Optimization of Advanced Molecular Genetic Testing Utilization in Hematopathology: A Goldilocks Approach to Bone Marrow Testing.

PURPOSE: This study investigated the effectiveness of algorithmic testing in hematopathology at the Brigham and Women's Hospital and Dana-Farber Cancer Institute (DFCI). The algorithm was predicated on test selection after an initial pathologic evaluation to maximize cost-effective testing, especially for expensive molecular and cytogenetic assays. MATERIALS AND METHODS: Standard ordering protocols (SOPs) for 17 disease categories were developed and encoded in a decision support application. Six months of retrospective data from application beta testing was obtained and compared with actual testing practices during that timeframe. In addition, 2 years of prospective data were also obtained from patients at one community satellite site. RESULTS: A total of 460 retrospective cases (before introduction of algorithmic testing) and 109 prospective cases (following introduction) were analyzed. In the retrospective data, 61.7% of tests (509 of 825) were concordant with the SOPs while 38.3% (316 of 825) were overordered and 30.8% (227 of 736) of SOP-recommended tests were omitted. In the prospective data, 98.8% of testing was concordant (244 of 247 total tests) with only 1.2% overordered tests (3 of 247) and 7.6% omitted tests (20 of 264 SOP-recommended tests; overall P < .001). The cost of overordered tests before implementing SOP indicates a potential annualized saving of $1,347,520 in US dollars (USD) in overordered testing at Brigham and Women's Hospital/DFCI. Only two of 316 overordered tests (0.6%) returned any additional information, both for extremely rare clinical circumstances. CONCLUSION: Implementation of SOPs dramatically improved test ordering practices, with a just right number of ancillary tests that minimizes cost and has no significant impact on acquiring key informative test results.

Corrigendum to "Instability of 7-aminoclonazepam in frozen storage conditions" [Clin. Mass Spectrom. 9 (2018) 23-24].

[This corrects the article DOI: 10.1016/j.clinms.2018.07.002.].

Pandemic Response in the Clinical Laboratory: The Utility of Interactive Dashboards.

The ability to access and analyze data is critical to manage a laboratory and respond and adapt to changes, particularly during a pandemic. Data analytic tools can not only improve laboratory operations, but also increase the visibility of the laboratory in the healthcare system and demonstrate the positive impact of the laboratory on patient care. In this article, we describe the creation and utility of laboratory dashboards. Several dashboards were designed to assist with pandemic response. For each dashboard, a stored procedure was created that performed a SQL query of our laboratory information system mirror database. We utilized the business analytics platform, Tableau, for data visualization. Users could modify the data by selecting a specific date range, time window, work shift, institution(s), specific test(s), and/or testing platform(s). Access was controlled by OKTA integration to the host server over the web, behind the hospital firewall. During the April 2020 surge, we saw an increase in blood gas testing and corresponding decrease in non-critical testing such as Vitamin D. At our institution, SARS-CoV-2 molecular testing was performed using four primary platforms, four in-house and one send-out. Weekly and hourly testing volumes as well as turnaround times fluctuated based on reagent availability, new testing requests, staffing, and operational changes. Productivity dashboards indicated that coagulation testing volumes were highest on the third shift and that all three analyzers may not be necessary. Further, specimen volumes and productivity of accessioning staff varied throughout the day. Phlebotomy venipuncture volumes and patient wait times also varied throughout the pandemic. A decrease in ambulatory draws was seen during the surge but after reopening draw volumes, particularly at offsite locations, surpassed prepandemic volumes. We demonstrate that data analytics and interactive dashboards are powerful tools, are helpful in response to a pandemic and lead to improved TAT, supply utilization, staffing and workflows. Furthermore, dashboards provide objective data to review with hospital leadership and promote collaboration.

Impact of marijuana legalization on cannabis-related visits to the emergency department.

BACKGROUND: Cannabis is widely used in the United States despite federal laws. In US states that have progressed toward legalization, there have been various reported impacts on cannabis-related emergency department (ED) visits. However, studies on the impact of legalization in Massachusetts (MA) EDs are lacking. METHODS: Cannabinoid immunoassay (THC IA) results and cannabis-related ICD-10 codes were obtained for consecutive patient ED visits at two academic medical centers in Boston, MA over the following legalization periods (January 2012-December 2019): decriminalized (DEC), before medical dispensaries (MED BD), medical dispensaries available (MED DISP), before recreational dispensaries (REC BD) and recreational dispensaries available (REC DISP). Trends and monthly positivity rates for THC IA and ICD-10 codes were determined for these legalization periods. RESULTS: There was an increase in both THC IA (p < .0001) and cannabis-related ICD-10 codes (p < .0001) in the ED as legalization progressed at both institutions. Positivity rates significantly increased by 7% for THC IA and 0.4% for ICD-10 codes. Increases in THC IA positivity were seen in females, patients aged 30-39, older adults (>59 years), and those in the highest income tertile. There was an increasing trend in amphetamine positivity and decreasing trend in opiate positivity in patients with positive THC IA. Unlike THC IA, significant trends per patient demographics were not seen with ICD-10 codes. CONCLUSIONS: Legalization of marijuana in MA has led to an increase in cannabis use as indicated by both increasing rates of positive THC IA results, in older adults, as well as increasing cannabis-related ICD-10 codes. Data suggest a steady increase in THC use associated with legalization that was not associated with an increase in opiate, fentanyl, or cocaine use. We recommend using ED THC IA positivity, an objective laboratory measure, to monitor THC use and the impact of state-specific progression in cannabis legalization.

How SARS-CoV-2 Transformed the Clinical Laboratory: Challenges and Lessons Learned.

The COVID-19 pandemic has made a devastating impact on global health and continues to challenge healthcare infrastructure and delivery. The clinical laboratories were no exception as they are responsible for diagnostic testing that dictates many clinical, infection control, and public health decisions. Information technology and laboratory management tools are critical assets for maintaining and adapting operations in response to crises. When utilized effectively, they promote the integration between the clinical laboratory specialties (e.g., chemistry, hematology, microbiology, and molecular pathology). During the COVID-19 pandemic, our systems and processes were strained due to high testing volumes, demand for rapid turnaround times, supply chain constraints, and constantly evolving testing algorithms and result interpretations as our knowledge of the virus and of diagnostics increased over time. In this report, we describe those challenges and subsequent adaptations made by each clinical laboratory section. We hope these details help to provide potential solutions and approaches for other hospitals facing COVID-19 surges or other future pandemics.

Laboratory-Generated Urine Toxicology Interpretations: A Mixed Methods Study.

BACKGROUND: Clinicians frequently order urine drug testing (UDT) for patients on chronic opioid therapy (COT), yet often have difficulty interpreting test results accurately. OBJECTIVES: To evaluate the implementation and effectiveness of a laboratory-generated urine toxicology interpretation service for clinicians prescribing COT. STUDY DESIGN: Type II hybrid-convergent mixed methods design (implementation) and pre-post prospective cohort study with matched controls (effectiveness). SETTING: Four ambulatory sites (2 primary care, 1 pain management, 1 palliative care) within 2 US academic medical institutions. METHODS: Interpretative reports were generated by the clinical chemistry laboratory and were provided to UDT ordering providers via inbox message in the electronic health record (EHR). The Partners Institutional Review Board approved this study.Participants were primary care, pain management, and palliative care clinicians who ordered liquid chromatography-mass spectrometry UDT for COT patients in clinic. Intervention was a laboratory-generated interpretation service that provided an individualized interpretive report of UDT results based on the patient's prescribed medications and toxicology metabolites for clinicians who received the intervention (n = 8) versus matched controls (n = 18).Implementation results included focus group and survey feedback on the interpretation service's usability and its impact on workflow, clinical decision making, clinician-patient relationships, and interdisciplinary teamwork. Effectiveness outcomes included UDT interpretation concordance between the clinician and laboratory, documentation frequency of UDT results interpretation and communication of results to patients, and clinician prescribing behavior at follow-up. RESULTS: Among the 8 intervention clinicians (median age 58 [IQR 16.5] years; 2 women [25%]) on a Likert scale from 1 ("strongly disagree") to 5 ("strongly agree"), 7 clinicians reported at 6 months postintervention that the interpretation service was easy to use (mean 5 [standard deviation {SD}, 0]); improved results comprehension (mean 5 [SD, 0]); and helped them interpret results more accurately (mean 5 [SD, 0]), quickly (mean 4.67 [SD, 0.52]), and confidently (mean 4.83 [SD, 0.41]). Although there were no statistically significant differences in outcomes between cohorts, clinician-laboratory interpretation concordance trended toward improvement (intervention 22/32 [68.8%] to 29/33 [87.9%] vs. control 21/25 [84%] to 23/30 [76.7%], P = 0.07) among cases with documented interpretations. LIMITATIONS: This study has a low sample size and was conducted at 2 large academic medical institutions and may not be generalizable to community settings. CONCLUSIONS: Interpretations were well received by clinicians but did not significantly improve laboratory-clinician interpretation concordance, interpretation documentation frequency, or opioid-prescribing behavior.

Significant Operational Improvements with Implementation of Next Generation Laboratory Automation.

OBJECTIVES: To investigate the benefits and challenges of introducing next generation chemistry and coagulation automation. METHODS: We replaced the Roche modular preanalytic system attached to Roche Cobas 6000 analyzers with the Roche 8100 preanalytical line attached to the Roche Cobas 8000 and Stago STA R Max analyzers. The system included 2 add-on buffers (AOBs) for automated specimen archival and retrieval and primary-tube specimen processing. We measured turnaround time (TAT) from specimen receipt to result for chemistry and coagulation tests before, during, and after system implementation. TAT for add-on tests was also measured. RESULTS: We completed the system implementation during a 17-month period using existing laboratory space. The TAT for chemistry, coagulation, and add-on tests decreased significantly (P <.005, P <.001, and P <.005, respectively). We encountered several challenges, including barcode-label errors, mechanical problems, and workflow issues due to lack of bidirectional track for coagulation testing. CONCLUSIONS: Next generation laboratory automation yielded significantly shortened and less-variable TAT, particularly for add-on testing. Our approach could help other laboratories in the process of implementing and configuring automated systems.

The Impact of Outpatient Laboratory Alerting Mechanisms in Patients with AKI.

Background: AKI is an abrupt decrease in kidney function associated with significant morbidity and mortality. Electronic notifications of AKI have been utilized in patients who are hospitalized, but their efficacy in the outpatient setting is unclear. Methods: We evaluated the effect of two outpatient interventions: an automated comment on increasing creatinine results (intervention I; 6 months; n=159) along with an email to the provider (intervention II; 3 months; n=105), compared with a control (baseline; 6 months; n=176). A comment was generated if a patient's creatinine increased by >0.5 mg/dl (previous creatinine ≤2.0 mg/dl) or by 50% (previous creatinine >2.0 mg/dl) within 180 days. Process measures included documentation of AKI and clinical actions. Clinical outcomes were defined as recovery from AKI within 7 days, prolonged AKI from 8 to 89 days, and progression to CKD with in 120 days. Results: Providers were more likely to document AKI in interventions I (P=0.004; OR, 2.80; 95% CI, 1.38 to 5.67) and II (P=0.01; OR, 2.66; 95% CI, 1.21 to 5.81). Providers were also more likely to discontinue nephrotoxins in intervention II (P<0.001; OR, 4.88; 95% CI, 2.27 to 10.50). The median time to follow-up creatinine trended shorter among patients with AKI documented (21 versus 42 days; P=0.11). There were no significant differences in clinical outcomes. Conclusions: An automated comment was associated with improved documented recognition of AKI and the additive intervention of an email alert was associated with increased discontinuation of nephrotoxins, but neither improved clinical outcomes. Translation of these findings into improved outcomes may require corresponding standardization of clinical practice protocols for managing AKI.

Comparison of Oral Fluid and Urine for Detection of Cocaine Abuse Using Liquid Chromatography with Tandem Mass Spectrometry.

BACKGROUND: Requests for urine (UR) and oral fluid (OF) drug testing at our institutions are increasing. However, few studies have assessed the accuracy of each matrix using paired specimens and LC-MS/MS. We compared OF and UR for detection of cocaine (COC) abuse in addiction medicine-psychiatry (AMP) clinics. METHODS: We measured COC and benzoylecgonine (BZE) in OF (limit of detection (LOD) 2.0 µg/L) and BZE in UR (LOD 5 µg/L) by LC-MS/MS in 258 paired samples, and compared the two matrices when higher UR cutoffs of 25, 50, and 150 µg/L were employed. RESULTS: UR detected more COC abuse than OF at the LOD (5 µg/L). BZE was detected in 63 UR specimens and COC and/or BZE in 40 OF specimens (29 OF+UR+, 11 OF+UR-, 34 OF-UR+). UR creatinine was lower in OF+UR- specimens. COC and BZE were detected in 88% (35/40) and 75% (30/40) of OF specimens, respectively. OF was equivalent to UR at detecting COC abuse using a 25 µg/L cutoff, and detected more COC abuse than UR using 50 and 150 µg/L cutoffs. The ratio of OF COC/BZE increased with decreasing UR BZE concentrations. CONCLUSIONS: We demonstrate that OF detects more COC abuse in an AMP setting when UR BZE cutoffs ≥ 50 µg/L are utilized, and that UR creatinine concentrations are significantly lower in specimens positive for COC and/or BZE in OF and negative for BZE in UR. The presence of only COC in OF and low concentrations of UR BZE likely indicates remote use of COC.

Rates of Fentanyl Positivity in Neonatal Urine Following Maternal Analgesia During Labor and Delivery.

BACKGROUND: Fentanyl is commonly given as an analgesic during labor and delivery. The extent of transplacental drug transfer and fetal exposure is not well studied. We analyzed the relationship between neonatal urine fentanyl results and various peripartum factors. METHODS: A total of 96 neonates with urine toxicology screening between January 2017 and September 2018 were included in the study. Medical record review was used to obtain maternal, neonatal, and anesthesia parameters. A subset of 9 specimens were further tested for levels of fentanyl and norfentanyl by liquid chromatography-tandem mass spectrometry. RESULTS: In 29% (n = 24) of cases associated with fentanyl-containing labor analgesia, neonatal toxicology screens were positive for the presence of fentanyl. Positive test results strongly correlated with the cumulative dose and duration of labor analgesia (P < 0.001). The odds of positive neonatal fentanyl screen results increased 4-fold for every 5 hours of maternal exposure to labor analgesia. Importantly, however, neonatal outcomes for infants with positive and negative urine fentanyl screens were the same. CONCLUSIONS: Our study establishes that maternal fentanyl analgesia is strongly associated with positive neonatal urine fentanyl screens and suggests that more judicious use of these laboratory tests may be warranted.

Tracking Expansions of Stable and Threshold Length Trinucleotide Repeat Tracts In Vivo and In Vitro Using Saccharomyces cerevisiae.

Trinucleotide repeat (TNR) tracts are inherently unstable during DNA replication, leading to repeat expansions and/or contractions. Expanded tracts are the cause of over 40 neurodegenerative and neuromuscular diseases. In this chapter, we focus on the (CAG)n and (CTG)n repeat sequences that, when expanded, lead to Huntington's disease (HD) and myotonic dystrophy type 1 (DM1), respectively, as well as a number of other neurodegenerative diseases. TNR tracts in most individuals are relatively small and stable in terms of length. However, TNR tracts become increasingly prone to expansion as tract length increases, eventually leading to very long tracts that disrupt coding (e.g. HD) or noncoding (e.g., DM1) regions of the genome. It is important to understand the early stages in TNR expansions, that is, the transition from small, stable lengths to susceptible threshold lengths. We describe PCR-based in vivo assays, using the model system Saccharomyces cerevisiae, to determine and characterize the dynamic behavior of TNR tracts in the stable and threshold ranges. We also describe a simple in vitro system to assess tract dynamics during 5' single-stranded DNA (ssDNA) flap processing and to assess the role of different DNA metabolism proteins in these dynamics. These assays can ultimately be used to determine factors that influence the early stages of TNR tract expansion.

Provider Misinterpretation, Documentation, and Follow-Up of Definitive Urine Drug Testing Results.

BACKGROUND: Urine drug testing (UDT) is an essential tool to monitor opioid misuse among patients on chronic opioid therapy. Inaccurate interpretation of UDT can have deleterious consequences. Providers' ability to accurately interpret and document UDT, particularly definitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) results, has not been widely studied. OBJECTIVE: To examine whether providers correctly interpret, document, and communicate LC-MS/MS UDT results. DESIGN: This is a retrospective chart review of 160 UDT results (80 aberrant; 80 non-aberrant) between August 2017 and February 2018 from 5 ambulatory clinics (3 primary care, 1 oncology, 1 pain management). Aberrant results were classified into one or more of the following categories: illicit drug use, simulated compliance, not taking prescribed medication, and taking a medication not prescribed. Accurate result interpretation was defined as concordance between the provider's documented interpretation and an expert laboratory toxicologist's interpretation. Outcome measures were concordance between provider and laboratory interpretation of UDT results, documentation of UDT results, results acknowledgement in the electronic health record, communication of results to the patient, and rate of prescription refills. KEY RESULTS: Aberrant results were most frequently due to illicit drug use. Overall, only 88 of the 160 (55%) had any documented provider interpretations of which 25/88 (28%) were discordant with the laboratory toxicologist's interpretation. Thirty-six of the 160 (23%) documented communication of the results to the patient. Communicating results was more likely to be documented if the results were aberrant compared with non-aberrant (33/80 [41%] vs. 3/80 [4%], p < 0.001). In all cases where provider interpretations were discordant with the laboratory interpretation, prescriptions were refilled. CONCLUSIONS: Erroneous provider interpretation of UDT results, infrequent documentation of interpretation, lack of communication of results to patients, and prescription refills despite inaccurate interpretations are common. Expert assistance with urine toxicology interpretations may be needed to improve provider accuracy when interpreting toxicology results.

A Rapid Dilute-and-Shoot UPLC-MS/MS Assay to Simultaneously Measure 37 Drugs and Related Metabolites in Human Urine for Use in Clinical Pain Management.

BACKGROUND: Monitoring of medication compliance and drug abuse is used by clinicians to increase patient prescription drug compliance and reduce illicit drug abuse and diversion. Despite available immunoassays, chromatography-mass spectrometry-based methods are considered the gold standard for urine drug monitoring owing to higher sensitivities and specificities. Herein, we report a fast, convenient ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay to detect or quantify 37 clinically relevant prescription drugs, drugs of abuse, and related glucuronides and other metabolites in human urine by single diluted sample injection. METHODS: Analytes consisted of prescription and illicit opioids, benzodiazepines, and drugs of abuse, including parent compounds and glucuronidated and nonglucuronidated metabolites. Urine samples were diluted with water and supplemented with deuterated internal standards without enzymatic hydrolysis, analyte extraction, or sample purification. Analytes were separated by reversed-phase UPLC and quantified by positive-mode electrospray ionization and collision-induced dissociation MS. Assay validation followed Food and Drug Administration bioanalytical guidelines. RESULTS: Total analytical run time was 5.5 min. All analytes demonstrated acceptable inter- and intraassay accuracy, imprecision, and linearity throughout clinically relevant analytical ranges (1-2000 ng/mL, depending on analyte). All analytes demonstrated acceptable selectivity, stability, matrix effects, carryover, and performance compared to national reference laboratory or previously validated in-house methods. A total of 23 and 14 analytes were validated for quantitative and qualitative testing, respectively. CONCLUSIONS: A convenient UPLC-MS/MS assay for simultaneously monitoring 37 analytes in human urine was validated for use in pain management testing. Advantages of this multiplex assay include facile sample preparation and higher-throughput definitive detection including glucuronide metabolite quantification.

Urine is superior to oral fluid for detecting buprenorphine compliance in patients undergoing treatment for opioid addiction.

BACKGROUND: Buprenorphine (BUP) is commonly used in opioid agonist medication-assisted treatment (OA-MAT). Oral fluid (OF) is an attractive option for compliance monitoring during OA-MAT as collections are observed and evidence suggests that OF is less likely to be adulterated than urine (UR). However, the clinical and analytical performance of each matrix for monitoring BUP compliance has not been well studied. METHODS: We collected 260 paired OF and UR specimens. Concentrations of buprenorphine (BUP) and norbuprenorphine (NBUP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in each matrix. The glucuronide metabolites and naloxone concentrations were also measured in UR by LC-MS/MS. Medications were reviewed and UR creatinine concentrations were determined. RESULTS: 147/260 specimens (57%) were positive for BUP and/or metabolites in one or both matrices. BUP and/or metabolites were more likely to be detected in UR (p < 0.001). 1 OF specimen and 12 UR specimens were considered adulterated/substituted. The majority of patients prescribed BUP were positive for BUP in UR (97%) as opposed to OF (78%). The detection of undisclosed use approximately doubled in UR. CONCLUSIONS: UR is the preferred matrix for detecting both buprenorphine compliance and undisclosed use. Clinicians should consider the ease of collection, risk of adulteration and detection of illicit drug use when deciding on an appropriate matrix. If OF testing is clinically necessary, UR should be measured in conjunction with OF at least periodically to avoid false negative BUP results.

Clinical Benefits of Direct-to-Definitive Testing for Monitoring Compliance in Pain Management.

BACKGROUND: The technical advantages of direct-to-definitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) urine testing for monitoring patient compliance in pain management are well known. However, the design and implementation of LC-MS/MS methods are more controversial, including factors such as determining appropriate cutoffs, specimen processing (e.g., specimen hydrolysis), reporting of qualitative and/or quantitative results, and test menu. OBJECTIVES: The objective of the research was to compare the clinical performance of our previous urine pain toxicology panel, a combination of immunoassay (IA) screens and LC-MS/MS, to our current pain toxicology panel, which features direct-to-definitive LC-MS/MS for 34 drugs and metabolites. STUDY DESIGN: Six months of results from our previous pain toxicology panel were compared to 5.5 months of results from our current pain toxicology panel, enabling us to make conclusions regarding clinical performance. SETTING: The research took place at Brigham and Women's Hospital in Boston, MA. METHODS: The percentage of false positive IA results was evaluated for our previous pain toxicology panel. The positivity rates for each drug and/or metabolite were calculated for both the previous and current panels, including rates of detection of both prescribed and illicit drugs. The turnaround time (TAT), direct and send-out costs associated with each approach, as well as projected cost savings were also determined. RESULTS: False positive rates with IA ranged from 0% to 29%; the highest false positive rate was seen for 6-acetylmorphine (6-AM). The elimination of IA, addition of metabolites, and/or lowering of cutoffs increased the detection rate of 6-AM, benzoylecgonine (cocaine metabolite), fentanyl, morphine, and oxycodone. The ability to differentiate compliance from simulated compliance improved after eliminating specimen hydrolysis. The TAT improved significantly and projected yearly cost savings with the current panel was $95,003 (USD). In our opinion, qualitative results appeared sufficient to assess compliance in the majority of cases. LIMITATIONS: Our study was performed in a single academic center in a specific geographic region; therefore, our results may not be generalizable to other types of centers or regions. CONCLUSION: Direct-to-definitive LC-MS/MS testing has several clinical benefits, including reduction of false positive results, improved assessment of patient compliance, decreased TAT, and increased detection of drug use and abuse. Cost savings were also realized using this approach. KEY WORDS: Direct-to-definitive, LC-MS/MS, immunoassay, sensitivity, cost, pain management, turnaround time, patient compliance.

Development and Validation of an Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for the Concurrent Measurement of Gabapentin, Lamotrigine, Levetiracetam, Monohydroxy Derivative of Oxcarbazepine, and Zonisamide Concentrations in Serum in a Clinical Setting.

BACKGROUND: Therapeutic drug monitoring of antiepileptic drugs (AEDs) is often necessary to prevent associated destructive toxicities. Tandem mass spectrometry (MS/MS) with stable-isotope-labeled internal standards is considered the gold standard for the measurement of AEDs. This study presents the development and validation of a clinical ultra-performance liquid chromatography-MS/MS method for the concurrent measurement of gabapentin, lamotrigine, levetiracetam, monohydroxy derivative of oxcarbazepine, and zonisamide in human serum. METHODS: To determine the optimal assay analyte range, one year of AED therapeutic drug monitoring results (n = 1825) were evaluated. Simple protein precipitation with acetonitrile containing isotopically labeled internal standards was used. Reverse-phase ultra-performance liquid chromatography chromatographic separation was used, having a total run time of 3 minutes. Quantification of analytes was accomplished using electrospray ionization in positive ion mode and collision-induced dissociation MS. Assay parameters were evaluated per Food and Drug Administration bioanalytical guidelines. RESULTS: After evaluating internal patient data, the analytical measuring range (AMR) of the assay was established as 0.1-100 mcg/mL. All AEDs were linear across the AMR, with R values ranging from 0.9988 to 0.9999. Imprecision (% coefficient of variation) and inaccuracy (% difference) were calculated to be <20% for the lower limit of quantitation and <15% for the low, mid, and high levels of quality controls across the AMR. All AEDs demonstrated acceptable assay parameters for carryover, stability under relevant storage conditions, matrix effects, recovery, and extraction and processing efficiency. In addition, the assay displayed acceptable concordance to results obtained from a national reference laboratory, with Deming regression R of 0.99 and slope values ranging from 0.89 to 1.17. CONCLUSIONS: A simple, cost-effective, and robust ultra-performance liquid chromatography-tandem mass spectrometry method for monitoring multiple AEDs was developed and validated to address the clinical needs of patients at our institution.

Monitoring opioid and benzodiazepine use and abuse: Is oral fluid or urine the preferred specimen type?

BACKGROUND: Oral fluid (OF) has become an increasingly popular matrix to assess compliance in pain management and addiction settings as it reduces the likelihood of adulteration. However, drug concentrations and windows of detection are not as well studied in OF as in urine (UR). We compared the clinical utility and analytical performance of OF and UR as matrices for detecting common benzodiazepines and opioids. METHODS: OF and UR concentrations of 5 benzodiazepines and 7 opioids were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 263 paired OF and UR specimens. UR creatinine was measured and prescription medications were reviewed. RESULTS: The benzodiazepines 7-aminoclonazepam, lorazepam, and oxazepam exhibited statistically higher detection rates in UR. For opioids, 6-AM was statistically more likely to be detected in OF, while hydromorphone and oxymorphone were statistically more likely to be detected in UR. Chemical properties including glucuronidation explain preferential detection in each matrix, not UR creatinine nor prescription status. CONCLUSION: We found that OF is the preferred matrix for 6-AM, while UR is preferred for 7-aminoclonazepam, lorazepam, oxazepam, hydromorphone, and oxymorphone. However, OF should be considered if the risk of adulteration is high and use and/or misuse of benzodiazepines, hydromorphone, and oxymorphone is low.

Economics of Pain Management Testing.

BACKGROUND: Chronic pain management accounts for a significant portion of health-care costs and has important societal implications, including the increasing availability of prescription narcotics. Urine drug testing (UDT) is an effective tool to monitor adherence to prescription medications and has been recommended by several guidelines. Furthermore, the clinical and technical benefits of UDT using definitive testing methods such as LC-MS/MS are well documented. However, the cost-effectiveness is not well studied. CONTENT: In this article, we discuss the cost considerations associated with different UDT methodologies, including point-of-care immunoassays, laboratory-based immunoassays, and definitive testing by LC-MS/MS. The costs of reagents, consumables, instrumentation, service, and labor are described, as well as the opportunity each methodology offers in relation to test utilization and clinical cost savings. An overview of how to assess the cost-effectiveness of insourcing definitive testing and how to generate a comprehensive insourcing proposal is provided. Billing options for UDT and the recent changes in current procedural terminology codes are also discussed. SUMMARY: Given the current health-care environment, additional studies and recommendations that incorporate the cost-effectiveness of definitive testing to monitor compliance in pain management are needed. The decreasing cost of mass spectrometry, the increasing visibility of the value of the laboratory medicine, the new prescriber regulations for opioids, and the push to change reimbursement for definitive UDT will all contribute to the cost-effectiveness of definitive LC-MS/MS to monitor patients with chronic pain.

Increased Patient Satisfaction and a Reduction in Pre-Analytical Errors Following Implementation of an Electronic Specimen Collection Module in Outpatient Phlebotomy.

BACKGROUND: Patient satisfaction in outpatient phlebotomy settings typically depends on wait time and venipuncture experience, and many patients equate their experiences with their overall satisfaction with the hospital. METHODS: We compared patient service times and preanalytical errors pre- and postimplementation of an integrated electronic health record (EHR)-laboratory information system (LIS) and electronic specimen collection module. We also measured patient wait time and assessed patient satisfaction using a 5-question survey. RESULTS: The percentage of patients waiting less than 10 minutes increased from 86% preimplementation to 93% postimplementation of the EHR-LIS (P ≤.001). The median total service time decreased significantly, from 6 minutes (IQR, 4-8 minutes), to 5 minutes (IQR, 3-6 minutes) (P = .005). The preanalytical errors decreased significantly, from 3.20 to 1.93 errors per 1000 specimens (P ≤.001). Overall patient satisfaction improved, with an increase in excellent responses for all 5 questions (P ≤.001). CONCLUSIONS: We found several benefits of implementing an electronic specimen collection module, including decreased wait and service times, improved patient satisfaction, and a reduction in preanalytical errors.

Top ten challenges when interfacing a laboratory information system to an electronic health record: Experience at a large academic medical center.

BACKGROUND: Recent U.S. government regulations incentivize implementation of an electronic health record (EHR) with computerized order entry and structured results display. Many institutions have also chosen to interface their EHR to their laboratory information system (LIS). Reported long-term benefits include increased efficiency and improved quality and safety. In order to successfully implement an interfaced EHR-LIS, institutions must plan years in advance and anticipate the impact of an integrated system. It can be challenging to fully understand the technical, workflow and resource aspects and adequately prepare for a potentially protracted system implementation and the subsequent stabilization. OBJECTIVES: We describe the top ten challenges that we encountered in our clinical laboratories following the implementation of an interfaced EHR-LIS and offer suggestions on how to overcome these challenges. METHODS: This study was performed at a 777-bed, tertiary care center which recently implemented an interfaced EHR-LIS. Challenges were recorded during EHR-LIS implementation and stabilization and the authors describe the top ten. RESULTS: Our top ten challenges were selection and harmonization of test codes, detailed training for providers on test ordering, communication with EHR provider champions during the build process, fluid orders and collections, supporting specialized workflows, sufficient reports and metrics, increased volume of inpatient venipunctures, adequate resources during stabilization, unanticipated changes to laboratory workflow and ordering specimens for anatomic pathology. A few suggestions to overcome these challenges include regular meetings with clinical champions, advanced considerations of reports and metrics that will be needed, adequate training of laboratory staff on new workflows in the EHR and defining all tests including anatomic pathology in the LIS. CONCLUSION: EHR-LIS implementations have many challenges requiring institutions to adapt and develop new infrastructures. This article should be helpful to other institutions facing or undergoing a similar endeavor.