Comparison of the analytical performance of the PATHFAST high sensitivity cardiac troponin I using fresh whole blood vs. fresh plasma samples.

OBJECTIVES: The PATHFAST hs-cTnI (high-sensitivity cardiac troponin) assay is the first point-of-care assay with a high-sensitivity designation that received FDA approval for diagnosis of myocardial infarction (MI). Testing from whole blood does not need centrifugation and therefore is faster and more convenient in the emergency room instead of plasma. However, there is sparse evidence whether point-of-care testing of Tn from whole blood is as reliable as from plasma samples. METHODS: We investigated the agreement between plasma and whole blood hs-cTnI by using the PATHFAST hs-cTnI assay. Hs-cTnT measured on Cobas 602 in the central laboratory and compared to a final diagnosis of NSTEMI using serial hs-cTnT served as reference. We assessed biases, limits of agreement (±1.96 SD) and coefficients of correlation, and tested the discriminatory ability of the baseline sample of plasma and whole blood hs-cTnI and plasma hs-cTnT to discriminate non-ST-segment elevation myocardial infarction (NSTEMI). RESULTS: A total of 224 paired fresh samples were collected simultaneously from 191 patients presenting with suspected acute coronary syndrome. There was an excellent correlation between plasma and whole blood hs-cTnI (r=0.99), and a very good inter-rater agreement (k=0.93) between elevated and normal plasma and whole blood results. Precision evaluation according to CLSI ep 15 revealed comparable coefficients of variation (CV) in whole blood and plasma. The discriminatory ability of baseline hs-cTnT, plasma and whole blood hs-cTnI was excellent (AUC 0.967, AUC 0.954 and AUC 0.953) without significant difference. CONCLUSIONS: Whole blood can be used interchangeably with plasma for more convenient and less time and labor-consuming testing of hs-cTnI on the PATHFAST instrument.

Diagnostic Evaluation of a High-Sensitivity Troponin I Point-of-Care Assay.

BACKGROUND: Increasing numbers of patients are presenting worldwide to emergency departments with suspected myocardial infarction. The use of point-of-care troponin assays might enable faster decision-making in this high-risk population and reduce the burden on emergency facilities. Here, we evaluate the diagnostic performance of a point-of-care high-sensitivity troponin I assay. METHODS: We conducted a prospective cohort study including patients presenting to the emergency department with suspected myocardial infarction from July 2013 to July 2016. A diagnostic algorithm for a high-sensitivity troponin I point-of-care assay was developed in a derivation data set with 669 patients and validated in an additional 610 patients. RESULTS: The derived 0/1 h algorithm for the point-of-care assay consisted of an admission troponin I <4 ng/L and a δ from 0 h to 1 h <3 ng/L for rule out and an admission troponin I ≥90 ng/L or a δ from 0 h to 1 h ≥20 ng/L for rule in of non-ST-elevation myocardial infarction. Application to the validation cohort showed a negative predictive value of 99.7% (95% CI, 98.1%-100.0%) and 48.0% of patients ruled out, whereas 14.6% were ruled in with a positive predictive value of 86.5% (95% CI, 77.6%-92.8%). The diagnostic performance of the point-of-care high-sensitivity assay was highly comparable to guideline-recommended use of a laboratory-based high-sensitivity troponin assay. CONCLUSIONS: The clinical application of a 0/1 h diagnostic algorithm based on a high-sensitivity troponin I point-of-care assay is safe, and diagnostic performance is comparable to a laboratory-based high-sensitivity troponin I assay.

Presepsin (sCD14-ST) Is a Novel Marker for Risk Stratification in Cardiac Surgery Patients.

BACKGROUND: Presepsin (soluble cluster-of-differentiation 14 subtype [sCD14-ST]) is a humoral risk stratification marker for systemic inflammatory response syndrome and sepsis. It remains unknown whether presepsin can be used to stratify risk in elective cardiac surgery. The authors therefore determined the usefulness of presepsin for risk stratification in patients having elective cardiac surgery. METHODS: Eight hundred fifty-six cardiac surgical patients were prospectively studied. Preoperative plasma concentrations of presepsin, procalcitonin, N-terminal pro-hormone natriuretic peptide, cystatin C, and the additive European System of Cardiac Operative Risk Evaluation 2 were compared to mortality at 30 days (primary outcome), 6 months, and 2 yr. Discrimination was assessed with C statistic. Logistic regression analysis was used to calculate univariable and multivariable odds ratios. RESULTS: Thirty-day mortality was 3.2%, 6-month mortality was 6.1%, and 2-yr mortality was 10.4% across the population. Median preoperative presepsin concentrations were significantly greater in 30-day nonsurvivors than in survivors: 842 pg/ml (interquartile range, 306 to 1,246) versus 160 pg/ml (interquartile range, 122 to 234); difference, 167 pg/ml (interquartile range, 92 to 301; P < 0.001). The results were similar for 6-month and 2-yr mortality. Compared to the European System of Cardiac Operative Risk Evaluation 2, presepsin concentration provided better discrimination for postoperative mortality at all follow-up periods, including 30 days (C statistic 0.88 vs. 0.74), 6 months (0.87 vs. 0.76), and 2 yr (0.81 vs. 0.74). Presepsin also provided better discrimination than cystatin C, N-terminal pro-hormone natriuretic peptide, or procalcitonin. Elevated presepsin remained an independent risk predictor after adjustment for potential confounding factors. CONCLUSIONS: Elevated preoperative plasma presepsin concentration is an independent predictor of postoperative mortality in elective cardiac surgery patients and is a stronger predictor than several other commonly used assessments.

Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest.

BACKGROUND: An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome. METHODS: Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score ≥ 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed. RESULTS: Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48 h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p < 0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p < 0.0001; AUC = 0.70 ± 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p < 0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p < 0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74 ± 0.04 (p < 0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076-2.399], p = 0.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834-1.596], p = 0.387). CONCLUSIONS: Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.

Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial.

INTRODUCTION: Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT). METHODS: This is a retrospective, case-control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment. RESULTS: Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 µg/L (median 3.4 to 45.2) and 10.8 µg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65). CONCLUSIONS: In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.

Performance of the AQT90 FLEX cTnI point-of-care assay for the rapid diagnosis of acute myocardial infarction in the emergency room.

BACKGROUND: International guidelines stipulate that primarily cardiac troponin (cTn) assays with a coefficient of variation (CV) < or = 10% at the 99th percentile cutoff should be used for diagnosing myocardial infarction. Point-of-care (POC) assays usually do not meet these criteria. Here, we sought to confirm the manufacturer-recommended 99th percentile cutoff and CV of the POC assay AQT90 FLEX cTnI. METHODS: 119 healthy persons without cardiac disorders were examined to determine the 99th percentile cutoff and the corresponding CV. This cutoff was validated in a cohort of 80 patients with unstable angina and 71 patients with non-ST-segment elevation myocardial infarction (NSTEMI), who were admitted to a chest pain unit. cTnI concentrations were measured in serial serum samples obtained from these patients at presentation, 3 and 6 hours after admission. RESULTS: A cTnI concentration of 20 ng/L was found as the 99th percentile cutoff (CV 6.7%). cTnI was > or = 20 ng/L in 51 (75%), 59 (87%), and 60 (88%) of the NSTEMI patients 0, 3 and 6 hours after admission, respectively. At admission, sensitivity was 76% and specificity 95%. Three and six hours later, sensitivity and negative predictive values increased to 88% and 98.8%, and to 92% and 97%, respectively. CONCLUSIONS: We confirmed the manufacturer recommended 99th percentile cutoff of 23 ng/L and established a CV of 6.7% at 20 ng/L. These results demonstrated that the POC assay AQT90 FLEX cTnI must be classified as "guideline acceptable".

High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide predict mortality in stable coronary artery disease: results from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

BACKGROUND: The simultaneous assessment of high-sensitivity cardiac troponin T (hscTnT) and NT-proBNP for predicting death in stable coronary artery disease (CAD) has yet not been examined. We investigated the additional contribution of hscTnT to the risk of mortality prediction of NT-proBNP in patients with stable CAD. METHODS: We studied 1469 patients with stable CAD enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). hscTnT and NT-proBNP were measured in baseline samples using immunoassays (Roche Diagnostics, Germany). RESULTS: Thirty-five percent (n=525) of the patients died during a median follow-up of 7 and a half years. In total 59.0% of the non-survivors and 25.2% of the survivors exhibited concentrations of hscTnT≥14 ng/L. Logistic regression analysis identified hscTnT and NT-proBNP as independent risk markers for short-term (1-year follow-up) and long-term (9-years follow-up) mortality. ROC curve analysis determined optimal univariate cut-offs at 14 ng/L and 443 µg/L for hscTnT (AUC 0.725, p<0.0001) and NT-proBNP (AUC 0.742, p<0.0001), respectively. Kaplan-Meier survival analysis based on optimized cut-offs for the simultaneous determination of both biomarkers confirmed the usefulness of additive hscTnT especially in prediction of short-term mortality. The prognostic benefit of the combined assessment of hscTnT and NT-proBNP could be confirmed by a significantly increased reclassification index (NRI) of 24.2%. CONCLUSIONS: The majority of non-survivors exhibited increased hscTnT concentrations above 14 ng/L. The simultaneous determination of NT-proBNP and hscTnT was superior for risk stratification compared to determining either marker alone. Especially the prediction of the clinically important 1-year mortality was significantly improved by addition of hscTnT to NT-proBNP.

High-sensitivity troponin T improves the prognostic value of N-terminal pro-B-type natriuretic peptide in patients with stable coronary artery disease: results from the LURIC Study.

BACKGROUND: Cardiac troponin T is an established prognostic marker in patients with acute coronary syndromes, but not in stable coronary artery disease (CAD) like N-terminal pro-B-type natriuretic peptide (NT-proBNP). We examined the additive prognostic value of a high-sensitivity troponin T (hsTnT) assay to predict adverse clinical outcomes in stable CAD. METHODS: A retrospective nested case-control analysis of 256 patients with stable CAD who participated in the LURIC study: 128 cases who died from cardiovascular causes during a median follow-up of 7.5 years and 128 survivors (controls) matched for age and gender, were included. hsTnT and NT-proBNP were determined in baseline samples using immunoassays (Roche Diagnostics, Germany). RESULTS: Sixty-two percent of the 256 subjects exhibited concentrations of hsTnT≥14 ng/L, the manufacturer recommended cut-off to diagnose myocardial infarction in patients with acute chest pain. hsTnT, NT-proBNP, diabetes mellitus and fasting glucose were associated with cardiovascular mortality in univariate analysis. Logistic regression identified hsTnT and NT-proBNP as independent risk markers. Receiver operator characteristic (ROC) curves analysis identified optimal cut-offs at 15 ng/L and 352 µg/L for hsTnT (AUC 0.728, p<0.05) and NT-proBNP (AUC 0.751, p=0.07), respectively. Patients with one or two positive markers exhibited 5-year cardiovascular mortalities of 40% and 60%, respectively, compared to 10% in patients with negative markers. The addition of hsTnT to NT-proBNP significantly increased c-statistics of proportional hazards calculated from survival times as well as net reclassification indexes. CONCLUSIONS: Many patients with stable CAD exhibited increased concentrations of hsTnT. The combined determination of NT-proBNP and hsTnT was superior for risk stratification compared to determining either marker alone.

Utility of presepsin (sCD14-ST) as a diagnostic and prognostic marker of sepsis in the emergency department.

BACKGROUND: Presepsin (PSEP) is released during infectious diseases and can be detected in the blood. PSEP has shown promising results as sepsis marker. We examined the diagnostic and prognostic validity of PSEP in patients suspicious of sepsis on admission in the emergency department (ED). METHODS: One hundred twenty three patients with signs of SIRS and/or sepsis and 123 healthy individuals were enrolled. PSEP was determined on admission, after 8, 24 and 72 h. RESULTS: Mean PSEP concentrations of the control group and the patient group were 130 and 1945 pg/ml. PSEP differed between SIRS, sepsis, severe sepsis and septic shock and showed strong association with 30-day mortality ranging from 10.3% in the 1st to 32.1% in the 4th quartile. The ROC curve analyses revealed an AUC value of 0.743. Combined assessment of PSEP and MEDS score increased the AUC up to 0.878 demonstrating the close relationship with outcome. Based on the PSEP values in the different severity degrees, decision thresholds for risk stratification were established. The course of PSEP during the first 72 h was associated with effectiveness of treatment and outcome. CONCLUSIONS: PSEP allowed outcome prediction already on admission to a similar degree as the clinical scores MEDS and APACHE II. Combination of PSEP with MEDS score improved the discriminatory power for outcome prediction.

Quantitative bedside testing of troponin T: is it equal to laboratory testing? The Cardiac Reader Troponin T (CARE T) study.

The progressive evolution of cardiac marker testing in patients with acute coronary syndromes has extended their role into risk stratification and guidance of therapeutic regimen. To provide utilization of cardiac markers around the clock and facilitate the diagnostic work-up of patients with acute chest pain in the emergency room, a point-of-care system for quantitative troponin T and myoglobin testing in whole blood samples was developed. Aim of this multicenter study was to evaluate bedside quantitative determination of myoglobin and troponin T in chest pain patients in a clinical routine setting. Five hospitals in Germany were contributing to blood sampling and 741 patients were included four hours (median) after onset of cardiac pain. Comparison between the rapid test and the established laboratory-based method showed a sufficient agreement of results with a correlation of r = 0.89 (Y = 0.856x + 0.029) for troponin T and r = 0.912 (Y= +1.145x + 3.457) for myoglobin. Diagnostic sensitivity and prognostic power of the troponin T results obtained in the emergency unit were thoroughly equivalent to the laboratory-based method. The results show that the cardiac reader system represents a promising alternative to central laboratory testing with an accuracy sufficiently for rapid decision making in the emergency room. Myoglobin results in this study did not add supplementary information to the cardiac reader troponin result. However, point-of-care testing of troponin T is advantageous whenever marker results could positively effect initial triage decisions and interventional management choices.

N-terminal pro brain natriuretic peptide in the management of patients in the medical emergency department (PROMPT): correlation with disease severity, utilization of hospital resources, and prognosis in a large, prospective, randomized multicentre trial.

AIMS: N-terminal pro brain natriuretic peptide (NT-proBNP) is a potent marker of heart failure and other cardiac diseases. The value of NT-proBNP testing in the medical emergency department (ED) was assessed in patients >65 years old. METHODS AND RESULTS: This large, prospective, randomized, controlled, multicentre trial was conducted in six medical EDs. Data for evaluation of the primary endpoint of hospitalization were available for 1086 patients. Median NT-proBNP was 582 pg/mL. A total of 16% of patients presented with NT-proBNP <150 pg/mL (low), 55% with NT-proBNP between 150 and 1800 pg/mL (intermediate), and 29% with NT-proBNP >1800 pg/mL (high). NT-proBNP was positively correlated with hospital admission [ odds ratio (OR) for high vs. low 2.9, P < 0.0001], length of stay (8.5 days vs. 3.5 days for high vs. low, P < 0.01), in-hospital death (3.9% vs. 0% for high vs. low, P < 0.01), 6 months re-hospitalization (OR for high vs. low 5.1, P < 0.0001), and 6 months death or re-hospitalization (OR for high vs. low 5.7, P < 0.0001). Knowledge of NT-proBNP had no significant effect on the primary endpoint hospital admission and the secondary endpoints intermediate/intensive care unit (IMC/ICU) admission, length of stay, re-hospitalization and death, or re-hospitalization in the total cohort. However, patients with high open NT-proBNP (>1800 pg/mL) were more likely to be admitted to the hospital (P < 0.05) and IMC/ICU (P < 0.05), whereas patients with low open NT-proBNP (<150 pg/mL) were less likely to be admitted (P < 0.05) compared with patients with blinded NT-proBNP. CONCLUSION: Although NT-proBNP does not affect overall hospitalization, it is associated with better stratification of patient care and is strongly correlated with subsequent utilization of hospital resources and prognosis.

N-terminal pro-B-type natriuretic peptide concentrations predict the risk of cardiovascular adverse events from antiinflammatory drugs: a pilot trial.

BACKGROUND: we investigated whether higher concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs. METHODS: NT-proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the therapeutic effect of a novel metalloproteinase inhibitor. We monitored CV-AEs and retrospectively investigated their relationship to the concomitant use of selective cyclooxygenase-2 inhibitors (coxibs), traditional nonsteroidal antiinflammatory drugs (tNSAIDs), and glucocorticoids. CV-AEs included myocardial infarction, stroke, new or worsening of preexisting arterial hypertension, congestive heart failure, and several less severe CV-AEs. RESULTS: we observed 82 mild to serious CV-AEs during an observational period of 200 days. The risk of such events was 1.95-fold higher in patients who were taking tNSAIDs, glucocorticoids, or coxibs (i.e., any inhibitor) and who had NT-proBNP concentrations > or = 100 ng/L than in patients taking any inhibitor who had NT-proBNP values <100 ng/L (P < 0.05). Patients taking coxibs (alone or in addition to tNSAIDs or glucocorticoids) with baseline NT-proBNP values > or = 100 ng/L had a 7.41-fold higher risk for CV-AEs than those with baseline values <100 ng/L (P < 0.01). Patients who were taking 2 or more antiinflammatory drugs and had NT-proBNP values > or = 100 ng/L had a 3.74-fold higher risk for CV-AEs than those with NT-proBNP values <100 ng/L (P < 0.05). An NT-proBNP value <100 ng/L was associated with negative predictive values of >85% across all treatment groups. CONCLUSIONS: NT-proBNP may be a useful marker for anticipating cardiovascular risk associated with the use of antiinflammatory drugs for osteoarthritis.

Increased plasma concentrations of soluble CD40 ligand in acute coronary syndrome depend on in vitro platelet activation.

BACKGROUND: Soluble CD40 ligand (sCD40L) was suggested as a novel biomarker of cardiovascular risk. We examined the effect of preanalytical variation on the measurement of sCD40L concentration. METHODS: From healthy control individuals (n = 20) and patients with acute coronary syndrome (ACS) (n = 20) or sepsis (n = 20), we obtained blood drawn into 5 tubes containing citrate or a mixture of citrate, theophylline, adenosine, and dipyridamole (CTAD). The tubes were incubated for 30 min at room temperature or 0 degrees C before a single or double centrifugation (15 min, 2500 g) at room temperature or 4 degrees C, respectively. sCD40L, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4) concentrations were measured using immunoassays. RESULTS: Concentrations of sCD40L were very low in all CTAD and citrated samples maintained at 0 degrees C (median < or = 0.076 microg/L). Although increased betaTG and PF4 confirmed disease-related in vivo platelet activation, sCD40L was not higher in patients than in controls. In contrast, if the samples were processed at room temperature, sCD40L was significantly higher in ACS patients than in controls (P <0.02 in CTAD and citrated plasma at room temperature). Moreover, the betaTG:PF4 ratio decreased in patient but not control CTAD samples, suggesting a greater susceptibility of patient platelets to in vitro activation. CONCLUSIONS: Increased sCD40L concentrations resulted from in vitro platelet activation during sample preparation. Disease-related in vivo activation did not contribute to sCD40L concentrations in plasma. Therefore, published studies of sCD40L demand cautious interpretation, because their preanalytical conditions were not standardized.

Performance evaluation of automated assays for beta-CrossLaps, N-MID-Osteocalcin and intact parathyroid hormone (BIOROSE Multicenter Study).

INTRODUCTION: Biochemical markers of bone metabolism have been mainly determined manually until now and the precision and accuracy of these methods have not always been satisfactory. This has been shown in several external quality assessment schemes (EQAS). OBJECTIVE AND STUDY DESIGN: A study named BIOROSE was undertaken to evaluate new automated assays for serum markers of bone metabolism. The main focus was to evaluate the assay performance in a multicenter setting with 20 laboratories participating in Germany. The evaluation consists of a familiarization phase to determine precision and accuracy and an EQAS to evaluate the comparability between laboratories. MATERIALS: The parameters beta-CrossLaps (CTX), N-MID-Osteocalcin (OC) and intact parathyroid hormone (PTH) were measured with reagents including calibrators and control sera obtained from Roche Diagnostics, Mannheim, Germany, with electrochemiluminescence immunoassays (ECLIA) on the automated analyzer Elecsys 2010. RESULTS: We calculated for the control samples, PCB 1-3, the mean and median values from the measured values of all participating laboratories and used these as target values. From these target values, a recovery range for the participating laboratories was calculated for beta-CrossLaps, OC and intact PTH of better than 80-126% for PCB 2 and PCB 3, and for PCB 1 (low concentration range) for beta-CrossLaps 79-129%, OC 90-120% and intact PTH 78-126%. The between-day imprecision was 2.4-7.2% for beta-CrossLaps, 1.1-5.9% for OC and 1.7-5.5% for intact PTH in the elevated range (sample PCB 2). In the EQAS, the inter-laboratory imprecision for beta-CrossLaps in the sample with a value of 0.8 ng/ml (above the upper limit of normal, which is 0.6 ng/ml) was 9.8% on day 1 and 9.7% on day 2. CONCLUSION: The performance evaluation of automated assays for beta-CrossLaps, N-MID-Osteocalcin and intact parathyroid hormone in the BIOROSE multicenter study showed that the participating laboratories had no problems in setting up these methods and they yielded results for precision and accuracy that are superior to results achieved in external quality assessment schemes for manually performed methods. In addition, at the clinically important decision level of the upper limit of the normal range, all three tested analytes gave precise results that improved medical decisions.