Clinical decision support to improve CBC and differential ordering.

OBJECTIVES: Complete blood count and differential (CBC diff) is a common laboratory test that may be overused or misordered, particularly in an inpatient setting. We assessed the ability of a clinical decision support (CDS) alert to decrease unnecessary orders for CBC diff and analyzed its impact in the laboratory. METHODS: We designed 3 CDS alerts to provide guidance to providers ordering CBC diff on inpatients at frequencies of daily, greater than once daily, or as needed. RESULTS: The 3 alerts were highly effective in reducing orders for CBC diff at the frequencies targeted by the alert. Overall, test volume for CBC diff decreased by 32% (mean of 5257 tests per month) after implementation of the alerts, with a corresponding decrease of 22% in manual differentials performed (mean of 898 per month). Turnaround time for manual differentials decreased by a mean of 41.5 minutes, with a mean decrease of up to 90 minutes during peak morning hours. CONCLUSIONS: The 3 CDS alerts successfully decreased inpatient orders for CBC diff and improved the quality of patient care by decreasing turnaround time for manual differentials.

Establishing optimal cutoff values for high-sensitivity cardiac troponin algorithms in risk stratification of acute myocardial infarction.

Acute myocardial infarction (AMI) is a leading cause of mortality globally, highlighting the need for timely and accurate diagnostic strategies. Cardiac troponin has been the biomarker of choice for detecting myocardial injury. A dynamic change in concentrations supports the diagnosis of AMI in the setting of evidence of acute myocardial ischemia. The new generation of high-sensitivity cardiac troponin (hs-cTn) assays has significantly improved analytical sensitivity but at the expense of decreased clinical specificity. As a result, sophisticated algorithms are required to differentiate AMI from non-AMI patients. Establishing optimal hs-cTn cutoffs for these algorithms to rule out and rule in AMI has been the subject of intensive investigations. These efforts have evolved from examining the utility of the hs-cTn 99th percentile upper reference limit, comparing the percentage versus absolute delta thresholds, and evaluating the performance of an early European Society of Cardiology-recommended 3 h algorithm, to the development of accelerated 1 h and 2 h algorithms that combine the admission hs-cTn concentrations and absolute delta cutoffs to rule out and rule in AMI. Specific cutoffs for individual confounding factors such as sex, age, and renal insufficiency have also been investigated. At the same time, concerns such as whether the small delta thresholds exceed the analytical and biological variations of hs-cTn assays and whether the algorithms developed in European study populations fit all other patient cohorts have been raised. In addition, the accelerated algorithms leave a substantial number of patients in a non-diagnostic observation zone. How to properly diagnose patients falling in this zone and those presenting with elevated baseline hs-cTn concentrations due to the presence of confounding factors or comorbidities remain open questions. Here we discuss the developments described above, focusing on criteria and underlying considerations for establishing optimal cutoffs. In-depth analyses are provided on the influence of biological variation, analytical imprecision, local AMI rate, and the timing of presentation on the performance metrics of the accelerated hs-cTn algorithms. Developing diagnostic strategies for patients who remain in the observation zone and those presenting with confounding factors are also reviewed.

Evaluation of the rapid Quidel Sofia Lyme fluorescent immunoassay as a first-tier test in a modified 2-tier testing algorithm for Lyme disease: A comparison with the Zeus ELISA Borrelia VlsE1/pepC10 lgG/IgM assay followed by the Zeus monovalent IgM/IgG confirmatory assay.

OBJECTIVES: Recently modified 2-tier testing (MTTT) algorithms using 2 enzyme immunoassays (EIAs) as opposed to an EIA followed by immunoblot have been approved by the US Food and Drug Administration (FDA) for the screening and confirmation of Lyme disease. The Quidel Sofia Lyme fluorescent immunoassay is a rapid lateral-flow method that can be performed in real time, permitting on-demand testing. We evaluated the performance of the Sofia assay as a first-tier test in an MTTT algorithm. METHODS: We compared the Sofia Lyme test with the Zeus ELISA Borrelia VlsE1/pepC10 lgG/IgM test, followed by the Zeus monovalent IgM/IgG EIA as the confirmatory test. RESULTS: When used as a first-tier test compared with a standard Zeus MTTT assay, the positive percentage agreement was 91.4%% (95% CI, 77.6%-97.0%). The negative percentage agreement was 100% (95% CI, 94.0%-100%). The overall agreement was 98.3% (95% CI, 94.2%-99.4%). κ = 0.945, indicating "almost perfect agreement." CONCLUSIONS: The Sofia Lyme test performs well compared with an FDA-approved MTTT.

Evaluation of the Rapid Quidel Sofia 2 Lyme Immunoassay as a First-Tier Test in a Two-Tier Testing Algorithm for Lyme Disease: Comparison to the Zeus ELISA Borrelia VlsE1/pepC10 IgG/IgM Assay Followed by Immunoblot.

OBJECTIVES: Two-tiered serologic testing for Lyme disease is usually performed using an enzyme-linked immunosorbent assay (ELISA) as the first-tier test. The Quidel Sofia 2 Lyme test is a relatively new lateral flow method to provide more rapid turnaround time. We evaluated its performance in comparison to an established ELISA method. The test can be performed on demand rather than batching assays in a central laboratory. METHODS: We compared the Sofia 2 assay to the Zeus VlsE1/pepC10 IgG/IgM test in a standard two-tiered testing algorithm. RESULTS: Comparison of the Sofia 2 to the Zeus VlsE1/pepC10 IgG/IgM showed an overall agreement of 89.9% (κ statistic of 0.750, indicating "substantial agreement"). When the tests were followed by immunoblot in a two-tier algorithm, the agreement was 98.9% (κ statistic of 0.973, indicating "almost perfect" agreement). CONCLUSIONS: The Sofia 2 Lyme test performs well when compared with the Zeus VlsE1/pepC10 IgG/IgM in a two-tiered testing algorithm.

Detection and localization of early- and late-stage cancers using platelet RNA.

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Measurement of High Sensitivity Troponin T in Patients with Early Stage Lyme Disease: Preliminary Evidence for Possible Subclinical Cardiac Involvement.

OBJECTIVE: In patients with early Lyme disease (ELD), cardiac involvement is known to occur in approximately 1% of patients. We measured high-sensitivity troponin T (hsTnT) in patients with early Lyme disease to evaluate the possibility of subclinical cardiac involvement. METHODS: We measured hsTnT in 41 patients with well characterized ELD. RESULTS: A total of 6/41 (14.6%) of patients exhibited hsTnT values above either the gender specific or gender neutral 99th percentile cutoff for a normal hsTnT. One patient had a value greater than the cutoff used for acute myocardial infarction. CONCLUSIONS: There are many possible explanations for increased hsTnT values in different types of patients in the absence of acute cardiac damage. Nonetheless our results raise the possibility that subclinical cardiac involvement may be more common in ELD than previously recognized. Further studies will be necessary to elucidate the significance of this finding.

Glucose meter standardization across a large academic hospital system.

BACKGROUND: To select and standardize point-of-care (POC) glucose meters across a multi-hospital system. METHODS: We formed a multidisciplinary POC glucose standardization working group including key stakeholders from each site. A set of selection criteria: usability, clinical and laboratory performance, indications for use, interface connectivity, ease of implementation and ongoing operational costs were used to develop a scoring schemato facilitate a consensus-driven selection process. RESULTS: Method comparison and consensus error grid evaluation against the clinically validated reference methods demonstrated that the analytical performance for all candidate meters was comparable for both the laboratory and clinical evaluation. However, Meter 1 ranked highest in usability evaluations, implementation and streamlined interface connectivity. The meter selection process and implementation were staggered across sites due to complexity of transitioning to a new manufacturer's meter and limitations in vendor support for training and ongoing troubleshooting of interface connectivity. CONCLUSIONS: Standardization of POC glucose meters in a large multi-hospital system is a complex undertaking requiring robust, multidisciplinary organizational structure both system-wide and locally, development of consensus-driven selection tools, usability evaluation by end-users, laboratory and clinical evaluation of the analytical performance, and a strong vendor-laboratory partnership during the implementation process.

Description of a point-of-care testing program in a large urban academic medical center: Technologies, management and program cost.

BACKGROUND: Point-of-care testing (POCT) is an important component of hospital-based and ambulatory laboratory testing. Despite its importance, there is relatively little in the peer reviewed literature describing the details of successful POCT programs. METHODS: Administrative records and test volumes from the Massachusetts General Hospital were compiled using POCT middleware (Telcor) and the hospital information system (Epic). Financial data was derived from vendor contracts and the hospital budget management system. RESULTS: Our POCT management team consists of 2.8 medical technologists and 0.1 medical director with an annual labor cost of $458,000 ($0.80/test). The team oversees quality and regulatory compliance for 143 testing sites. POCT constitutes 24 tests with an annual volume of over 573,000 tests (10.8% of all tests performed). Regular site inspections utilizing a compliance checklist with mandatory remedial action plans are employed. This approach has reduced inspection citations from 3.17 per testing site to 0.27 citations. The average cost of POCT tests is $1.89. CONCLUSIONS: POCT is widespread in our institution and comprises a significant percentage of the total test volume. A dedicated POCT team combined with regular site inspections using a comprehensive checklist facilitates regulatory compliance and quality testing.

The Impact of Point-of-Care Hemoglobin A1c Testing on Population Health-Based Onsite Testing Adherence: A Primary-Care Quality Improvement Study.

BACKGROUND: The hemoglobin A1c (HbA1c) is a gold-standard test to diagnose and monitor diabetes mellitus and has been incorporated into population health performance metrics for quality care. However, patients and practices remain challenged in completing timely HbA1c tests. Point-of-care testing (POCT) for HbA1c provides a quick, easy, reliable method for monitoring diabetes in the primary care office setting. The objectives of this quality improvement study were to evaluate the impact of HbA1c POCT on onsite HbA1c testing frequency as a component of population health performance, as well as to measure the utility of HbA1c POCT in identifying clinically meaningful change in disease. METHOD: Prospective quality improvement cohort study among sequentially scheduled adult patients with diabetes due for HbA1c testing across three primary care practices. RESULTS: Practices with HbA1c POCT were 3.7 times less likely to miss HbA1c testing at the time of the visit compared with practices in which HbA1c POCT was not available (P < .001). Nearly one in four patients in each group were found to have clinically worsening diabetes (defined by an increase in HbA1c of ≥0.5% or 5.5 mmol/mol). Nearly half of those patients in the intervention group were identified by POCT. CONCLUSIONS: HbA1c POCT can improve population health-driven HbA1c testing adherence at office visits in primary care and may enable more timely intervention of diabetes management for patients with worsening disease.

Use of Routine Complete Blood Count Results to Rule Out Anaplasmosis Without the Need for Specific Diagnostic Testing.

BACKGROUND: Anaplasmosis presents with fever, headache, and laboratory abnormalities including leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) is the preferred diagnostic but is overutilized. We determined if routine laboratory tests could exclude anaplasmosis, improving PCR utilization. METHODS: Anaplasma PCR results from a 3-year period, with associated complete blood count (CBC) and liver function test results, were retrospectively reviewed. PCR rejection criteria, based on white blood cell (WBC) and platelet (PLT) counts, were developed and prospectively applied in a mock stewardship program. If rejection criteria were met, a committee mock-refused PCR unless the patient was clinically unstable or immunocompromised. RESULTS: WBC and PLT counts were the most actionable routine tests for excluding anaplasmosis. Retrospective review demonstrated that rejection criteria of WBC ≥11 000 cells/µL or PLT ≥300 000 cells/µL would have led to PCR refusal in 428 of 1685 true-negative cases (25%) and 3 of 66 true-positive cases (5%) involving clinically unstable or immunocompromised patients. In the prospective phase, 155 of 663 PCR requests (23%) met rejection criteria and were reviewed by committee, which endorsed refusal in 110 of 155 cases (71%) and approval in 45 (29%), based on clinical criteria. PCR was negative in all 45 committee-approved cases. Only 1 of 110 mock-refused requests yielded a positive PCR result; this patient was already receiving doxycycline at the time of testing. CONCLUSIONS: A CBC-based stewardship algorithm would reduce unnecessary Anaplasma PCR testing, without missing active cases. Although the prospectively evaluated screening approach involved medical record review, this was unnecessary to prevent errors and could be replaced by a rejection comment specifying clinical situations that might warrant overriding the algorithm.

Integrating Decision Support into a Laboratory Utilization Management Program.

Overuse of clinical laboratory testing increases costs, contributes to iatrogenic anemia, and results in downstream costs, including unnecessary work-ups and treatments. Physicians order unnecessary laboratory tests because of lack of knowledge, the practice of defensive medicine and adherence to historical test ordering. Utilization management is increasingly important to control costs and ensure patients receive appropriate tests for diagnosis and management. Clinical decision support is essential for a successful utilization management program. Successful programs rely on clinical informatics to identify misutilization, implement interventions, and track effectiveness. We describe the role of clinical decision support in a laboratory utilization management program.

Development of a Commercial Reference Laboratory Elective Rotation for Residents in Clinical Pathology.

OBJECTIVES: To develop a curriculum for a commercial reference laboratory clinical pathology training elective. METHODS: A 4-day elective at Quest Diagnostics was developed. The elective included 32 sessions composed of interactive didactic sessions and laboratory tours/demonstrations. Ten residents who attended the elective completed a written evaluation and scored each component of the curriculum. RESULTS: Written comments were very positive and demonstrated the goals of the elective were achieved. Laboratory tours and one-on-one sessions with the medical directors were especially well received. Most of the residents stated that the rotation gave them exposure to an area of laboratory medicine that they were not familiar with. CONCLUSIONS: The elective provided a resident training experience that was highly regarded and exposed residents to an area of laboratory medicine not encountered in most pathology training programs. Our curriculum could serve as a model for establishing a similar elective in other training programs.

Creation and Use of an Electronic Health Record Reporting Database to Improve a Laboratory Test Utilization Program.

OBJECTIVES: Laboratory-based utilization management programs typically rely primarily on data derived from the laboratory information system to analyze testing volumes for trends and utilization concerns. We wished to examine the ability of an electronic health record (EHR) laboratory orders database to improve a laboratory utilization program. METHODS: We obtained a daily file from our EHR containing data related to laboratory test ordering. We then used an automated process to import this file into a database to facilitate self-service queries and analysis. RESULTS: The EHR laboratory orders database has proven to be an important addition to our utilization management program. We provide three representative examples of how the EHR laboratory orders database has been used to address common utilization issues. We demonstrate that analysis of EHR laboratory orders data has been able to provide unique insights that cannot be obtained by review of laboratory information system data alone. Further, we provide recommendations on key EHR data fields of importance to laboratory utilization efforts. CONCLUSION: We demonstrate that an EHR laboratory orders database may be a useful tool in the monitoring and optimization of laboratory testing. We recommend that health care systems develop and maintain a database of EHR laboratory orders data and integrate this data with their laboratory utilization programs.

Quality Control Practices for Chemistry and Immunochemistry in a Cohort of 21 Large Academic Medical Centers.

OBJECTIVES: In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program. METHODS: We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing. RESULTS: We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features. CONCLUSIONS: This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

The effects of transport temperature and time on routine and specialized coagulation assays.

: Coagulation laboratories have largely stopped transporting whole blood specimens on ice, due to adverse effects on factor VIII, von Willebrand factor, and the prothrombin time. However, it is unknown whether ice should be required or avoided for other coagulation assays. Furthermore, the amount of time that specimens remain stable during transportation at room temperature (RT) is also largely unknown for many coagulation tests. Therefore, this study investigated specimen stability on ice and RT for a comprehensive panel of coagulation tests. One tube of whole blood from each volunteer (n = 22) was centrifuged immediately (time 0), one was stored for 4 h on ice, and one was stored for 4 h at RT before centrifugation. Among time 0, 4 h on ice, and 4 h at RT samples, no statistically significant differences were found for fibrinogen, activated protein C resistance, thrombin time, reptilase time, antithrombin activity, chromogenic protein C, factor XII, and antiplasmin activity. Prothrombin time, activated partial thromboplastin time, factors IX, XI, protein S activity, and plasminogen activity showed statistically, but not clinically, significant differences. On ice, the only analytes that showed clinically significant changes (≥6.0% from time 0) were factors VII, VIII, von Willebrand factor antigen, and ristocetin cofactor, which were 14.0% higher, and 19.2, 9.5, and 18.8% lower than time 0, respectively. At RT, all analytes were stable except factor VIII was 9.4% lower than time 0. Only factors II, V, X, and PTT-LA lupus anticoagulant showed a possible slight benefit from ice, but the statistically significant differences were not clinically significant. Ice did not substantially benefit any of the coagulation assays. All tests were stable at RT, except more study is needed regarding factor VIII.

Implementation of an expanded point-of-care site inspection checklist in an academic medical center: An eight year experience.

BACKGROUND: We evaluated the effectiveness of an expanded point-of-care (POCT) site inspection checklist over an extended 8-y period. METHODS: A retrospective review of site inspection deficiency reports in a large academic medical center from 2010 to 2017 (year to date). RESULTS: There was a significant decrease in the number of cited deficiencies per site/inspection from 2010 (3.17) to 2017 (0.27) (p<0.001). The percentage of sites without deficiencies steadily increased from 2010 (8.7%) to 2017 (80.7%) (p<0.001). The most common citation was documentation of competency assessment followed by results documentation and annual procedure review. CONCLUSIONS: Regular inspections of sites performing POCT are necessary to maintain regulatory compliance. Over time significant improvements in compliance are achievable.

Analysis of Daily Laboratory Orders at a Large Urban Academic Center: A Multifaceted Approach to Changing Test Ordering Patterns.

OBJECTIVES: We sought to address concerns regarding recurring inpatient laboratory test order practices (daily laboratory tests) through a multifaceted approach to changing ordering patterns. METHODS: We engaged in an interdepartmental collaboration to foster mindful test ordering through clinical policy creation, electronic clinical decision support, and continuous auditing and feedback. RESULTS: Annualized daily order volumes decreased from approximately 25,000 to 10,000 during a 33-month postintervention review. This represented a significant change from preintervention order volumes (95% confidence interval, 0.61-0.64; P < 10-16). Total inpatient test volumes were not affected. CONCLUSIONS: Durable changes to inpatient order practices can be achieved through a collaborative approach to utilization management that includes shared responsibility for establishing clinical guidelines and electronic decision support. Our experience suggests auditing and continued feedback are additional crucial components to changing ordering behavior. Curtailing daily orders alone may not be a sufficient strategy to reduce in-laboratory costs.