Carol Shalapay

Accuracy of Glycemic Measurements in the Critically Ill

BACKGROUND Recent evidence emphasizes the importance of maintaining normoglycemia in critically ill patients to reduce morbidity and mortality. Different analytical methods of varying accuracy exist for obtaining and measuring blood glucose in critically ill patients. The purpose of this study was to determine if there were differences in blood glucose values measured by whole blood capillary and arterial samples using three different bedside blood glucose meters and a blood gas analyzer as compared to a reference blood glucose analyzer. METHODS Sixty subjects were recruited from a university hospital medical/surgical intensive care unit. Matching capillary and arterial samples were analyzed by a clinical blood glucose reference analyzer (YSI, Yellow Springs Instrument, Yellow Springs, OH) and three blood glucose meters (Lifescan [Milpitas, CA] SureStepFlexx, Roche [Indianapolis, IN] Accu-Chek Inform, and Abbott [Alameda, CA] FreeStyle). Additionally, the arterial samples were analyzed by a point-of-care blood gas analyzer (Chiron 865, Bayer, Tarrytown, NY). RESULTS Data analysis included repeated-measures analysis of variance, Consensus Error Grid analysis, Bland-Altman plots, and numerical estimates of inaccuracy. With capillary samples there were high numbers of errors as compared to the reference instrument. Measurement of blood glucose with arterial samples demonstrates a higher degree of accuracy. With arterial samples, the Abbott FreeStyle blood glucose meter and the blood gas analyzer glucose exhibited the lowest median and mean relative absolute deviation. CONCLUSION In critically ill adult patients, measurement of blood glucose using arterial samples is recommended. Using arterial blood, the Abbott FreeStyle blood glucose meter and the point-of-care blood gas analyzer (Bayer Chiron 865) were shown to be highly accurate instruments to measure arterial blood glucose.

Evaluation of the accuracy of self-reported smoking in pregnancy when the biomarker level in an active smoker is uncertain

INTRODUCTION Our main objective was to estimate smoking prevalence as well as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of self-reported smoking among pregnant women in Edmonton, Canada, at 15-16 weeks of gestation. METHODS We used serum samples to assemble a cohort of pregnant women who underwent an optional second-trimester screening for chromosomal and developmental anomalies. We determined cotinine concentrations for 92 self-reported smokers (11% of the cohort) and for 285 self-reported nonsmoking mothers, using adapted urinary cotinine assay. Self-reports were collected at the time of delivery. In a validation study, serum cotinine was determined for known smokers and nonsmokers and used, within a Bayesian statistical framework, to define the distribution of cutoffs that differentiate true smokers from nonsmokers. This distribution of cutoffs was used to construct multiple two-by-two tables to obtain the distribution of sensitivity, specificity, PPV, NPV, and prevalence. RESULTS Sensitivity was poor (M = 47.4%, SD = 17.3%), but specificity was nearly perfect (M = 94.9%, SD = 1.1%). PPV (M = 66.6%, SD = 11.7%) was smaller than NPV (M = 84.7%, SD = 14.3%). In our sample, the prevalence of true smoking at 15-16 weeks of gestation was described by a skewed distribution with a mean of 21.6% (SD = 13.8%) and a median of 16.6%. DISCUSSION The strength of the present study includes blinding of subjects to the intention to test their sera for a biomarker of smoking. A limitation was the use of a nonrandom sample restricted to pregnancies that resulted in live births. We discuss data collection methods that would elicit more accurate smoking histories from pregnant women.

The effect of paraproteins and rheumatoid factor on four commercial immunoassays for vancomycin: implications for laboratorians and other health care professionals.

Background: Paraproteins, immunoglobulins (Igs), which are elevated in various autoimmune disorders, are known to interfere with various laboratory immunoassays, including vancomycin (VANC). Rheumatoid factor (RF), a known immunoassay interferant, may cause falsely elevated results. Objectives: The aims of this study were to (1) evaluate the effect of 3 paraproteins (IgA, IgG, and IgM) on 4 commercial VANC immunoassays [fluorescence polarization immunoassay; enzyme multiplied immunoassay; 2 particle-enhanced turbidimetric inhibition immunoassays]; (2) determine the concentration at which the effect is obtained, and (3) examine the influence of RF on the VANC methods. Method: Serum and plasma pools from patients prescribed VANC and a spiked VANC pool (20 mg/L) were each mixed 1:1 with individual patient specimens containing IgA (6–63 g/L), IgG (6–54 g/L), IgM (3–30 g/L) (n = 4 for each Ig), and a patient RF pool (196 IU/L). The mixtures (n = 39) were split and distributed for VANC analysis. Results: IgA and IgG in serum and plasma did not affect any of the VANC immunoassays. RF added to plasma specimens did not interfere, but in serum, elevated VAN results were observed. IgM did not affect the fluorescence polarization immunoassay and enzyme multiplied immunoassay methods but did attenuate VANC concentrations by both particle-enhanced turbidimetric inhibition immunoassays (Siemens, Beckman Coulter), with a more pronounced effect on the latter, producing concentrations >20% lower than expected in the patient serum and spiked plasma pools. The effect was progressively negative at effective IgM concentrations of 10 and 15 mg/L. Conclusions: This phenomenon is a major analytical and clinical issue that must be communicated to health care professionals caring for patients receiving VANC, so optimal therapy is achieved.

Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical Decision-making for IBD Outpatients on Maintenance Infliximab Therapy

Background:Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an objective marker of disease activity or therapeutic drug monitoring affects clinical decisions regarding maintenance infliximab therapy in outpatients with IBD. Methods:Consecutive patients with IBD on maintenance infliximab therapy were invited to participate by providing preinfusion stool and blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were measured by enzyme linked immunosorbent assay. Three decisions were compared: (1) actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c) clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves were used to assess the ability of FCP and ITL in predicting clinical disease activity or remission. Results:A total of 36 sets of blood and stool were available for analysis; median FCP 191.5 &mgr;g/g, median ITLs 7.3 &mgr;g/mL. The actual clinical decision differed from the hypothetical decision in 47.2% (FCP algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4% (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL) cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95% confidence interval [CI], 0.197–0.641) and subtherapeutic ITL (AUC = 0.774; 95% CI, 0.536–1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254–0.742) and objective remission (AUC = 0.773; 95% CI, 0.622–0.924). Conclusions:Using FCP and ITLs in addition to clinical data results in an increased number of decisions to optimize management in outpatients with IBD on stable maintenance infliximab therapy.

A comparison of cyclosporine assays using sequential samples from selected transplant patients

The monitoring of cyclosporine (CsA) whole blood concentrations is an integral part of immunosuppressive treatment with this drug. Although such monitoring has been facilitated by the introduction of monoclonal immunoassay techniques, there is a paucity of published data comparing the assays longitudinally in selected patients. The purpose of our study was to co-evaluate two monoclonal immunoassays (Cyclosporine FPIA whole blood assay, Abbott Laboratories; Cyclo-Trac® SP-whole blood RIA, Incstar Inc.) and a high-performance liquid chromatorgraphy (HPLC) technique for quantitating CsA in sequentially collected trough whole blood samples from 14 patients up to 75 days after renal (n=6), hear (n=3), and liver (n=5) transplantation. HPLC CsA metabolite analyses (AM1, AM9, AM4N) were performed. Although CsA concentrations within most patients were significantly higher (p 0.05). CsA levels within nine patients were not significantly different (p > 0.05 when FPIA and RIA were compared, but results within three patients, (one liver, two renal) were significantly higher ([itp < 0.05]) by RIA compared pared to FPIA, but results within one patient (heart)_were significantly higher (< 0.05) by FPIA. Our results demonstrate first that dependinding on the patient, HPLC-derived CsA results are not consistently lower than results generated by immunoassay techniques and second that CsA levels obtained by FPIA are statistically equivalent or in some patients statistically less than RIA-derived levels.

Validating New Reagents: Roadmaps Through the Wilderness

One of the most frequent quality control issues faced by laboratory professionals is how to respond appropriately to a shift in quality control (QC) following a reagent lot change. Possible actions include adjusting the control range, checking for shifts in patient data, or simply ignoring the QC shift. We offer a systematic approach to shifted quality control and/or patient data following a reagent lot change. We divide laboratory tests into 3 types, (1) tests for which the analysis of QC specimens is sufficient, (2) tests which demonstrate between reagent lot shifts infrequently, and (3) tests with between lot variation. Depending on the test type, specific information is gathered about the magnitude of the shifts in either the QC and/or the patient data. The control mean is reset following an isolated quality control shift. Evaluation of the shift in patient data is initiated by the laboratory director when the shift exceeds a multiple of the allowable error.

A Comparison of Cyclosporine Assays Using Sequential Samples from Selected Transplant Patients

The monitoring of cyclosporine (CsA) whole blood concentrations is an integral part of immunosuppressive treatment with this drug. Although such monitoring has been facilitated by the introduction of monoclonal immunoassay techniques, there is a paucity of published data comparing the assays longitudinally in selected patients. The purpose of our study was to co-evaluate two monoclonal immunoassays (Cyclosporine FPIA whole blood assay, Abbott Laboratories; Cyclo-Trac SP-whole blood RIA, Incstar Inc.) and a high-performance liquid chromatography (HPLC) technique for quantitating CsA in sequentially collected trough whole blood samples from 14 patients up to 75 days after renal (n = 6), heart (n = 3), and liver (n = 5) transplantation. HPLC CsA metabolite analyses (AM1, AM9, AM4N) were performed. Although CsA concentrations within most patients were significantly higher (p < 0.05, paired t test) when measured by both immunoassay techniques compared to HPLC, levels determined in three patients, (one liver, two renal) for the FPIA/HPLC comparison and one patient (liver) for the RIA/HPLC comparison were not significantly different (p > 0.05). CsA levels within nine patients were not significantly different (p > 0.05) when FPIA and RIA were compared, but results within three patients, (one liver, two renal) were significantly higher (p < 0.05) by RIA compared to FPIA, but results within one patient (heart) were significantly higher (p < 0.05) by FPIA. Our results demonstrate first that depending on the patient, HPLC-derived CsA results are not consistently lower than results generated by immunoassay techniques and second that CsA levels obtained by FPIA are statistically equivalent or in some patients, statistically less than RIA-derived levels.