Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: A propensity score matched analysis from the AHEAD registry.

BACKGROUND: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. METHODS: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 µmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers. RESULTS: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group). CONCLUSION: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.

Worse prognosis of real-world patients with acute heart failure from the Czech AHEAD registry in comparison to patients from the RELAX-AHF trial.

AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial. METHODS AND RESULTS: A total of 5856 patients from the AHEAD registry (Czech registry of AHF) were divided into two groups according to RELAX-AHF criteria: relax-comparable (n = 1361) and relax-non-comparable (n = 4495). As compared with the relax-non-comparable group, patients in the relax-comparable group were older, had higher levels of systolic and diastolic blood pressure, lower creatinine clearance, and a higher number of comorbidities. Relax-comparable patients also had significantly lower short-term as well as long-term mortality rates in comparison to relax-non-comparable patients, but a significantly higher mortality rate in comparison to the placebo group of patients from the RELAX-AHF trial. Using AHEAD score, we have identified higher-risk patients from relax-comparable group who might potentially benefit from new therapeutic approaches in the future. CONCLUSIONS: Only about one in five of all evaluated patients met criteria for the potential treatment with the new vasodilator serelaxin. AHF patients from the real clinical practice had a higher mortality when compared with patients from the randomized clinical trial.

AHEAD score--Long-term risk classification in acute heart failure.

BACKGROUND: The role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A--atrial fibrillation, H--haemoglobin<130 g/l for men and 120 g/l for women (anaemia), E--elderly (age>70years), A--abnormal renal parameters (creatinine>130 µmol/l), D--diabetes mellitus) scoring system. METHODS: AHEAD--multicentre prospective Czech registry of AHF patients; GREAT registry--international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315). RESULTS: Main outcome was one year all-cause mortality. The mean age of patients was 72±12 years, with 61.6% of patients aged >70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine>130 mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001). CONCLUSION: The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.

Positive influence of being overweight/obese on long term survival in patients hospitalised due to acute heart failure.

BACKGROUND: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the "obesity paradox" on a large cohort with long-term follow-up are lacking. METHODS: Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5-25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. RESULTS: In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26-1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09-1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11-1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. CONCLUSION: These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Prevalence and clinical significance of liver function abnormalities in patients with acute heart failure.

AIMS: Liver pathology caused by cardiac dysfunction is relatively well recognized, however, its clinical importance has not been fully evaluated. The aim of this study was to assess the prevalence of liver function tests (LFTs) abnormalities and to identify associated factors mediating hepatic impairment in patients with acute heart failure (AHF). METHODS: The AHEAD (Acute Heart Failure Database) registry is a database conducted in 9 university hospitals and 5 regional health care facilities in the Czech Republic. From December 2004 to October 2012, the data of 8818 patients were included. The inclusion criteria for the database followed the European guidelines for AHF. Serum activities of all LFTs and total bilirubin were available in 1473 patients at the baseline. RESULTS: In patients with AHF, abnormal LFTs were seen in 76% patients (total bilirubin in 34%, γ-glutamyltransferase in 44%, alkaline phosphatase in 20%, aspartate aminotransferase in 42%, alanine aminotransferase in 35%). Patients with cardiogenic shock were more likely to have LFTs abnormalities compared to mild AHF and pulmonary oedema. LFTs abnormalities were strongly associated with AHF severity (left ventricular ejection fraction and NYHA functional class) and clinical manifestation. While hepatocellular LFTs pattern predominated in left sided forward AHF, cholestatic profile occurred mainly in bilateral and right sided AHF. Additionally, patients with moderate to severe tricuspid regurgitation had significantly higher prevalence of abnormalities in cholestatic LFTs. CONCLUSIONS: Defining the LFTs profile typical for AHF plays an important role in management of AHF patients, since it may avoid redundant hepatic investigations and diagnostic misinterpretations.

ECG in patients with acute heart failure can predict in-hospital and long-term mortality.

Initial risk stratification in patients with acute heart failure (AHF) is poorly validated. Previous studies tended to evaluate the prognostic significance of only one or two selected ECG parameters. The aim of this study was to evaluate the impact of multiple ECG parameters on mortality in AHF. The Acute Heart Failure Database (AHEAD) registry collected data from 4,153 patients admitted for AHF to seven hospitals with Catheter Laboratory facilities. Clinical variables, heart rate, duration of QRS, QT and QTC intervals, type of rhythm and ST-T segment changes on admission were collected in a web-based database. 12.7 % patients died during hospitalisation, the remainder were discharged and followed for a median of 16.2 months. The most important parameters were a prolonged QRS and a junctional rhythm, which independently predict both in-hospital mortality [QRS > 100 ms, odds ratio (OR) 1.329, 95 % CI 1.052-1.680; junctional rhythm, OR 3.715, 95 % CI 1.748-7.896] and long-term mortality (QRS > 120 ms, OR 1.428, 95 % CI 1.160-1.757; junctional rhythm, OR 2.629, 95 % CI 1.538-4.496). Increased hospitalisation mortality is predicted by ST segment elevation (OR 1.771, 95 % CI 1.383-2.269) and prolonged QTC interval >475 ms (OR 1.483, 95 % CI 1.016-2.164). Presence of atrial fibrillation and bundle branch block is associated with increased unadjusted long-term mortality, but mostly reflects more advanced heart disease, and their predictive significance is attenuated in the multivariate analysis. ECG in patients admitted for acute heart failure carries significant short- and long-term prognostic information, and should be carefully evaluated.

Risk of in-hospital mortality identified according to the typology of patients with acute heart failure: classification tree analysis on data from the Acute Heart Failure Database-Main registry.

PURPOSE: The purposes of this study are to identify the strongest clinical parameters in relation to in-hospital mortality, which are available in the earliest phase of the hospitalization of patients, and to create an easy tool for the early identification of patients at risk. MATERIALS AND METHODS: The classification and regression tree analysis was applied to data from the Acute Heart Failure Database-Main registry comprising patients admitted to specialized cardiology centers with all syndromes of acute heart failure. The classification model was built on derivation cohort (n = 2543) and evaluated on validation cohort (n = 1387). RESULTS: The classification tree stratifies patients according to the presence of cardiogenic shock (CS), the level of creatinine, and the systolic blood pressure (SBP) at admission into the 5 risk groups with in-hospital mortality ranging from 2.8% to 66.2%. Patients without CS and creatinine level of 155 µmol/L or less were classified into very-low-risk group; patients without CS, creatinine level greater than 155 µmol/L, and SBP greater than 103 mm Hg, into low-risk group, whereas patients without CS, creatinine level greater than 155 µmol/L, and SBP of 103 mm Hg or lower, into intermediate-risk group. The high-risk group patients had CS and creatinine of 140 µmol/L or less; patients with CS and creatinine level greater than 140 µmol/L belong to very-high-risk group. The area under receiver operating characteristic curve was 0.823 and 0.832, and the value of Brier's score was estimated on level 0.091 and 0.084, for the derivation and the validation cohort, respectively. CONCLUSIONS: The presented classification model effectively stratified patients with all syndromes of acute heart failure into in-hospital mortality risk groups and might be of advantage for clinical practice.

Long-term survival following acute heart failure: the Acute Heart Failure Database Main registry (AHEAD Main).

BACKGROUND: The in-hospital mortality of patients with acute heart failure (AHF) is reported to be 12.7% and mortality on day 30 after admission 17.2%. Less information is known about the long-term prognosis of those patients discharged after hospitalization. As such, the aim of this study was to investigate long-term survival in a cohort of patients who had been hospitalized for AHF and then discharged. METHODS: The AHEAD Main registry includes 4153 patients hospitalized for AHF in 7 different medical centers, each with its own cathlab, in the Czech Republic. Patient survival rates were evaluated in 3438 patients who had survived to day 30 after admission, and were used as a measurement of long-term survival. RESULTS: The most common etiologies were acute coronary syndrome (32.3%) and chronic ischemic heart disease (20.1%). The survival rate after day 30 following admission was 79.7% after 1 year and 64.5% after 3 years. No statistically significant difference in syndromes was found in survival after day 30. Independent predictors of a worse prognosis were defined as follows: age>70 years, comorbidities, severe left ventricular systolic dysfunction, valvular disease or ACS as an etiology of AHF. A better prognosis was defined for de-novo AHF patients, and those who were taking ACE inhibitors at the time of discharge. In a sub-analysis, high levels of natriuretic peptides were the most powerful predictors of high-risk, long-term mortality. CONCLUSION: The AHEAD Main registry provides up-to-date information on the long-term prognosis of patients hospitalized with AHF. The 3-year survival of patients following day 30 of admission was 64.5%. Higher age, LV dysfunction, comorbidities and high levels of natriuretic peptides were the most powerful predictors of worse prognosis in long-term survival.

Impact of antecedent hypertension on outcomes in patients hospitalized with severe forms of acute heart failure.

OBJECTIVE: Even though several studies described a positive influence of elevated initial blood pressure on the outcome in acute heart failure (AHF), data specifically addressed to a population with severe AHF associated with antecedent hypertension, regardless of admission blood pressure values, are missing. METHODS AND RESULTS: From the 4153 consecutive patients enrolled in the Czech AHF registry we selected 1343 patients who suffered from pulmonary oedema or cardiogenic shock and compared them according to the presence of antecedent hypertension. Demographic, clinical, laboratory, treatment profiles and mortality rates were assessed and predictors of short- and long-term outcome were identified. Patients with antecedent hypertension (n = 1053, 78%) were older (P < 0.001), more often women (P = 0.001), having more co-morbidities and a worse laboratory profile. A trend for worse survival of hypertensive patients was observed when compared to a non-hypertensive cohort (1-, 2-, 3-year survival 70.0, 61.5, 55.5% vs. 72.6, 68.2, 64.0%, P = 0.062). Age and creatinine levels were independently associated with mortality during the whole follow-up period (P < 0.001). Low left ventricular ejection fraction, need of mechanical ventilation, inotropic and vasopressor support, were adversely related to in-hospital mortality (P < 0.001). On the other hand, presence of initial tachycardia improved short-term outcome (P = 0.007). Long-term survival was worsened by initial atrial fibrillation (P = 0.036) and anaemia (P < 0.001) while the presence of de-novo AHF improved it (P = 0.009). CONCLUSIONS: Long-term antecedent hypertension is not significantly correlated with mortality after an episode of severe AHF, but probably still participates in vascular and end-organ damage. Survival of these patients is determined by other associated co-morbidities.

Gender differences in total cholesterol levels in patients with acute heart failure and its importance for short and long time prognosis.

AIM: The purpose of this study was to evaluate whether there are gender differences in total cholesterol levels in patients with acute heart failure and if there is an association of this parameter with short and long time mortality. METHODS: The AHEAD MAIN registry is a database conducted in 7 university hospitals, all with 24 h cath lab service, in 4 cities in the Czech Republic. The database included 4 153 patients hospitalised for acute heart failure in the period 2006-2009. 2 384 patients had a complete record of their total cholesterol levels. 946 females and 1437 males were included in this analysis. According to the admission total cholesterol levels, patients were divided into 5 groups: < 4.50 mmol/l (group A), 4.50-4.99 mmol/l (group B), 5.0-5.49 mmol/l (group C), 5.50-5.99 mmol/l (group D) and > 6.0 mmol/l (group E). The median total cholesterol levels were 4.24 in males and 4.60 in females (P<0.001). There were differences in the distribution of total cholesterol levels between men and women: group A 57.6 vs 45.0%, group B 13.8 vs 16.3%, group C 9.8 vs 12.5%, group D 7.7 vs 11.4%, group E 11.1 vs 14.8% respectively (all P<0.001). The median age of men was 68.7 vs 77.3 years in women (P<0.001). In all total cholesterol categories women were older than men: group A 77.7 vs 69.5 years, group B 78.6 vs 69.1 years, group C 77.3 vs 68.8 years, group D 76.8 vs 64.2 years, group E 75.6 vs 64.4 years (all P<0.001). For the calculation of long term mortality, the cohort was divided into three groups: total cholesterol levels below 4.50 mmol/l, 4.50-5.49 mmol/l and above 5.50 mmol/l. The log rank test was used for the analysis. RESULTS: There were no differences in hospital mortality between male and female in general (9.2 vs 10.8%, P<0.202), or in total cholesterol levels in subgroups. Total cholesterol levels were associated with in-hospital mortality (P<0.002). In the long-term follow up (78 months) patients with total cholesterol levels below 4.5 mmol/l had the worst prognosis (P<0.001). An independent influence of total cholesterol level on mortality and survival was confirmed in the multivariate model as well. CONCLUSIONS: Women with acute heart failure had higher total cholesterol levels than men in all ages. There was a higher percentage of women with total cholesterol levels above 6 mmol/l and lower percentage in the group below 4.5 mmol/l than in men. In all, total cholesterol categories women were older than men. Total cholesterol levels are important for in- hospital mortality and long term survival of patients admitted for acute heart failure.

Baseline characteristics and hospital mortality in the Acute Heart Failure Database (AHEAD) Main registry.

INTRODUCTION: The prognosis of patients hospitalized with acute heart failure (AHF) is poor and risk stratification may help clinicians guide care. The objectives of the Acute Heart Failure Database (AHEAD) registry are to assess patient characteristics, etiology, treatment and outcome of AHF. METHODS: The AHEAD main registry includes patients hospitalized for AHF in seven centers with a Catheterization Laboratory Service in the Czech Republic. The data were collected from September 2006 to October 2009. The inclusion criteria for the database adhere to the European guidelines for AHF (2005) and patients were systematically classified according to the basic syndromes, type and etiology of AHF. RESULTS: Of 4,153 patients, 12.7% died during hospitalization. The median length of hospitalization was 7.1 days. Mean age of patients was 71.5 ± 12.4 years; men were younger (68.6 ± 12.4 years) compared to women (75.5 ± 11.5 years) (P < 0.001). De-novo heart failure was seen in 58.3% of the patients. According to the classification of heart failure syndromes, acute decompensated heart failure (ADHF) was reported in 55.3%, hypertensive AHF in 4.4%, pulmonary edema in 18.4%, cardiogenic shock in 14.7%, high output failure in 3.3%, and right heart failure in 3.8%. The mortality of cardiogenic shock was 62.7%, of right AHF 16.7%, of pulmonary edema 7.1%, of high output HF 6.1%, whereas the mortality of hypertensive AHF or ADHF was < 2.5%. According to multivariate analyses, low systolic blood pressure, low cholesterol level, hyponatremia, hyperkalemia, the use of inotropic agents and norepinephrine were predictive parameters for in-hospital mortality in patients without cardiogenic shock. Severe left ventricular dysfunction and renal insufficiency were predictive parameters for mortality in patients with cardiogenic shock. Invasive ventilation and age over 70 years were the most important predictive factors for mortality in both genders with or without cardiogenic shock. CONCLUSIONS: The AHEAD Main registry provides up-to-date information on the etiology, treatment and hospital outcomes of patients hospitalized with AHF. The results highlight the highest risk patients.

Does previous hypertension affect outcome in acute heart failure?

BACKGROUND: The effect of previous long-term hypertension on mortality in acute heart failure (HF), regardless of blood pressure values, has not been well studied. METHODS: Acute Heart Failure Database (AHEAD) - Czech HF registry enrolled 4153 consecutive patients with acute HF. We excluded severe forms (cardiogenic shock, pulmonary oedema, right HF) and analysed 2421 patients with known presence or absence of previous hypertension. Demographic, clinical and laboratory profile, treatment and mortality rates were assessed and predictors of outcome were identified. RESULTS: Patients with previous hypertension (71.5%) were older, more of female gender, with worse pre-hospitalisation NYHA class, increased incidence of co-morbidities and higher left ventricular ejection fraction (LVEF). Although in-hospital mortality was similar in both cohorts (2.6%), survival at 1, 2 and 3-year was worse in the hypertensive group (75.6%, 65.9% and 58.7% vs. 80.7%, 74.2% and 69.8%; P<0.001). Nevertheless, hypertension was not associated with mortality in multivariate analysis and stronger predictors of outcome were identified (P<0.05): new-onset acute HF [hazard ratio (HR) 0.62] and increased body mass index (HR 0.68) proved to have a protective role. Advanced age (HR 1.86), diabetes (HR 1.45), lower LVEF (HR 1.28) and admission blood pressure (HR 1.54), elevated serum creatinine (HR 1.63), hyponatremia (HR 1.77) and anaemia (HR 1.40) were associated with worse survival. CONCLUSION: Antecedent hypertension is frequent in patients with acute HF and contributes to organ and vascular impairment. However its presence has no independent influence on short- and medium-term mortality, which is influenced by other related co-morbidities.

[Correlation of intracardiac pressures and electrical atrial potentials with morphology and function of overloaded atria assessed by echocardiography]. / Korelace intraatriálních elektrických potenciálu a tlaku s morfologickými a funkcními ukazateli pretízených síní stanovenými echokardiografií.

BACKGROUND: In patients with chronic complete heart block or single chamber pacing and preserved sinus depolarization, left and right atria (LA, RA) may suffer from increased intraatrial pressure resulting from atrioventricular dyssynchrony (AVDys), dilate and lose their contractile function. The purpose of the study was to find out whether any correlation exists between the echocardiographically measured LA, RA morphological and functional parameters on one hand and the intracardiac RA pressures and electrical potentials on the other hand in patients with chronic AVDys. METHODS: In 26 pts (77 +/- 10 years, 16 males), where a chronic AVDys was the most important patophysiological mechanism of atrial overloading, the intraatrial pressures (atrial, right ventricular, pulmonary arterial and wedge pressure/PWP/) and electrical potentials (upper, middle, lower part of RA and RA appendage) were correlated with atrial diameters, volumes, ejection fraction and filling parameters. RESULTS: There was a moderate inverse correlation between the LA ejection fraction and PWP: r = -0,489, p = 0,025 at a level of significance 0.05, but no relationship between PWP and LA size/volumes. No correlation between RA potentials or intracardiac pressures and RA morphologic or functional features were documented. CONCLUSIONS: In this study, an inverse correlation between the capillary wedge pressure and left atrial ejection fraction in pts with chronic atrioventricular dyssynchrony was documented. No other correlation between echocardiographic parameters and intracardiac pressures or electrical potentials was found.

Potential role of selected biomarkers for predicting the presence and extent of coronary artery disease.

INTRODUCTION: Since atherosclerosis may in part be an inflammatory disease, circulatory factors related to inflammation may be predictors of coronary artery disease. The aim of this study was to evaluate the association between the level of some circulating biomarkers and the extent of coronary artery disease. METHODS: Blood samples were taken from 128 patients with stable forms of coronary heart disease. Macrophage chemoattractant protein-1 (MCP-1), matrix-metalloproteinase-3 (MMP-3), soluble CD40 ligand (sCD40L) and soluble tumour necrosis factor receptor-2 (sTNFR2) were measured by ELISA. Coronary angiography and grading with the SYNTAX score followed. RESULTS: There was no significant interdependence of circulating MCP-1, sCD40L, sTNFR2 levels and SYNTAX score. MMP-3 levels were significantly different in subgroup with coronary artery disease (SYNTAX score > 0): 38.1 µg/l (13.6; 84.1) and subgroup without coronary artery disease (SYNTAX score = 0): 20.4 µg/l (13.1; 82.8), p=0.001. According to the Spearman correlation coefficient there was significant association between MMP-3 level and SYNTAX score (0.358, a=0.05). CONCLUSIONS: Our data suggest association between the extent of coronary artery disease and circulating MMP-3. We failed to demonstrate any association with the other investigated biomarkers.

Obesity, hypertension and insulin resistance in childhood--a pilot study.

BACKGROUND: Obesity and arterial hypertension are a serious risk factor for insulin resistance patients leading to diabetes and other disorders. Obesity is one of the most common nutritional problems in developed countries. Actually the incidence of obesity is increasing considerably, obesity is emerging in alarming rates between the last 10 years. Obesity and hypertension beginning in childhood often precedes the hyperinsulinemic state. The metabolic syndrome is rapidly increasing in prevalence with rising childhood obesity and sedentary lifestyles worldwide. The aim of this study was to compare average levels of the homeostatic indices HOMA and QUICKI in obese children compared to healthy and hypertonic children in order to find convenient markers for insulin sensitivity in clinical pediatric practice. METHODS: 49 obese children (11 girls, 38 boys), 42 children healthy (33 boys and 9 girls) and 37 hypertensive children (4 girls, 33 boys) were selected. RESULTS: The average level of HOMA in obese children was 4.58; in healthy children 1.8 and in the group of hypertonic children the level was 2.75. The average level of QUICKI in obese children was 0.22; in healthy children 0.29 and in hypertonic children 0.28. CONCLUSIONS: The results demonstrate the possibility of insulin sensitivity assessment using these indices in pediatric practice. QUICKI has a narrower confidence interval and thus a lower variability. QUICKI an HOMA indexes are useful predominantly for epidemiological purposes, mainly for maping the scope of insulinoresistance among children.

Biosafety, antioxidant status, and metabolites in urine after consumption of dried cranberry juice in healthy women: a pilot double-blind placebo-controlled trial.

This study assessed the effect of an 8 week consumption of dried cranberry juice (DCJ) on 65 healthy young women. Basic biochemical and hematological parameters, antioxidant status, presence of metabolites in urine, and urine ex vivo antiadherence activity were determined throughout the trial. A 400 mg amount of DCJ/day had no influence on any parameter tested. A 1200 mg amount of DCJ/day resulted in a statistically significant decrease in serum levels of advanced oxidation protein products. This specific protective effect against oxidative damage of proteins is described here for the first time. Urine samples had an inhibitory effect on the adhesion of uropathogenic Escherichia coli strains, but no increase in urine acidity was noted. Hippuric acid, isomers of salicyluric and dihydroxybenzoic acids, and quercetin glucuronide were identified as the main metabolites. In conclusion, cranberry fruits are effective not only in the prevention of urinary tract infection but also for the prevention of oxidative stress.

Web-based instruction and its impact on the learning activity of medical students: a review.

BACKGROUND: The aim of this review was to summarise the experience on implementation of information technology to support the teaching and learning process in medicine. Particular attention was paid to web-based tutorials, their impact on increasing the effectiveness of medical instruction and motivation of students towards self-directed learning. Most of the studies selected for the purpose of the review comprised evaluation of the web-tutorials in view of practical implementation, strengths, weaknesses, and main preferences in comparison with traditional lecture-based education. METHOD AND RESULTS: We searched MEDLINE via PubMed using MeSH term "computer-assisted learning" between 1996 and 2005 and selected for inclusion in this review were studies on the implementation and evaluation of web based tutorials in medical education. Additional related papers were obtained through cross-referencing. We found that overall, students prefer Web tutorials to traditional lecture-based classes for accessibility, ease of use, freedom of navigation, high medical image quality and advantage of repeated practice, that web-based learning has been continually developing and that it is a very important tool in Evidence Based Medicine. CONCLUSIONS: Web based education is an important tool in medical training. It will require transformation in the way medicine is taught from instructor based to self directed learning. It is above all seen as a device for information retrieval and storage.