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A common practice exists in hospitals where extra tubes of blood are collected for possible add-on testing, this practice contributes to wastage of consumables. Baseline estimates from a 5-month local lab information system audit revealed that ~65 extra tubes per day were being collected, with an additional 2-week manual audit of all extra tubes received in the laboratory confirming the practice. The audits showed that the majority of the tubes (~99%) were being drawn from the adult emergency department (ED). Furthermore, only 5% of the extra tubes were being used for add-on testing, whereas the remaining tubes had no testing performed on them and were discarded at the end of the day. This translates to over 23 000 extra tubes being wasted annually.After initial discussion with ED leadership, the practice was identified as primarily nurse driven. An educational intervention was created and entitled 'Every Tube Counts', with the aim to reduce extra tube collections in the adult ED by 50% within the first month of intervention. First, a memo with initial findings and a request to stop the practice of extra tube collection was sent out to all ED staff. After 2 weeks of additional data collection, it was noticed that extra tubes were still being collected. A second intervention, which consisted of another communication and utilisation of nurse educators to disseminate the information to nursing staff, saw a remarkable ~80% reduction in collection of extra tubes in the following few months after the second intervention. The practice was followed for an additional 15 months, which saw a slight increase of extra tube collections over time with a levelling off towards the latter period of the study. However, the target goal was maintained over the entire study period., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Urinary stone disease (USD) historically has affected older men, but studies suggest recent increases in women, leading to a near identical sex incidence ratio. USD incidence has doubled every 10 years, with disproportionate increases amongst children, adolescent, and young adult (AYA) women. USD stone composition in women is frequently apatite (calcium phosphate), which forms in a higher urine pH, low urinary citrate, and an abundance of urinary uric acid, while men produce more calcium oxalate stones. The reasons for this epidemiological trend are unknown., Methods: This perspective presents the extent of USD with data from a Canadian Province and a North American institution, explanations for these findings and offers potential solutions to decrease this trend. We describe the economic impact of USD., Findings: There was a significant increase of 46% in overall surgical interventions for USD in Ontario. The incidence rose from 47.0/100,000 in 2002 to 68.7/100,000 population in 2016. In a single United States institution, the overall USD annual unique patient count rose from 10,612 to 17,706 from 2015 to 2019, and the proportion of women with USD was much higher than expected. In the 10-17-year-old patients, 50.1% were girls; with 57.5% in the 18-34 age group and 53.6% in the 35-44 age group. The roles of obesity, diet, hormones, environmental factors, infections, and antibiotics, as well as the economic impact, are discussed., Interpretation: We confirm the significant increase in USD among women. We offer potential explanations for this sex disparity, including microbiological and pathophysiological aspects. We also outline innovative solutions - that may require steps beyond typical preventive and treatment recommendations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Filler, Dave, Ritter, Ross, Viprakasit, Hatch, Bjazevic, Burton, Gilleskie, Gilliland, Lin, Jain, McClure, Razvi, Bhayana, Wang, Coulson, Sultan, Denstedt, Fearrington and Diaz-Gonzalez de Ferris.)

BACKGROUNDThe role of humoral immunity in COVID-19 is not fully understood, owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome.METHODSUsing SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients' plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution.RESULTSWe identified linear epitopes from the spike (S) and nucleocapsid (N) proteins and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. Specifically, we found that antibody responses to the S-811-825, S-881-895, and N-156-170 epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant of concern B.1.1.7 altered the specificity of the corresponding epitopes.CONCLUSIONEpitope-resolved antibody testing not only affords a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, but it also may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern in both the peptide array and latex agglutination formats.FUNDINGOntario Research Fund (ORF) COVID-19 Rapid Research Fund, Toronto COVID-19 Action Fund, Western University, Lawson Health Research Institute, London Health Sciences Foundation, and Academic Medical Organization of Southwestern Ontario (AMOSO) Innovation Fund.

We have developed a rapid, accurate, and cost-effective serologic test for SARS-CoV-2 virus, which caused the COVID-19 pandemic, on the basis of antibody-dependent agglutination of antigen-coated latex particles. When validated using plasma samples that are positive or negative for SARS-CoV-2, the agglutination assay detected antibodies against the receptor-binding domain of the spike (S-RBD) or the nucleocapsid protein of SARS-CoV-2 with 100% specificity and ∼98% sensitivity. Furthermore, we found that the strength of the S-RBD antibody response measured by the agglutination assay correlated with the efficiency of the plasma in blocking RBD binding to the angiotensin-converting enzyme 2 in a surrogate neutralization assay, suggesting that the agglutination assay might be used to identify individuals with virus-neutralizing antibodies. Intriguingly, we found that >92% of patients had detectable antibodies on the day of a positive viral RNA test, suggesting that the agglutination antibody test might complement RNA testing for the diagnosis of SARS-CoV-2 infection., Competing Interests: S.E., C.V., and S.S.-C.L. are co-inventors in a US Provisional patent application on the agglutination assay submitted by Western University., (© 2021 The Authors.)

Background: Autoimmunity is an increasingly recognized cause of encephalitis with a similar prevalence to that of infectious etiologies. Over the past decade there has been a rapidly expanding list of antibody biomarker discoveries that have aided in the identification and characterization of autoimmune encephalitis. As the number of antibody biomarkers transitioning from the research setting into clinical laboratories has accelerated, so has the demand and complexity of panel-based testing. Clinical laboratories are increasingly involved in discussions related to test utilization and providing guidance on which testing methodologies provide the best clinical performance., Content: To ensure optimal clinical sensitivity and specificity, comprehensive panel-based reflexive testing based on the predominant neurological phenotypic presentation (e.g., encephalopathy) is ideal in the workup of cases of suspected autoimmune neurological disease. Predictive scores based on the clinical workup can aid in deciding when to order a test. Testing of both CSF and serum is recommended with few exceptions. Appropriate test ordering and interpretation requires an understanding of both testing methodologies and performance of antibody testing in different specimen types., Summary: This review discusses important considerations in the design and selection of neural antibody testing methodologies and panels. Increased collaboration between pathologists, laboratorians, and neurologists will lead to improved utilization of complex autoimmune neurology antibody testing panels., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Testing of 25-hydroxy (25-OH) vitamin D serum levels has increased drastically in recent years and much of it is considered inappropriate based on current guidelines., Methods: In consultation with our physician groups (experts and frequent orderers), we modified existing guidelines and implemented a rational policy for 25-OH vitamin D testing and 1,25 dihydroxy (1,25 di-OH) vitamin D testing at a tertiary care centre. A computer decision support tool requiring selection of one of five acceptable testing indications was created for each test as part of a computerised physician order entry system., Results: As a result of our intervention, we observed a 27% decrease in the average monthly test volume for 25-OH vitamin D from 504±62 (mean±SD) tests per month to 370±33 (p<0.001). 1,25 di-OH vitamin D testing decreased 58% from 71±18 to 30±10 (p<0.001). The departments ordering the tests were similar during the preintervention and postintervention periods, and further audits, patient chart reviews and individualised physician feedback were required to ensure appropriate ordering of 1,25 di-OH vitamin D. The most common ordering reasons selected were malabsorption/dietary concerns (46%) for 25-OH vitamin D and renal failure (42%) for 1,25 di-OH vitamin D., Conclusions: Limitations of our computer decision support tool include a dependence on an honour system in selecting the testing indication and an inability to limit ordering frequency. Periodic monitoring of test volumes will be required to ensure adherence to guidelines. Despite these limitations, we have improved appropriate utilisation of these tests and reduced costs by approximately $C60 375 per year., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mandatory enrichment of wheat flour in Canada with folic acid since 1998 has caused folate deficiency to be rare. There were 3019 red blood cell (RBC) folate tests performed during an 18-month period at London Health Sciences Centre (LHSC)/St. Joseph's Healthcare London (SJHC) without any folate deficiency detected. We implemented a quality improvement initiative to reduce RBC folate testing at LHSC/SJHC. We began with a retrospective review of RBC folate tests performed during the previous 18 months. We identified physicians who had ordered more than five tests during this period and sent them an educational email to inform them of our intentions and solicit their input. We then discontinued RBC folate testing in-house and a pop-up window was introduced to the computerised physician order entry system stating that biochemist approval would be needed before samples would be sent out for testing. During the audited 18-month period, the average monthly test volume was 168 (SD 20). The three departments ordering the most RBC folate testing were nephrology (15%), haematology (7%) and oncology (7%). Physician feedback was supportive of the change, and during the 2 months after targeted email correspondence, the average monthly test volume decreased 24% (p<0.01) to 128 (SD 1). On discontinuation of the test in-house and implementation of the pop-up, the average monthly test volume decreased another 74% (p<0.01) to 3 (SD 2). In the 10 months following discontinuation of the test on-site, there were only 39 RBC folate tests performed with no deficiency detected. This initiative significantly reduced unnecessary RBC folate orders. The change in ordering on email contact suggests that physician education was an important factor reducing overutilisation. However, the most significant decrease came from restricting the test so that only orders approved by a biochemist would be performed., Competing Interests: Competing interests: None declared.