 days of surgery. Secondary endpoints were length of hospital stay, intensive care unit admission, readmissions, and concentrations of marine n-3 FAs and arachidonic acid in granulocyte membranes. RESULTS: Some 148 consecutive patients (68 women, 80 men; mean age 71 (range 41-89) years) were randomized. There was no significant difference between groups in infectious or non-infectious postoperative complications (P = 1.000). Granulocyte levels of EPA, DHA and docosapentaenoic acid (DPA) were significantly higher in the n-3 FA-enriched supplement group compared with the control group (P < 0.001). The arachidonic acid level in granulocytes was significantly lower in the enriched group than in the control group (P < 0.001). CONCLUSION: EPA, DHA and DPA were incorporated into granulocytes in patients receiving n-3 FAs, but this was not associated with improved postoperative outcomes. REGISTRATION NUMBER: NCT00488904 (http://www.clinicaltrials.gov).

Parity and risk of diabetes in a Danish nationwide birth cohort.

AIMS: The purpose was to elucidate the association between parity and the incidence of diabetes using national register data. METHODS: The study population consisted of all Danish women with a singleton delivery in 1982/1983 (n = 100,669), who subsequently had 74,966 deliveries. The included women were followed up via registries until the end of 2006 for subsequent deliveries, diagnosis of diabetes and death/emigration. RESULTS: A total of 2021 cases (2.0%) were diagnosed with diabetes in connection with hospitalization or outpatient treatment during follow-up. Analyses were adjusted for fetal weight and duration of gestation, both at index pregnancy. Cox regression analysis with parity as a time-varying exposure, stratified in two age groups, showed an association between parity and risk of a diagnosis of diabetes. In women <33 years of age, parity 2, 3 and 4 + were associated with an increased risk of being diagnosed with diabetes compared with parity 1 [relative risks: 1.6 (95% confidence interval 1.1-2.3), 2.8 (1.8-4.3) and 2.5 (1.3-4.8), respectively]. Among women >33 years of age, parity 2 was associated with a significantly lower risk of diabetes diagnosis compared with parity 1, whereas parity 4 + was associated with a significantly higher risk of diabetes diagnosis compared with parity 1. CONCLUSIONS: The study shows that the risk of diabetes diagnosis increases with parity in young Danish women. This may support a causal association between diabetes and parity.

Changes in blood culture methodology have an impact on time trends of bacteraemia: a 26-year regional study.

The incidence of bacteraemia has increased considerably during the last decades. This may be related to population ageing, increased use of invasive procedures, and increased ascertainment of bacteraemia. Generalized additive and generalized linear models were used to analyse the impact of four successive improvements in blood culture methodology on the recovery of prevalent blood culture isolates while simultaneously controlling for underlying time trend and seasonal variation. Between 1981 and 2006, 20 091 bacteraemias comprising 22 800 blood culture isolates were diagnosed. The changes in methodology increased the recovery of some bacterial groups; the greatest impact was observed for Enterobacteriaceae, pneumococci and Staphylococcus aureus whereas recovery of ß-haemolytic streptococci, Pseudomonas aeruginosa, other Gram-negative aerobes, and fungi was not affected. Changes in blood culture methodology should be taken into account when assessing time trends of bacteraemia.

Maternal blood glucose in diabetic pregnancies and cognitive performance in offspring in young adulthood: a Danish cohort study.

AIMS: Maternal diabetes is a known risk factor for perinatal complications, but there are little data on consequences for long-term intellectual outcome in offspring. We assess cognitive performance in military conscripts according to maternal blood glucose levels during pregnancy. METHODS: We identified a cohort of 60 Danish male offspring of insulin-treated diabetic mothers born between 1976 and 1984 and followed this cohort to military conscription. From medical records, we extracted data on all available values of maternal blood glucose categorized as fasting and non-fasting and by day in pregnancy, together with maternal White class, smoking habits and socio-economic status. The main outcome was cognitive performance at conscription measured with a validated intelligence test. The association between maternal blood glucose level and cognitive performance was assessed by multivariate linear regression and a fitted fractional polynomial. RESULTS: Median fasting blood glucose values in the second half of pregnancy was negatively associated with cognitive scores at conscription [adjusted coefficient -1.7; 95% confidence interval (CI) -3.0; -0.4]. Restriction to only first-born sibling slightly strengthened the association (coefficient -1.9; 95% CI -3.3; -0.5), but after exclusion of two pregnancies with the blood glucose > 10 mmol/l the association became insignificant (coefficient -0.6; 95% CI -2.6; 1.4). CONCLUSIONS: Maternal blood glucose level during diabetic pregnancy is negatively associated with cognitive performance in offspring at military conscription. In pregnancies with fasting blood glucose levels below 10 mmol/l, the association is weak and considered to be without clinical relevance.

Fatty acid composition of the internal mammary artery in relation to dietary intake of marine n-3 polyunsaturated fatty acids and association with flow-mediated vasodilation.

Some evidence suggests that long-chain marine n-3 polyunsaturated fatty acids (n-3 PUFA) may increase production of vasodilatory nitric oxide from vascular endothelium. Fatty acids may therefore play a role for the left internal mammary artery (LIMA) graft function in coronary artery bypass grafting (CABG). However, little is known about the composition of fatty acids in the vessel wall of the LIMA. Using gas chromatography we investigated fatty acid composition in segments of the LIMA, in plasma nonesterified fatty acids (NEFA), in plasma phospholipid (PL) and in the pericardial adipose tissue (PAT) from 22 patients undergoing CABG. Furthermore, we investigated whether there was an association between the n-3 PUFA composition in LIMA and flow-mediated vasodilation (FMD). Self-reported fish consumption and supplementation of eicosapentaenoic acid and docosahexaenoic acids were reflected by the fatty acid composition in NEFA, PL and in PAT, but less so in the LIMA. There was no association between FMD and fatty acid composition of the LIMA.

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.

Sensation and distribution of stress and deformation in the human oesophagus.

Evaluation of the distribution of stresses and strains in relation to distension-induced sensation in the human oesophagus is valuable for understanding oesophageal biomechanics and mechano-sensation. In 12 healthy volunteers a specially designed oesophageal bag containing an endoscopic ultrasound probe was inflated to the moderate pain level. Ultrasound images, bag pressure and perceived sensation were recorded before and after pharmacological relaxation of the smooth muscle with butylscopolamine. The oesophagus was assumed to be circular and thick-walled. Distension induced a tensile circumferential stretch, radial compression and longitudinal shortening. Both circumferential strain and stress were highest at the mucosal surface and decreased throughout the wall. The stiffness increased throughout the wall and was highest at the outer surface (P < 0.001). The decrease in stiffness in response to butylscopolamine was non-significant. The infused volume (P = 0.012) and circumferential stress (P < 0.001) were most closely associated with the distension-induced sensation (adjusted R2 = 0.88). The perceived sensation was highly individual but was unaffected by butylscopolamine (P > 0.08). The present study provides a method for computation of the stress-strain distribution throughout the wall and the mechano-sensory interaction in the human oesophagus. In the future, this may be useful for understanding of mechanoreceptor responses and generation of symptoms in visceral organs in health and in disease.

The North Jutland County Diabetic Retinopathy Study: population characteristics.

BACKGROUND: Several population-based studies have reported blood glucose levels and blood pressure to be risk factors for the development of diabetic retinopathy. These studies were initiated more than two decades ago and may therefore reflect the treatment and population composition of a previous era, suggesting new studies of the present population with diabetes. AIM AND METHODS: This cross-section study included 656 people with type 1 diabetes and 328 with type 2 diabetes. Crude prevalence rates of proliferative diabetic retinopathy, clinically significant macular oedema and several specific retinal lesions were assessed, together with their association to a simplified and internationally approved retinal grading. RESULTS: The point prevalence of proliferative retinopathy was found to be 0.8% and 0.3% for type 1 and type 2 diabetes. Equivalent prevalence rates of clinically significant macular oedema were 7.9% and 12.8%, respectively. The most frequently occurring retinal manifestations increased in number until retinopathy level 3, and then decreased. CONCLUSION: The point prevalence of proliferative retinopathy is lower than that found in previous studies, whereas it is increased for clinically significant macular oedema. These data suggest different risk factors for these clinical entities.

An evaluation of clinical estimation of fetal weight and symphysis fundal distance for detection of SGA infants.

In 58 small for gestational age (SGA) infants and 141 non-SGA infants, the measuring of symphysis fundal distance (SF) was compared with clinical estimation of fetal weight in order to evaluate the efficacy of the two methods of predicting SGA. By regression analyses, the SF curve deviation explains 22% of the variation of birthweight. The estimated fetal weight (EFW) curve deviation explains 40%. By combining the two values, 42% of the variation in birthweight is explained. When receiver operating characteristic (ROC) curve analyses, Kappa index and relative risk were applied the clinical estimation of fetal weight by abdominal palpation was found to be as reliable a predictor of SGA at birth as the measurement of the SF distance. Statistical analyses of the SF curve and EFW curve do not improve the results compared with the last measurement of SF distance and EFW. Combination of the EFW and SF measurements results in a higher sensitivity (one test positive) or a higher predictive value (both tests positive). Only marginal additional diagnostic information was achieved, however, as the ROC curves, Kappa index and Relative risk were nearly unchanged, regardless of combination of EFW and SF measurements.

[Infants with colic. A heterogenous group possible to cure? Treatment by pediatric consultation followed by a study of the effect of zone therapy on incurable colic]. / Spaedbørn med skrigeture. En heterogen gruppe med mulig helbredelse? Behandling hos børnelaege med efterfølgende undersøgelse af zoneterapiens effekt på uhelbredelige skrigeture.

INTRODUCTION: The aim of the study was to investigate and treat infants with colic by conventional medicine followed by an investigation of the effect of reflexological treatment. MATERIAL AND METHODS: The investigation was prospective, followed by a randomised, single-blind, double-controlled, prospective study of reflexological treatment with an interview and diary. Sixty-three infants aged 1-3 months referred by general practitioners with crying for > 90 minutes a day were given a paediatric examination and intervention. The cause of crying was discovered in 33 infants: Vitamin D (5), elimination of cow's milk protein (3), and anal stenosis (3); counselling on feeding, sleep, reduction of stimulation, and avoidance of passive smoking (22). Thirty infants without the benefit of paediatric consultation were randomised to three groups for a duration of two weeks: A: Presumed non-effective reflexological treatment vs B: Presumed effective reflexological treatment vs C: No treatment--only observation. The most important parameter was the number of crying hours over 24 hours. Cure was defined as crying for less than or equal to 30 minutes. RESULTS: Examination by the paediatrician: Thirty-three of 63 infants benefited with a reduction in crying of less than 90 minutes and 13 of these infants were cured. The randomised study: In group C (control), none of the patients was cured. In groups A and B (presumed non-effective reflexological treatment and presumed effective treatment), half the patients were cured, which was significantly better than in group C. There was no significant difference between groups A and B, but B seemed better than group A. B was significantly better than C. DISCUSSION: Infantile colic had a significant cure rate at paediatric consultation and the children who did not benefit from this intervention had a significantly better outcome after reflexological treatment than had the observation group. Further investigations in reflexological treatment in infants are recommended.

No effect of high-dose atorvastatin on leukotriene B4 formation from neutrophils in patients treated with coronary bypass surgery: a randomized placebo-controlled double-blinded trial with a crossover design.

Inflammation plays a pivotal role in the pathophysiology of cardiovascular disease, (CVD) and leukotrienes may play a role in atherogenesis. Statins reduce mortality from CVD by reducing LDL cholesterol and potentially by other (pleiotropic) mechanisms. The aim of this study was to investigate if atorvastatin exerts an anti-inflammatory effect by reducing leukotriene B4 (LTB4) formation from stimulated neutrophils in patients treated with coronary artery bypass grafting. The study was a randomized, placebo-controlled, double-blinded crossover study. Patients (n=80) were allocated to 80 mg atorvastatin or placebo for 6 weeks before crossing over to the opposite treatment for another 6 weeks. There was no significant correlation between baseline LDL cholesterol levels on formation of LTB4, and atorvastatin had no effect on LTB4 formation. Hence, this study does not support any effect of atorvastatin on LTB4 formation as part of the explanation for its beneficial effect on CVD.

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.

Blood reinfusion combined with femoral nerve block in total knee replacement for patients with increased risk of bleeding.

PURPOSE: To compare patients with increased risk of bleeding who received combined blood reinfusion and femoral nerve block in total knee replacement (TKR) to regular patients treated routinely with respect to pain relief, blood loss, and knee function. METHODS: In a consecutive series of 67 patients who underwent unilateral TKR, 12 patients with increased risk of bleeding owing to cardiac disease or previous thromboembolic events received continuous femoral nerve block and blood reinfusion, without tranexamic acid (TA) injection. The remaining 55 patients were controls who received standard postoperative treatment (TA injection, local injection of analgesics, and suction drainage without reinfusion). The volume of blood loss (drained or reinfused), pain score (using a visual analogue scale) and knee function (using the Knee Society Score [KSS]) in the 2 groups were compared. RESULTS: In the study group, patients were 5 years older and tended to have a lower preoperative KSS function score (35 vs. 45, p=0.08) and a higher function-related pain score (6.5 vs. 6, p=0.10). The mean volume of drained blood wasted in the study group did not differ significantly from the mean total volume of drained blood in the control group (235 vs. 300 ml, p=0.14). Similarly, the mean decrease in postoperative haemoglobin concentration did not differ significantly between the respective groups (2.1 vs. 2.1 mmol/l, p=0.97). A significantly greater proportion of patients received allogenic blood transfusion in the study group than in controls (3/12 vs. 2/55, p<0.01). The study group exhibited significantly higher pain scores during training (1.7 vs. 1.4, p=0.03) and lower escape oxycodone consumption (5 vs. 15 mg/kg, p=0.06) on postoperative day 1 (but not other days). The duration of hospitalisation was also longer (5.5 vs. 4 days, p=0.04). CONCLUSION: In TKR patients with increased risk of bleeding, blood reinfusion combined with femoral nerve block is safe and comparable to standard methods of pain control (local injection of analgesics).

Baseline C-reactive protein level as a predictor of mortality in bacteraemia patients: a population-based cohort study.

We examined the association between C-reactive protein (CRP) level at time of blood culture (BC) draw and mortality following bacteraemia. Our population-based cohort study comprised all first-time monomicrobial bacteraemia episodes in adults in a Danish county during 1996-2004 (n = 5267). CRP was measured within 24 h of the first positive BC draw. Cox regression was used to compute mortality rate ratios (MRRs) associated with CRP level quartiles (10-64 (reference), 65-143, 144-240 and 241-688 mg/L), controlling for age, gender, comorbidity, specialty, acquisition of infection, and infection focus. We also looked for a biological interaction between CRP level and high magnitude of bacteraemia (three of three culture bottles positive). Thirty-day mortality increased with higher CRP level: adjusted 0-30-day MRRs for patients in the second, third and fourth CRP quartiles were 1.38 (95% CI 1.13-1.69), 1.70 (95% CI 1.40-2.06), and 2.38 (95% CI 1.96-2.87), respectively (p for trend <10(-4)). In contrast, mortality associations with CRP during 31-365 days of follow-up were weak (adjusted MRRs for the second to fourth quartiles ranged from 1.18 to 1.28). A high magnitude of bacteraemia strengthened the association between high CRP level and 30-day mortality. We conclude that the CRP level, measured concurrently with the first positive BC, independently predicted 30-day mortality in adult bacteraemia 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.

The North Jutland County Diabetic Retinopathy Study (NCDRS) 2. Non-ophthalmic parameters and clinically significant macular oedema.

BACKGROUND: The influence of non-ophthalmic parameters on the prevalence of clinically significant macular oedema has not been unambiguously established. The present study was initiated with the aim of clarification. METHODS: This cross-sectional study comprised 656 type 1 and 328 type 2 diabetic subjects undergoing retinopathy screening in the county of North Jutland. The association between the presence of clinically significant macular oedema and blood pressure, HbA1c, BMI, age, onset of diabetes, duration of diabetes, blood-pressure-reducing medication, lipid-lowering medication, neuropathy and urinary albumin excretion was explored using multiple logistic regression analysis. RESULTS: We found no significant association between the presence of clinically significant macular oedema and any of the examined parameters in type 1 diabetic subjects. In type 2 diabetic subjects, the duration of diabetes, HbA1c, neuropathy and increased urinary albumin excretion was significantly associated with the presence of clinically significant macular oedema. CONCLUSIONS: The risk factors for clinically significant macular oedema differ in type 1 and type 2 diabetic subjects and can account only in part for this manifestation.

High preoperative prevalence of deep venous thrombosis in patients with colorectal cancer.

BACKGROUND: Deep venous thrombosis (DVT) is a major complication of cancer and a predictor of reduced survival. The postoperative prevalence of DVT in colorectal cancer surgery is high, but the preoperative prevalence is unknown. The aim of this observational study was to estimate the preoperative prevalence of DVT in patients with colorectal cancer. METHODS: Some 193 consecutive patients with newly diagnosed colorectal cancer admitted for intended curative surgery were examined with compression ultrasonography for DVT before surgery. RESULTS: DVT was detected in 15 (7.8 per cent) of the 193 patients, with a prevalence of 16 per cent in women (12 of 76) versus 2.6 per cent in men (three of 117 (adjusted odds ratio (OR) 5.8 (95 per cent confidence interval (c.i.) 1.4 to 23.2)). The risk of DVT was strongly correlated with increasing American Society of Anesthesiologists (ASA) risk score: adjusted OR 6.8 (95 per cent c.i. 1.6 to 28.7 for ASA group III or IV versus ASA group I or II). Pulmonary embolism was detected in two patients (1.0 per cent). CONCLUSION: A high preoperative prevalence of DVT was observed in patients with colorectal cancer, especially among women and patients in ASA groups III and IV.

A multivariate growth curve model for pregnancy.

A model is proposed for consecutive multivariate observations of pregnancy-related quantities for a particular mother assuming proportionally with an underlying univariate growth process. Apart from the longitudinal aspect of the multivariate time series, the cross-sectional distribution of growth curves is also discussed. The model is examined as regards problems of estimation and model checking, and the results are applied to data consisting of bivariate time series of symphyseal fundal distances and fetal weight estimates from 91 mothers. We find some evidence in the data on departures from the model.

A longitudinal study of emergency room visits and air pollution for Prince George, British Columbia.

A new method for regression analysis of longitudinal counts is applied to data from Prince George, British Columbia, previously analysed by Knight et al. The data consist of daily recordings of the number of emergency room visits for each of four categories of respiratory diseases, along with measurements of meteorological variables and air pollution. We use a state-space model assuming conditionally independent Poisson counts for the four categories given a latent morbidity process, the latent process being a gamma Markov process. The main objective of the investigation was to examine the relationship between air pollution and respiratory morbidity, taking into account seasonality and meteorological conditions. We found that total reduced sulphur significantly influences the expected number of emergency room visits for the four disease categories, in agreement with the conclusion by Knight et al. However, our final model is simpler than theirs; in particular we found no evidence of seasonal variation beyond that explained by the meteorological variables.