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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 μg/g, median ITLs 7.3 μg/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.

Background: Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists., Objectives: To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab., Methods: Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients' records were reviewed for dermatological and infusion reactions to infliximab., Results: One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg⁄mL [interquartile range (IQR) 2.0 μg⁄mL to 13.3 μg⁄mL] versus 6.6 μg⁄mL [IQR 3.2 μg⁄mL to 12.7 μg⁄mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg⁄mL [IQR 0.1 μg⁄mL to 5.7 μg⁄mL]) was lower than that of patients who experienced no such AEs (6.6 μg⁄mL [IQR 3.2 μg⁄mL to 12.7 μg⁄mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg⁄mL [IQR 8.8 μg⁄mL to 17.4 μg⁄mL]; P<0.001)., Conclusion: One-quarter of IBD outpatients receiving stable maintenance infliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events.

Objectives: HbA(1c) has been recently recommended as the primary diagnostic test for diabetes. This study evaluated the positive predictive value (PPV) and negative predictive value (NPV) of HbA(1c) against the oral glucose tolerance test (OGTT) in three locations., Design and Methods: Three years of data with concurrent OGTT and HbA(1c) tests were extracted from Laboratory Information Systems (LIS) and receiver operator (ROC) curves and positive and negative predictive values calculated comparing the OGTT with the HbA(1c) values using a 10% prevalence of diabetes., Results: The recommended threshold HbA(1c) value of 6.5% did not give the optimal combination of NPV (0.93 to 0.92) and PPV (0.40 to 0.61) compared to a threshold HbA(1c) value of 7.0% (NPV 0.91 to 0.92, PPV 0.61 to 0.73)., Conclusion: The optimal HbA(1c) value for the diagnosis of diabetes is 7.0% but even at this HbA(1c) the PPV is suboptimal and may cause up to 12% of patients without diabetes, as defined by a normal OGTT, to be classified having diabetes mellitus., (Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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.

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.

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.