Marion L. Snyder

Patient Misidentifications Caused by Errors in Standard Bar Code Technology

BACKGROUND Bar code technology has decreased transcription errors in many healthcare applications. However, we have found that linear bar code identification methods are not failsafe. In this study, we sought to identify the sources of bar code decoding errors that generated incorrect patient identifiers when bar codes were scanned for point-of-care glucose testing and to develop solutions to prevent their occurrence. METHODS We identified misread wristband bar codes, removed them from service, and rescanned them by using 5 different scanner models. Bar codes were reprinted in pristine condition for use as controls. We determined error rates for each bar code-scanner pair and manually calculated internal bar code data integrity checks. RESULTS As many as 3 incorrect patient identifiers were generated from a single bar code. Minor bar code imperfections, failure to control for bar code scanner resolution requirements, and less than optimal printed bar code orientation were confirmed as sources of these errors. Of the scanner models tested, the Roche ACCU-CHEK® glucometer had the highest error rate. The internal data integrity check system did not detect these errors. CONCLUSIONS Bar code-related patient misidentifications can occur. In the worst case, misidentified patient results could have been transmitted to the incorrect patient medical record. This report has profound implications not only for point-of-care testing but also for bar coded medication administration, transfusion recipient certification systems, and other areas where patient misidentifications can be life-threatening. Careful control of bar code scanning and printing equipment specifications will minimize this threat to patient safety. Ultimately, healthcare device manufacturers should adopt more robust and higher fidelity alternatives to linear bar code symbologies.

A New Highly Specific Buprenorphine Immunoassay for Monitoring Buprenorphine Compliance and Abuse

Urine buprenorphine screening is utilized to assess buprenorphine compliance and to detect illicit use. Robust screening assays should be specific for buprenorphine without cross-reactivity with other opioids, which are frequently present in patients treated for opioid addiction and chronic pain. We evaluated the new Lin-Zhi urine buprenorphine enzyme immunoassay (EIA) as a potentially more specific alternative to the Microgenics cloned enzyme donor immunoassay (CEDIA) by using 149 urines originating from patients treated for chronic pain and opioid addiction. The EIA methodology offered specific detection of buprenorphine use (100%) (106/106) and provided superior overall agreement with liquid chromatography-tandem mass spectrometry, 95% (142/149) and 91% (135/149) using 5 ng/mL (EIA[5]) and 10 ng/mL (EIA[10]) cutoffs, respectively, compared to CEDIA, 79% (117/149). CEDIA generated 27 false positives, most of which were observed in patients positive for other opioids, providing an overall specificity of 75% (79/106). CEDIA also demonstrated interference from structurally unrelated drugs, chloroquine and hydroxychloroquine. CEDIA and EIA[5] yielded similar sensitivities, both detecting 96% (22/23) of positive samples from patients prescribed buprenorphine, and 88% (38/43) and 81% (35/43), respectively, of all positive samples (illicit and prescribed users). The EIA methodology provides highly specific and sensitive detection of buprenorphine use, without the potential for opioid cross-reactivity.

A new automated urine fentanyl immunoassay: technical performance and clinical utility for monitoring fentanyl compliance.

BACKGROUND Opiate and other drugs of abuse screening assays have been available for many years, and successfully utilized for monitoring patient medication compliance and for detecting misuse. However, immunoassays designed to rapidly detect the highly potent synthetic opioid, fentanyl, have not been available. METHODS We evaluated a new fentanyl homogeneous enzyme immunoassay (HEIA) (Immunalysis Corporation) for its ability to accurately detect fentanyl in 307 urine samples from patients prescribed chronic opioid therapy. Samples were screened by HEIA and confirmed by LC-MS/MS and ELISA for diagnostic comparison. HEIA precision and interference studies were performed. RESULTS HEIA diagnostic sensitivity, specificity and accuracy were 97%, 99%, and 99%, respectively, in comparison with LC-MS/MS and ELISA. HEIA detected 37 of the 38 LC-MS/MS positive samples identified in our initial evaluation, including some that contained very low levels of fentanyl, <1 ng/ml (<3 fmol/l). HEIA showed minimal cross-reactivity with other opioid analgesics and commonly encountered drugs. Interferences by common urine contaminants were negligible, but we observed considerable signal suppression in acidic samples (pH<4.0). CONCLUSIONS The HEIA urine fentanyl assay allows for rapid and accurate fentanyl detection, illustrating its utility in monitoring fentanyl compliance and abuse.

Development of a fast and simple liquid chromatography-tandem mass spectrometry method for the quantitation of argatroban in patient plasma samples.

An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the direct measurement of argatroban in human plasma was developed and compared with the activity-based Hemoclot Thrombin Inhibitors assay. UPLC-MS/MS was performed using diclofenac as an internal standard. In summary, argatroban and diclofenac were extracted from 100 μL of plasma using a methanol precipitation protocol, and chromatographic separation was performed on an ACQUITY TQD mass spectrometer using a UPLC C18 BEH 1.7 μm column with a water and methanol gradient containing 0.1% formic acid. The detection and quantitation were performed using positive ion electrospray ionization and multiple reaction monitoring (MRM) mode. The UPLC-MS/MS method was linear over the concentration range of 0.003-3.0 μg/mL, with a lower limit of quantitation for argatroban of 0.003 μg/mL. The intra- and inter-assay imprecision was less than 12% at the plasma argatroban concentrations tested. Good correlation was demonstrated between the UPLC-MS/MS method and the indirect activity-based assay for determination of argatroban. However, increased plasma fibrinogen levels caused underestimation of argatroban levels using the indirect activity-based assay, whereas the UPLC-MS/MS method was unaffected. UPLC-MS/MS provides a relatively simple, sensitive, and rapid means of argatroban monitoring. It has successfully been applied to assess plasma argatroban concentrations in hospitalized patients and may provide a more accurate determination of argatroban concentrations than an activity-based assay in certain clinical conditions.

Falsely Increased hCG in Patients with High Leukocyte Counts

To the Editor: Falsely increased plasma troponin (Tn) I and T results have been reported for several Tn methods, including the Beckman Coulter UniCel DxI AccuTnI assay (Beckman Coulter, Chaska, MN) (1–3). We and others have also observed falsely increased human chorionic gonadotropin (hCG) using the Beckman Coulter Access Total βhCG on the UniCel DxI (1). These false increases were identified by the finding of substantially lower results following high-speed recentrifugation and reanalysis, suggesting a particulate interference. However, the sources of these false increases were not previously determined. In reviewing clinical data for patients from whom plasma samples were found to generate falsely high hCG results on the UniCel DxI in our laboratories, we found these patients had high blood leukocyte counts. Based on this finding, we investigated the interference of leukocytes in the Beckman Coulter Access Total βhCG assay. This study was approved by the Emory Institutional Review Board. First, we measured hCG in leftover plasma samples from patients with known high blood leukocyte content of >25 × 103/μL. The thirteen randomly selected samples (10 male, 3 female) were inverted several times in the original lithium heparin plasma separator tubes (PSTs) (Becton Dickinson) to disturb any particulates settled during storage (up to 24 h refrigerated) and then measured …

Significant cost savings achieved by in-sourcing urine drug testing for monitoring medication compliance in pain management.

INTRODUCTION Reference laboratory testing can represent a significant component of the laboratory budget. Therefore, most laboratories continually reassess the feasibility of in-sourcing various tests. We describe the transfer of urine drug testing performed for monitoring medication compliance in pain management from a reference laboratory into an academic clinical laboratory. METHODS The process of implementing of both screening immunoassays and confirmatory LC-MS/MS testing and the associated cost savings is outlined. RESULTS The initial proposal for in-sourcing this testing, which included the tests to be in-sourced, resources required, estimated cost savings and timeline for implementation, was approved in January 2009. All proposed testing was implemented by March 2011. CONCLUSIONS Keys to the successful implementation included budgeting adequate resources and developing a realistic timeline, incorporating the changes with the highest budget impact first. We were able to in-source testing in 27 months and save the laboratory approximately

Method comparison of a 25-hydroxy vitamin D enzyme immunoassay to liquid chromatography tandem mass spectroscopy.

1 million in the first 3 year.

Drug Addiction or False Conviction

and Petr Jarolim 1, * 1 Department of Pathology , Brigham and Women ’ s Hospital, Harvard Medical School, Boston, MA , USA 2 Department of Pathology , Greenville Hospital System, University Medical Center, Greenville, SC , USA 3 Irving Institute of Clinical and Translational Research , New York City, NY , USA 4 Division of Endocrinology , Columbia University Medical Center, New York City, NY , USA

Improved Buprenorphine Immunoassay Performance After Urine Treatment with β-Glucuronidase

A 25-year-old woman with a history of multiple medical problems including a distal pancreatectomy and splenectomy 6 months earlier for pancreatic mass (solid pseudopapillary tumor with negative margins), systemic lupus erythematous (SLE),3 Crohn disease, and a history of alcohol abuse presented to her pain management physician with weakness, decreased appetite, worsening joint pain, abdominal pain, and diarrhea (five episodes per day, some visibly bloody). At presentation, her vital signs included temperature 97.1 °F, blood pressure 127/89 mmHg, and heart rate 97 beats/min. Physical exam was remarkable for hyperactive bowel sounds, diffuse joint pain, and periumbilical pain at the surgical incision site described as constant and gnawing and graded 8 out of 10. She was prescribed morphine and oxycodone (as needed) for pain; hydroxychloroquine and prednisone for SLE; and mesalamine, docusate, and infliximab for Crohn disease. She was referred to her gastroenterologist for management of her gastrointestinal complaints. Her dosages of prednisone and hydroxychloroquine were maintained to control her SLE. Pulse doses of steroids and a higher dose of prednisone were considered, but the risk of infection was determined to be too great. Before refilling her morphine and oxycodone prescriptions, her physician confirmed that her previous urine drug testing results showed the presence of her prescribed medications (and related metabolites), suggesting medication compliance, as well as no unexpected drugs. The physician also performed a pill count and documented her last dose of morphine (that morning) and oxycodone (3 days before). In addition, she was asked to complete a Screener and Opioid Assessment for Patients with Pain questionnaire (1), designed to assess her risk of medication noncompliance and abuse. On the basis of her responses to the questionnaire, the pill count, and her previous consistent urine drug testing results, the physician felt she was at low risk for noncompliance and renewed …

Cirrhosis Originally Diagnosed as Nonalcoholic Steatohepatitis

Buprenorphine (BUP), a semi-synthetic opioid analgesic, is increasingly prescribed for the treatment of chronic pain and opioid dependence. Urine immunoassay screening methods are available for monitoring BUP compliance and misuse; however, these screens may have poor sensitivity or specificity. We evaluated whether the pretreatment of urine with β-glucuronidase (BG) improves the sensitivity and overall accuracy of three BUP enzyme immunoassays when compared with liquid chromatography-tandem mass spectrometry (LC-MS-MS). Urine samples sent to our laboratories for BUP testing (n = 114) were analyzed before and after BG pretreatment by cloned enzyme donor immunoassay (CEDIA), enzyme immunoassay (EIA) and homogenous EIA (HEIA) immunoassays using a common 5 ng/mL cutoff. Total BUP and norbuprenorphine (NBUP) concentrations were measured by LC-MS-MS as the reference method. Urine BG pretreatment improved EIA, HEIA and CEDIA sensitivities from 70, 82 and 94%, respectively, to 97% for each of the three methods, when compared with LC-MS-MS. While the specificity of the EIA and HEIA remained 100% after BG pretreatment, the specificity of the CEDIA decreased from 74 to 67%. Urine pretreatment with BG is recommended to improve sensitivity of the EIA and HEIA BUP screening methods.