bluuebunny/crossref_metadata_2025_split huggingface dataset:
A-176 Barriers and Enablers to Laboratory Stewardship Across a 16 Hospital Regional System
Authors: McCudden C R , Brehaut J , McCleary N 
Published: September 2023

Abstract

Background
Evidence indicates substantial inappropriate and inefficient use of resources in laboratory medicine. Commonly-used approaches that can be effective in improving practice include education, changes to processes or systems, and audit & feedback. The overall aims of this project were to survey the experiences of individuals implementing laboratory stewardship activities across a regional lab system, focusing on identifying key enablers and barrier to success.

Methods
We used a mixed methods approach beginning with a questionnaire to gather brief details about implementation efforts (what was done, how interventions were implemented, when, and by whom). These preliminary findings served as a precursor to conducting focus groups with implementation teams at each of the sites. We probed the implementation process, drivers of success, and barriers faced. Focus group transcripts were analyzed using thematic analysis.

Results
Forty individuals took part in the surveys and focus groups. Results revealed a range of progress with lab stewardship initiatives across sites, with a variety of initiatives having been implemented. A wide range of factors impacting progress with laboratory stewardship, both negatively and positively, were discussed. These were grouped into four broad topics: 1) Roles, responsibilities, and relationships—the “Who”; 2) Generating interest in stewardship—the “Why”; 3) Implementation strategies and processes—the “What”; 4) Project management and resources—the “How”. Key barriers identified included: lack of a clear vision which reduces relative priority, lack of resources, emphasis on financial outcomes, and that over-use problems have complex causes. Key enablers identified included active participation of hospital clinical and administrative champions, ability to implement system level changes (e.g., changing electronic orders and processes), focusing on patient safety outcomes, using established change methodologies which support systematic identification of root causes to help select appropriate change strategies as well as formal evaluation.

Conclusion
While some sites progressed with stewardship initiatives with relative ease, most faced challenges along the way. Surfacing these challenges supports the development of strategies to help address them such that lab stewardship activities can have maximal impact in improving quality of care. Structured and systematic approaches to laboratory stewardship are more likely to be successful than those without designed root cause analysis with targeted interventions and clear outcome metrics.
A-194 Intravenous Fluid Contamination of Basic Metabolic Panels Is Underrecognized by Manual Workflows
Authors: Spies N C , Farnsworth C W , Zaydman M A 
Published: September 2023

Abstract

Background
Erroneous laboratory results contribute to delays in diagnosis, incorrect treatment decisions, and increased healthcare costs. Of these errors, most occur in the preanalytical phase, before the sample makes it to the laboratory. One particularly common source of pre-analytical error is contamination by intravenous crystalloids (IV fluids). Current workflows for detecting IV fluid contamination rely on manual intervention by technologists, which is labor-intensive, variable between technologists, and may lack sensitivity.

Methods
9 627 320 chemistry results were aggregated. IV fluid contamination was simulated by mixing a random sample of results in silico with normal saline (NS), lactated Ringer’s (LR), and their 5% dextrose-containing counterparts (D5NS and D5LR). This simulation procedure was validated by in vitro experiments. Machine learning models were trained to predict contamination and mixture percentage using the simulated results and the prior unaffected result from that patient. A random sample of 100 predicted positives were manually chart reviewed and adjudicated. Predictions from the models on retrospective data were compared to real-world technologist flags.

Results
The ML pipeline identified 3023, 1488, 161, and 236 results as being likely contaminated with NS, LR, D5NS, and D5LR respectively (Fig. 1). Of these, 684 (23%), 84 (6%), 103 (64%), and 148 (63%) had already been flagged by technologists as contaminated. 100/100 manually-reviewed predictions were confirmed. The median contamination ratio for each fluid detected by the pipeline was lower than the current workflow for NS (95% CI of difference: −0.1 to −0.07) and LR (CI: −0.13 to −0.1). The number-needed-to-test to detect one additional contaminated specimen was 125 samples.

Conclusion
A machine learning pipeline uncovers a substantial number of potentially contaminated results that were previously undetected using manual workflows, especially among non-D5 fluids.
A-196 Trend Analysis in Proficiency Testing—Does it Work?
Authors: Bandeira A C , Banzato J M , Utiyama A H , Coutinho V F , Ramadan D R , Tufik S 
Published: September 2023

Abstract

Background
Trend analysis is a powerful tool in any data analysis due to its preventive characteristics. In proficiency testing (PT) it is also important because it can anticipate errors that could impact on patient’s results. Therefore, it is a key tool to patient safety. Although this is the current and logical premise, efficacy of trend analysis has not been measured by laboratories. This work aims to share our laboratory’s enhancements after implementing trend analysis for PT results.

Methods
PT results from a Brazilian national program for two years were analyzed: one year before the implementation of trend analysis (2020) and another year after the process had already been fully established (2022). Qualitative tests were not considered and a total of 432 quantitative analytes were included in the study. Trends were classified by CAP’s recommendations for single mailing patterns (Troubleshooting guide for proficiency testing data—ww.cap.org). The percentage of results classified as inadequate and inadequate results with previous trend alert were calculated. Ten results from both years were compared by Chi-square.

Results
Over 7000 results were analyzed and classified. In 2022, overall inadequate results were 37% lower than 2020. Comparing both periods, Chi-square was high (ꭓ2 = 9,74), corroborating that the enhancements observed were statistically significant. Before trend analysis was implemented, 14 inadequate results presented biased results in previous rounds. If trend analysis had not been implemented, we estimate there would be 15 analytes in this situation. However, only 5 were found, which represents a 297, 8% improvement. For this metric (inadequate results with previous trend alert), Chi-square from both periods was 5087.

Conclusion
Using a simple trend analysis technique we were able to reach an important improvement in the PT process, contributing to preventive actions for potential problems that could affect patient results and decreasing the number of inadequate results. Hence, in our laboratory trend analysis can be considered worth it.
A-201 Deriving Information from the Lipid Panel as Spherical Coordinates
Authors: Cole J , Sampson M L , Remaley A T 
Published: September 2023

Abstract

Background
Lipid panel assays are used to calculate LDL-C as a proxy for cardiovascular disease risk. Further investigations are required to classify the patient’s dyslipidemia into a phenotype to assist with management. We explored the information contained within the lipid panel with two aims: First, to estimate cardiovascular risk directly, bypassing LDL-C calculation. Second, to provide a novel phenotypic classification system.

Methods
Various transformations of lipid panel data were explored as inputs to a logistic regression model of cardiovascular risk, and to produce a spherical coordinate system for phenotyping. Area under the receiver operating characteristic (AUROC) curve was used to assess the predictive ability of the model. Clinical utility metrics were calculated and Kaplan-Meier survival curves were used to determine the prognostic value of the model.

Results
Transforming the lipid panel data into indices allowed derivation of a spherical coordinate system. The spherical coordinates proved to be the best input values for logistic regression to provide the probability of high cardiovascular risk. When we added age, sex and race as variables in the model, the AUROC for predicting cardiovascular events approached that of the American Heart Association’s pooled cohort equation (PCE). The final model was more sensitive than the PCE, and provided greater prognostic ability than LDL-C. The spherical coordinate system classified individuals into “normal” or one of eight phenotypes, which were differentially associated with clinical features such as elevated CRP or metabolic syndrome.

Conclusion
The new model uses all three lipid panel parameters and other routinely available laboratory data to directly predict cardiovascular risk with similar accuracy to the PCE. Conversion of the parameters to a spherical coordinate system allows classification into one of 9 phenotypic groups, which may alert clinicians to underlying or consequent pathological processes to be managed.
A-207 Analytical Validation of Helena SPIFE Touch to Determine ApoB-Containing Lipoproteins Lp(a)-P, LDL-P and VLDL-P
Authors: Scott R J , Donato L , Jaffe A , Meeusen J , Vasile V 
Published: September 2023

Abstract

Background
Elevated Lp(a) is an independent risk factor for atherosclerotic (ASCVD) events and associates with aortic stenosis. Accurate immunochemical measurement of Lp(a) is complicated by heterogeneity of Lp(a) molecular size. The objective of this study was to validate the analytical performance of an electrophoretic assay for measurement of ApoB-containing lipoprotein particles including Lp(a)-P, LDL-P, and VLDL-P and to compare results to other standard clinical methods.

Method
Lp(a)-P, LDL-P, and VLDL-P were quantified by electrophoretic serum separation followed by immuno-staining with an ApoB antibody using the SPIFE Touch (Helena Laboratories, Beaumont, TX). Stability was evaluated by comparison to results at time zero (n = 10). Precision was assessed by 5 measurements twice daily for five days. Limit of quantitation (LoQ) was determined by 20 replicate measurements. Linearity was assessed by mixing high and low concentrations at various ratios. Accuracy was assessed by split sample comparison (n = 126) with Helena Laboratories. Lp(a)-P and LDL-P results were compared to nuclear magnetic resonance (NMR) using a Bruker Ascend 600 NMR (Bruker, Billerica, MA) with AXINON software (numares, AG, Regensberg, Germany) (n = 114). Lp(a)-P is included with LDL-P by NMR. Therefore, the SPIFE Lp(a)-P + LDL-P was compared to NMR LDL-P. SPIFE Lp(a)-P was compared directly to Roche cobas c501 Lp(a) immunoassay calibrated to molar units (Roche Diagnostics, Indianapolis, IN) (n = 126).

Results
The analytical performance of Lp(a)-P, LDL-P, and VLDL-P measured on the SPIFE Touch met all acceptance criteria. Bias to the reference method was &lt;20% with R2 &gt; 0.98. All analytes were stable 14 days refrigerated and 14 days frozen. Lipoprotein particle measurements on SPIFE Touch correlated to those obtained by both NMR and Roche assays.

Conclusion
The analytical performance of the SPIFE Touch for measuring the concentration of ApoB-containing lipoproteins is acceptable. Further studies are needed to determine clinical implications and utility compared to NMR and Roche assays.
A-215 Calculated LDL-cholesterol: Comparability of the extended Martin-Hopkins,Sampson-NIH, Friedewald and four other equations in South African patients
Authors: Carelse A , Rossouw H M , Steyn N , Martins J , Pillay T S 
Published: September 2023

Abstract

Background
Ultracentrifugation for LDL-C (low-density lipoprotein cholesterol) measurement is the gold standard, but it is unsuitable for routine use. Direct LDL-C assays and predictive equations such as the Friedewald equation are thus used as alternatives. The Friedewald equation is known to be error-prone in hypertriglyceridaemic patients, as well as in LDL-C levels &lt; 1.8 mmol/L (70 mg/dL) which has become increasingly attainable with the use of pro-protein convertase subtilisin/kexin type 9 inhibitors. This study evaluates the comparability of the Friedewald, extended Martin/Hopkins, Sampson/NIH and four other equations to a direct LDL-C assay to establish a suitable alternative to the Friedewald equation.

Methods
We analysed 44 194 lipid profiles from a mixed South African population. The Friedewald, extended Martin/Hopkins and Sampson/NIH LDL-C and four other predictive equations (Vujovic, Puavilai, Delong, Anandaraja) were compared to the Beckman Coulter direct LDL-C assay. Non-parametric statistics were used to analyse the data.

Results
The extended Martin/Hopkins equation displayed the best correlation with direct LDL-C, having the most values fall within the desirable bias (59%) and total allowable error (89%) specifications. In patients with TG values between 4.5 mmol (400 mg/dL) and 9.0 mmol/L (800 mg/dL), the extended Martin/Hopkins equation was more likely to overestimate LDL-C levels, showing a positive median bias of 7.3%, while Friedewald (−21.2%) and Sampson/NIH (−9.8%) showed larger negative median biases as compared to the direct LDL-C assay. The direct LDL-C assay classified 13.9% of patients in the low LDL-C (1.0–1.8 mmol/L) (39–70 mg/dL) category, in comparison to the Martin/Hopkins equation (13.4%), the Sampson equation (14.6%) and the Friedewald equation (16.0%). The extended Martin/Hopkins equation performed better than Sampson/NIH equation in the cohort.

Conclusion
We suggest the extended Martin/Hopkins equation as an alternative to Friedewald’s equation and direct LDL-C assay. Careful consideration is advised as the choice of analyser platform for the lipid profile used in the equations may influence their performance.
A-218 Analytical Performance Evaluation of Lipid Panel Assays on the Atellica CI 1900 Analyzer
Authors: Kolewe K , Singh S , Tyler C , Arrode-Bruses G , Rhea-McManus J , Snyder J 
Published: September 2023

Abstract

Background
The Atellica® CI 1900 Analyzer is an automated, mid-throughput, integrated chemistry and immunoassay analyzer utilizing both Atellica CH and Atellica IM assays. This study was designed to evaluate the analytical performance of the Atellica CH Creatinine (CREA_2)*, Enzymatic Creatinine (ECre_3)*, Urinary/Cerebrospinal Fluid Protein (UCFP)*, and Microalbumin_2 (µALB_2)* assays on the Atellica CI 1900 Analyzer*.

Methods
The Atellica CI 1900 CH CREA_2, ECre_3, UCFP, and µALB_2 assays use the same reagents and calibrators as the Atellica CH assays. Precision and method comparison (MC) were used as performance indicators for the Atellica CI 1900 Analyzer. Precision studies were performed according to CLSI EP05-A3 using native and contrived human urine samples. One aliquot of each sample pool was tested in duplicate in two runs per day &gt;2 h apart on each analyzer for &gt;20 days. MC studies were performed according to CLSI EP09-A3. Individual native and contrived human urine samples were analyzed using the Atellica CH assays on both the Atellica CH and Atellica CI 1900 Analyzers.

Results
Representative precision and MC results observed from one reagent lot across indicated sample ranges are listed for each assay in the table below. Over the four assays tested, repeatability and within-lab %CVs were &lt;5.1% and &lt;6.0%, respectively. Slopes determined by the Deming linear regression model were approximately equal to 1.

Conclusion
Evaluation of the Atellica CH CREA_2, ECre_3, UCFP, and µALB_2 assays using the Atellica CI 1900 Analyzer demonstrated good precision and equivalent performance compared to the same assays on the Atellica CH Analyzer.
*The products/features mentioned here are not commercially available in all countries. Their future availability cannot be guaranteed.
A-223 Lipoprotein (a) Profile in Patients with Diabetes and Coronary Artery Disease
Authors: Castelo M C , Fernandes V O , Lima Verde J L , Ballalai M S , Montenegro A D , Montenegro R M , Lopes A C 
Published: September 2023

Abstract

Background
Changes in the lipid profile that cause an increase in cardiovascular risk are basically those that occur with an increase in apolipoprotein B-100 (apoB). This lipoprotein is present in LDL, VLDL, IDL and lipoprotein a or Lp(a). Lp(a) is a molecule similar to LDL being formed by the junction of apoB with apolipoprotein A. Lp (a) levels are virtually independent of diet or environmental factors. Around 90% is defined by the patient’s genetic heritage. Lp(a) has the potential to cause atherosclerosis by LDL-like mechanisms (vascular wall impairment, oxidation), However, there are several other mechanisms that are proposed to explain the increased cardiovascular risk caused by increased Lp(a) levels. Some would result in a high risk of thrombogenicity, others of atherogenesis. The aim of this study was to describe the Lp(a) profile in individuals with diabetes and coronary artery disease.

Methods
This is a descriptive cross-sectional study carried out in 2 reference centers in the care of patients with diabetes and high cardiovascular risk in Fortaleza-Ceará, Brazil.We evaluated lp(a) level was and the presence of multivessel coronary artery diseaseThe statistical analysis of the data was performed with the Microsoft Excel program.

Results
Of the 34 patients evaluated, 47% (16) were male and 53% (18) female, with a mean age of 58.3 ± 9.34 years old, The mean time that the coronary event had occurred was 7.85 ± 6.27 years, and the mean age at the first thrombotic event was 51.56 ± 9.311 years old. There was found 44.1% of dyslipidemia before the first thrombotic and 61.7% had multivessel coronary artery disease. Lp(a) median was 23.5 mg/dL (min &lt; 3-max 149).70.5% of the evaluated patients had Lp(a) &lt; 50 mg/dL, 20.5% between 50–90 mg/dL, and 8.8% had Lp(a) &gt; 90 mg/dL.

Conclusion
Most patients with diabetes studied had normal or subnormal levels of lp(a) even though they were patients at very high cardiovascular risk. More studies need to be carried out, but this finding could suggest that in diabetic individuals, as well as LDL-c, we could have lower cutoff points than in the general population.
A-257 Association Between Matrix Metalloproteinase-3 and its Post-Transcriptional Regulator miR-17-5p in the Pathogenesis of Tuberculous Meningitis Patients
Authors: Aggarwal A , Sharma S R , Modi M , Sharma K , Verma I , Singla N , Konar M , Kaur M , Sharma K 
Published: September 2023

Abstract

Background
Tuberculosis, a communicable disease caused by Mycobacterium tuberculosis is one of the top 10 causes of death worldwide. Tuberculous meningitis (TBM), an extra-pulmonary central nervous system tuberculosis is the most severe form with maximum mortality. To combat the complications of disease, host immune response gets activated which initially protects the host but later an exaggerated response leads to aggravation of the disease. This causes tremendous neuroinflammation which further increases the complications of the disease. Matrix metalloproteinase (MMPs) like MMP-9, 2 and 3 are known to cause damage to the blood brain barrier and have a role in the pathogenesis of disease particularly increasing the neuroinflammation. MMPs are regulated at post-transcriptional level by microRNAs (miRNA) that alter their levels by targeting various genes. Based on available literature we found miR-17-5p to be a key regulator of MMP3. In this study, we assessed the levels of MMP3 and its post-transcriptional regulator miR-17-5p in the cerebrospinal fluid (CSF) of TBM patients, healthy controls (HC) and non-infectious neuroinflammatory disease patients (NID).

Methods
In this study, 100 TBM patients were recruited based on the Lancet scoring system and CSF samples were collected. For NID control group, 25 patients with other non-infectious neuroinflammatory diseases like Guillain-Barre syndrome, multiple sclerosis were recruited. Twenty five HC CSF samples were collected from patients undergoing spinal anaesthesia for any lower limb surgery. The samples were stored at −80°C and processed when required for ELISA and quantitative real time PCR.

Results
We found a significant increase in levels of median MMP3 levels in the CSF of TBM patients compared to HC group (2.719 ng/ml vs 1.696 ng/ml). The MMP3 levels were also significantly elevated in the NID control group as compared to HC group (3.116 ng/ml vs 1.696 ng/ml). A stagewise comparison in TBM group showed an increase in levels of MMP3 with respect to HC but within stages results were comparable. The expression of MMP3 regulator miR-17-5p showed an upregulation in the CSF of TBM group as compared to NID and HC group.

Conclusion
An increase in levels of MMP3 was observed in both TBM and NID group which infers that MMP3 might have a role in neuroinflammation in neurological conditions. In our study groups we did not find any relation between miR-17-5p expression and MMP3 levels, indicating that there might be some other regulatory pathway altering the levels of MMP3 in neurological conditions. Hence, further studies can be done to highlight the explicit role of MMP3 in neuroinflammation which can then be targeted therapeutically to relieve the associated complications.
A-282 Coinfection Rates of SARS-CoV-2, Influenza, and Respiratory Syncytial Virus
Authors: Pratt G W , Platt M , Wong C , Rao L V 
Published: September 2023

Abstract

Background
In late 2022, a severe spike of respiratory syncytial virus (RSV) cases in the United States alongside seasonal influenza and the ongoing SARS-CoV-2 crisis underscored the potential consequences for respiratory coinfections. Coinfections of respiratory viruses can complicate treatment and increase the likelihood of severe cases. It is not well understood how prevalent respiratory coinfections were during this time in the general and pediatric populations. In this retrospective analysis we examine respiratory molecular diagnostic testing results to estimate the rates of coinfection in the study population.

Methods
Respiratory sample results from a clinical laboratory for a 107-day period in autumn 2022 were analyzed. Assays were performed on two platforms: the Roche cobas® SARS-CoV-2 & Influenza A/B Test and the Cepheid Xpert® Xpress CoV-2/Flu/RSV plus assay. Overall positivity and coinfection rates were calculated. Coinfection results of the pediatric population were further investigated.

Results
A total of 26 657 respiratory testing results were analyzed. Cases of coinfection of SARS-CoV-2, influenza A, influenza B, and RSV were seen. Positivity ranged from 0.03% to 21.86% and coinfection rates ranged from 0.00% to 2.28% depending upon the pathogen. Overall, 9800 samples (36.76%) came from pediatric patients (age ≤21). Pediatric positivity ranged from 0.04% to 24.70% and coinfection rates ranged from 0.00% to 6.00% depending on the pathogen (Table).

Conclusion
Overall, coinfections were observed in 0.55% of samples comprising 1.33% of all positive results. In this study population, pediatric samples accounted for a disproportionately high percentage of positive results for influenza A, RSV, and SARS-CoV-2 coinfections when compared to the overall percentages from the complete study population.