Connie Prosser

Vitamin D Receptor Polymorphisms and the Risk of Acute Lower Respiratory Tract Infection in Early Childhood

To investigate associations of 2 vitamin D receptor (VDR) gene polymorphisms and acute lower respiratory tract infection (ALRI), we compared 56 young children hospitalized with ALRI and 64 children without a history of ALRI. The FokI ff genotype was associated with an adjusted relative odds of ALRI that was approximately 7 times that of FokI FF. A weaker association with the TaqI polymorphism was also found. These data provide preliminary evidence of associations of VDR polymorphisms with the risk of ALRI (predominantly viral bronchiolitis) in young children, consistent with a potential role of vitamin D in the immune response to respiratory tract infection.

Thiopurine Methyltransferase Enzyme Activity Determination before Treatment of Inflammatory Bowel Disease with Azathioprine: Effect on Cost and Adverse Events

BACKGROUND Azathioprine (AZA), used to treat inflammatory bowel disease (IBD), is metabolized by thiopurine methyltransferase (TPMT). The accumulation of individual metabolites varies because humans display genetic polymorphism for TPMT expression. Deficiencies in TPMT result in accumulation of toxic metabolites, followed by neutropenia and hepatic inflammation. Concern over acute toxicity frequently leads to under dosing and frequent monitoring tests and visits. OBJECTIVE To determine whether assessment of TPMT activity before the administration of AZA would predict acute toxicity and, thus, allow for reductions in health care costs related to biochemical screening for, and management of, AZA-induced adverse events. METHODS Before AZA treatment, 29 patients with IBD were prospectively randomized to one of two groups: group 1, in which no TPMT assay was performed, was started on AZA at 1 mg/kg/day and then titrated every two weeks to a target dose of 2.5 mg/kg/day; and group 2, in which TPMT assays were performed, was started on AZA at the target dose of 2.5 mg/kg/day. For both groups, complete blood count and liver enzymes were monitored weekly for six weeks and at monthly intervals thereafter. Additional tests and health care interventions were undertaken at the discretion of the attending physicians. RESULTS Of the 29 patients in the study, 15 were randomly assigned to group 1 and 14 to group 2. Demographics and disease activity were similar for both groups. Mean follow-up time was 7.1 months (range 3.5 to 10.7 months). Eight patients from group 1 and six patients from group 2 withdrew as a result of AZA-induced adverse events. There was no correlation between the TPMT activity and the development of AZA-induced adverse events. The direct health care costs for group 1 (300.11 dollars per patient) were lower than in group 2 (348.87 dollars per patient). CONCLUSION The prospective assessment of TPMT enzyme activity before initiating AZA therapy in IBD patients incurred additional cost and did not predict AZA-induced toxicity.

Trace Elements and Vitamins at Diagnosis in Pediatric-Onset Inflammatory Bowel Disease

Aim. To compare serum vitamin and mineral levels at diagnosis in children with inflammatory bowel disease (IBD) versus a control group without. Methods. In a retrospective cohort study, serum levels of iron, zinc, folate, selenium, vitamin B 12, vitamin A, and vitamin E in children with IBD at diagnosis were compared with gender- and age-matched controls. Results. A total of 154 patients with IBD (mean age 11.27 ± 3.74 years, 83 boys, 80 with Crohn’s disease) were recruited. The mean duration of symptoms prior to diagnosis was 5.4 ± 3.2 months for patients with Crohn’s disease and 4.6 ± 2.9 months for patients with ulcerative colitis. A control group of 64 children was recruited. The mean serum zinc levels were 11.33 ± 4.16 µmol/L for ulcerative colitis, 8.74 ± 2.08 µmol/L for Crohn’s disease and 11.49 ± 1.63 µmol/L for controls (P < .001). Conclusions. In newly diagnosed children with IBD, serum zinc levels are significantly lower compared with children without IBD.

Evaluation of the CLINITEK ATLAS for routine macroscopic urinalysis.

OBJECTIVES To evaluate the performance of a new, benchtop, fully automated urine analyzer the CLINITEK ATLAS and compare it with the URICHEM 1000 CHEMSTRIP UA analyzer. Macroscopic analysis included measurement of 8 urine analyte chemistries and specific gravity by the refractive index method (SgRl). METHODS The analytical performance studies conducted were calibration stability, precision (within-run and day-to-day), comparison of results of 437 fresh patient urine specimens, analysis of time performance, and problem logging over a 16-day evaluation period. RESULTS Satisfactory calibration reproducibility, within-run (n = 10), and day-to-day (n = 16) precision was found because results fell within the +/- one color-block by the proposed National Committee for Clinical Laboratory Standards (NCCLS) criteria. Patient results (n = 437) from the 2 analyzers giving the same color-block agreement was found to be for pH, 52%; glucose, 92%; ketones, 86%; protein, 79%; bilirubin, 97%; leukocytes, 72%; blood, 80%; and nitrite, 98%. The concordance defined by the NCCLS criteria as the agreement of results +/- one color-block between the 2 analyzers was found to be for pH, 96%; glucose, 99%; ketones, 100%; protein, 95%; bilirubin, 100%; leukocytes, 97%; and blood 86%. The SgRl determined on ATLAS was correlated with the RD-10 Rapid Density analyzer with the following results: slope = 0.97, intercept = 0.033, r = 0.94, Syx = 0.003, for a range of values from 1.002 to 1.070. CONCLUSION Our preliminary data indicate that the analytical performance, and automatable features for complete walk-away function of this analyzer can significantly increase the overall testing efficiency in the urinalysis laboratory.

Testing Vitamin D Levels and Choosing Wisely

Author Contributions: Dr Kirkpatrick had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kirkpatrick, Hauptman, Swetz, Blume, Maurer, Goodlin. Acquisition, analysis, or interpretation of data: Kirkpatrick, Hauptman, Swetz, Blume, Gauvreau, Maurer. Drafting of the manuscript: Kirkpatrick, Hauptman. Critical revision of the manuscript for important intellectual content: Hauptman, Swetz, Blume, Gauvreau, Maurer, Goodlin. Statistical analysis: Gauvreau. Administrative, technical, or material support: Kirkpatrick, Blume, Maurer. Study supervision: Kirkpatrick, Hauptman.

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.

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.

Position statement of the Canadian Society of Clinical Chemists and Canadian Association of Medical Biochemists on hemoglobin A1c measurement and reporting

a Clinical Biochemistry and Genetics, Diagnostic Services of Manitoba, 820 Sherbrook Street, Winnipeg, MB, Canada b Laboratory Medicine, University of Alberta Hospitals, 8440-112 Street, Edmonton, AB, Canada c Victoria Reference Laboratory, Life Labs, 7862 Scohon Pl, Saanichton, BC, Canada d Clinical Chemistry, DynaLIFEDx, 200-10150 102 Street, Edmonton, AB, Canada e Pathology and Laboratory Medicine, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK, Canada f Clinical Chemistry and Immunology, Hamilton Regional Lab Med Program, 2N32 1200 Main Street, Hamilton, ON, Canada g Clinical Pathology, Sunnybrook Health Science Centre 2075 Bayview Avenue, Toronto, ON, Canada h Division of Biochemistry, The Ottawa Hospital, Ottawa, ON, Canada i Laboratory Medicine and Pathology, Sudbury Regional Hospital, 41 Ramsey Lake Road, Sudbury, ON, Canada j Biron-Laboratoire Medical, 4105 F Matte, Brossard, Quebec, Canada k Centre hospitalier régional de Trois-Rivières, 1991 Boul du Carmel Trois-Rivieres, QC, Canada l Edmunston Regional Hospital, 275 Boul Hebert, Edmunston, NB, Canada m Laboratory Medicine, Memorial University 300 Prince Phillip Drive, St. Johns, NF, Canada

A Canadian Study toward Changing Local Practice in the Diagnosis of Pediatric Celiac Disease

Background. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition endorses serological diagnosis (SD) for pediatric celiac disease (CD). The objective of this study was to pilot SD and to prospectively evaluate gastrointestinal permeability and mucosal inflammation at diagnosis and after one year on the gluten-free diet (GFD). We hypothesized that SD would be associated with similar short term outcomes as ED. Method. Children, 3–17 years of age, referred for possible CD were eligible for SD given aTTG level ≥200 U/mL, confirmed by repeat aTTG and HLA haplotypes. Gastrointestinal permeability, assessed using sugar probes, and inflammation, assessed using fecal calprotectin (FC), at baseline and after one year on a GFD were compared to patients who had ED. Results. Enrolled SD (n = 40) and ED (n = 48) patients had similar demographics. ED and SD groups were not different in baseline lactulose: mannitol ratio (L : M) (0.049 versus 0.034; p = 0.07), fractional excretion of sucrose (%FES; 0.086 versus 0.092; p = 0.44), or fecal calprotectin (FC; 89.6 versus 51.4; p = 0.05). At follow-up, urine permeability improved and was similar between groups, L : M (0.022 versus 0.025; p = 0.55) and %FES (0.040 versus 0.047; p = 0.87) (p > 0.05). FC improved but remained higher in the SD group (37.1 versus 15.9; p = 0.04). Conclusion. Patients on the GFD showed improved intestinal permeability and mucosal inflammation regardless of diagnostic strategy. This prospective study supports that children diagnosed by SD have resolving mucosal disease early after commencing a GFD.

A139 AGREEMENT OF IBDOC® AND QUANTON CAL® RAPID LATERAL FLOW-BASED FECAL CALPROTECTIN TESTS WITH ACCEPTED LAB-BASED ASSAYS FOR MONITORING INFLAMMATORY BOWEL DISEASE

Background Fecal calprotectin (FCP) is a useful biomarker for monitoring inflammatory bowel disease, showing good correlation to endoscopic disease activity. Currently used lab tests take 2–4 weeks to return a result, limiting their usefulness. Recently, lateral flow-based rapid tests have been combined with smartphone applications to allow patients to complete FCP testing at home, with their physician receiving the result the same day.