Test Menu Research Articles

Evaluation of autoimmune neurology testing clinical utility and stewardship initiatives

Abstract Testing for neural autoantibodies associated with autoimmune neurological diseases has an important role in clinical care. However, as they are niche tests for relatively rare diseases, they often have longer turn-around-times and more expensive costs than many other laboratory tests. In addition, due to the low yield of positive results, they often appear as attractive stewardship targets. Our objective was to review current utilization and ordering patterns and evaluate the impact of ongoing stewardship efforts to inform next steps regarding stewardship of these tests. Methods: Data on utilization and ordering patterns of autoimmune and paraneoplastic neural autoantibody panels from January 1 to December 31, 2023, was obtained from reference laboratory and electronic medical record (EMR) data. Additional data on best practice advisories from the most recent six months was obtained from the EMR. Results: Overall, we observed that providers tested 2270 patients both from our defined test menu (five total tests, ~89% of total orders) and through the miscellaneous route (12 total tests, ~11% of total orders), which allows providers to place orders for tests not currently on our menu. Just under one third of the orders were in cerebrospinal fluid (CSF) (n=725), while the remaining were for serum (n=1545). The percent positivity was generally higher in serum specimens, ranging from 0 to 50% per test (n=227 total positive specimens). The percent positivity in CSF specimens ranged from 0 to 40% per test (n=29 total positive specimens), which is generally consistent with previously published literature. Most of the orders were placed by neurology providers (56%). The best practice advisories (BPAs) currently in use are soft stops that target repeat tests in the same specimen type within thirty days of a previous order. Of note, these BPAs can only catch orders placed through the defined process. In six months, the BPA for repeat serum orders fired 104 times for 42 unique patients; the BPA for repeat CSF orders fired 96 times for 38 unique patients. The serum BPA resulted in elimination of the repeat order for 43% of patients (n=18), while the CSF BPA resulted in elimination of the repeat order for 24% of patients (n=9). We observed some situations in which the BPA appeared to be firing when previous orders were incorrectly collected and so not able to be sent out. Conclusion: Based on these data, we plan three main steps to continue to refine autoimmune neurology testing: 1) update our test menu to offer the most clinically useful orders through the defined route, 2) pilot review of tests ordered through the miscellaneous route, and 3) optimize BPAs to target situations with inappropriate utilization rather than technical issues.

A-330 Implementation of a Point of Care Emergency Preparedness policy: Are you ready for a disaster?

Abstract Background CAP Gen.73800 requires laboratories to have an Emergency Preparedness and Response policy. Hospital standards for Joint Commission Accreditation, EM.09.01.01, EM.12.02.09, and EM.16.01.01 require hospitals to have a comprehensive emergency management program including an ability to manage resources and assets during an emergency and conduct exercises to evaluate its plan. According to a survey of 27 POCT departments, only 35% have a POCT policy separate from the main lab and 50% of POCT programs are involved with emergency preparedness drills. With the continuing growth of POC testing, the University of Pittsburgh Medical Center (UPMC) POCT team recognized a need for a collaborative effort between main laboratories, the emergency management team, and POCT to develop a POCT emergency preparedness policy. Methods UPMC POCT team collaborated with emergency management to decide what details regarding POC tests and devices would be needed if the main laboratory was rendered not functional. Additionally, a hazard vulnerability review identified potential internal and external events that could impact patient care. POC coordinators from across the system supplied feedback as to what situations within POC could impact patient safety. Results An evaluation of hazards considered debilitating to the main laboratory included external events, such as weather emergencies or evacuation of the hospital due to safety concerns. Potential internal events including a loss of water or impeded functionality of an instrument platform were identified. Available POC tests may offer solutions to deficits in main lab testing. The POCT program is not immune to potential emergency situations. Connectivity/IT issues can require extensive troubleshooting. Supply chain disruptions that affect the availability of consumables may lead to a reverse scenario where emergency management may assist. On-line training modules are a consideration when labor strikes or staffing shortages require POCT programs to quickly onboard replacement workers as new operators. During pandemics, Coordinators may need to rapidly implement new testing. The UPMC Emergency Preparedness policy was developed as a guide to the POCT team to ensure the continuation of testing ability in these emergent situations and addresses the need for communication with Incident Command. The UPMC POCT Emergency Preparedness policy is linked to a Microsoft Form that can be quickly completed by POC coordinators throughout the system. Responses to the form can be exported to an Excel spreadsheet and will supply emergency management with POC device-specific information, listing devices as battery operated, wireless capable, tabletop or hand-held and provides test menus. This spreadsheet allows coordinators to decide the number of devices and consumables that could be pooled from all facilities within the system. Conclusions Ninety-three percent of survey respondents acknowledged that they could potentially benefit from a POCT emergency preparedness policy. Increasing the number of POCT programs involved in emergency preparedness drills would improve response to emergency management challenges. The UPMC POCT Emergency Management Policy guides POC coordinators through situations, allowing them to pool resources to allow for the continuity of testing necessary for quality patient care.

A-334 Vital one: a point-of-care platform for rapid, comprehensive, central-lab quality blood testing

Abstract Background Diagnostic tools are fundamental to informed healthcare decisions, but the current state of in vitro diagnostics presents barriers to providing timely access to a wide menu of tests. This poster discusses a method for overcoming these challenges with a novel and miniaturized point-of-care (PoC) solution, the VitalOneTM. While many PoC solutions have limited test menus tailored for specific scenarios, Vital Biosciences introduces a comprehensive test menu in a compact PoC format that uses centrifugal microfluidic workflows to deliver quantitative results for over 50 analytes spanning hematology, clinical chemistry, and immunoassay modalities, ensuring central-lab quality results for a wide variety of use cases in a 20-min time frame (or 15 min for a Comprehensive Metabolic Panel (CMP) lipid panel, and liver panel). The VitalOneTM is designed to perform a complete blood count (CBC), a comprehensive panel with a full array of immunoassays and clinical chemistry assays, returning over 50 results with as little as 300-750 µL of whole blood. This poster provides a comprehensive and transparent view of both our results and underlying methods of operation. By comparing the VitalOneTM system with established benchmarks like Roche, Sysmex, and Beckman Coulter instrument systems, we demonstrate consistent assay performance, resilience to interference, and performance that is compliant with CLIA Total Allowable Error standards. Methods A method comparison analysis of measurements on VitalOneTM platform was performed against predicate instruments that are commonly used in centralized laboratories (Roche Cobas, Beckman AU480, Beckman Coulter DxH500, Beckman Access 2, and Sysmex 140). Additionally, a 5-8 point calibration curve was generated for each analyte across the desired assay measuring range (AMR) using commercially available validation kits on three separate days, resulting in a master calibration curve. To check for sensitivity to potential interferences that may be present in patient samples, endogenous and exogenous interference testing was performed following Clinical & Laboratory Standards Institute (CLSI) guidelines. Lastly, robustness testing was carried out to mimic the extremes of variances in volumes, times, or temperatures that may be encountered when running an assay protocol. Results The method comparison analysis (n = 840 samples) and precision studies revealed that the VitalOne exhibited a strong correlation with the benchmark instruments and were in compliance with CLIA's total allowable error limits, reinforcing the reliability and clinical relevance of our diagnostic system. Assays across Hematology, Clinical Chemistry, and immunoassays demonstrated >95% of data within CLIA TEa% and run-to-run imprecision ≤ 5%. Additionally, linearity studies revealed that each analyte AMR spans across physiologically relevant concentrations, defined by medical decision levels and reference intervals for each analyte. Our robustness and endogenous and exogenous interference testing performed as per CLSI guidelines has demonstrated that the VitalOneTM system closely matches, and in certain parameters, such as biotin interference, even surpasses that of the predicate instruments. Conclusions In summary, the VitalOneTM platform represents a significant advancement in point-of-care diagnostics, offering a comprehensive, accurate, and efficient alternative to traditional laboratory testing. This innovation is poised to transform the way clinicians approach diagnostics, enabling more informed decision-making and ultimately enhancing patient outcomes.

A-357 Evaluation of a home kit for lay user collection, centrifugation, and refrigeration of capillary blood specimens

Abstract Background While solutions enabling at-home self-collection of capillary blood samples are maturing, many analytes require blood separation and controlled shipping temperatures for stable analysis in centralized laboratories. Here we present results of a pilot lay user study evaluating usability and specimen quality of at-home blood collection with centrifugation and refrigerated shipping of capillary serum specimens. Methods N=45 consented subjects were mailed kits including supplies for a capillary blood self-collection using a Tasso+™ device, a Labcorp TrueTherm™ reusable shipper containing a temperature tracker, a Labcorp TrueSpin™ battery-powered centrifuge, written instructions, and a usability survey. Subjects independently followed the instructions for blood collection, separation, and thermal protection and returned the kits to Labcorp via overnight shipping. Received kits were evaluated for correct return, volume of blood collected, volume of serum, visual hemolysis, and temperature throughout shipment. Results Of the n=45 consented subjects, 39 subjects returned the kits, one subject unsuccessfully attempted to collect blood two times, and the remaining five subjects did not return the kits. Primary analysis parameters are outlined in Table 1. Conclusions Untrained subjects were able to collect their own capillary blood samples, process them, and ship them using the investigational home collection kits. While kit return can be a challenge with home collection, the vast majority of subjects were able to return a testable sample. Combining blood separation prior to shipment using the Labcorp TrueSpin centrifuge and temperature control with the reusable Labcorp TrueTherm device successfully protected samples from hemolysis. These results indicate that such kits are a promising at-home blood collection method and may increase test accuracy and menu availability for sensitive analytes.

B-121 Optimizing Test Ordering: Leveraging Heuristics in Naming Conventions - A PSA Case Study

Abstract Background A common screening test for prostate cancer is the Prostate-Specific Antigen (PSA) test, which may also be referred to as total PSA or total PSA plus free PSA, among other variations. Looking at the test menus of two major reference laboratories, it's apparent that PSA can be ordered under thirteen different test names. From an end-user perspective, the question arises: which of these thirteen tests should be ordered, and why are there so many options? This plethora of choices can lead to confusion and uncertainty for clinicians and patients alike. According to various guidelines, ordering Free PSA is only warranted when PSA values exceed 4 ng/ml. In such cases, the ratio of free PSA to total PSA can aid in further clinical decision-making and patient workup. At Zuckerberg San Francisco General Hospital (ZSFGH), we offer two tests for PSA. The first is named “Prostate Specific Antigen” is total PSA done in house, while the second is labeled “Prostate Spec. Ag. Total and Free.” which is sent out to a reference lab. Upon reviewing our send-out orders, we observed a significant increase (376%) from 2022 to 2023 in the use of the send out order. Methods The ordering data for our providers was collected from February 2022 to January 2024 for both in-house and send-out orders. The data was analyzed using descriptive statistics in Microsoft Excel. Results In our population, we observed an abnormal concentration of send-outs originating from a select group of physicians. Additional we also identified a group of providers who only selected the send out test order. Analysis of in-house assay results for PSA revealed that only 15% (1292 out of 8136) exceeded the cutoff of 4 ng/ml, necessitating further testing to inform clinical decision-making. Yet our send out volume of 4157 test is in discordance with how many PSA would need further evaluation. Based on a cost analysis reducing the send out volume by 80% could result in $53,210 savings. Therefore, to reduce the send out amount and to keep the naming convention similar we decided to implement a new test name that would reflex the PSA to Free PSA if the PSA is above 4 ng/ml. We decided on the name “Prostate Specific Antigen total with reflex to Free Prostate Specific Antigen”. Conclusions Our investigation into the variability in PSA test ordering revealed a significant disparity in the number of send-out orders, particularly originating from a select group of physicians. However, the disproportionately high volume of send-out tests suggested an inefficiency in the current testing approach. To address this issue and align with clinical guidelines, we decided to process a request to our medical executive committee for approval for this reflex test in order to meet reimbursement compliance with the Office of the Inspector General. This change aims to streamline the process, reduce unnecessary send-out tests, and ultimately improve the efficiency and accuracy of prostate cancer screening at our institution.

A-067 Simultaneous Measurement of Aldosterone and Plasma Renin Activity in Human Serum Using Liquid Chromatography Coupled to Tandem Mass Spectrometry for Clinical Research

Abstract Background The combination of primary aldosteronism (PA) and alterations in plasma renin activity (PRA) is a leading cause of secondary hypertension. An accurate measurement of Renin Angiotensin-Aldosterone System (RAAS) pathway improves the recognition of symptoms related to stroke, coronary disease, heart failure and metabolic syndrome. Methods Previously, surrogate matrices have been used when demonstrating the analytical performance of LC-MS/MS clinical research methods for the measurement of aldosterone and angiotensin I. Here, we have developed an analytically sensitive and reliable analytical strategy for simultaneous measurement of Aldosterone and Angiotensin I in human matrices. In-house calibrators and quality control samples were prepared, containing varying ranges of both aldosterone (20-2000pg/mL; 55-5548pmol/L) and angiotensin 1 (0.6-240ng/mL; 0.46-185nmol/L). The samples were extracted using the Oasis™ MAX 96-well µElution plate and then separated through the ACQUITY™ UPLC™ I-Class FL System using a XBridge™ Premier Peptide BEH™ C18 Column, over a run time of 3 minutes. Samples were then injected to Xevo™ TQ Absolute Mass Spectrometer, using both positive and negative acquisition modes. The downstream LC-MS/MS data analysis was performed using MassLynx™ MS Software. The analytical performance was demonstrated by extracting and quantifying two replicates of samples on two occasions per day over five separate days. Additionally, the stability of aldosterone and angiotensin I over the period of incubation (3-5hr) was evaluated, which is necessary when investigating the plasma renin activity in human Serum/Plasma samples. Results High reproducibility and repeatability were both determined, indicating total precision and repeatability (<15%CV) for both analytes and no significant changes were found in Aldosterone and Angiotensin I concentrations over 3-5hr of incubation. No significant system carryover (<10% of the lowest calibrator) from high concentration samples into subsequent blank injections was observed. In addition, calibration lines in human serum/plasma were linear, with coefficient of determinations (r2) >0.992 for all analyses at different incubation times. The analytical sensitivity of the clinical research method allows for precise quantification at 55 pmol/L for aldosterone and 0.46 nmol/L/hr for angiotensin I, with both analytes providing S/N (PtP) ≥10:1 and %RSD of <15% at these concentrations. Conclusions An analytically sensitive and selective clinical research method has been developed for the analysis of aldosterone and angiotensin I, using the Xevo TQ Absolute Mass Spectrometer. The Xevo TQ Absolute Mass Spectrometer enables the simultaneous analysis of physiologically low levels of aldosterone and plasma renin activity in human samples, (20pg/mL; 55pmol/L), (0.6ng/mL; 0.46nmol/h/L). A single test that improves instrument utilization, reduces cost, and allows the user to expand their existing test menu on the same platform has been established.

B-023 Workflow evaluation of the new Siemens Atellica CI Analyzer

Abstract Background The Atellica® CI Analyzer, Model 1900 is an integrated clinical chemistry and immunoassay analyzer that has the same user interface, general workflow, and planned test menu to that of the larger Atellica® Solution. Atellica CI Analyzer also shares the same reagents and consumables as the Atellica Solution. The purpose of this study was to evaluate workflow performance of the Atellica CI Analyzer in a routine-like clinical laboratory setting. Methods The study was conducted at four international laboratory facilities over a four-month period. Basic throughput of the Atellica CI Analyzer was evaluated at each site by testing quality control (QC) and remnant anonymized patient samples using an 8:2 mixture of chemistry (ion selective electrolytes [IMT], clinical chemistry analytes) and immunochemistry assays. Additionally, the impact of interrupting routine testing for STAT high-sensitivity cardiac troponin samples was also evaluated. Daily, weekly, and monthly maintenance activities were observed, and data collected through direct observations, time and motion studies, and system run logs. Results The Atellica CI Analyzer aspirated patient samples in as little as two minutes (mins) with the time to first result for the mixed assay worklist ranging from 1 to 12 mins from the time of first barcode read. Across the four sites, the time to last result for the mixed assay worklist (average n=495 test results per site) ranged from 52 to 65 mins. The average turn around time (TAT) for high-sensitivity troponin was 9 mins from barcode read. Daily maintenance and QC activities for the Atellica CI Analyzer are comprised of both automated and manual activities. The average daily maintenance hands-on time was 3.6 min, ranging from 1.6 to 6.4 mins across the four sites. Daily QC preparation required <5 mins of hands-on time. The total average hands-on time to complete weekly maintenance for the Atellica CI Analyzer was 7.5 min. Conclusions The Atellica CI Analyzer demonstrated consistent system performance across all four study sites. Implementation of the Atellica CI Analyzer has the potential to increase laboratory efficiency given the minimal hands-on time required for daily and weekly maintenance activities and short TATs.

Comparison between standard hematological parameters and blood doping biomarkers in dried blood spots within the athlete population of Swiss Sport Integrity.

The study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context. The aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, "DBS OFF-score". Ten athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards. Most athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu. In this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP.

Improving the Determination of Carbon Isotope Ratios of Endogenous Steroids Found in Human Serum.

The determination of serum concentrations of testosterone (T) and 4-androstenedione (A4) was implemented into the steroidal module of the Athlete Biological Passport in 2023. Monitoring T, A4, and the ratio of T/A4 in a longitudinal manner enables the detection of the misuse of low-dose T administrations especially in female athletes, whereas urinary markers of the steroid profile may not be influenced significantly. In contrast to the urinary steroid profile, knowledge on confounding factors regarding serum concentrations of T and A4 is yet comparably scarce, and corroborating exogenous sources of the target analytes by isotope ratio mass spectrometry (IRMS) is desirable. In a recent study, it was demonstrated that carbon isotope ratios (CIRs) of serum steroids can be determined if analyte concentrations permit. The therein-employed method utilized 2D-GC/IRMS, and only a limited number of potential endogenous reference compounds were available. The here-presented approach uses complementary analyte purification strategies, addressing previous limitations. A high-performance liquid chromatography cleanup was developed and fully validated for serum steroids in order to enable all doping control laboratories to potentially implement this method alongside existing protocols for urinary steroids. Besides the already-investigated endogenous steroids cholesterol, dehydroepiandrosterone sulfate, androsterone sulfate, and epiandrosterone sulfate, two additional steroids were included in the test menu, namely, pregnenolone sulfate and 5-androstene-3β,17β-diol sulfate. Serum steroid concentrations down to 25 ng/mL were found to allow robust CIR determinations, and a reference population encompassing 124 male and female athlete samples was investigated to enable the calculation of population-based thresholds for all relevant steroid combinations.

Analyzing laboratory test utilization trends in belgian primary care: a decade of insights with international perspectives

BackgroundClinical laboratory testing, essential for medical diagnostics, represents a significant part of healthcare activity, influencing around 70% of critical clinical decisions. The automation of laboratory equipment has expanded test menus and increased efficiency to meet the growing demands for clinical testing. However, concerns about misutilization remain prevalent. In Belgium, primary care has seen a dramatic increase in lab test usage, but recent utilization data is lacking.MethodsWe conducted a comprehensive retrospective analysis of laboratory test utilization trends within the primary care settings of Belgium over a ten-year period, spanning from 2012 to 2021, incorporating a vast dataset of 189 million test records for almost 1.5 million persons. This was the first study to integrate the metadata from both the INTEGO & THIN databases, which are derived from the two major electronic medical record (EMR) systems used in primary care in Belgium, providing a comprehensive national perspective. This research provides crucial insights into patient-level patterns, test-level utilization, and offers international perspectives through comparative analysis.ResultsWe found a subtle annual increase in the average number of laboratory tests per patient (ranging from approximately 0.5-1%), indicative of a deceleration in growth in laboratory test ordering when compared to previous decades. We also witnessed stability and consistency of the most frequently ordered laboratory tests across diverse patient populations and healthcare contexts over the years.ConclusionsThese findings emphasize the need for continued efforts to optimize test utilization, focusing not only on tackling overutilization but on enhancing the diagnostic relevance of tests ordered. The frequently ordered tests should be prioritized in these initiatives to ensure their continued effectiveness in patient care. By consolidating extensive datasets, employing rigorous statistical analysis, and incorporating international perspectives, this study provides a solid foundation for evidence-based strategies aimed at refining laboratory test utilization practices. These strategies can potentially improve the quality of healthcare delivery while simultaneously addressing cost-effectiveness concerns in healthcare.

Detection of doping substances in paired dried blood spots and urine samples collected during doping controls in Danish fitness centers.

The use of dried blood spot (DBS) in anti-doping can be advantageous in terms of collection, transportation, and storage compared with the traditional anti-doping testing matrices urine and venous blood. There could, nonetheless, be disadvantages such as shorter detection windows for some substances compared with urine, but real-life comparison of the detectability of prohibited substances in DBS and urine is lacking. Herein, we present a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based screening method for simultaneous detection of 19 target analytes from the doping substance categories S1-S5 in a single spot. Ninety-eight urine and upper-arm DBS (Tasso-M20) sample pairs were collected from fitness centers customers notified for doping control by Anti Doping Denmark, and three sample pairs were collected from active steroid users undergoing clinical evaluation and treatment at a Danish hospital. The analytical findings were cross compared to evaluate the applicability of the developed DBS testing menu in terms of feasibility and analytical performance. To our knowledge, this is the first study to compare the detectability of prohibited substances in DBS and urine samples collected in a doping control setting. Twenty-seven of the urine samples and 23 DBS samples were positive, and we observed a very high concordance (95%) in the overall analytical results (i.e., positive or negative samples for both urine and DBS). Collectively, these results are very promising, and DBS seems suitable as a stand-alone matrix in doping control in fitness centers likely because of the high analyte concentration levels in these samples.

Prevalence of Positive Urine Drug Screen for Fentanyl and its Analogs in Indianapolis

Background and Hypothesis: IU Health Pathology Laboratory (IUHPL) recently added qualitative fentanyl screening to its test menu. However, fentanyl screening is not currently part of the urine drugs of abuse (DAU) panel which includes amphetamine, barbiturates,benzodiazepines, buprenorphine, cannabinoids, methadone, cocaine, opiates, oxycodone, and phencyclidine. Since fentanyl screen is a standalone test, we were interested in determining how often specimens had this ordered in conjunction with the DAU, as we suspected not all of them did. Our hypothesis was that positive urine drug screens may also be positive for fentanyl/fentanyl analogs.
 Project Methods: Urine specimens sent for routine drug screens at IU Health Arnett, Ball, Bloomington, and IUHPL between June and mid-July 2023 were subjected to fentanyl screening. Specimen that screened positive were confirmed by LC-MS/MS for presence offentanyl and norfentanyl. Additionally, specimens were tested for 4ANPP (fentanyl precursor) and xylazine; if they were positive for either, they were sent to an outside laboratory to ascertain if other fentanyl analogs or designer opioids were present.
 Results: Of the 1,893 DAU specimens received, 51.2% were positive for at least one drug class. Only 28 had an associated fentanyl screen order. Cannabinoids represented the most prevalent drug class with a 26.7% positivity rate. Only 1,724 samples were available to screen for fentanyl as part of this study. Of these, 214 specimens were positive for fentanyl, with a positivity screen rate of 12.4%. Confirmatory testing by LC-MS/MS indicated 206 of the 214 were true positives.
 Conclusion and Impact: These results highlight the need for fentanyl testing and continued clinician education to increase awareness about the inability of standard urine drug screens to detect fentanyl. Dialogue between patients and clinicians would potentially decrease overdoses and/or result in more treatment referrals. Additionally, integrating fentanyl screening into the DAU panel will facilitate qualitative fentanyl testing.

Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses.

Recent decades have witnessed the emergence and re-emergence of numerous medically important viruses that cause central nervous system (CNS) infections in children, e.g., Zika, West Nile, and enterovirus/parechovirus. Children with immature immune defenses and blood-brain barrier are more vulnerable to viral CNS infections and meningitis than adults. Viral invasion into the CNS causes meningitis, encephalitis, brain imaging abnormalities, and long-term neurodevelopmental sequelae. Rapid and accurate detection of neurotropic viral infections is essential for diagnosing CNS diseases and setting up an appropriate patient management plan. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis/encephalitis. However, the expansion of test menu has led to new challenges in selecting appropriate tests and making accurate interpretation of test results. There are unmet gaps in development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses. Herein we will discuss the advances and challenges in the laboratory diagnosis of viral CNS infections in children. This review not only sheds light on selection and interpretation of a suitable diagnostic test for emerging/re-emerging neurotropic viruses, but also calls for more research on development and clinical utility study of novel molecular assays. IMPACT: Children with immature immune defenses and blood-brain barrier, especially neonates and infants, are more vulnerable to viral central nervous system infections and meningitis than adults. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis and encephalitis. There are unmet gaps in the development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses.

Recycling Opportunities in a High Volume Academic Clinical Chemistry Laboratory

Abstract Many sectors of industry, including the biomedical sector, have quantified waste, and created sustainability strategies to mitigate its environmental impact. One of these strategies utilizes the waste hierarchy, a model which ranks the concepts reduce, re-use and recycle in order of the most to least sustainable practice. However, to date, the clinical laboratory has seldom been evaluated for total waste production and mitigation strategies and additional public reporting of the physical amount of waste produced in these areas are lacking in the literature. In this study, we aimed to identify specific wastes produced from performing the CMP over the course of a year in our automated clinical chemistry laboratory and what proportion would be recyclable. The total in- and outpatient testing volumes as well as volumes of quality control and calibrations needed to perform the CMP at our institution were collected retrospectively from 07/14/2021 - 07/14/2022. We further identified disposables waste items such as calibrator kits, quality control kits, patient blood specimen tubes, shipping packaging and reagent wedge kits that are necessary to perform the CMP. In addition, to obtain a conservative and consistent evaluation to the total amount of waste produced from the CMP, the average weights for components of the reagent test wedge kits which includes plastic wedges, cardboard shipping boxes, and paper package inserts were calculated. These weights in conjunction with total testing volumes was used to determine the total, recyclable, and non-recyclable waste produced from these disposable items. A total of 1089.2 kg of reagent kit wastes were estimated to be produced by performing the CMP over the course of a year. Of this waste, cardboard shipping boxes and paper package inserts were determined to be recyclable (233.6 kg) and the plastic reagent wedges were determined to be non-recyclable (855.5 kg) as they were not labelled with the universally recognized recycling code, were composed of proprietary plastic material, and contained biohazardous contaminants. Overall, 21.4 % of the total specific waste weight was found to be recyclable. The CMP is a small subset of the clinical chemistry test menu that produces a considerable amount of recyclable and non-recyclable waste.

Simplifying molecular testing through electronic order entry

Abstract Our solid-tumor molecular laboratory receives more than 3,000 orders each year, with about two-thirds coming from internal providers. Before this project, molecular tests were ordered using one of two different paper forms, which the care team then faxed or e-mailed to the Genetics Preanalytical Service (GPS). These requests led to frequent modifications and cancellations due to the complexity of molecular testing. A small fraction of requisitions were lost due to transmission errors. We undertook a project to design, develop, and implement computerized physician order entry (CPOE) in Epic (Epic Systems Corp., Verona, WI) and Sunquest (Clinisys, Tucson, AZ). We conducted extensive interviews with the directors of the molecular lab, laboratory medicine IT, GPS, anatomic pathology staff, laboratory scientists, laboratory genetic counselors, oncologists, clinicians, and nurse coordinators. The order itself and other technical changes underwent iterative review and testing by a subset of interviewees. Five oncologists participated in formal beta-testing. The user interviews allowed us to produce a detailed process diagram that drew attention to specific areas of repetition or risk. We proposed a new workflow that would eliminate repetition, provide redundant order-tracking, and automate some lab processes. Once approved, we built the electronic order in Epic and modified existing laboratory programs and interfaces as needed. The process of placing an order, which previously typically involved both nurses and doctors over several calendar days, was now being completed in fewer than 5 minutes by a single practitioner. Requisition status events were no longer created manually in Sunquest by GPS. Certain data-entry tasks were eliminated through the incorporation of label printers. Within one month of launch, more than 50% of somatic molecular orders arrived via CPOE, increasing to 90% within six months. At a rate of 125 CPOE orders per month, time savings range from 20 hours per month for GPS staff, 50 hours per month for nursing, and 20 hours per month for physicians. The success of this project demonstrates the feasibility of replacing a paper-based process for a complex test menu with CPOE. Due to the intricacies of molecular testing, such a change will undoubtedly involve multiple divisions. We attribute the success of this project to early involvement by key stakeholder groups, including developers; an extended testing phase to ensure reliability at roll-out; creation of straightforward reference documents; and rapid response to user questions, especially during the first weeks post-launch.

Food Is Medicine for Individuals Affected by Homelessness: Findings from a Participatory Soup Kitchen Menu Redesign.

Health disparities among people experiencing homelessness are likely exacerbated by limited access to healthy, fresh, and minimally processed foods. Soup kitchens and shelters serve as essential food safety nets for preventing hunger in this population, and community interest is growing in the potential of "food is medicine" interventions to improve the mental and physical wellbeing of people who receive meals from these providers. This study describes our two-phase approach to first identify and prioritize nutrition needs within an urban soup kitchen community and then test and implement new recipes and menu guidelines to help the standard soup kitchen menu better align with those priorities. We began by first conducting a nutrition needs assessment, including a collection of intercept surveys from a convenience sample of soup kitchen guests to better understand their nutrition-related health needs, dental issues, food preferences, and menu satisfaction (n = 112), as well as a nutrition analysis of the standard menu based on seven randomly selected meals. Most respondents reported at least one chronic health condition, with depressive disorders (50.9%) and cardiovascular diseases (49.1%) being the most common. Nearly all guests requested more fruits and vegetables at mealtimes, and results from the menu analysis revealed opportunities to lower meal contents of sodium, saturated fat, and added sugars and to raise micronutrient, fiber, and omega-3 content. We then applied these nutrition needs assessment findings to inform the second phase of the project. This phase included the identification of new food inventory items to help support cardiovascular and mental health-related nutrition needs, taste test sampling of new healthy menu items with soup kitchen guests, and hands-on culinary medicine training to kitchen staff on newly-developed "food is medicine" guidelines to support menu transformation. All taste tests of new menu items received over 75% approval, which exceeded satisfaction ratings of the standard menu collected during the phase 1 needs assessment. Findings from this community-based participatory research project confirm the great potential for hunger safety net providers to support critical nutrition needs within this vulnerable population through strategic menu changes. However, more research is needed on the longitudinal impacts of such changes on health indicators over time.

A-382 Evaluation of the Labcorp TrueSpinTM for Decentralized Blood Sample Centrifugation

Abstract Background The increased demand for decentralized blood sample collection presents numerous operational challenges for diagnostics providers. Sample degradation including sample hemolysis due to time, temperature, and handling between collection and laboratory analysis leads to limited test menus and unreliable results. Here we evaluate the light-weight, portable Labcorp TrueSpin™ for rapid point-of-care blood separation using commercially available microvolume blood collection tubes. The TrueSpin is a class I FDA registered device designed for layperson use. The centrifuge runs on AA batteries and separates a blood sample in five minutes. Methods Here we show results of studies evaluating sample quality and analyte stability in serum samples collected into gel microtubes and processed using the TrueSpin. Hemolysis and residual red blood cell (RBC) concentration are compared between samples separated using the TrueSpin and conventional centrifugation. Additionally, we evaluate serum-based chemistry analyte stability in both separated and unseparated samples stored for three days refrigerated and unrefrigerated. Results No significant difference was seen in hemolysis or residual RBC concentration in serum samples prepared by TrueSpin compared to the reference centrifuge method. Furthermore, we show that many common serum-based chemistry analytes have limited (<1 day) stability if uncentrifuged, but improve to ≥3-day stability following TrueSpin separation and refrigerated or room temperature storage (see Table 1). Conclusions These findings suggest that the TrueSpin is a simple and effective solution for remote sample separation and may enable broader test menus and increased test result reliability for decentralized sample collection pursuits.

A-269 Post-pandemic Opportunities for Commercial Laboratories in Infectious Disease Diagnostics and Public Health

Abstract Background Aegis launched COVID-19 testing with a daily capacity of 3000 tests and scaled to over 100 000 tests/day in one year. The lab has performed over 14.2M COVID-19 tests to date, servicing a broad network of physicians, urgent care centers, nursing homes, public schools, departments of health, and retail pharmacies across the United States. As SARS-CoV-2 infections reach an equilibrium, Aegis recognized the opportunity to address broader public health needs and leveraged the partnerships, technologies, and infrastructure developed to build the Infectious Disease Testing (IDT) menu aimed at limiting the spread of health risks within the community. Methods Real-time polymerase chain reaction (RT-PCR) tests for common and rare bacterial, viral, and parasitic pathogens associated with genital health (GH) and sexually transmitted infections (STI), as well as infections of the urinary (UTI), gastrointestinal (GI), and respiratory tracts (RTI) were validated. These tests are performed in 384-well custom PCR plates, pre-spotted with primers and probes capable of detecting the presence of DNA or RNA (LOD = 10 copies/µL) from 30 different organisms in up to 12 patient samples simultaneously. Syndromic panels were developed for ordering based on similar intended use, and providers have the option to order panels or stand-alone tests based on medical necessity. Following receipt into the lab, the total nucleic acid is extracted from the primary specimen and pipetted into the PCR assay plate with Taq DNA polymerase master mix, and analysis and reporting of ordered targets are complete within nine hours, on average. Results and de-identified demographic data are parsed from the laboratory information management system (LIMS) to Microsoft PowerBI software to internally track testing trends, positivity rates, and outbreaks of infectious diseases. Results Historical data including ordered profiles, matrices, and pathogens detected combined with de-identified demographic data such as patient age, gender, race, residing state, and collection month were imported into PowerBI and used to create interactive visuals for a dashboard to monitor trends and predict future testing patterns. The IDT panels ordered most frequently include STI (27.1%), upper RTI (23.6%), bacterial vaginosis (21.0%), GI bacterial (15.1%), candidiasis (13.7%), and GI viral (13.0%). The majority (74%) of GH/STI tests were ordered for patients between the ages of 15 to 34 years, and the most prevalent infections detected were bacterial vaginosis (35%), mycoplasma hominis (22%), and chlamydia trachomatis (4%). Sixty-one percent (61%) of upper RTI tests were ordered for patients between the ages of 0 to 14 years, and fluctuations in positivity rates followed seasonal trends for pathogens such as rhinovirus, influenza, adenovirus, RSV, and enterovirus D68. GI profiles were predominantly ordered for the younger (0–14 years, 35%) and the older (>65 years, 18%) population with e. coli O157 (11%), norovirus (9%), sapovirus (6%), and astrovirus (4%) infections detected at the highest rates. Conclusion The COVID-19 pandemic underscored the importance of molecular diagnostics for SARS-CoV-2 infection and surveillance. Experience gained during the COVID-19 response allowed Aegis to repurpose the resources, capacity, and infrastructure to create business development opportunities aimed at laboratory growth in infectious diseases and public health.

A-193 Effects of Delayed Centrifugation and Delayed Testing on the Stability of Comprehensive Metabolic Profile Analytes

Abstract Background The centralization of clinical laboratory testing has become increasingly common in recent years. While centralization allows for consolidation of resources, expanded test menus, procedural standardization, and improved efficiencies, central laboratories can face significant logistical challenges related to sample transport. In particular, problems may arise when samples are received from distant sites or if the courier services used to transport samples are infrequent or unreliable. Policies aimed to mitigate pre-analytical issues such as the time-to-centrifugation, the time-to-testing, and storage temperature, are best devised when driven by empiric data. Objective In this study, we provide stability studies for the Comprehensive Metabolic Panel (CMP) analytes in paired serum and lithium heparin (LiHep) plasma samples. Our findings not only complement preexisting literature data but also help guide the current sample acceptance criteria and policy for receiving satellite clinic samples in our laboratory. Methods Serum and LiHep plasma were collected from healthy volunteers in gel separator tubes. In one set of experiments, samples of both specimen types were all centrifuged within 30 min of collection and tested at pre-determined time intervals (2, 4, 6, 12, and 24 h post collection) using Roche Cobas 8000 system. In a second set of experiments, samples of both specimen types collected from another set of volunteers were kept at room temperature and only centrifuged prior to testing at pre-determined time intervals (2, 4, 6, 12, and 24 h post collection). Sample storage prior to testing was at room temperature. The percent recovery of each result was calculated relative to the first sample of the series. The CMP includes the following analytes: glucose, sodium, potassium, chloride, carbon dioxide, urea nitrogen, creatinine, calcium, total bilirubin, total protein, albumin, alkaline phosphatase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Results Glucose in promptly centrifuged (i.e., within 30 min of collection) LiHep plasma samples showed acceptable recovery (≥90%) when tested within 12 h of collection in LiHep gel separator tubes, whereas glucose stability in serum stored at room temperature exceeded 24 h. In contrast, delayed centrifugation beyond 3 h led to unacceptably low recoveries in both LiHep plasma and serum sample types. All other analytes included in the CMP were stable beyond 24 h irrespective of whether the sample type is LiHep plasma or serum, or even if the time-to-centrifugation was up to 24 h. Conclusions Based on the study, our laboratory has updated our policy to accept pre-centrifuged (i.e., within 30 min of collection) LiHep plasma from satellite clinics up to 8 h from blood collection, which is a 2-hour increase as compared to our prior cut-off acceptability. Given the location of our satellite clinics and unpredictability of sample transport, this increase represents a positive change in reducing outpatient sample rejections while ensuring reliable laboratory results.

A-189 Volume Matters: Continuous Improvement to Reduce Blood Collection Volumes and Collection Tube Utilization

Abstract Background Clinical laboratories are constantly changing with automated analyzers and total lab automation (TLA) implemented and replaced over time. Some benefits of newer technologies include decreased specimen volume requirements, less need for repeat testing, and greater throughput. Recent implementation of new analyzers and replacement of TLA in the Central Clinical Laboratory (CCL) at Mayo Clinic, Rochester, MN, prompted the laboratory to reassess blood collection volumes for commonly ordered tests. Objectives The aim of this study was to evaluate whether updating the blood collection volumes for clinical chemistry and immunoassay tests performed in the CCL could reduce the volume of blood collected from patients and the number of blood collection tubes utilized. Methods Nearly 100 different serum assays from the CCL test menu were reviewed including the basic and comprehensive metabolic, hepatic function, renal function, electrolyte, and lipid panels as well as thyroid function tests, enzymes, hormones, electrolytes, and iron status tests. Cortisol, ferritin, folate, and Vitamin B12 testing were performed on the Beckman DxI800; all other testing was on Roche Diagnostics Cobas 8000 chemistry (ISE, c701, c502) and immunoassay (e801) analyzers. Updated blood volumes for each assay were calculated utilizing manufacturer’s analytical volumes and “dead volume” requirements. Baseline data retrieved from the laboratory information system (LIS) included blood collection volumes and number of tubes collected for 128 patients with physician-orders for laboratory testing on 5/2/21. The collection logic was then updated in the test LIS environment using the new blood volumes requirements and applied to the same 128 orders. Blood volumes and number of tubes collected per order were compared before and after the volume updates. Results Baseline data from 128 unique orders showed that 414 total tubes were collected with a median(range) of 3 (2–6) tubes per order and 5 (1–18) tests per tube. The total volume of blood requested at baseline was 2065 mL. Post-intervention, 197 tubes were needed with a median(range) of 2 (1–3) tubes per order and 13 (1–30) tests per tube. The total volume of blood requested after updating volumes was 851 mL. Conclusions The practice of reviewing and updating specimen volume requirements when replacing or implementing new analyzers or TLA can greatly reduce the volume of blood collected from patients and the number of blood collection tubes per order. In this study of 128 physician orders for common laboratory tests, updating blood collection information in the LIS reduced the requested blood collection volumes by 59% and decreased the number of blood collection tubes required by 52%. This not only benefits patients because less blood is collected but also conserves blood collection tubes and reduces supply chain demands. Additionally, fewer tubes on the TLA system has the potential to improve throughput and test turnaround time.