Creatinine standardization: a key consideration in evaluating whole blood creatinine monitoring systems for CKD screening.

Early detection of CKD using point of care creatinine and eGFR testing improves patient management outcomes. We undertook a field study to evaluate the use of a whole blood creatinine/eGFR device to screen a rural Nicaraguan population to determine the variability between creatinine methods and specimen types. All specimens including capillary and venous dried blood spots (DBS) were tested with an isotope dilution liquid chromatography mass spectrometry (ID-LCMS) gold standard method. This is to our knowledge the first time a capillary whole blood (POC) method has been directly compared to the gold standard IDMS method, through the novel approach of using dried blood spots. Capillary and venous whole blood specimens were obtained and tested directly with the BCMS method, and then, DBS samples were prepared. Venous plasma specimens were tested using three laboratory analyzer creatinine methods. DBS were sent to the site performing ID-LCMS. Control samples were also prepared to assess the stability of shipment and storage of DBS. The ID-LCMS method was aligned using primary and secondary standards. Sixty-six (66) patients participated in the study, and the CKD prevalence rate was 7.8%. While all creatinine methods showed a good correlation to ID-LCMS, there was a positive bias (mean absolute bias range: 0.21-0.63 mg/dL). All methods used were 100% sensitive, but specificity varied from 62.7 to 94.9% with PPV ranging from 25 to 62.5%. A correction factor was used to align the values from each method to ID-LCMS which improved the specificity of each method. This study used a unique DBS approach to align capillary whole blood creatinine to ID-LCMS. To ensure reliability of BCMS for identifying screened patients with CKD, it is important to establish IDMS traceability and alignment prior to undertaking CKD studies.

An insulin-dose error assessment grid: A new tool to evaluate glucose meter performance.

OBJECTIVE: To develop a tool to assess the clinical accuracy of glucose meter performance using an insulin dosing protocol to assess the frequency and extent of error in insulin dose categories. METHODS: Retrospective comparison of 1815 glucose meter and central laboratory glucose results obtained from 1698 critically ill patients was conducted using the Parkes error grid, Surveillance error grid and an insulin dose error assessment grid with a sliding scale insulin dosing protocol used to manage critically ill patients. RESULTS: Parkes error grid and Surveillance error grid analyses indicated little risk conferred with the glucose meter results. Insulin dose error assessment grid complemented the aforementioned consensus error grids by determining quantifiable metrics, insulin dose category errors. Insulin dose error analysis indicated that 76.8% (1395/1815) would not have any change in insulin dose, 99.2% (1800/1815) within ±1 insulin dose category, 99.9% (1814/1815) within ±2 categories and 100% within ±3 insulin dose categories. CONCLUSIONS: Analysis with an insulin dose error grid provides information about the frequency and extent of insulin dose category errors with a specific insulin dosing protocol and describes potential clinical impact of glucose meter error.

Bedside Glucose Monitoring-Is it Safe? A New, Regulatory-Compliant Risk Assessment Evaluation Protocol in Critically Ill Patient Care Settings.

OBJECTIVES: New data have emerged from ambulatory and acute care settings about adverse patient events, including death, attributable to erroneous blood glucose meter measurements and leading to questions over their use in critically ill patients. The U.S. Food and Drug Administration published new, more stringent guidelines for glucose meter manufacturers to evaluate the performance of blood glucose meters in critically ill patient settings. The primary objective of this international, multicenter, multidisciplinary clinical study was to develop and apply a rigorous clinical accuracy assessment algorithm, using four distinct statistical tools, to evaluate the clinical accuracy of a blood glucose monitoring system in critically ill patients. DESIGN: Observational study. SETTING: Five international medical and surgical ICUs. PATIENTS: All patients admitted to critical care settings in the centers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Glucose measurements were performed on 1,698 critically ill patients with 257 different clinical conditions and complex treatment regimens. The clinical accuracy assessment algorithm comprised four statistical tools to assess the performance of the study blood glucose monitoring system compared with laboratory reference methods traceable to a definitive standard. Based on POCT12-A3, the Clinical Laboratory Standards Institute standard for hospitals about hospital glucose meter procedures and performance, and Parkes error grid clinical accuracy performance criteria, no clinically significant differences were observed due to patient condition or therapy, with 96.1% and 99.3% glucose results meeting the respective criteria. Stratified sensitivity and specificity analysis (10 mg/dL glucose intervals, 50-150 mg/dL) demonstrated high sensitivity (mean = 95.2%, SD = ± 0.02) and specificity (mean = 95. 8%, SD = ± 0.03). Monte Carlo simulation modeling of the study blood glucose monitoring system showed low probability of category 2 and category 3 insulin dosing error, category 2 = 2.3% (41/1,815) and category 3 = 1.8% (32/1,815), respectively. Patient trend analysis demonstrated 99.1% (223/225) concordance in characterizing hypoglycemic patients. CONCLUSIONS: The multicomponent, clinical accuracy assessment algorithm demonstrated that the blood glucose monitoring system was acceptable for use in critically ill patient settings when compared to the central laboratory reference method. This clinical accuracy assessment algorithm is an effective tool for comprehensively assessing the validity of whole blood glucose measurement in critically ill patient care settings.

Investigating interferences of a whole-blood point-of-care creatinine analyzer: comparison to plasma enzymatic and definitive creatinine methods in an acute-care setting.

BACKGROUND: Although measurement of whole-blood creatinine at the point of care offers rapid assessment of renal function, agreement of point-of-care (POC) results with central laboratory methods continues to be a concern. We assessed the influence of several potential interferents on POC whole-blood creatinine measurements. METHODS: We compared POC creatinine (Nova StatSensor) measurements with plasma enzymatic (Roche Modular) and isotope dilution mass spectrometry (IDMS) assays in 119 hospital inpatients. We assessed assay interference by hematocrit, pH, pO(2), total and direct bilirubin, creatine, prescribed drugs, diagnosis, red blood cell water fraction, and plasma water fraction. RESULTS: CVs for POC creatinine were 1.5- to 6-fold greater than those for plasma methods, in part due to meter-to-meter variation. Regressioncomparison of POC creatinine to IDMS results gave a standard error (S(y|x)) of 0.61 mg/dL (54 µmol/L), whereas regression of plasma enzymatic creatinine to IDMS was S(y|x) 0.16 mg/dL (14 µmol/L). By univariate analysis, bilirubin, creatine, drugs, pO(2), pH,plasma water fraction, and hematocrit were not found to contribute to method differences. However, multivariate analysis revealed that IDMS creatinine, red blood cell and plasma water fractions, and hematocrit explained 91.8% of variance in POC creatinine results. CONCLUSIONS: These data suggest that whole-blood POC creatinine measurements should be used with caution. Negative interferences observed with these measurements could erroneously suggest adequate renal function near the decision threshold, particularly if estimated glomerular filtration rate is determined. Disparity between whole-blood and plasma matrices partially explains the discordance between whole-blood and plasma creatinine methods.

Evaluation of different disinfectants on the performance of an on-meter dosed amperometric glucose-oxidase-based glucose meter.

BACKGROUND: Off-meter dosed photometric glucose-oxidase-based glucose meters have been reported to be susceptible to interference by hydrogen-peroxide-based disinfecting agents. The objective of this study was to determine if a single application of hydrogen-peroxide-containing Accel® wipe to disinfect an on-meter dosed amperometric glucose-oxidase-based glucose meter will influence its performance. METHOD: The performance of five on-meter dosed amperometric glucose-oxidase-based glucose meters was determined before and after disinfecting the devices with a single application of either CaviWipes® (14.3% isopropanol and 0.23% diisobutyl-phenoxy-ethoxyethyl dimethyl benzyl ammonium chloride) or Accel (0.5% hydrogen peroxide) wipes. Replicate glucose measurements were conducted before disinfecting the devices, immediately after disinfecting, and then 1 and 2 min postdisinfecting, with measurements in triplicate. Analysis was sequentially completed for five different meters. Results were analyzed by a two-way analysis of variance (Analyze-it software). RESULTS: No clinical (<0.3 mmol/liter) or statistical differences (p > .05) in glucose concentration were detected when the on-meter dosed amperometric glucose-oxidase-based glucose meters were disinfected with either CaviWipes or Accel wipes and measured immediately or 1 or 2 min postdisinfecting. No clinically significant difference in glucose concentration was detected between meters (<0.3 mmol/liter). CONCLUSION: The on-meter dosed glucose oxidase amperometric-based glucose meters are not analytically susceptible to interference by a single application of hydrogen-peroxide-containing Accel disinfectant wipes.

Estimates of total analytical error in consumer and hospital glucose meters contributed by hematocrit, maltose, and ascorbate.

BACKGROUND: Patients and physicians expect accurate whole blood glucose monitoring even when patients are anemic, are undergoing peritoneal dialysis, or have slightly elevated ascorbate levels. The objective of this study was to estimate analytical error in two consumer and two hospital glucose meters contributed by variations in hematocrit, maltose, ascorbate, and imprecision. METHODS: The influence of hematocrit (20-60%), maltose, and ascorbate were tested alone and in combination with each glucose meter and with a reference plasma glucose method at three concentrations of glucose. Precision was determined by consecutive analysis (n=20) at three levels of glucose. Multivariate regression analysis was used to estimate the bias associated with the interferences, alone and in combination. Total analytical error was estimated as |% bias|+1.96 (% imprecision). RESULTS: Three meters demonstrated hematocrit bias that was dependent upon glucose concentration. Maltose had profound concentration-dependent positive bias on the consumer meters, and the extent of maltose bias was dependent on hematocrit. Ascorbate produced small but statistically significant biases on three meters. Coincident low hematocrit, presence of maltose, and presence of ascorbate increased the observed bias and was summarized by estimation of total analytical error. Among the four glucose meter devices assessed, estimates of total analytical error in glucose measurement ranged from 6 to 68% under the conditions tested. CONCLUSIONS: The susceptibility of glucose meters to clinically significant analytical biases is highly device-dependent, and low hematocrit exacerbated the observed analytical error.

Accuracy and reliability of the Nova StatStrip® glucose meter for real-time blood glucose determinations during glucose clamp studies.

AIMS/HYPOTHESIS: The Andres clamp technique, which requires accurate and timely determination of glucose, utilizes the Beckman or Yellow Springs Instruments (YSI) glucose analyzers. Both instruments require maintenance, a dedicated operator, preparation of a plasma sample, and a duplicate measurement that takes ≥2 minutes. The Nova StatStrip glucose meter was evaluated for accuracy, reliability, and near-real-time availability of glucose. METHODS: Blood samples from 24 patients who underwent 6-hour clamp studies and 12 patients who had a standardized meal tolerance test (SMT) were measured. Specimens were analyzed simultaneously and immediately upon collection by Beckman, YSI, and Nova. RESULTS: Of 1004 data pairs for the Nova device versus Beckman, the Nova data points ranged from 32 to 444, while Beckman ranged from 42 to 412. The coefficient for the slope of Beckman versus Nova was 1.009 (r = 0.978). Using error grid analysis, the number and percentage of values for Nova were 976 (97.2%) in the A zone and 28 (2.8%) in the B zone. Of 399 data pairs for the Nova device versus YSI, the Nova data points ranged from 46 to 255, whereas YSI ranged from 47 to 231. The coefficient for the slope of YSI versus Nova was 1.023 (r = 0.989). All Nova readings fell in the A zone. Time required for final reading, in duplicate, was 15 seconds for Nova and 120-180 seconds for Beckman and YSI. CONCLUSIONS: The simplicity of Nova and its reliability, accuracy, and speed make it an acceptable replacement device for Beckman and YSI in the conduct of clamps, especially when perturbations require rapid glucose determination.

Evaluation of the analytical performance of the Nova StatSensor creatinine meter and reagent strip technology for whole blood testing.

OBJECTIVE: To evaluate the analytical performance of the Nova StatSensor creatinine meter. DESIGN AND METHODS: Imprecision, linearity, patient correlation and interference studies were completed. RESULTS: Total imprecision was 4.5-9.1%CV and a linear measurement range of 93-863 micromol/L (1.05-9.76 mg/dL) was verified. Whole blood creatinine results correlated well with laboratory plasma measurements (R(2)=0.9328) but exhibited a negative proportional bias. In vitro, high levels of creatine and urea falsely elevated creatinine measurement. CONCLUSIONS: The creatinine meter provides reliable measurement across a clinically relevant range and has potential use in point-of-care testing.

A mathematical model to assess the influence of hematocrit on point of care glucose meter performance.

OBJECTIVES: To develop and apply a mathematical model of the relationship between hematocrit, meter glucose and reference glucose concentrations as a tool for evaluation of whole blood glucose meters. DESIGN AND METHODS: Patient blood gas specimens were used to compare the LifeScan SureStep Flexx and the Nova StatStrip glucose meters with reference results obtained from a Radiometer 725 blood gas analyzer. Linear regression analysis was conducted to determine the extent that patient hematocrit and reference glucose concentrations predicted the performance of the glucose meters. RESULTS: Bland-Altman graphic analysis depicted that both glucose meters showed variance with the reference method. A mathematical model was derived from IFCC consensus equations that relate glucose meter results, hematocrit and plasma glucose values. Using the model, multivariate regression depicted that hematocrit affected the results of the SureStep Flexx meter in a manner dependent on the glucose concentration, whereas the StatStrip meter was not affected by hematocrit. CONCLUSIONS: Linear regression can be used to quantify the extent of hematocrit interference on the performance of glucose meters.

Performance of a new interference-resistant glucose meter.

OBJECTIVES: Glucose meters are widely used in self and hospital monitoring of blood glucose. We examined the analytical performance of a StatStrip glucose monitoring system. DESIGN AND METHODS: Linearity, % recovery and within-run imprecision were studied using glucose-spiked whole blood. A total of 120 heparinized samples were used in method comparison using a plasma hexokinase on the Dimension RxL MAX analyzer as the comparison method. Common interferences were tested on the StatStrip, Accu-Chek Advantage and the MediSense Optium glucose meters at low, middle and high glucose levels. RESULTS: The StatStrip assay showed excellent linearity and recovery. The coefficient of variations for imprecision were <5%. This meter correlated well with the comparison method (y=0.994X+0.03; r=0.995, S(y/x)=0.05 mmol/L, bias=-0.01 mmol/L). Of the three meters tested, only the StatStrip showed interference <10% for all spiked levels of acetaminophen, ascorbic acid, maltose and hematocrit at three levels of glucose tested. CONCLUSIONS: The StatStrip meter showed good performance and is suitable for point-of-care hospital glucose testing.

Interference studies with two hospital-grade and two home-grade glucose meters.

BACKGROUND: Interference studies of four glucose meters (Nova Biomedical [Waltham, MA] StatStrip [hospital grade], Roche Diagnostics [Indianapolis, IN] Accu-Chek Aviva [home grade], Abbott Diabetes Care [Alameda, CA] Precision FreeStyle Freedom [home grade], and LifeScan [Milpitas, CA] SureStep Flexx [hospital grade]) were evaluated and compared to the clinical laboratory plasma hexokinase reference method (Roche Hitachi 912 chemistry analyzer). These meters were chosen to reflect the continuum of care from hospital to home grade meters commonly seen in North America. METHODS: Within-run precision was determined using a freshly prepared whole blood sample spiked with concentrated glucose to give three glucose concentrations. Day-to-day precision was evaluated using aqueous control materials supplied by each vendor. Common interferences, including hematocrit, maltose, and ascorbate, were tested alone and in combination with one another on each of the four glucose testing devices at three blood glucose concentrations. RESULTS: Within-run precision for all glucose meters was <5% except for the FreeStyle (up to 7.6%). Between-day precision was <6% for all glucose meters. Ascorbate caused differences (percentage change from a sample without added interfering substances) of >5% with pyrroloquinolinequinone (PQQ)-glucose dehydrogenase-based technologies (Aviva and Freestyle) and the glucose oxidase-based Flexx meter. Maltose strongly affected the PQQ-glucose dehydrogenase-based meter systems. When combinations of interferences (ascorbate, maltose, and hematocrit mixtures) were tested, the extent of the interference was up to 193% (Aviva), 179% (FreeStyle), 25.1% (Flexx), and 5.9% (StatStrip). The interference was most pronounced at low glucose (3.9-4.4 mmol/L). CONCLUSIONS: All evaluated glucose meter systems demonstrated varying degrees of interference by hematocrit, ascorbate, and maltose mixtures. PQQ-glucose dehydrogenase-based technologies showed greater susceptibility than glucose oxidase-based systems. However, the modified glucose oxidase-based amperometric method (Nova StatStrip) was less affected in comparison with the glucose oxidase-based photometric method (LifeScan SureStep Flexx).

Evaluation of the impact of hematocrit and other interference on the accuracy of hospital-based glucose meters.

BACKGROUND: Most glucose meter comparisons to date have focused on performance specifications likely to impact subcutaneous dosing of insulin. We evaluated four hospital-based glucose meter technologies for accuracy, precision, and analytical interferences likely to be encountered in critically ill patients, with the goal of identifying and discriminating glucose meter performance specifications likely to impact intensive intravenous insulin dosing. METHODS: Precision, both within-run and day-to-day, was evaluated on all four glucose meters. Accuracy (bias) of the meters and analytical interference were evaluated by comparing results obtained on whole blood specimens to plasma samples obtained from these whole blood specimens run on a hexokinase reference method. RESULTS: Precision was acceptable and differed little between meters. There were significant differences in the degree to which the meters correlated with the reference hexokinase method. Ascorbic acid showed significant interference with three of the four meters. Hematocrit also affected the correlation between whole blood and plasma hexokinase glucose on three of the four glucose meters tested, with the magnitude of this interference also varying by glucose meter technology. CONCLUSIONS: Correlation to plasma hexokinase values and hematocrit interference are the main variables that differentiate glucose meters. Meters that correlate with plasma glucose measured by a reference method over a wide range of glucose concentrations and minimize the effects of hematocrit will allow better glycemic control for critically ill patients.

Nonoperative management of spontaneous splenic rupture in infectious mononucleosis: a case report and review of the literature.

Spontaneous rupture of the spleen is a rare complication of infectious mononucleosis with no clear consensus on appropriate management. Although management of traumatic splenic rupture has largely moved to nonoperative treatment, splenectomy is still frequently used in dealing with rupture of the diseased spleen. Here we report the case of a 16-year-old boy with splenic rupture secondary to laboratory-confirmed infectious mononucleosis in the absence of trauma. Nonoperative management including ICU admission, serial computed tomography scans, and activity limitation was used successfully. Our experience, along with a review of the literature, leads us to conclude that splenic preservation can be a safe alternative to splenectomy in hemodynamically stable patients with spontaneous splenic rupture. This is of particular importance in the pediatric population, which is at higher risk for postsplenectomy sepsis.

MODULAR ANALYTICS: A New Approach to Automation in the Clinical Laboratory.

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality.

Surgical management of chronic unremitting constipation and fecal incontinence associated with megarectum: A preliminary report.

BACKGROUND/PURPOSE: Functional constipation with associated fecal incontinence responds poorly to medical management once megarectum has developed. The authors describe resecting the dilated rectum and inserting a cecostomy button for antegrade enemas in this difficult condition. METHODS: Four children, ages 9 to 15 years, with a history of unremitting constipation and fecal incontinence were referred for evaluation after not responding to medical management. All patients had exhibited normal lumbosacral magnetic resonance images (MRI) and open rectal biopsies; however, all 4 patients had a megarectum on contrast enema. In addition, anorectal manometry was consistent with functional fecal retention. The dilated rectum was resected by anastamosing the nondilated sigmoid colon to the distal rectum, and a standard gastrostomy button was inserted into the cecum for antegrade enemas. Mean follow-up was 35 months (range, 8 to 60 months). RESULTS: Constipation and incontinence resolved within 6 months in all patients, and all children remained continent without the aid of cathartic agents. There were no postoperative episodes of fecal impaction. The only complication was antibiotic-associated diarrhea in 1 patient. Cecostomy buttons were removed at 1 year postplacement in all 4 patients with continued success. Three patients underwent repeat anorectal manometry; all 3 had normal rectal sensory threshold volumes and anorectal inhibitory reflexes. Barium studies also were obtained in the 3 patients without evidence of recurrent rectal dilation. CONCLUSIONS: Refractory constipation and incontinence associated with megarectum may be amenable to surgical intervention in selected patients. The authors' limited experience suggests that proctectomy and button cecostomy is an effective treatment option that improves the quality of life in these patients. Furthermore, proctectomy alone may be curative.