Visual access trumps gender in 3- and 4-year-old children's endorsement of testimony.

Several studies have investigated how preschoolers weigh social cues against epistemic cues when taking testimony into account. For instance, one study showed that 4- and 5-year-olds preferred to endorse the testimony of an informant who had the same gender as the children; by contrast, when the gender cue conflicted with an epistemic cue--past reliability--the latter trumped the former. None of the previous studies, however, has shown that 3-year-olds can prioritize an epistemic cue over a social cue. In Experiment 1, we offer the first demonstration that 3-year-olds favor testimony from a same-gender informant in the absence of other cues. In Experiments 2 and 3, an epistemic cue-visual access--was introduced. In those experiments, 3- and 4-year-olds endorsed the testimony of the informant with visual access regardless of whether it was a same-gender informant (Experiment 3) or a different-gender informant (Experiment 2). These results demonstrate that 3-year-olds are able to give more weight to an epistemic cue than to a social cue when evaluating testimony.

Children weigh the number of informants and perceptual uncertainty when identifying objects.

The aim of this study was to evaluate how 3- to 5-year-old children (N = 150) identify an object when they are confronted with conflicting evidence, notably when the available perceptual evidence is contradicted by the testimony of either a lone informant or a three-informant consensus. Results showed that (a) 5-year-olds were more likely than 3- or 4-year-olds to rely on the perceptual evidence, ignoring claims made by the informants; (b) the three-informant consensus had more impact than a single informant for all age groups; and (c) children were more likely to make a perception-based response if the stimulus was perceptually unambiguous rather than equivocal with respect to its identity. Moreover, when children's task was to identify equivocal stimuli, they endorsed the three-informant consensus more than the lone informant. In contrast, when they needed to identify unambiguous stimuli, the number of informants did not influence children's responses. Taken together, the results show that the tendency to resist testimony on the basis of perceptual evidence increases with age. Moreover, preschoolers monitor both the characteristics of their informants and the relative ambiguity of the perceptual stimuli when they need to weigh verbal testimony against perceptual evidence.

A combined index of cardiac biomarkers as a risk factor for early cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiac biomarkers, including cardiac troponin-I (cTn-I) and N-terminal pro brain natriuretic peptide (NT-proBNP) have been associated with poor outcome in hemodialysis (HD) patients. The present study was designed to evaluate these biomarkers as biological risk factors for early and late mortality in HD patients. In addition, a multimarker approach including inflammatory index was performed in order to improve the cardiovascular risk assessment of these patients. METHODS: cTnI, NT-proBNP and C-reactive protein (CRP) were measured at baseline (October through November 2002) in 130 HD patients [median age 69.0 (23.4-87.7) years old, 76 females, 54 males]. Patients were followed during 8 years. Adjusted hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: During the follow-up, 82 patients died, mainly from cardiac cause (63.4%). Elevated cTnI, NT-proBNP or CRP were all associated with increased early (death within 2 years of follow-up) but not late mortality. Moreover, the combination of all parameters (CRP ≥10.51 mg/L and cTnI ≥0.037 µg/L and NT-proBNP ≥10,204 pg/mL) dramatically increased the short-term mortality especially the cardiovascular mortality (HR 8.58, 95% CI 1.59-46.2; p=0.0007). CONCLUSIONS: A combined index of cardiovascular risk factors could provide supplementary risk stratification in HD patients for early cardiovascular mortality, strongly supporting the annual routine determination of these biomarkers.

Fine-tuning of the prediction of mortality in hemodialysis patients by use of cytokine proteomic determination.

BACKGROUND AND OBJECTIVES: Inflammation-induced atherosclerosis and enhanced susceptibility to infection are linked to immune dysfunction and account for an important part of mortality in hemodialysis patients. This 4-yr prospective study aimed to use cytokine proteomic determination for predicting cardiovascular and noncardiovascular mortality in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Levels of 12 cytokines were measured using a proteomic biochip system in 134 patients who were on stable hemodialysis and compared with a control group of 150 healthy volunteers. Cox proportional hazards regression analysis was used to determine the relationship between cytokine and clinical outcome. RESULTS: A proinflammatory state characterized by decreased anti-/proinflammatory cytokine ratio was evidenced in hemodialysis patients compared with control subjects. After adjustment for age, gender, smoking, and high-sensitivity C-reactive protein levels, IL-6 and (IL-4+IL-10)/IL-6 ratio were associated with a significant and specific enhanced hazard ratio of cardiovascular mortality (hazard ratio 11.32 [95% confidence interval 2.52 to 50.90; P < 0.01] and hazard ratio 3.14 [95% confidence interval 1.20 to 8.22; P < 0.05], respectively, when comparing the third and first tertiles). It is interesting that (IL-4+IL-6+IL-10)/(IL-2+IFN-gamma) ratio, used as a marker of lymphocytes T helper subsets cytokine secretion, was associated only with noncardiovascular mortality (hazard ratio 4.93; 95% confidence interval 1.03 to 23.65; P < 0.05). CONCLUSION: Beyond the strong prediction of cardiovascular mortality by IL-6, determination of cytokine ratios can be useful to identify hemodialysis patients with increased noncardiovascular mortality risk.

Creatinine index and transthyretin as additive predictors of mortality in haemodialysis patients.

BACKGROUND: Malnutrition and inflammation are recognized as important predictors of poor clinical outcome in haemodialysis (HD). This study was designed to estimate the relative contribution of known biological markers of inflammation, malnutrition and muscle mass in the prognosis of HD patients. METHODS: A total of 187 HD patients (100 women, 87 men, median age 66.7 years [22.3-93.5]) were followed-up yearly for 5 years. At baseline, pre-dialysis values of C-reactive protein (CRP), albumin, transthyretin, total HDL- and LDL-cholesterol and triacylglycerol were determined. Estimation of creatinine index (CI) as muscle mass marker was determined by creatinine kinetic modelling using pre- and post-dialysis creatinine values. RESULTS: During the follow-up period, 89 deaths (53 from cardiovascular causes) were observed. After adjustment for age, gender, dialysis vintage, smoking, diabetes mellitus and hypertension, the highest tertile of CRP and lowest tertile of transthyretin and CI were significantly associated with all-cause mortality (relative risk (RR)=1.98 [1.12-3.47], 2.58 [1.48-4.50], 2.71 [1.42-5.19], respectively). In addition, low CI had an additive value to low levels of transthyretin. In contrast, high cholesterol (RR=0.47 [0.27-0.83], P=0.0091) and vitamin E concentrations (RR=0.46 [0.26-0.80], P= 0.006) showed a protective trend for all-cause mortality. In the multivariate analysis, transthyretin appeared as the most predictive biological marker of non-CV mortality (RR=3.78 [1.30-10.96], P=0.014), and CI of CV mortality (RR=2.61 [1.06-6.46], P=0.038), respectively. Discussion. These results confirm that uraemic malnutrition constitutes an important risk factor for mortality in HD. Beyond transthyretin, CI seems to be an additional marker routinely available and monthly determined in HD patients.

Heparin plasma sampling as an alternative to EDTA for BNP determination on the Access-Beckman Coulter--effect of storage at -20 degrees C.

To determine BNP, EDTA plasma is the only suitable specimen recommended by the manufacturer. Since many laboratories, especially in Europe, use heparin plasma rather than EDTA plasma for many or most of their clinical assays and in particular for determination of cardiac markers (cTnI, myoglobin), it appeared critical to evaluate the use of heparin plasma samples, in comparison to EDTA plasma, for BNP determination on a automated immunochemiluminescent analyzer. The aim of this study was first, to evaluate the use of heparin plasma samples for Biosite BNP testing on the Beckman Coulter Access Immunoassay System (n=88) and second, to evaluate the effect of storage at -20 degrees C, without protease inhibitors, on the Biosite BNP assay. We obtained acceptable imprecision results with CVs ranging from 1.7 to 11.7% regardless of the anticoagulant used. The linearity of EDTA samples was good and comparable to the results observed with heparin plasma. The concentration of BNP was categorized according to the classification of the New York Heart Association (NYHA). With EDTA fresh samples as reference anticoagulant, 90% vs. 89% of subjects were classified as "concordant" with heparin fresh vs heparin frozen plasma samples, respectively. After storage at -20 degrees C, only 86% of the values of EDTA frozen were concordant with values of EDTA fresh. No subject varied by two NYHA classes. Heparin plasma is an attractive alternative to the established EDTA samples which can be used for BNP determination. This flexibility allows the simultaneous determination of CK, CK-MB, cTnI and BNP on a single heparin specimen, which facilitates blood collection for clinicians and nursing staff in an emergency unit. In addition, our results suggest that BNP could be stored at -20 degrees C for at least one month in order to perform retrospective studies.

Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination.

BACKGROUND: Controversial results on hyperhomocysteinemia and cardiovascular risk in hemodialysis (HD) could be due in part to the methodology used for homocysteine (Hcy) determination. OBJECTIVE: The aim of this study was to compare the influence of the method used for Hcy determination (chromatography or immunoassay) with regard to the association of Hcy with cardiovascular mortality rate in HD patients in a 3-year prospective study. METHODS: A total of 162 patients undergoing HD were included in a cohort study. Baseline Hcy levels were measured by HPLC and fluorescence polarization immunoassay (FPIA). Cysteine and cysteinylglycine were determined simultaneously with Hcy measurement by HPLC. RESULTS: Hcy levels obtained with both methods were highly correlated (r(2)=0.927, p<0.0001). An increased relative risk (RR) for cardiovascular mortality (n=31) was found between the highest against lowest tertile of Hcy for both HPLC (RR 2.74, 95% CI 1.07-7.02; p<0.05) and FPIA (RR 2.76, 95% CI 0.99-7.70; p=0.05). Interestingly, increased cysteine (> or =452 micromol/L) and cysteinylglycine (> or =36.6 micromol/L) levels were associated with a decreased RR of non-cardiovascular death (n=26) (RR 0.27, 95% CI 0.09-0.79; p=0.02) for cysteine and (RR 0.28, 95% CI 0.09-0.90; p=0.03) for cysteinylglycine when compared to the first tertile. CONCLUSIONS: This study demonstrated an increased risk of cardiovascular mortality in HD patients with Hcy values in the third tertile, independent of the method used. HPLC offers the advantage of simultaneous determination of other aminothiols that appear to be associated with non-cardiovascular mortality.

Is tenofovir involved in hypophosphatemia and decrease of tubular phosphate reabsorption in HIV-positive adults?

OBJECTIVES: Tubulopathy with hypophosphatemia have been observed in HIV-positive patients receiving a tenofovir-containing regimen. However, the real incidence and prevalence of hypophosphatemia and their relation to tubular reabsorption disorders in tenofovir-treated patients remain uncertain. The aim of our study was to explore the effect of tenofovir on phosphatemia and on tubular phosphate reabsorption. METHODS: In a first transversal study, 145 HIV-positive adults (44+/-9 years) receiving tenofovir 300 mg daily with a mean exposure of 11+/-9 months were included. In a second prospective study, 29 HIV-positive antiretroviral experienced adults (44+/-10 years) were evaluated before introduction of tenofovir 300 mg daily (M0) and at 3 months (M3) and 6 months (M6), thereafter. Phosphate, creatinine, glucose and protein levels were determined in plasma and urine. The ratio of maximal reabsorption capacity (TmPO4)/glomerular filtration rate (GFR) was determined by using the normogramm of Walton and Bijvoet. RESULTS: In the transversal study, 26% of patients had hypophosphatemia (<0.84 mmol/l) while 47% of patients had a decreased TmPO4/GFR (<0.8 mmol/l). In the prospective study, baseline prevalence of hypophosphatemia (<0.84 mmol/l) and decreased TmPO4/GFR (<0.8mmol/l) was 31 and 41%, respectively. Three and 6 months after starting tenofovir, there is no significant change in mean phosphate levels (M0:0.91 mmol/l, M3:0.97 mmol/l, M6:0.98 mmol/l) and mean TmPO4/GFR (M0:0.80 mmol/l, M3:0.88 mmol/l, M6:0.84 mmol/l). Moreover, prevalence of hypophosphatemia (M3:28%, M6:28%) and decreased TmPO4/GFR (M3:41%, M6:45%) remained stable. CONCLUSION: Hypophosphatemia linked to a decreased proximal tubular reabsorption was frequently observed in HIV-positive adults independently of the use of tenofovir. In this preliminary study, no worsening effect on phosphatemia and tubular phosphate reabsorption was observed 6 months after introduction of tenofovir in treatment experienced patients.

Plasma osteoprotegerin is associated with mortality in hemodialysis patients.

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with Kaplan-Meier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium x phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006) and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels of sRANKL were associated with a protective effect for all-cause mortality (RR 0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor outcome. These results show that regulating-bone molecules, especially OPG, are strong predictors of mortality in HD patients, suggesting that OPG is a vascular risk factor, in particular in patients who have high C-reactive protein levels. OPG determination therefore should be added to the biologic follow-up of these patients.

Association between novel indices of malnutrition-inflammation complex syndrome and cardiovascular disease in hemodialysis patients.

BACKGROUND: Inflammation and malnutrition are recognized as important risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients. Owing to substantial short-term variability of serum C-reactive protein (CRP), more reliable markers of malnutrition-inflammation complex syndrome should be sought with stronger associations with the risk of CVD in HD patients. We therefore explored the clinical relevance of a composite inflammatory index (prognostic inflammatory and nutritional index [PINI]) and of muscle protein mass indicators, derived from creatinine kinetics. METHODS: This cross-sectional study included 177 HD patients (89 women and 88 men; median age, 67.73 years). CVD and risk factors were assessed using medical charts, clinical examination, and biochemical measurements performed at inclusion. Lean body mass (LBM) was derived from creatinine kinetic modeling, whereas PINI was calculated as the ratio (CRP xalpha1-acid-glycoprotein)/(albumin x transthyretin). Patients were divided according to the presence or absence of established CVD. RESULTS: The traditional risk factors diabetes (odds ratio [OR], 5.83; p = 0.0045) and smoking (OR, 3.50; p < 0.02) were associated with an increase in prevalent CVD. Low transthyretin (OR, 3.79; p < 0.02) and high levels of CRP (OR, 2.70; p < 0.05), PINI (OR, 3.44; p < 0.02), observed LBM (OR, 3.01; p < 0.05), and the ratio of observed/expected LBM (OR, 4.24; p < 0.01) were associated with CVD after adjustment for age, sex, dialysis center, and dialysis vintage. After additional adjustment for diabetes and smoking, only PINI (OR, 2.85; p = 0.0446) and observed/expected LBM (OR, 2.96; p = 0.0361) were still significant. CONCLUSION: PINI and LBM are associated with increased relative risk for having CVD and could be used routinely to examine the degree of severity of malnutrition inflammation complex syndrome.

Measurement of circulating troponin Ic enhances the prognostic value of C-reactive protein in haemodialysis patients.

BACKGROUND: Cardiac Troponin I (cTnI) levels are considered an important diagnostic tool in acute coronary events. They could be of predictive value in haemodialysis (HD) patients. However, the relationship between cTnI and the HD-induced inflammatory state remains unclear. The aim of this study was to explore the prognostic relevance to all-cause and cardiovascular mortalities in HD patients of cTnI, in combination with highly sensitive C-reactive protein (hs-CRP) levels. METHODS: We measured cTnI and hs-CRP at baseline (March 10 to November 16, 2001) in 191 HD patients without clinical signs of acute coronary artery disease [median age 66.7 years (range 22.3-93.5), 94 females, 97 males]. We used a cTnI concentration with a total imprecision of 10% (0.03 microg/l), determined in the laboratory, as the analytical threshold value. Patients were followed for mortality until 1 January, 2003 (median follow-up 418 days). The adjusted relative risks (RRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: A significant proportion (25.1%) of patients had elevated CTnl, > or =0.03 microg/l; 40.3% of patients had CRP concentrations > or =10 mg/l. During follow-up, 29 patients died, 44.8% due to cardiac causes. Elevated cTnI or CRP levels were associated with increased mortality [RR adjusted for age, sex and duration of dialysis 4.2 (1.9-9.0) for cTnI > or =0.03 microg/l and 3.6 (1.6-8.1) for CRP > or =10 mg/l], cTnI being particularly predictive of cardiovascular death. Moreover, the combination of elevated hs-CRP (> or =10 mg/l) and circulating cTnI (> or =0.03 microg/l) dramatically impaired the HD survival rate [adjusted RR for all-cause mortality 16.9 (4.5-63.8)]. CONCLUSION: Circulating cTnI was associated with poor prognosis, especially when combined with elevated CRP, strongly supporting the adoption of regular cTnI testing in HD patients.