Radiometer Medical Research Articles

Optimization of Patient Management in the Gynecology Emergency Department Using Point-of-Care Beta hCG.

Background: Point-of-care testing (POCT) provides shorter turn-around times and, in many cases, potentially improves medical decision making. The AQT90 FLEX® benchtop immunoanalyzer (Radiometer Medical ApS, Copenhagen, Denmark) allows for the determination of beta-human chorionic gonadotropin (βhCG) in 18 min. The main aim of this study was to evaluate the impact of measuring βhCG using the AQT90 analyzer in the gynecology emergency department (ED) compared to the standard practice of using central laboratory blood testing on the patient length of stay (LOS). Methods: The evaluation consisted of two parts. The first one, conducted in the central laboratory, focused on the analytical performances of the AQT βhCG assay. The second one, conducted in the ED, aimed at determining the impact of POCT βhCG implementation on the timeframe in which ED patients require βhCG assessment. Results: The within-lab imprecisions at the mean values of 17 and 287 IU/L were 2.7% and 3.7%, respectively. Using Deming regression (n = 60), the following equation was obtained in the central lab: AQT90 βhCG = 1.1 Roche βhCG—12.9 (r = 0.997). The implementation of POCT βhCG in the ED significantly reduced patient LOS (145 (90–212) min vs. 205 (155–265) with and without AQT90, respectively, p < 0.001). At the 2 IU/L decision level, a 99.7% agreement with the Roche assay was reported (kappa statistics, 0.99). Conclusions: We confirm that the analytical qualities of the AQT 90 were in line with those obtained in the central lab. The implementation of the POCT βhCG is associated with a shorter LOS in the ED due to the faster availability of the results and the faster decision-making possibilities.

Performance Evaluation of the i-SmartCare 10 Analyzer and Method Comparison of Six Point-of-Care Blood Gas Analyzers.

Blood gas, electrolyte, glucose, and lactate level measurement have an immediate and critical impact on patient care. We evaluated the performance of i-SmartCare 10 (i-SENS Inc., Seoul, Korea) and conducted a method comparison study of five point-of-care (POC) analyzers with i-SmartCare 10 as the comparator, according to the CLSI guidelines. Ten analytes (pH, pCO2, pO2, Na+, K+, Cl-, iCa2+, glucose, lactate, and Hct) were tested on six analyzers: i-SmartCare 10, ABL90 FLEX PLUS (Radiometer Medical ApS, Copenhagen, Denmark), i-Stat (Abbott Point of Care Inc., Princeton, NJ, USA), RapidLab 1265 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA), Stat Profile pHOx Ultra (Nova Biomedical, Waltham, MA, USA), and Gem Premier 5000 (Instrumentation Laboratory, Bedford, MA, USA). The total imprecision and linearity (r2>0.99) were excellent, except for a few analytes that narrowly escaped the preset criteria. Interference was noted for Na+ in the presence of a high K+ level and for iCa2+ in the presence of high K+ and Mg2+ levels. Forty of 48 items demonstrated either a proportional or systematic difference in regression analysis; the relative mean difference (%) of 14/48 items escaped the allowable total error in the difference plot analysis. i-SmartCare 10 shows acceptable performance, and using a single POC blood gas analyzer is recommended for monitoring.

A case of pseudohyperchloraemia caused by sodium nitrate ingestion

Emergency department presentations of sodium nitrate poisoning are increasing in frequency. Point-of-care blood gas analysis is useful for identifying methaemoglobinaemia and other abnormalities in such patients. Topically applied nitrate is known to positively interfere with chloride measurement in both point-of-care instruments and automated analysers of the clinical chemistry laboratory. In this article, the authors describe a case of pseudohyperchloraemia caused by sodium nitrate, which was consumed orally for the purpose of suicide. Consistent with the established pattern of interference, the ABL800 (Radiometer Medical, Brønshøj Copenhagen) blood gas analyser produced spuriously high chloride results, whilst the Alinity (Abbott Diagnostics, Abbot Park, Illinois) automated analyser resulted in chloride measurements comparable to those of inductively coupled mass spectrometry (ICP-MS). Both instruments, measure chloride with ion-selective electrodes (ISEs). The ABL800 (Radiometer) uses a membrane electrode, which is vulnerable to permeation by lipophilic nitrate ions, whereas the Alinity (Abbott) employs a silver chloride redox electrode system that is resistant to precipitation of silver nitrate due to its relatively high solubility. These mechanistic differences likely explain why nitrate interferes with some point-of-care devices but does not appear to affect the results of automated analysers.

Evaluation of time courses of agreement between minutely obtained transcutaneous blood gas data and the gold standard arterial data from spontaneously breathing Asian adults, and various subgroup analyses

BackgroundUsual clinical practice for arterial blood gas analysis (BGA) in conscious patients involves a one-time arterial puncture to be performed after a resting period of 20–30 min. The aim of this study was to evaluate the use of transcutaneous BGA for estimating this gold standard arterial BGA.MethodsSpontaneously breathing Asian adults (healthy volunteers and respiratory patients) were enrolled (n = 295). Transcutaneous PO2 (PtcO2) and PCO2 (PtcCO2) were monitored using a transcutaneous monitor (TCM4, Radiometer Medical AsP, Denmark) with sensors placed on the chest, forearm, earlobe or forehead. Transcutaneous BGA at 1-min intervals was compared with arterial BGA at 30 min. Reasonable steps to find severe hypercapnia with PaCO2 > 50 mmHg were evaluated.ResultsSensors on the chest and forearm were equally preferred and used because of small biases (n = 272). The average PCO2 bias was close to 0 mmHg at 4 min, and was almost constant (4–5 mmHg) with PtcCO2 being higher than PaCO2 at ≥8 min. The limit of agreement for PCO2 narrowed over time: ± 13.6 mmHg at 4 min, ± 7.5 mmHg at 12–13 min, and ± 6.3 mmHg at 30 min. The limit of agreement for PO2 also narrowed over time (± 23.1 mmHg at 30 min). Subgroup analyses showed that the PaCO2 and PaO2 levels, gender, and younger age significantly affected the biases. All hypercapnia subjects with PaCO2 > 50 mmHg (n = 13) showed PtcCO2 ≥ 50 mmHg for until 12 min.ConclusionsAlthough PtcCO2 is useful, it cannot completely replace PaCO2 because PCO2 occasionally showed large bias. On the other hand, the prediction of PaO2 using PtcO2 was unrealistic in Asian adults. PtcCO2 ≥ 50 mmHg for until 12 min can be used as a screening tool for severe hypercapnia with PaCO2 > 50 mmHg.

Evaluation of automatic mixing versus manual mixing for point of care hemoglobin measurement

ObjectiveWe compared hemoglobin results from manually mixed blood gas (BG) Portex syringes (Smiths Medical) and automatically mixed safePICO BG syringes (Radiometer Medical) measured on the ABL90 FLEX blood gas analyzer at the Point of Care with a laboratory hematology analyzer (XN-series, Sysmex) to determine whether automatic mixing improved the accuracy and precision of hemoglobin measurement relative to the standardized method. MethodsNinety-nine lithium heparin tubes and EDTA tubes were collected simultaneously from selected patients at five participating institutions. The lithium heparin tubes were then split between the Portex ABG syringe and the safePICO aspirator. The Portex syringe was mixed manually according to routine procedures, while the safePICO syringe was mixed automatically on the ABL90 FLEX using the automatic mixing ball. The two syringes were mixed and run on the ABL90 FLEX analyzer by the same lab personnel. Total hemoglobin results obtained from the EDTA tubes on the Sysmex XN hematology analyzer were used as the reference values. ResultsManual mixing demonstrated a larger scatter of hemoglobin values (R2 ​= ​0.515 and Mean diff.: -0.9 ​g/dL) while automatic mixing at the point of care yielded a significantly better correlation (R2 ​= ​0.986 and Mean diff.: -0.2 ​g/dL) when compared to a reference hematology analyzer. ConclusionUsing the safePICO syringe with automatic mixing at the point of care results in a significantly better correlation of hemoglobin with the standardized method.

КИСЛОТНО-ОСНОВНОЕ СОСТОЯНИЕ, ГАЗОВЫЙ СОСТАВ КРОВИ И ЭХОКАРДИОГРАФИЧЕСКИЕ ИЗМЕНЕНИЯ МИОКАРДА ПРИ БРОНХИАЛЬНОЙ АСТМЕ У ДЕТЕЙ

Objective: To examine the acid-base balance, blood gases and echocardiographic changes in bronchial asthma in children. Methods: The results of the examination of 60 children suffering from bronchial asthma (BA), aged from 5 to 14 years are presented. The patients were divided into 2 groups depending on their age. The first group consisted of 28 children from 5 to 10 years old, the second – 32 children aged 11 to 14 years. The control group included 20 healthy children, identical to the surveyed groups in terms of gender and age. Echocardiography was performed on a Vivad 3 apparatus (GE, USA), the acid-base balance and blood gases were studied on an ABL 800 Flex apparatus (Radiometer Medical, Denmark). Results: Studies have shown that children with asthma had significant changes in the ventilation capacity of the lungs in the form of perfusion and diffusion disorders, which undoubtedly influenced the severity of their condition. In children of both groups, there was a significant lack of bases (p&lt;0.001) and a decrease of pH average value in comparison with similar indicators of healthy children. A significant difference in BE and pH values was found between the two groups of patients (p&lt;0.01). The main changes in hemodynamics were reflected in the indicators of TV A and TV E/A. As in children under 10 years of age with BA, and in children over 10 years of age with BA, TV A was higher than in children of the control group (0.48±0.02 versus 0.38±0.02 (p&lt;0.05) and 0.59±0.02 versus 0.49±0.02 (p&lt;0.05) respectively), while the TV E/A ratio was lower in children with BA (1.22±0.03 versus 1.42±0.05 (p&lt;0.05) and 1.31±0.04 versus 1.59±0.06 (p&lt;0.05) respectively). Conclusions: It was found that third patients in the interictus period of the disease have mild hypoxemia, which, as a rule, is combined with a drop in the alveolar-arterial O2 gradient. The examined patients were characterized by respiratory acidosis. The detected echocardiographic changes confirmed the presence of myocardial dystrophy and the development of «cor pulmonale» in 2 children of the second group with more than 6 years and occurring frequent exacerbations. Keywords: Bronchial asthma, children, heart, echocardiography, acid-base balance, blood gases.

Effect of Coagulation Factor Concentrates on Markers of Endothelial Cell Damage in Experimental Hemorrhagic Shock.

Plasma-based resuscitation showed protective effects on the endothelial glycocalyx compared with crystalloid resuscitation. There is paucity of data regarding the effect of coagulation factor concentrates (CFC) on the glycocalyx in hemorrhagic shock (HS). We hypothesized that colloid-based resuscitation supplemented with CFCs offers a therapeutic value to treat endothelial damage following HS. Eighty-four rats were subjected to pressure-controlled (mean arterial pressure (MAP) 30-35 mm Hg) and lab-guided (targeted cutoff: lactate >2.2. mmol/L and base deficit > 5.5 mmol/L) HS. Animals were resuscitated with fresh frozen plasma (FFP), human albumin (HA) or Ringer's lactate (RL) and RL or HA supplemented with fibrinogen concentrate (FC) or prothrombin complex concentrate (PCC). Serum epinephrine and the following markers of endothelial damage were assessed at baseline and at the end-of-observation (120 min after shock was terminated): syndecan-1, heparan sulfate, and soluble vascular endothelial growth factor receptor 1 (sVEGFR 1). Resuscitation with FFP had no effect on sVEGFR1 compared with crystalloid-based resuscitation (FFP: 19.3 ng/mL vs. RL: 15.9 ng/mL; RL+FC: 19.7 ng/mL; RL+PCC: 18.9 ng/mL; n.s.). At the end-of-observation, syndecan-1 was similar among all groups. Interestingly, HA+FC treated animals displayed the highest syndecan-1 concentration (12.07 ng/mL). Resuscitation with FFP restored heparan sulfate back to baseline (baseline: 36 ng/mL vs. end-of-observation: 36 ng/mL). The current study revealed that plasma-based resuscitation normalized circulating heparan sulfate but not syndecan-1. Co-administration of CFC had no further effect on glycocalyx shedding suggesting a lack of its therapeutic potential. VExperimental in vivo study.

Performance Evaluation of Cardiac Troponin I Assay: A Comparison Between the Point-of-care Testing Radiometer AQT90 FLEX and the Central Laboratory Siemens Advia Centaur Analyzer.

BackgroundTo validate the point of care testing (POCT) Trop-I analyzer and compare it with a central laboratory-based chemiluminescence immunoassay, in order to evaluate its performance for use in critical care areas. Moreover, for clinical decision-making, it is imperative to know the extent to which patient stratification will differ based on the analytic method being used. In particular, the aim of this study was to evaluate the analytical performance of the point-of-care analyzer and demonstrate the agreement with the central laboratory measurements in patients presenting to the emergency department (ED) with chest pain and suspected acute coronary syndrome (ACS).MethodsThis cross-sectional study was performed at the section of chemical pathology, department of pathology and laboratory medicine, the Aga Khan University (AKU), Karachi, from October to November 2017. Samples from patients and the quality control material of Trop-I were analyzed for imprecision, linearity, and method comparison on Advia Centaur (Siemens Diagnostics, CA, USA), and the AQT90 FLEX analyzer (Radiometer Medical ApS, Brønshøj, Denmark) with photometric detection at the section of chemical pathology, AKU. Statistical analysis was done using Microsoft Excel (Microsoft Corporation, Washington, United States) and EP Evaluator version 10.3.0.556 (Data Innovations, LLC, VT, US). Quantitative variables were represented in terms of mean ± SD. For precision, the computed SD was compared with allowable random error. Furthermore, Cohen’s kappa was applied to observe the agreement between the two methods.ResultsThe Trop-I Precision study on the POCT analyzer showed a coefficient of variation (CV) of 2.4% using a pooled patient sample with a mean Trop-I of 2.15 ± 0.05 ng/ml. Three standards ranging from 0.034 to 1.316 ng/ml were run in triplicate to verify accuracy and linearity. The allowable systematic error (SEa) was 10.0%. The maximum deviation for a mean recovery from 100% was 4.1%. All three of the mean recoveries were accurate and within the allowable error limits. The results were linear with slope 1.04, intercept 0.0. On a method comparison, Trop-I showed good agreement, yielding a kappa value of 0.95.ConclusionThis study has validated the performance of a POCT Trop-I assay against a central laboratory immunoassay and found acceptable results. POCT assays for cTnI should be implanted in emergency settings to ensure the fast triage of patients with chest pain, as well as timely diagnosis.

Is the new, noninvasive, continuous cardiorespiratory monitoring reliable during neonatal ECMO?

BackgroundAdvances in cardiorespiratory monitoring have made the extracorporeal membrane oxygenation (ECMO) technique safer for the patient. Noninvasive, continuous tools are available, although data on their applications in the neonatal ECMO setting are lacking. ObjectiveWe retrospectively described the neonatal clinical application of this continuous, noninvasive ECMO monitor and compared the analyzed parameters from those derived from blood gas analysis. Materials and methodsWe performed 897 h of cardiorespiratory monitoring during neonatal venoarterial-ECMO (VA-ECMO) for four patients affected by (cardio-) respiratory failure, to compare the reliability of a noninvasive, continuous monitoring Spectrum M4® (M4) (Spectrum Medical, Gloucester, England) to an invasive, intermittent co-monitoring with blood gas analyzer (Radiometer Medical ApS, Brønshøj, Denmark). ResultsA range of 117 pairs (time-matched BGA-derived vs. M4-derived parameters) was retrospectively analyzed. T-test, linear regression and Bland–Altman analysis for hemoglobin, hematocrit, venous oxygen saturation, oxygen delivery, oxygen consumption, oxygen extraction ratio, oxygen partial pressure, and carbon dioxide partial pressure showed a strong relationship between the two monitors for all parameters analyzed (p < 0.0001). ConclusionsContinuous, noninvasive cardiorespiratory monitoring appears to be feasible and reliable, although its accuracy needs to be verified in a more extensive cohort.

Measuring Transcutaneous Oxygenation to Validate the Duration Required to Achieve Electrode Equilibration.

The transcutaneous oxygenation measurement (TCOM) system is useful in assessing tissue viability. There are no clear recommendations regarding the duration required for the electrode to equilibrate and reliably evaluate tissue oxygenation values. The objective of this study was to validate the duration required to achieve electrode equilibration in a clinical setting. Minute-by-minute recordings using TCOM (TCOM3; Radiometer Medical ApS, Brønshøj, Copenhagen) were obtained for 82 limbs in 50 participants. Twenty-five limbs were in patients with peripheral vascular disease; 30 were in patients with no known peripheral vascular disease; and 27 were in healthy volunteers. Transcutaneous partial pressure of oxygen and carbon dioxide (TcPO2 and TcPCO2) were recorded over a 15-minute period. Participants' TcPO2 decreased and TcPCO2 increased over time. Both changed in a nonlinear fashion, eventually settling at an "equilibrium" where the measurements became stable. The difference in proportional change of TcPO2 between minutes 14 and 15 was 0.8%, and for TcPCO2was 2.9%. Changes in TCOM measurements over time were similar among the 3 groups. This is the first study to target minute-by-minute variation in TcPO2 and TcPCO2 measurements. Recording for a minimum of 15 minutes allows a reliable period for the TCOM electrode to equilibrate to record absolute values and determine wound healing potential.

Method comparison and validation of a prototype device for measurement of ionized calcium concentrations cow-side against a point-of-care instrument and a benchtop blood-gas analyzer reference method

The objective of this study was to assess an optimized ion-selective electrode Ca-module prototype as a potential cow-side device for ionized Ca (iCa) measurements in bovine blood. A linearity experiment showed no deviation from linearity over a range of iCa concentrations compared with a commercial point-of-care (POC) device commonly used in the field (POCVS; VetScan i-STAT, Abaxis North America, Union City, CA) and a laboratory gold standard benchtop blood-gas analyzer [reference analyzer (RA); ABL-800 FLEX, Radiometer Medical, Copenhagen, Denmark]. Coefficient of variation on 3 samples with high, within-range, and low iCa concentrations ranged from 1.0 to 3.9% for the prototype. A follow-up validation experiment was performed, in which our objectives were to (1) assess the performance of the prototype cow-side against the POCVS (farm gold-standard) using fresh non-anticoagulated whole-blood samples; (2) assess the performance of the prototype and the POCVS against the RA in a diagnostic laboratory using blood collected in a heparin-balanced syringe; and (3) assess the agreement of the prototype and POCVS on-farm (fresh non-anticoagulated whole blood) against the RA on heparin-balanced blood. Finally, sensitivity and specificity of the results obtained by the prototype and the POCVS cow-side compared with the results obtained by the laboratory RA using 3 different iCa cut points for classification of subclinical hypocalcemia were calculated. A total of 101 periparturient Holstein cows from 3 dairy farms in New York State were used for the second experiment. Ionized Ca results from the prototype cow-side were, on average, 0.06 mmol/L higher than the POCVS. With heparin-balanced samples under laboratory conditions, the prototype and POCVS measured an average 0.04 mmol/L higher and lower, respectively, compared with the RA. Results from the prototype and POCVS cow-side were 0.01 mmol/L higher and 0.05 mmol/L lower, respectively, compared with results from the laboratory RA on heparinized blood. Sensitivity and specificity for the prototype and the POCVS under farm conditions at 3 potential subclinical hypocalcemia cut points were 100 and ≥93.5%, respectively. This novel ion-selective electrode Ca-module could become a rapid low-cost tool for assessing iCa cow-side, while qualitatively allowing classification of subclinical hypocalcemia on-farm.

Validation protocol for multiple blood gas analyzers in accordance with laboratory accreditation programs

Introduction:The results of blood gas analysis using different instrumentation can vary widely due to the methodological differences, the calibration procedures and the use of different configurations for each type of instrument.Objective:The objective of this study was to evaluate multiple analytical systems for measurement of blood gases, electrolytes and metabolites in accordance with the accreditation program (PALC) of Sociedade Brasileira de Patologia Clinica/Medicina Laboratorial (SBPC/ML).Materials and methods:20 samples were evaluated in three ABL800 Flex (Radiometer Medical ApS, Denmark) blood gas analyzers, and the results were compared with those of the device in use, which was considered the reference. The analysis of variance (Anova) was applied for statistical purposes, as well as the calculation of mean, standard deviation and coefficient of variation.Results:The p values obtained in the statistical analysis were: pH = 0.983, pO2 = 0.991, pCO2 = 0.353, lactate = 0.584, glucose = 0.995, ionized calcium = 0.983, sodium = 0.991, potassium = 0.926, chlorine = 0.029.Conclusion:The evaluation of multiple analytical systems is an essential procedure in the clinical laboratory for quality assurance and accuracy of the results.

Normative Data and Predictors of Leg Muscle Function and Postural Control in Children

At the present there are limited tools available to measure muscle function in young children. Ground reaction force plates measure lower-body function and postural control in older children and adults. The purpose of this study was threefold: 1) develop normative data for evaluating global muscle development; 2) determine the reproducibility of ground reaction force plates for assessing muscle function in preschool-age children; and 3) identify predictors of skeletal muscle function. Children's (n = 81, 1.8 to 6.0 yr; M = 52%) muscle function and postural control was measured for jump (JMP), sit-to-stand (STS), and both undistracted and distracted body sway tests using a ground reaction force plate (Kistler 9200A). Whole body composition used dual-energy x-ray absorptiometry (Hologic 4500A Discovery Series). Plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations were measured by chemiluminescence (Liaison, Diasorin, Mississauga, ON, Canada) as well as ionized calcium (ABL80 FLEX, Radiometer Medical A/S). Demographics, and anthropometry were collected. ANOVA and linear regression were used to identify predictors. Reproducibility was assessed by intersubject coefficient of variation. Age was a consistent predictor in all models; body size or fat and lean mass were important predictors in 3 of the models - STS peak force, STS peak power, and JMP peak power. STS was the most reproducible maneuver (average coefficient of variation =15.7%). Distracted body sway testing was not appropriate in these youngsters. The novel data presented in this study demonstrate a clear age (developmental) effect without any effect of sex on muscle function and postural control in young children. Lean muscle mass was important in some models (STS peak force and JMP peak power). The STS test was the best of the 4 maneuvers.

Vitamin D Status is Associated With Bone Mineral Density and Bone Mineral Content in Preschool-Aged Children

This study examined the associations between vitamin D status, bone mineral content (BMC), areal bone mineral density (aBMD), and markers of calcium homeostasis in preschool-aged children. Children (n = 488; age range: 1.8–6.0 y) were randomly recruited from Montreal. The distal forearm was scanned using a peripheral dual-energy X-ray absorptiometry scanner (Lunar PIXI; GE Healthcare, Fairfield, CT). A subset (n = 81) had clinical dual-energy X-ray absorptiometry (cDXA) scans (Hologic 4500A Discovery Series) of lumbar spine (LS) 1–4, whole body, and ultradistal forearm. All were assessed for plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations (Liaison; Diasorin), ionized calcium (ABL80 FLEX; Radiometer Medical A/S), and dietary vitamin D and calcium intakes by survey. Age (p < 0.001) and weight-for-age Z-score (p < 0.001) were positively associated with BMC and aBMD in all regression models, whereas male sex contributed positively to forearm BMC and aBMD. Having a 25(OH)D concentration of >75 nmol/L positively associated with forearm and whole body BMC and aBMD (p < 0.036). Sun index related to (p < 0.029) cDXA forearm and LS 1–4 BMC and whole-body aBMD. Nutrient intakes did not relate to BMC or aBMD. In conclusion, higher vitamin D status is linked to higher BMC and aBMD of forearm and whole body in preschool-aged children.

Comments on Point of Care D-Dimer Testing in the Emergency Department: A Bioequivalence Study

Dear Editor We read with interest the article Point of Care D-Dimer Testing in the Emergency Department: A Bioequivalence Study by Perveen et al. published in Ann Lab Med 2013;33:34-38 [1]. In this article, the authors compared the performance of the D-dimer assays on the AQT90 FLEX analyzer (Radiometer Medical Aps, Akandevej, Denmark) and the VIDAS analyzer (bioMerieux SA, RCS Lyon, France). The study had 2 objectives: To determine any significant difference between the 2 assays in the time from sample draw until result. To quantify the agreement between the results obtained by the 2 assays when performed on samples from the same sample draw. A pilot study determined that a minimum sample size of 100 patients was required for the first objective. The main study included 104 patients and revealed a significant difference between the 2 assays in the time from sample draw until result. For the second objective, determining the agreement between the results obtained by the 2 assays, the pilot study did not determine a minimum sample size; however, the data from the 104 patients were used in this regard. Additionally, imaging results were available for 40 patients in the study sample. Among these, 7 patients had positive imaging and 33 patients had negative imaging results. Only these 40 imaging results were used to calculate the sensitivity and the specificity for the 2 assays. Therefore, we agree with the authors when they state that the sample size was not large enough to compare the clinical performance of both assays with respect to venous thromboembolism. Discordant results between the 2 assays were found in 8 patients. In all of these 8 cases, a positive result was found with the VIDAS assay and a negative result with the AQT90 FLEX assay. All of these 8 patients had negative imaging results. The authors have presented the results for these 8 patients in a table. Then, the authors measured the ratios between the AQT90 FLEX and VIDAS results. The range is presented as 0.34-2.13. However, this must be a typographical error since the results for sample 7 in Table 2, using the 2 analyzers, is 318 ng/mL and 1,300 ng/mL. Thus, we assume the true range to be 0.24-2.13. This means that there is a 9-fold difference between the highest and the lowest ratio. The authors concluded that the average ratio is 0.85. The authors claim that the average ratio of 0.85 is the reason behind the 8 discrepant results and that this difference between the assays raises the question of whether it is acceptable to use the AQT90 FLEX assay in the emergency department. We disagree with that statement since the imaging results yielded negative findings in the 8 cases. There is no consensus on the standardization of D-dimer assays. Goodacre et al. [2] found in their meta-analysis, which included 97 study reports on 198 D-dimer assays in 99 different patient groups, a substantial heterogeneity, particularly with regard to specificity. Even though linear regression analysis may show a good correlation between the 2 D-dimer assays, the correlations are often not good across the measuring range [3]. The variation, which can be seen especially near the cutoff, is clearly shown by Sukhu et al. [4]. Although 12% of their samples showed discordant values, the 2 assays (Stalia and VIDAS) did not differ significantly in clinical performance. A useful comparison of the D-dimer assay performance is the one made against a gold standard or truth. For D-Dimer assays, that gold standard is imaging. Since the imaging results, were in agreement with the AQT90 FLEX D-Dimer results in the discrepant cases (VIDAS vs. AQT90 FLEX), we believe that the data from Perveen et al. support the findings by Sidelmann et al. [5] who compared the AQT90 FLEX assay to several other assays including the VIDAS. Sidelmann et al. [5] concluded that the AQT90 FLEX D-dimer assay demonstrated excellent performance and that it was comparable to routine D-dimer assays.

Factors Affecting the Performance of 5 Cerebral Oximeters During Hypoxia in Healthy Volunteers

Cerebral oximetry is a noninvasive optical technology that measures frontal cortex blood hemoglobin-oxygen saturation. Commercially available cerebral oximeters have not been evaluated independently. Unlike pulse oximeters, there are currently no Food and Drug Administration standards for performance or accuracy. We tested the hypothesis that cerebral oximeters accurately measure a fixed ratio of the oxygen saturation in cerebral mixed venous and arterial blood. We evaluated the performance of 5 commercially available cerebral oximeters: the EQUANOX® 7600 in 3- and 4-wavelength versions (Nonin Medical, Plymouth, MN), FORE-SIGHT® (Casmed, Branford, CT), INVOS® 5100C (Covidien, Boulder, CO), and the NIRO-200NX® (Hamamatsu Photonics, Hamamatsu City, Japan) during stable isocapnic hypoxia in volunteers. Twenty-three healthy adults (14 men, 9 women) had sensors placed on each side of the forehead. The subject's inspired oxygen (FIO2) was then changed to produce 6 steady-state arterial oxygen saturation (SaO2) levels between 100% and 70%, while end-tidal CO2 was maintained constant. At each plateau, simultaneous blood samples from the jugular bulb and radial artery were analyzed with a hemoximeter (OSM-3, Radiometer Medical A/S, Copenhagen, Denmark). Each cerebral oximeter's bias was calculated as the difference between the instrument's reading (cerebral saturation, ScO2) with the weighted saturation of venous and arterial blood (Sa/vO2), as specified by each manufacturer (INVOS: 25% arterial/75% venous; FORE-SIGHT, EQUANOX, and NIRO: 30% arterial/70% venous). Five hundred forty-two comparisons between paired blood samples and oximeter readings were analyzed. The pooled root mean square error was 8.06%, a value higher than for pulse oximeters, which is ±3% by Food and Drug Administration standards. The mean % bias ± SD (precision) and root mean square errors were: FORE-SIGHT 1.76 ± 3.92 and 4.28; INVOS 0.05 ± 9.72 and 9.69; NIRO-200NX -1.13 ± 9.64 and 9.68; EQUANOX-3 λ 2.48 ± 8.12 and 8.47; EQUANOX-4 λ 2.84 ± 6.27 and 6.86. The FORE-SIGHT, NIRO-200NX, and EQUANOX-3 λ had significantly more positive bias at lower SaO2. The amount of bias during hypoxia was reduced when the bias was calculated on the basis of difference between oximeter reading and the arterial and mixed venous saturation difference rather than the weighted average of blood saturation, indicating that differences in the ratio between arterial and venous blood volumes account for some of the positive bias at low saturation. Dark skin pigment tended to produce more negative bias in all instruments but bias was significantly larger than zero only for the FORE-SIGHT oximeter. Bias was significantly more negative in women for INVOS and EQUANOX devices but not for the FORE-SIGHT device. While responsive to desaturation, cerebral oximeters exhibited large variation in reading errors between subjects, with mean bias possibly related to variations in the ratio of arterial and venous blood in the sampling area of the brain. This ratio is probably not fixed, as assumed by the manufacturers, but dynamically changes with hypoxia. Better understanding these factors could improve the performance of cerebral oximeters and help establish saturation or blood flow thresholds for brain well-being.

Point of Care D-Dimer Testing in the Emergency Department: A Bioequivalence Study

BackgroundD-dimer is used widely as a diagnostic aid in low- and moderate-risk patients with suspected venous thromboembolism (VTE). While our laboratory utilizes VIDAS D-dimer analyzer (bioMérieux SA, France), our emergency department (ED) recently procured a D-dimer analyzer AQT90 FLEX (Radiometer Medical ApS, Denmark) for point of care testing (POCT) to facilitate patient management. We aimed to determine whether the time taken to receive D-dimer results using the 2 different analyzers differed significantly and to quantify the limits of agreement between the results of the 2 methods measured on the same patient.MethodsAdult patients presenting to the ED and requiring diagnostic workup for suspected VTE were included in this prospective observational study. Patients underwent simultaneous D-dimer measurements using the 2 different analyzers.ResultsThe paired results from 104 patients were analyzed. The median time for the D-dimer results from triage by VIDAS was 258 min (Inter-quartile range [IQR], 173-360) and by POCT was 146 min (IQR, 55-280.5); the median time difference was 101.5 min (IQR, 82-125.5). On an average, POCT D-dimer values were 15% lower on the same sample (limits of agreement, 34-213%). POCT predicted 83% of VIDAS positive results (sensitivity, 83.3% [95% confidence interval (CI), 70.4-91.3%]; specificity, 100% [95% CI, 93.6-100%]). All patients with positive imaging were identified correctly by both methods.ConclusionsPOCT delivers D-dimer results in significantly shorter turnaround times than pathology services; however, poor bioequivalence between VIDAS and POCT raises the issue of acceptability for use in the ED.

Low prevalence of iron deficiency and iron deficiency anemia in children attending daycare in a large Canadian city

Children are vulnerable to iron deficiency (ID) and iron deficiency anemia (IDA) due to rapid tissue expansion. Recent Canadian surveys reported that 1–3 y and 4–8 y in Québec had an iron intake of 10.1 mg and 13.7 mg/day respectively; however, iron status was not assessed. This study examined the prevalence of ID and IDA and iron intake in children (n=523) from randomly selected daycares in Montréal. Ferritin was measured using an autoanalyzer (Liason®, DiaSorin) and hemoglobin using a radiometer (ABL80 FLEX Radiometer Medical A/S) in capillary samples. Iron intake over 24 h for 469 children with 72 having a repeat assessment was analyzed using Nutritionist Pro™ (Axxya Systems LLC.) and the Canadian Nutrient File. The data was adjusted for day‐to‐day variation, and all children met the EAR (3 mg/day for 1–3 y, 4 mg/day for 4–5 y olds). Mean daily intake for these age groups was 10.22±5.70 mg (n=272) and 11.06±5.32 mg (n=197), respectively, was similar to national data. ID (ferritin &lt;12 μg/L) was present in 13.4% of children and IDA (hemoglobin &lt;110 g/L) in 2.9% of this population. Corresponding means were 22±13 μg/L and 126±19 g/L. This data complements our recent cross‐sectional study reporting ID in 18.0% and IDA in 5.4% in 3–5 y Inuit children; confirming that urban dwelling preschoolers in a large Canadian city have a lower prevalence of ID and IDA. Supported by the Beef Information Centre.

Subcutaneous glucose measurements and glucose regulation (?)

Sir: Andrea Stoszkova et al. [1] conclude, based on a correlation coefficient of 0.69 comparing subcutaneous glucose values (Guardian RT) and blood glucose values (Central Laboratory) in 15 patients, that subcutaneous devices should not be used in critically ill patients. However, Holzinger et al. [2] in the August issue report a good correlation between subcutaneous and arterial glucose values, even in critically ill patients treated with norepinephrine. We also evaluated the accuracy and feasibility of a comparable continuous subcutaneous glucose monitoring system (CGMS System Gold, Medtronic Minimed) and found a correlation coefficient of 0.87 with the point-of-care blood gas/glucose analyzer ABL 715 (Radiometer Medical, Copenhagen, Denmark), which we validated in ICU patients previously [3]. We drew 786 arterial blood samples from 60 consecutive ICU patients, of whom 37 patients received vaso-active medication (only norepinephrine) and 13 patients were treated with steroids. Blood glucose ranged from 2.2 to 20.1 mmol/l. In the Clarke error grid (Fig. 1), 85.1% of measurements were in zone A (clinically accurate, leading to correct and safe treatment decisions), 13.2% were in zone B (clinically acceptable), 0.13% were in zone C, and 1.5% were in zone D. Zone D means failure-to-detect (high or low blood glucose) errors, resulting in failure to treat either low or high blood glucose results appropriately. The readings in zone D were found in nine patients, of whom eight were treated with vasopressors. One could argue that—with a correlation coefficient of 0.87 and 98.3% of glucose values in the clinically acceptable zones—rejection of s.c. glucose determination in the ICU seems premature. Fig. 1 Clarke error-grid analysis On the other hand, looking more precisely at zone D of the Clarke error grid (Fig. 1), a difference of nearly 4 mmol/l in the lower glucose zone (reference 2.8 mmol/l versus s.c. sensor 6.5 mmol/l) observed in one patient could have severe consequences in this individual patient, if this results in an inappropriate rise in insulin dose. Unlike other diagnostic procedures, which usually are interpreted in conjunction with additional findings, a single glucose measurement has direct consequences for treatment, with potentially detrimental effects. In other words, tight glucose regulation in ICU patients using a subcutaneous device may lead to more severe adverse events than the zone interpretation of the error grid suggests. The fact that we now have safe computerized protocols, which give excellent glucose regulation with a very low chance of hypoglycemic events [4], adds to the feeling that for glucose regulation in critically ill patients only the best point-of-care glucose analyzer and protocol should be used [5]. In an era where the beneficial effect of tight glucose regulation is questioned we cannot afford the introduction of treatment-related morbidity.

Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury

Immune activation represents an adaptive reaction triggered by both noxious exogenous (microbes) and endogenous [high mobility group box-1 protein (HMGB1), S100 calcium binding proteins] inducers of inflammation. Cell stress or necrosis lead the release of HMGB1 and S100 proteins in the extracellular compartment where they act as damage-associated molecular pattern molecules (or alarmins) by engaging the receptor for advanced glycation end-products (RAGE). Although the biology of RAGE is dictated by the accumulation of damage-associated molecular pattern molecules at sites of tissue injury, the role of RAGE in mediating antenatal fetal injury remains unknown. First, we studied the relationships at birth between the intensity of human fetal inflammation and sRAGE (an endogenous RAGE antagonist), HMGB1, and S100beta protein. We found significantly lower sRAGE in human fetuses that mounted robust inflammatory responses. HMGB1 levels correlated significantly with levels of interleukin-6 and S100beta in fetal circulation. We then evaluated the levels and areas of tissue expression of RAGE, HMGB1, and S100beta in specific organs of mouse fetuses on E16. Using an animal model of endotoxin-induced fetal damage and preterm birth, we determined that inflammation induces a significant change in expression of RAGE and HMGB1, but not S100beta, at sites of tissue damage. Our findings indicate that RAGE and HMGB1 may be important mediators of cellular injury in fetuses delivered in the setting of inflammation-induced preterm birth.