Karon, Brad S.

ABSTRACT Blood culture contamination can lead to false-positive blood culture results, potentially contributing to increased costs and unneeded antibiotic utilization. Initial specimen diversion devices (ISDD) have been proposed to reduce blood culture contamination rates. A single-center, observational study conducted at Mayo Clinic Rochester compared blood culture contamination rates using Steripath or Kurin ISDDs versus standard blood culture collection protocols. Over 255 phlebotomists were trained in the use of the ISDDs, with 31,215 blood cultures, 410 of which were contaminated, collected from adults in the emergency department and inpatient wards. Baseline contamination rates were 1.29%–2.53% with standard collection methods. The Steripath ISDD with direct-to-media inoculation of blood culture bottles (Steripath-DTM) reduced blood culture contamination compared to standard practice (0.34% vs. 1.43%, respectively, P < 0.001). Follow-up studies with the alternative Steripath configuration with an integrated syringe (Steripath-syringe), and then the Kurin ISDD with syringe collection (Kurin-syringe), did not meet the primary endpoint of <0.5% contamination (Steripath-syringe: 1.28%; Kurin-syringe: 1.76%). All three ISDD configurations failed to meet our goal of >75% utilization, with an average measured utilization of 26% for the Steripath-DTM, 26.4% for the Steripath ISDD (combined DTM and syringe) in a follow-up study, and 41.5% in the Kurin study. Additionally, a survey of phlebotomists revealed low staff satisfaction with both Steripath ISDD configurations. Staff reported multiple ergonomic barriers limiting the Steripath ISDD’s utility, which precluded implementation of the Steripath-DTM in routine clinical practice. IMPORTANCE We conducted a very large, real-world study of two blood diversion devices to determine whether either would meet goals for reduced blood culture contamination and a high rate of utilization by phlebotomists.

Abstract Background The first international clinical standards of care for the gender-diverse population were formulated in the late 1970s. In the last 15 years, multiple subspecialty societies within the United States have developed clinical care guidelines for those with gender dysphoria, including gender-affirming hormone therapy (GAHT) and surgical treatments. To date, there are no pathology- and laboratory medicine–specific recommendations in the United States for the gender-diverse population. Content This document outlines pathology- and laboratory medicine–specific recommendations for providing optimal care to the gender-diverse population, with a predominant focus on the adult population. The scope of this document focuses on the following 5 topics: (a) reference intervals and interpretation of laboratory tests impacted by use of GAHT (testosterone for transgender men; estradiol with or without antiandrogens for transgender women), focusing on those stably on GAHT for 6 months or longer; (b) transfusion medicine considerations for the gender-diverse patient population, (c) consideration of gender diversity in autopsy and death investigation, (d) interpretation of histology from tissues that are impacted by GAHT and surgical procedures; and (e) pathology and laboratory medicine informatics challenges and opportunities. Summary A relatively small group of laboratory tests is significantly impacted by GAHT. The histology of some tissues shows changes attributable to GAHT or to nonhormonal medical procedures. Autopsy and transfusion medicine practices for the gender-diverse population currently lack standardization, although this is evolving. The landscape of pathology informatics related to gender diversity is complicated by varying electronic health record and laboratory informatics systems functionality.

Abstract Background Thyroid function testing is a common laboratory service that can be optimized by implementing evidence-based algorithms. The thyroid function cascade testing approach at Mayo Clinic Labs is utilized to effectively evaluate and monitor functional thyroid status. The cascade begins with thyroid-stimulating hormone (TSH) as a screening marker. When TSH levels are normal, no additional testing is necessary. When the TSH result is abnormal, appropriate follow-up free T4, total T3, and/or TPO testing will automatically be performed. Providers at our institution can order thyroid function testing with this cascade testing approach or as standalone individual orderable tests. Initial data analysis showed patterns of TSH ordered concurrently with free T4, total T3, and/or anti-TPO. Further analysis revealed that a high number of concurrently ordered tests would not have been necessary had the algorithmic approach been followed. This opportunity for improvement led to the thyroid function testing initiative to direct providers to order the cascade test rather than individual thyroid tests, thereby reducing concurrent and unnecessary testing to improve patient care. Methods The initiative involved creating a new Epic order panel directing providers to order the cascade rather than the individual orderable tests. This intervention is a soft stop that allows providers to proceed by ordering individual tests if desired. We evaluated the impact of the initiative on test utilization, cost savings, and quality indicators using pre- and post-intervention data from all Mayo Clinic sites over a 9-month period. We compared the monthly volumes of concurrent and unnecessary orders of Free T4, Total T3, and TPO before and after the intervention. Concurrent orders were defined as tests collected from the same patient on the same date and time as TSH tests. Unnecessary orders were defined as tests that were outside the reflex range according to the thyroid function ordering algorithm. Cost savings were calculated based on the 2024 CMS reimbursement rates for the associated test CPT® codes. We also monitored and addressed feedback and requests from providers and laboratory staff throughout the initiative. Results The intervention resulted in a 20% average monthly reduction in concurrent orders and an 18% average monthly reduction in unnecessary orders of free T4, total T3, and anti-TPO tests. Estimated savings based on 2024 CMS reimbursement rates are $5,000 monthly and nearly $60,000 annually. Thyroid testing quality was also improved by aligning with clinical guidelines, reducing over-testing, and minimizing the risk of misdiagnosis. Conclusion The thyroid function testing initiative was a successful laboratory stewardship project that reduced redundant testing, improved patient care, and reduced costs. The initiative demonstrated the feasibility and effectiveness of using evidence-based reflex algorithms to optimize laboratory testing. The lessons learned include assessing all tests related to the disease condition to mitigate potential unintended increases in test usage and accounting for patient groups that are not covered by the intended algorithm*s target population. Future directions include expanding the cascade approach to other areas of laboratory medicine, evaluating the long-term outcomes of the initiative, and engaging with providers to ensure the adoption of the initiative.

Abstract Background Community Paramedic (CP) programs use specially trained paramedics to provide healthcare in the community to increase access to care, reduce unnecessary emergency department visits, and improve timeliness of care. Mayo Clinic in Rochester, MN recently launched a CP Program to provide in-home care for patients who require regular intravenous medications, wound care, diuresis for heart failure, medication reconciliation, care plan compliance/education. CP utilizes i-STAT1 CHEM8+ and Lactate (CG4+) testing (Abbott Point of Care, Abbott Park, IL) to make therapy decisions primarily for heart failure patients based on rapid laboratory results. Having results available at the point of care (POC) eliminates delays between testing and treatments, expediting care for the patient. Prior to using i-STAT, CP traveled to the patient’s residence, drew blood tubes, delivered the tubes to Mayo Clinic, waited for test results, returned to the patient’s home, and provided treatment. In this observational study, we assessed the benefit of in-home POC i-STAT1 testing performed by our CP Program to improve patient care and increase efficiency. Methods Patients within a 40-mile radius of Mayo Clinic were eligible to receive CP service. Whole blood venous specimens were collected and tested using the i-STAT1 CHEM8+ metabolic panel cartridge according to manufacturer instructions to measure: ionized calcium, chloride, glucose, hematocrit, total carbon dioxide, blood urea nitrogen, creatinine, potassium, sodium, anion gap while the i-STAT1 CG4+ cartridge measures lactate. The laboratory information system was used to extract laboratory results, and Excel (Microsoft, Redmond, WA) was used to filter data and perform calculations. Results November 2022 through December 2024, CP performed testing with 353 i-STAT cartridges (3862 tests) on 102 unique patients who each had 1-12 separate orders. Patient ages were 25 to 97 years. 41.2% (1590/3862) of the individual results obtained were outside of our reference intervals (23.0% high, 18.0% low), with 10.8% being ionized calcium, 10.2% chloride, 10.3% glucose, 13.0% hematocrit, 7.6% total carbon dioxide, 18.2% blood urea nitrogen, 16.4% creatinine, 6.7% potassium and 6.9% sodium. Additionally, 0.13% of results were critically high (ionized calcium, potassium, and sodium) and 0.10% were critically low (potassium and ionized calcium). Hypokalemic patients were sent to the infusion therapy center for IV potassium. Patients experiencing hyperkalemia were retested and sent to the emergency department (ED). Hyponatremic and hypercalcemic patients were sent to the ED for further treatment. Abnormal (non-critical) results were reviewed by CP personnel to make treatment recommendations or medication adjustments. Conclusion i-STAT1 home testing performed by CP facilitated rapid therapeutic interventions and expedited decision-making. POC testing has increased the group’s efficiency—alleviating the need to transport specimens to the central laboratory and wait on test results before returning to the patient for treatment. Paramedicine emphasizes a proactive and preventative approach to medicine. We anticipate that this model of care and testing will expand to cover other chronic health conditions due to the program’s early success.

Abstract Background Platelet function tests (PFT) help assess bleeding risk and guide appropriate hemostatic measures in patients on antiplatelet therapy undergoing emergent surgical interventions. Light transmission aggregometry (LTA, BioData Corporation), the gold standard for assessing platelet function, cannot be performed rapidly enough for emergent interventions. In this study, we compared two PFT, Plateletworks (Helena Laboratories) and TEG 6S (TEG, Haemonetics) adenosine diphosphate-(ADP) and arachidonic acid (AA)-induced platelet function, evaluating analytical imprecision and their ability to differentiate healthy controls from patients with acute coronary syndrome (ACS) on dual antiplatelet therapy. Methods Fresh specimens were collected from healthy donors (HD, N=19) and a patient group (PG, N=17) on both aspirin and clopidogrel taken within 24 hours of procedure. Percent aggregation was measured according to manufacturers’ instructions using Plateletworks and TEG, utilizing both AA and ADP and compared to LTA performed on a PAP-8E Platelet Aggregometer. Two separate venipuncture collections from HD were used to obtain repeat measures of Plateletworks and TEG to assess variability in platelet function due to pre-analytical variables. Using a two-way nested ANOVA model on data from HD, we estimated variability between replicates of a single sample (intra-assay imprecision) and between blood draws within a single patient (inter-assay imprecision), reported as coefficient of variation (CV%). Platelet function results were summarized as median (interquartile range [IQR; 25th-75th percentiles]) and compared between groups using nonparametric Wilcoxon rank-sum test. Receiver operating characteristic (ROC) analysis (using duplicate means from first blood draw) was performed. Results Plateletworks AA % aggregation, medians (IQR) were 96.3 (95.3-97.1) for HD and 48.9 (46.8-54.8) for PG (p&lt;0.001); ADP % aggregation were 97.0 (94.5-98.2) and 37.1 (28.0-53.0) for HD and PG, respectively (p&lt;0.001). TEG AA % aggregation was 97.8 (94.4-99.8) for HD and 13.5 (7.9-26.8) for PG (p&lt;0.001); ADP % aggregation was 98.3 (95.3-99.9) for HD and 83.3 (77.8-87.7) for TG (p&lt;0.001). LTA AA % aggregation was 55.0 (44.0-64.8) for HD and 0.0 (0.0-1.5) for PG (p&lt;0.001); ADP % aggregation of 59.0 (40.8-70.8) and 14.5 (4.5-19.5) for HD and PG, respectively (p&lt;0.001). Intra- and inter-assay imprecision estimates (CV%), respectively, in HD were 1.4 and 5.1 for Plateletworks AA, 5.5 and 15.9 for Plateletworks ADP, 3.0 and 0.0 for TEG AA, and 2.6 and 0.8 for TEG ADP. Intra-assay precision estimates for LTA AA and LTA ADP were 19.3 and 8.2. In PG, intra-assay precision was estimated as 7.0 for Plateletworks AA, 9.6 for Plateletworks ADP, 61.3 for LTA AA, 11.9 for LTA ADP, 37.6 for TEG AA, and 4.1 for TEG ADP. In our limited data set, ROC analysis showed optimal cutpoints (sensitivity/specificity) for Plateletworks AA 65.5 (1.0/1.0) and ADP 84.5 (1.0/0.90), TEG AA 87.1 (1.0/1.0) and ADP 92.7 (1.0/1.0), and LTA AA 8.75 (0.94/1.0) and ADP 25.0 (0.82/0.90) Conclusion Plateletworks most effectively distinguished % aggregation between healthy donors and patients on dual antiplatelet therapy. TEG also differentiated the groups, but differences in median ADP-induced aggregation were smaller than with Plateletworks. Both AA and ADP assays on LTA showed more variability than either Plateletworks or TEG.

Background: Evaluation of the performance of Cobas ® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators. Methods: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip ® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed by the Food and Drug Administration guidance criteria. Results: Two studies are presented. In the first, 2678 samples (622 arterial, 706 capillary, 1203 venous, 147 heel stick) were collected from 1577 patients in 14 US and three European sites. All accuracy criteria were met for arterial and venous samples considering all data combined. BGMSA showed better accuracy than BGMSB for arterial, venous, and heel stick, and similar results to BGMSB for capillary WB vs venous comparator. No endogenous interference from pO 2 , hematocrit, and sodium was identified. BGMSA was also accurate when analyzing contrived samples used to show accuracy over a wide range of glucose concentrations, alone and when combined with extreme hematocrit. In the second study, 117 capillary fingerstick samples collected at one US site were measured on both BGMSA and the comparator, and all accuracy criteria were met. No clinically significant medical risks were observed via Diabetes Technology Society Error Grids. Conclusions: BGMSA was effective for determining blood glucose in venous, arterial, neonatal arterial, neonatal heel stick, and capillary WB samples.

Importance Anemia is a common complication of surgery and acute illness that is associated with adverse clinical outcomes. The role of anemia prevention and treatment strategies in this setting remains unclear. Objective To evaluate the effect of a multifaceted anemia management bundle vs standard care on posthospitalization hemoglobin recovery and multidimensional functional outcomes in survivors of acute illness. Design, Setting, and Participants This parallel group randomized clinical trial, known as the Practical Anemia Bundle for Sustained Blood Recovery, was conducted at postsurgical and medical intensive care units at a large US medical center. Critically ill patients (aged ≥18 years) with moderate to severe anemia (hemoglobin concentration &amp;lt;10 g/dL) were enrolled between March 2022 and November 2023. Participants were randomly assigned 1:1 to the intervention or standard care group. Intention-to-treat analyses were performed between July 2024 and January 2025. Intervention The intervention bundle was delivered throughout the duration of hospitalization and included optimized phlebotomy practices, clinical decision support, and pharmacological anemia treatment with intravenous iron. Main Outcomes and Measures The primary outcome was the mean difference in hemoglobin concentration at 1 month after hospital discharge. Results A total of 100 patients (median [IQR] age, 68 [61-72] years; 57 men [57.0%]; 65 [65.0%] with postsurgical admission to the intensive care unit) were enrolled during acute illness. Forty-nine patients (49.0%) were assigned to receive the intervention, and 51 (51.0%) were assigned to receive standard care. Hemoglobin concentration at 1 month after discharge was greater in patients receiving the intervention vs standard care (median [IQR], 12.2 [11.8-13.0] g/dL vs 11.5 [10.2-12.6] g/dL; adjusted mean difference, 0.69 [95% CI, 0.13-1.20] g/dL; P = .02). Conclusions and Relevance This randomized clinical trial found that a multifaceted anemia prevention and treatment bundle was feasible, was well tolerated, and improved posthospitalization hemoglobin concentrations up to 3 months in critically ill adults. These findings can inform the design of future trials. Trial Registration ClinicalTrials.gov Identifier: NCT05167734

Abstract Background Managing preanalytical variables is critical to providing quality laboratory test results. However, this can be a challenge for laboratory staff, particularly with manual detection of interfering substances and complicated workflows. For coagulation testing, we assess specimen integrity and acceptability by visual checks and quantification of interfering substance on a chemistry analyzer. To improve this subjective process, we evaluated the technical performance of a new model of coagulation analyzer with automated preanalytical specimen integrity detection. Our objective was to determine if we could reduce the number of specimens requiring visual inspection/off-analyzer interference testing in order to simplify our testing workflow. Methods Citrated plasma specimens received in the Hospital Clinical Laboratory at Mayo Clinic (Rochester, MN) were tested on the TOP ACL 500 or TOP ACL 550 Series Coagulation analyzers (Werfen, Boston, MA) according to manufacturer’s instruction. Specimens tested on the TOP 500 were visually inspected for hemolysis, icterus, and lipemia (HIL). If the technologist detected a possible interferent, an aliquot of plasma was analyzed on our cobas c501 chemistry analyzer (c501) (Roche Diagnostics, Indianapolis, IN) to obtain HIL values. Laboratory-established or manufacturer-defined interference thresholds were applied in determining specimen acceptability. For samples tested on the TOP 550, specimen integrity was assessed by the instrument’s automated interference detection module. The analyzer reported HIL as an “interference cloud” or estimated range, rather than a single value like the c501. HIL values were estimated by visual assessment of the low end of the “interference cloud”. Values were confirmed on the c501 only for specimens with an “interference cloud” at/exceeding the test-specific interference thresholds. We analyzed data from a 2-month period pre- (TOP 500) and post-implementation (TOP 550). The percent of specimens requiring quantitation/confirmation on the c501 was calculated. Statistical significance was calculated using the Chi-squared test where significance was defined as p&lt;0.01. Correlation between c501 and TOP 550 estimated HIL values was evaluated. Results A total of 2.2% (171/7605) and 1.3% (113/8983) of specimens tested on the TOP 500 and TOP 550, respectively, required HIL measurements on the c501 (p&lt;0.001). Of those samples, 8.2% (14/171) and 14.2% (16/113) from the TOP 500 and TOP 550, respectively, had HIL values above the interference thresholds and were rejected by the laboratory. Comparison of the estimated HIL values from the “interference cloud” and from the c501 resulted in slopes (Pearson correlation coefficients) of: H 1.56 (0.77), I 0.67 (0.97), and L 1.35 (0.99). Conclusions In comparison to our workflow with visual assessment of interference, use of the automated interference detection functionality on the TOP 550 instrument resulted in a lower percentage of specimens requiring HIL measurements on the chemistry analyzer. Agreement between interference measurements obtained on the c501 and the TOP 550 was moderate where TOP 550 overestimated the degree of hemolysis and lipemia and underestimated icterus. Implementation of automated interference detection on the TOP 550 analyzer improved our workflow by eliminating the need for tedious and subjective visual checks and reducing the percentage of specimens requiring additional HIL measurements.

Abstract Background Turnaround time (TAT), defined as time of collection to time of result verification, is monitored monthly for cardiac Troponin (cTnT). Within our STAT laboratory, our TAT goal is 85% of cTnT results verified within 45 min. In October 2021, our lab began observing an increase in TAT. A quality improvement project was launched to identify a root cause and possible solutions. Methods cTnT TAT data from the Hospital Clinical Laboratory (STAT lab) at Mayo Clinic, Rochester, MN was extracted from our Laboratory Information System (LIS) using Tableau (Salesforce Inc., Seattle, WA). The data were categorized into three components: collection time, in lab processing and testing time, and time to result verification. Goal metrics for each component are: collection &lt;10 min, in lab processing and testing &lt;25 min, and result verification to LIS &lt;5 min. The average time for each component and percentage not meeting TAT goals were calculated in Microsoft Excel. TAT while performing manual verification of results (January 2022) and after autoverification was implemented (December 2022) were compared. Results Prior to implementation of cTnT autoverification, total orders for January 2022 were 1408 with 82.0% meeting TAT of 45 min. Of the 18.0% not meeting TAT, 207 (14.7%) orders exceeded goals for one or more components (percentages do not total 100%): collection delays 131 (63.0%), in lab processing and testing delay 175 (85.0%), and delay in result verification to LIS 80 (39.0%). For those orders not meeting the 45 min TAT goal, mean times were 17.6, 40.3, and 8 min for collection time, in lab processing and testing, and result verification to LIS, respectively. Post implementation of autoverification, total orders for December 2022 were 1444 with 88.6% meeting TAT of 45 min. Of the 11.4% not meeting TAT, 93 (6.4%) orders were outside goals for multiple components: collection delays 51 (55.0%), in lab processing and testing delay 67 (72.0%), and result verification to LIS 0 (0.0%) orders. For those orders not meeting the 45 min TAT goal, mean times 16.6, 39.7, and 0 min for collection time, in lab processing and testing, and result verification to LIS, respectively. Conclusion Achieving TAT goals agreed upon by the laboratory and clinical practice is critical to quality patient care. An investigation into our delayed TAT for cTnT highlighted several opportunities for intervention within the control of the lab. We chose to implement autoverification of results to easily and consistently eliminate the time required for manual result verification. TAT was improved by 6.6% (82.0% to 88.6%) through autoverification of results, allowing technologists to focus on other clinical work.