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Background: Many fentanyl immunoassays are limited in their ability to detect norfentanyl. Urine specimens collected from individuals who have been exposed to fentanyl frequently have detectable concentrations of norfentanyl (≥2 ng/mL) but low concentrations of fentanyl (<2 ng/mL) by LC-MS/MS. The Lin-Zhi Fentanyl II Immunoassay (Lin-Zhi) claims 100% cross-reactivity with norfentanyl and therefore may detect exposure missed by other assays., Methods: In addition to verifying the manufacturer's analytical sensitivity claims, we selected 92 urine specimens with low-positive Lin-Zhi results (1-99 absorbance units, lowest 10%) for analysis by the Immunalysis Health Equity Impact Assessment and ARK II fentanyl methods. The accuracy of the 3 immunoassays was compared to LC-MS/MS as the reference method., Results: Spiking studies using purified fentanyl and norfentanyl and a set of 100 consecutive specimens confirmed the manufacturer's claims of limit of detection for fentanyl (3.8 ng/mL) and norfentanyl (5.0 ng/mL). However, the 92 low-positive patient specimens demonstrated concentrations of norfentanyl and fentanyl below 2.0 ng/mL by LC-MS/MS, with 47 (51%) having only norfentanyl detected. When comparing Lin-Zhi to the Immunalysis and ARK II immunoassays, only 27 (29%) of the 92 specimens were concordant. Fifty-two (57%) of the specimens were positive by LC-MS/MS and Lin-Zhi but false negative by one or both other immunoassays. Seven specimens (8%) were positive by Lin-Zhi but negative by the other immunoassays and had undetectable concentrations (<2 ng/mL) of fentanyl and norfentanyl by LC-MS/MS., Conclusions: The clinical sensitivity of the Lin-Zhi exceeds the manufacturer's claims, providing results comparable to LC-MS/MS methods., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background: The COVID-19 pandemic reportedly had a significant impact on drug and alcohol use. In this article, we determine positivity rates for urine drugs of abuse and blood alcohol in 5 emergency departments (ED) in the greater Boston metropolitan area over a 4-year period (pre-, during, and post-COVID-19 pandemic)., Methods: Positivity rates for the urine drug screening (UDS) panel and blood alcohol concentration (>80 mg/dL; over the legal limit in MA) were calculated in patients presenting to one of the 5 ED (2 academic hospitals in Boston, MA and 3 community hospitals outside Boston, MA) during each of the 4 different time periods: pre-COVID (January 1, 2019 to December 31, 2019), stay-at-home (March 24, 2020 to May 18, 2020), during COVID (May 19, 2020 to March 28, 2021), and post-COVID (May 12, 2023 to August 31, 2023). Trend analysis was performed. Additionally, positivity rates during and post-COVID were compared to pre-COVID to determine any significant changes in drug positivity., Results: Stimulant (amphetamines and cocaine), cannabinoid, and methadone positivity increased during the pandemic and cocaine, cannabinoid, and methadone positivity remains elevated. By contrast, benzodiazepine and opioid (opiates, fentanyl, oxycodone) positivity decreased and remains lower post-COVID compared to pre-COVID. Patients in the ED with blood alcohol over the legal limit decreased both during and post-COVID., Conclusion: Our study showed that the COVID-19 pandemic significantly affected drug and alcohol positivity rates in patients presenting to the ED in greater Boston area. We encourage other institutions to perform similar analyses to help determine local drug use patterns and appropriate composition of UDS panels., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Benzodiazepines are frequently prescribed and misused therefore urine drug screening (UDS) is performed in many patient populations. Most current benzodiazepine immunoassays have poor sensitivity, particularly for detecting the metabolites of newer benzodiazepines such as lorazepam in urine., Objectives: We aimed to verify the clinical performance of the new qualitative Roche Benzodiazepines II (BNZ2) immunoassay, as well as compare its performance to the Roche Benzodiazepines Plus (BENZ) assay in two patient populations: UDS in the emergency department (ED) and compliance monitoring., Methods: An initial verification study was performed, selecting for samples containing clonazepam and lorazepam metabolites. Performance of the BNZ2 and BENZ assays was compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the reference method. Sensitivity, specificity, false positive rate (FPR) and false negative rate (FNR) were determined., Results: We verified the performance claims in the initial verification and demonstrated similar precision, with coefficient of variations (CVs) of 12.8% and 7.7% for negative and positive controls, respectively. Furthermore, we observed higher clinical sensitivity and lower FNR with the BNZ2 assay in both the ED and compliance monitoring populations due to improved cross-reactivity for lorazepam and clonazepam metabolites. Despite these improvements, the BNZ2 assay was unable to detect 27% of specimens positive by LC-MS/MS, including specimens from patients using benzodiazepines without prescription., Discussion: Due to its improved performance and rapid turnaround time, the BNZ2 assay should be implemented for UDS in the ED. However, the assay should not replace LC-MS/MS testing for compliance monitoring, as unsuspected benzodiazepine use may go undetected., (© 2024 THE AUTHORS.)

Background: Serologic assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proposed to assist with the acute diagnosis of infection, support epidemiological studies, identify convalescent plasma donors, and evaluate vaccine response., Methods: We report an evaluation of nine serologic assays: Abbott (AB) and Epitope (EP) IgG and IgM, EUROIMMUN (EU) IgG and IgA, Roche anti-N (RN TOT) and anti-S (RS TOT) total antibody, and DiaSorin (DS) IgG. We evaluated 291 negative controls (NEG CTRL), 91 PCR positive (PCR POS) patients (179 samples), 126 convalescent plasma donors (CPD), 27 healthy vaccinated donors (VD), and 20 allogeneic hematopoietic stem cell transplant (HSCT) recipients (45 samples)., Results: We observed good agreement with the method performance claims for specificity (93-100%) in NEG CTRL but only 85% for EU IgA. The sensitivity claims in the first 2 weeks of symptom onset was lower (26-61%) than performance claims based on > 2 weeks since PCR positivity. We observed high sensitivities (94-100%) in CPD except for AB IgM (77%), EP IgM (0%). Significantly higher RS TOT was observed for Moderna vaccine recipients then Pfizer (p-values < 0.0001). A sustained RS TOT response was observed for the five months following vaccination. HSCT recipients demonstrated significantly lower RS TOT than healthy VD (p < 0.0001) at dose 2 and 4 weeks after., Conclusions: Our data suggests against the use of anti-SARS-CoV-2 assays to aid in acute diagnosis. RN TOT and RS TOT can readily identify past-resolved infection and vaccine response in the absence of native infection. We provide an estimate of expected antibody response in healthy VD over the time course of vaccination for which to compare antibody responses in immunosuppressed patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: As hypoxemia and hypoxia are central elements of disease pathophysiology and disease-related morbidity and mortality in individuals affected by sickle cell disease (SCD), clinical management aims to optimize oxygenation., Content: Hypoxemia is primarily screened for with pulse oximetry. However, in SCD pulse oximetry can inaccurately reflect arterial saturation, posing the risk of undetected (occult) hypoxemia. Solely relying on pulse oximetry might therefore lead to misdiagnosis or mismanagement, with devastating effects on tissue oxygenation. The interpretation of oxygenation status is multifaceted, and "oxygen saturation" is often used as an umbrella term to refer to distinctly different measured quantities-estimated oxygen saturation (O2Sat), hemoglobin oxygen saturation (SO2) by either pulse oximetry or co-oximetry, and fractional oxyhemoglobin (FO2Hb). While in many clinical situations this ambiguous use is of little consequence, O2Sat, SO2, and FO2Hb cannot be used interchangeably in the setting of SCD, as dyshemoglobins, anemia, cardiopulmonary comorbidities, concomitant medications, and frequent transfusions need to be accounted for. This article describes the parameters that determine blood and tissue oxygen concentration, discusses laboratory method performance characteristics and the correct interpretation of currently available clinical laboratory testing, and reviews the literature on noninvasive vs invasive oxygenation measurements in SCD., Summary: By correctly establishing and interpreting oxygenation parameters, clinical and laboratory teams can ensure high-quality, equitable healthcare, counteracting systemic exacerbations of health disparities frequently experienced by individuals with SCD., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Many states in the United States have progressed towards legalization of marijuana including decriminalization, medicinal and/or recreational use. We studied the impact of legalization on cannabis-related emergency department visits in states with varying degrees of legalization., Methods: Seventeen healthcare institutions in fifteen states (California, Colorado, Connecticut, Florida, Iowa, Kentucky, Maryland, Massachusetts, Missouri, New Hampshire, Oregon, South Carolina, Tennessee, Texas, Washington) participated. Cannabinoid immunoassay results and cannabis-related International Classification of Diseases (ninth and tenth versions) codes were obtained for emergency department visits over a 3- to 8-year period during various stages of legalization: no state laws, decriminalized, medical approval before dispensaries, medical dispensaries available, recreational approval before dispensaries and recreational dispensaries available. Trends and monthly rates of cannabinoid immunoassay and cannabis-related International Classification of Diseases code positivity were determined during these legalization periods., Results: For most states, there was a significant increase in both cannabinoid immunoassay and International Classification of Diseases code positivity as legalization progressed; however, positivity rates differed. The availability of dispensaries may impact positivity in states with medical and/or recreational approval. In most states with no laws, there was a significant but smaller increase in cannabinoid immunoassay positivity rates., Conclusions: States may experience an increase in cannabis-related emergency department visits with progression toward marijuana legalization. The differences between states, including those in which no impact was seen, are likely multifactorial and include cultural norms, attitudes of local law enforcement, differing patient populations, legalization in surrounding states, availability of dispensaries, various ordering protocols in the emergency department, and the prevalence of non-regulated cannabis products.

Rationale & Objective: Estimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery., Study Design: Retrospective observational cohort study., Setting & Participants: 1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories., Predictors: Serum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review., Analytical Approach: Univariate and multivariable linear and logistic regression., Results: Cystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ = 0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P < 0.001), whereas age (OR per year OR, 1.03; 95% CI [1.02, 1.04]; P < 0.001) and Elixhauser score (OR per point OR, 1.22; 95% CI [1.10, 1.36]; P < 0.001) were associated with a higher likelihood of change to a later stage., Limitations: Single center, no direct measurement of clearance for comparison, and inconsistent self-identification of race/ethnicity., Conclusions: Cystatin C eGFR correlates strongly with creatinine eGFR but can have a substantial effect on CKD staging. As cystatin C is adopted, clinicians must be informed on this impact., (© 2023 The Authors.)

Objective: To examine the relationship between point-of-care (POC) measurement of combined umbilical arterial and venous (CUAV) lactate and umbilical artery (UA) lactate to determine whether POC assessment of this sample could be an alternative screening modality for neonatal acidosis and aid prediction of neonatal morbidity., Methods: In this cross-sectional pilot study, UA and CUAV cord blood samples were collected from live, singleton neonates delivered between June and August 2019, at a tertiary care center. UA samples were analyzed for pH and lactate using a blood gas analyzer. CUAV lactate was also assessed on a blood gas analyzer and at the POC. Linear regression was used to determine the correlation between these samples., Results: A total of 152 neonates were included. There was a statistically significant correlation between CUAV lactate concentrations and UA lactate concentrations (R 2  = 0.744). Additionally, CUAV lactate concentration measured at the POC was significantly correlated with that measured on a traditional blood gas analyzer (R 2  = 0.928)., Conclusion: POC testing of CUAV lactate is reliable and closely correlated with UA lactate concentrations, making POC testing of CUAV lactate a potential screening test for neonatal acidosis. More data are needed to establish standardization of this test relative to its predictive value in clinical neonatal outcomes., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: To select and standardize point-of-care (POC) glucose meters across a multi-hospital system., Methods: We formed a multidisciplinary POC glucose standardization working group including key stakeholders from each site. A set of selection criteria: usability, clinical and laboratory performance, indications for use, interface connectivity, ease of implementation and ongoing operational costs were used to develop a scoring schemato facilitate a consensus-driven selection process., Results: Method comparison and consensus error grid evaluation against the clinically validated reference methods demonstrated that the analytical performance for all candidate meters was comparable for both the laboratory and clinical evaluation. However, Meter 1 ranked highest in usability evaluations, implementation and streamlined interface connectivity. The meter selection process and implementation were staggered across sites due to complexity of transitioning to a new manufacturer's meter and limitations in vendor support for training and ongoing troubleshooting of interface connectivity., Conclusions: Standardization of POC glucose meters in a large multi-hospital system is a complex undertaking requiring robust, multidisciplinary organizational structure both system-wide and locally, development of consensus-driven selection tools, usability evaluation by end-users, laboratory and clinical evaluation of the analytical performance, and a strong vendor-laboratory partnership during the implementation process., (Copyright © 2022. Published by Elsevier B.V.)

Laboratories faced many challenges throughout the COVID-19 pandemic. Point-of-care (POC) SARS-CoV-2 nucleic acid amplification tests (NAATs) provided a key solution to the need for rapid turnaround time in select patient populations and were implemented at the POC but also within laboratories to supplement traditional molecular assays. Clinical Laboratory Improvement Amendments-waived rapid POC SARS-CoV-2 NAATs offer the benefit of reduced educational requirements for operators and can be performed by non-laboratory-trained individuals. However, these methods must be validated to ensure the manufacturer's performance specifications are met and they are found to be fit-for-purpose in the clinical workflows they are implemented., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cannabis is widely used in the United States despite federal laws. In US states that have progressed toward legalization, there have been various reported impacts on cannabis-related emergency department (ED) visits. However, studies on the impact of legalization in Massachusetts (MA) EDs are lacking., Methods: Cannabinoid immunoassay (THC IA) results and cannabis-related ICD-10 codes were obtained for consecutive patient ED visits at two academic medical centers in Boston, MA over the following legalization periods (January 2012-December 2019): decriminalized (DEC), before medical dispensaries (MED BD), medical dispensaries available (MED DISP), before recreational dispensaries (REC BD) and recreational dispensaries available (REC DISP). Trends and monthly positivity rates for THC IA and ICD-10 codes were determined for these legalization periods., Results: There was an increase in both THC IA ( p  < .0001) and cannabis-related ICD-10 codes ( p  < .0001) in the ED as legalization progressed at both institutions. Positivity rates significantly increased by 7% for THC IA and 0.4% for ICD-10 codes. Increases in THC IA positivity were seen in females, patients aged 30-39, older adults (>59 years), and those in the highest income tertile. There was an increasing trend in amphetamine positivity and decreasing trend in opiate positivity in patients with positive THC IA. Unlike THC IA, significant trends per patient demographics were not seen with ICD-10 codes., Conclusions: Legalization of marijuana in MA has led to an increase in cannabis use as indicated by both increasing rates of positive THC IA results, in older adults, as well as increasing cannabis-related ICD-10 codes. Data suggest a steady increase in THC use associated with legalization that was not associated with an increase in opiate, fentanyl, or cocaine use. We recommend using ED THC IA positivity, an objective laboratory measure, to monitor THC use and the impact of state-specific progression in cannabis legalization.

The use of anti-spike (S) serologic assays as surrogate measurements of SARS-CoV-2 vaccine induced immunity will be an important clinical and epidemiological tool. The characteristics of a commercially available anti-S antibody assay (Roche Elecsys anti-SARS-CoV-2 S) were evaluated in a cohort of vaccine recipients. Levels were correlated with pseudotype neutralizing antibodies (NAb) across SARS-CoV-2 variants. We recruited adults receiving a two-dose series of mRNA-1273 or BNT162b2 and collected serum at scheduled intervals up to 8 months post-first vaccination. Anti-S and NAb levels were measured, and correlation was evaluated by (i) vaccine type and (ii) SARS-CoV-2 variant (wild-type, Alpha, Beta, Gamma, and three constructs Day 146*, Day 152*, and RBM-2). Forty-six mRNA vaccine recipients were enrolled. mRNA-1273 vaccine recipients had higher peak anti-S and NAb levels compared with BNT162b2 ( P  < 0.001 for anti-S levels; P  < 0.05 for NAb levels). When anti-S and NAb levels were compared, there was good correlation (all r values ≥ 0.85) in both BNT162b2 and mRNA-1273 vaccine recipients across all evaluated variants; however, these correlations were nonlinear in nature. Lower correlation was identified between anti-S and NAb for the Beta variant ( r  = 0.88) compared with the wild-type (WT) strain ( r  = 0.94). Finally, the degree of neutralizing activity at any given anti-S level was lower for each variant compared with that of the WT strain, ( P  < 0.001). Although the Roche anti-S assay correlates well with NAb levels, this association is affected by vaccine type and SARS-CoV-2 variant. These variables must be considered when interpreting anti-S levels. IMPORTANCE We evaluated anti-spike antibody concentrations in healthy mRNA vaccinated individuals and compared these concentrations to values obtained from pseudotype neutralization assays targeting SARS-CoV-2 variants of concern to determine how well anti-spike antibodies correlate with neutralizing titers, which have been used as a marker of immunity from COVID-19 infection. We found high peak anti-spike concentrations in these individuals, with significantly higher levels seen in mRNA-1273 vaccine recipients. When we compared anti-spike and pseudotype neuralization titers, we identified good correlation; however, this correlation was affected by both vaccine type and variant, illustrating the difficulty of applying a "one size fits all" approach to anti-spike result interpretation. Our results support CDC recommendations to discourage anti-spike antibody testing to assess for immunity after vaccination and cautions providers in their interpretations of these results as a surrogate of protection in COVID-vaccinated individuals.

Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.

Background: Serological testing provides a record of prior infection with SARS-CoV-2, but assay performance requires independent assessment., Methods: We evaluated 3 commercial (Roche Diagnostics pan-IG, and Epitope Diagnostics IgM and IgG) and 2 non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 1083 unique samples that included 251 PCR-positive and 832 prepandemic samples., Results: The Roche assay registered the highest specificity 99.6% (3/832 false positives), the Ragon/MGH assay 99.5% (4/832), the primary Simoa assay model 99.0% (8/832), and the Epitope IgG and IgM 99.0% (8/830) and 99.5% (4/830), respectively. Overall sensitivities for the Simoa, Roche pan-IG, Epitope IgG, Ragon/MGH IgG, and Epitope IgM were 92.0%, 82.9%, 82.5%, 64.5% and 47.0%, respectively. The Simoa immunoassay demonstrated the highest sensitivity among samples stratified by days postsymptom onset (PSO), <8 days PSO (57.69%) 8-14 days PSO (93.51%), 15-21 days PSO (100%), and > 21 days PSO (95.18%)., Conclusions: All assays demonstrated high to very high specificities while sensitivities were variable across assays., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The COVID-19 pandemic has made a devastating impact on global health and continues to challenge healthcare infrastructure and delivery. The clinical laboratories were no exception as they are responsible for diagnostic testing that dictates many clinical, infection control, and public health decisions. Information technology and laboratory management tools are critical assets for maintaining and adapting operations in response to crises. When utilized effectively, they promote the integration between the clinical laboratory specialties (e.g., chemistry, hematology, microbiology, and molecular pathology). During the COVID-19 pandemic, our systems and processes were strained due to high testing volumes, demand for rapid turnaround times, supply chain constraints, and constantly evolving testing algorithms and result interpretations as our knowledge of the virus and of diagnostics increased over time. In this report, we describe those challenges and subsequent adaptations made by each clinical laboratory section. We hope these details help to provide potential solutions and approaches for other hospitals facing COVID-19 surges or other future pandemics., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Acute kidney injury (AKI) is a sudden episode of kidney damage or failure affecting up to 15% of hospitalized patients and is associated with serious short- and long-term complications, mortality, and health care costs. Current practices to diagnose and stage AKI are variable and do not factor in our improved understanding of the biological and analytical variability of creatinine. In addition, the emergence of biomarkers, for example, cystatin C, insulin-like growth factor binding protein 7, and tissue inhibitor of metalloproteinases 2, and electronic notification tools for earlier detection of AKI, highlights the need for updated recommendations to address these developments., Content: This AACC Academy guidance document is intended to provide laboratorians and clinicians up-to-date information regarding current best practices for the laboratory investigation of AKI. Topics covered include: clinical indications for further investigating potential AKI, analytical considerations for creatinine assays, the impact of biological variability on diagnostic thresholds, defining "baseline" creatinine, role of traditional markers (urine sodium, fractional excretion of sodium, fractional excretion of urea, and blood urea-to-creatinine ratio), urinary microscopic examination, new biomarkers, improving AKI-associated test utilization, and the utility of automated AKI alerts., Summary: The previous decade brought us a significant number of new studies characterizing the performance of existing and new biomarkers, as well as potential new tools for early detection and notification of AKI. This guidance document is intended to inform clinicians and laboratorians on the best practices for the laboratory investigation of AKI, based on expert recommendations where the preponderance of evidence is available., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: AKI is an abrupt decrease in kidney function associated with significant morbidity and mortality. Electronic notifications of AKI have been utilized in patients who are hospitalized, but their efficacy in the outpatient setting is unclear., Methods: We evaluated the effect of two outpatient interventions: an automated comment on increasing creatinine results (intervention I; 6 months; n =159) along with an email to the provider (intervention II; 3 months; n =105), compared with a control (baseline; 6 months; n =176). A comment was generated if a patient's creatinine increased by >0.5 mg/dl (previous creatinine ≤2.0 mg/dl) or by 50% (previous creatinine >2.0 mg/dl) within 180 days. Process measures included documentation of AKI and clinical actions. Clinical outcomes were defined as recovery from AKI within 7 days, prolonged AKI from 8 to 89 days, and progression to CKD with in 120 days., Results: Providers were more likely to document AKI in interventions I ( P =0.004; OR, 2.80; 95% CI, 1.38 to 5.67) and II ( P =0.01; OR, 2.66; 95% CI, 1.21 to 5.81). Providers were also more likely to discontinue nephrotoxins in intervention II ( P <0.001; OR, 4.88; 95% CI, 2.27 to 10.50). The median time to follow-up creatinine trended shorter among patients with AKI documented (21 versus 42 days; P =0.11). There were no significant differences in clinical outcomes., Conclusions: An automated comment was associated with improved documented recognition of AKI and the additive intervention of an email alert was associated with increased discontinuation of nephrotoxins, but neither improved clinical outcomes. Translation of these findings into improved outcomes may require corresponding standardization of clinical practice protocols for managing AKI., Competing Interests: M.L. Mendu reports having consultancy agreements with Bayer AG. N.V. Tol an reports receiving research funding from Abbott Diabetes Care and Biomerieux; and reports being a scientific advisor or member of the American Association for Clinical Chemistry, College of American Pathologists, and the Journal of Applied Laboratory Medicine. S. Ahmed reports having an ownership interest in The Kidney Health and Preventive Medicine Institute. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Objectives: To investigate the benefits and challenges of introducing next generation chemistry and coagulation automation., Methods: We replaced the Roche modular preanalytic system attached to Roche Cobas 6000 analyzers with the Roche 8100 preanalytical line attached to the Roche Cobas 8000 and Stago STA R Max analyzers. The system included 2 add-on buffers (AOBs) for automated specimen archival and retrieval and primary-tube specimen processing. We measured turnaround time (TAT) from specimen receipt to result for chemistry and coagulation tests before, during, and after system implementation. TAT for add-on tests was also measured., Results: We completed the system implementation during a 17-month period using existing laboratory space. The TAT for chemistry, coagulation, and add-on tests decreased significantly (P <.005, P <.001, and P <.005, respectively). We encountered several challenges, including barcode-label errors, mechanical problems, and workflow issues due to lack of bidirectional track for coagulation testing., Conclusions: Next generation laboratory automation yielded significantly shortened and less-variable TAT, particularly for add-on testing. Our approach could help other laboratories in the process of implementing and configuring automated systems., (© American Society for Clinical Pathology 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Drug and alcohol use are risk factors for trauma among operators of motor vehicles and contribute to trauma in pedestrians and bicyclists. We describe the prevalence of drug and alcohol use and clinical consequences in a cohort of pedestrians and bicyclists with trauma., Methods: We analyzed a 25-month data set of 916 trauma team activations from January 2017-January 2019 at an urban, level I trauma center. Blood ethanol levels and urine toxicology screens were obtained in 94 pedestrian and bicyclist trauma activations. We compared pedestrians or bicyclists with a positive urine or blood screen (n = 69) to those with negative screens (n = 25). We conducted a retrospective chart review to determine mechanism of injury, injury pattern, and disposition from the emergency department (ED)., Results: Overall, 38 (55%) of injured patients with positive screen were pedestrians and 31 (45%) were bicyclists. Fentanyl was the most commonly detected drug (n = 38; 40%), followed by opiates (n = 27; 29%), and tetrahydrocannabiol (THC) (n = 23; 25%). Twenty-one patients were positive for ethanol. Pedestrians and bicyclists with positive toxicology screens were significantly more likely to sustain fractures (p < .01), require an operative procedure (p < .05), or intensive care unit admission (p < .05)., Conclusion: Our study builds on previous literature which suggests that intoxicated bicyclists and pedestrians suffer frequent and more severe injury than their sober counterparts. Public health campaigns should educate bicyclists and pedestrians about the risks of cycling or walking in areas of road traffic while under the influence of alcohol or illicit drugs., Competing Interests: Declaration of Competing Interest The authors report no relevant conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Despite recommendations to limit vitamin D testing to specific clinical scenarios, test volume remains high in many clinical laboratories. Automated total vitamin D immunoassays frequently under- or over-recover 25-hydroxyvitamin D2 [25(OH)D2], making accurate assessment of vitamin D status difficult in patients taking high-dose 25(OH)D2 supplements. Mass spectrometry-based methods offer excellent recovery of 25(OH)D2 but are not practical for use in all laboratories. In this study, we evaluated 2 automated immunoassays against an LC-MS/MS method performed at a national reference laboratory., Methods: A method comparison against LC-MS/MS was performed for the Roche Elecsys Vitamin D total II assay and the IDS-iSYS 25 VitDS immunoassays using 49 patient specimens submitted for clinical 25(OH)D measurement. Mean bias was calculated, and vitamin D status was determined for each specimen according to the 2011 Endocrine Society clinical practice guidelines., Results: Theil-Sen regression lines relative to LC-MS/MS were y = 0.88x + 2.94 for Roche and y = 1.03x + 2.48 for IDS. Mean bias (±SD) in samples with 25(OH)D2 concentrations less than 5 ng/mL was -0.25 ng/mL (±6.30) for Roche and -1.45 ng/mL (±6.82) for the IDS. Mean bias (±SD) in samples with 25(OH)D2 concentrations greater than 5 ng/mL was -3.19 ng/mL (±6.61) for Roche and 5.52 ng/mL (±6.36) for IDS. Median percentage recovery of 25(OH)D2 was 87.1% (interquartile range 76.0-111.3) for Roche and 120.6% (interquartile range: 105.3-133.4) for IDS. Vitamin D status was misclassified in 7 samples by the Roche assay and 3 by the IDS assay. For all but one of the discordant pairs, the immunoassay result was within 1.7 ng/mL of the diagnostic cutoff., Conclusions: The automated immunoassays evaluated here demonstrate improved recovery of 25(OH)D2 relative to previous generations. Both are acceptable for use in the determination of vitamin D status., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

With the ever-increasing market share of direct-to-consumer (DTC) testing, projected to surpass $350 million this year, health care professionals must address the health literacy gap that exists between what the clinician knows and what the general public understands about clinical laboratory testing. Health literacy is lowest among people with lower socioeconomic status and results in poorer outcomes. However, these individuals represent those that would benefit most from valuable DTC testing. There is a need for unbiased and universally accessible tools to help improve consumers' understanding of test utility, limitations to the accuracy of results, and result interpretation., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Doctoral level board-certified clinical chemists play an invaluable role in many facets of laboratory medicine and healthcare. However, information concerning their total compensation is sparse., Content: A confidential self-reported compensation survey was conducted by the American Association for Clinical Chemistry's Society for Young Clinical Laboratorians (AACC SYCL) Core Committee from April 1 to April 17, 2018. Respondents provided information on geographic location, employment sector, gender, and years of experience to account for the influence of these variables on compensation. There were 199 respondents in total from the United States and Canada, however, only respondents employed in the United States with an earned doctoral degree and certification by the American Board of Clinical Chemistry (n = 133), were included in the full analysis. In comparison to compensation reported in AACC SYCL salary surveys conducted in 2010 and 2013, early career median salaries are trending upwards after correction for inflation., Summary: This survey is the first to collect the gender of respondents, and identify a pay gap for some geographic groups. However, this gap could be due in part to a difference in the years of experience, since males were highly represented in the group with >20 years of experience (25 out of 35, 71%). Future studies on compensation trends within clinical chemistry that do not rely on self-report are needed to ensure accuracy and completeness of the dataset., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Please verify edtis, "This article provides a brief introduction to some of the challenges associated with DTC testing, including: the concerns for overall limited healthcare value and unsubstantiated excessive monitoring of health and wellness markers, risks for reduced test quality from DTC testing companies claiming regulatory exemption, the impact of communication breakdown with a qualified healthcare professional leading to unnecessary worry and inappropriate self-management, and the downstream effects DTC testing has placed on our already overburdened healthcare system., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite great improvement in vitamin D assay standardization, inaccurate recoveries of 25(OH)D 2 remain for immunoassays and many laboratory-developed LC-MS/MS methods don't separate out the 3-epimer interferents. Through the process of obtaining FDA-clearance, we learned that communication is key. Mass spectrometry-based assays raise different questions of safety and efficacy than the predicate immunoassays, with fewer risks due to increased accuracy. This process required improving our quality management system to support the development and registration of an in vitro diagnostic device. There are similar examples for a number of analytes, requiring expeditious entry of FDA-cleared LC-MS/MS methods into clinical laboratories., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: With a 10-year sustained increase in 25-hydroxyvitamin D [25(OH)D] testing, laboratories have swapped their LC-MS/MS methods for high-throughput automated immunoassays. Although it is generally well-known that immunoassays have poor recoveries for 25-hydroxyvitamin D2 [25(OH)D2], the frequency and extent to which this impacts total 25(OH)D have not been previously demonstrated. We evaluated 3 automated immunoassays against the first FDA-cleared CDC/NIST-traceable LC-MS/MS method., Methods: Method comparison was performed for the Siemens ADVIA Centaur, Roche Elecsys Cobas, and Abbott Architect 25(OH)D immunoassay methods in real patient samples (n = 105). We calculated the mean bias in samples containing >20 ng/mL 25(OH)D2 and estimated the percent 25(OH)D2 cross-reactivities. We determined the prevalence of appreciable concentrations of 25(OH)D2 in our patient population through random sampling (n = 120) and projected the frequency of inaccurate 25(OH)D immunoassay results., Results: Linear regression for 25(OH)D was y = 1.09x - 4.44 (Centaur), y = 0.84 + 0.43 (Cobas), and y = 0.83x - 0.48 (Architect). The mean biases of 25(OH)D concentrations were 5.6 (11.0) ng/mL (Centaur), -17.5 (7.2) ng/mL (Cobas), and -20.3 (9.8) ng/mL (Architect) in samples containing >20 ng/mL 25(OH)D2. The observed percent cross-reactivities for 25(OH)D2 were 115% (Centaur), 52% (Cobas), and 44% (Architect). We estimate that 8% of our population has >20 ng/mL 25(OH)D2, thereby compromising the accuracy of 25(OH)D results in >3000 samples annually., Conclusions: We demonstrate that immunoassay manufacturer package inserts indicate much better recoveries of 25(OH)D2 than what is observed in unadulterated real patient samples. We estimate the frequency of inaccurate total 25(OH)D determination by these immunoassay methods to be largely dependent on the concentration of 25(OH)D2 in each sample., (© 2017 American Association for Clinical Chemistry.)

Background: Lactate, white blood cell (WBC) and neutrophil count, procalcitonin and immature granulocyte (IG) count were compared for the prediction of sepsis, and severe sepsis or septic shock, in patients presenting to the emergency department (ED)., Methods: We prospectively enrolled 501 ED patients with a sepsis panel ordered for suspicion of sepsis. WBC, neutrophil, and IG counts were measured on a Sysmex XT-2000i analyzer. Lactate was measured by i-STAT, and procalcitonin by Brahms Kryptor. We classified patients as having sepsis using a simplification of the 1992 consensus conference sepsis definitions. Patients with sepsis were further classified as having severe sepsis or septic shock using established criteria. Univariate receiver operating characteristic (ROC) analysis was performed to determine odds ratio (OR), area under the ROC curve (AUC), and sensitivity/specificity at optimal cut-off for prediction of sepsis (vs. no sepsis), and prediction of severe sepsis or septic shock (vs. no sepsis)., Results: There were 267 patients without sepsis; and 234 with sepsis, including 35 patients with severe sepsis or septic shock. Lactate had the highest OR (1.44, 95th% CI 1.20-1.73) for the prediction of sepsis; while WBC, neutrophil count and percent (neutrophil/WBC) had OR>1.00 (p<0.05). All biomarkers had AUC<0.70 and sensitivity and specificity <70% at the optimal cut-off. Initial lactate was the best biomarker for predicting severe sepsis or septic shock, with an odds ratio (95th% CI) of 2.70 (2.02-3.61) and AUC 0.89 (0.82-0.96)., Conclusion: Traditional biomarkers (lactate, WBC, neutrophil count, procalcitonin, IG) have limited utility in the prediction of sepsis., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: Point of care (POC) whole blood lactate testing may facilitate rapid detection of sepsis. We evaluated three POC methods against both plasma lactate comparison methods and a flow-injection mass spectrometric (MS) method., Design and Methods: Nova StatStrip, Abbott i-STAT CG4+ and Radiometer ABL90 POC lactate methods were evaluated against the mean of Cobas Integra 400 and Vitros 350 plasma lactate. POC methods were also compared to a flow-injection mass spectrometric assay measuring lactate in ZnSO 4 -precipitated whole blood extracts. Intra- and inter-assay precision was determined using quality control material. Method comparison included specimens from normal donors at rest, after exertion, and after spiking with lactic acid., Results: Intra- and inter-assay coefficient of variation was <5% for i-STAT and ABL90; but ranged from 3.1-8.2% on two StatStrip meters. Mean (±SD) bias between POC and plasma lactate ranged from -0.2±0.9 (i-STAT and ABL90) to -0.4±1.2 (StatStrip) mmol/L. At concentrations >6mmol/L, all POC methods showed proportional negative bias compared to plasma methods; but this bias was not observed when compared to the MS method. Despite proportional negative bias, all POC methods demonstrated acceptable concordance (94-100%) with plasma lactate within the reference interval (<2.3mmol/L) and >4mmol/L, commonly used clinical cut-offs for detection of sepsis., Conclusions: POC lactate methods demonstrate acceptable concordance with plasma lactate across commonly used clinical cut-offs for detection of sepsis. Due to systematic negative bias at higher lactate concentrations, POC and plasma lactate should not be used interchangeably to monitor patients with elevated lactate concentrations., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: Blood specimen hemolysis is a major cause of sample recollection in the neonatal intensive care unit. We aimed to reduce the hemolysis rate from 6.3% at baseline to less than 4% within the 9 months' duration of the study., Methods: Intravenous infusion of lipid emulsion during sample collection, sample collection site, and blood sample transportation methods were investigated as possible contributors to hemolysis. Subsequently, two practice improvements were implemented: pausing lipid emulsion infusion prior to collection and slowing withdrawal rates through arterial catheters., Results: Samples were more likely to be hemolyzed if they were collected during lipid infusion and subsequently transported by pneumatic tube or collected through an arterial catheter. Retrospective analysis demonstrated a decreased number of tests cancelled due to specimen hemolysis (3.5%) after our interventions., Conclusions: We identified three variables contributing to hemolysis and instituted two clinical practice interventions to significantly reduce test cancellations due to hemolysis., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Cobalt (Co) exposure has been documented to result in increased erythropoiesis. To evaluate the potential for implant-derived Co toxicity, we examined the relationship between serum Co (sCo) and erythrocyte counts (ERY) in a metal-containing total-hip arthroplasty implant population., Methods: Retrospective review of sCo concentrations identified 77 patients with concomitant ERY. Statistical analysis was performed to determine if there was a significant difference in ERY for patients divided into clinically relevant sCo ranges. A single detailed case review of a patient with a loose mal-positioned acetabular component and significantly elevated sCo was also performed for symptoms thought to arise from Co toxicity., Results: Statistical difference in ERY was not observed between patients with significantly elevated (>10 ng/mL), elevated (4-10 ng/mL), modestly elevated (1.0-3.9 ng/mL), or normal (<1.0 ng/mL) sCo. While the detailed case report was unremarkable for any of the clinical symptoms previously reported to be associated with Co toxicity and no increase in ERY was observed, this patient's sCo was 84 ng/mL., Conclusions: Increased erythropoiesis was not observed in patients with implant-derived increased sCo. Even with a sCo 100 × the upper-limit of normal, the patient presented did not have increased ERY nor exhibit any symptoms ascribed with Co toxicity., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Anticoagulation protocols used during mechanical circulatory support call for titration of antiplatelet agents. We compared the precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet therapy to distinguish their efficacy for titrating antiplatelet therapy., Methods: We assessed arachidonic acid-induced platelet function by light transmission aggregometry (LTA), Multiplate impedance aggregometry, VerifyNow, and platelet mapping by thromboelastography (TEG PM). We assessed ADP-induced platelet function by the same methods and flow cytometry. Forty healthy volunteers and 10-13 volunteers on daily aspirin and/or clopidogrel therapy were evaluated. We compared tests for intraassay precision, interassay precision (samples from 2 separate blood draws), and reliability coefficient., Results: For arachidonic acid-induced platelet aggregation in healthy volunteers, intra- and interassay CVs were ≤ 10% for all methods. Intra- and interassay precision among donors on daily aspirin was ≤ 30% for all methods except LTA (38% interassay CV) and TEG PM (95% intraassay and 104% interassay CV). For ADP-induced platelet function, intra- and interassay precision was ≤ 10% and ≤ 30% for all methods. Only Multiplate demonstrated moderate or greater (R > 0.40) reliability coefficients for arachidonic acid-induced platelet function among all subjects. All methods of ADP-induced platelet function, except TEG PM, demonstrated substantial or greater (R > 0.60) reliability among all subjects., Conclusions: TEG PM is least suited to monitor effects of antiplatelet agents. Multiplate impedance aggregometry was the only method to demonstrate an acceptable reliability coefficient among healthy volunteers and donors on both aspirin and clopidogrel therapy., (© 2014 American Association for Clinical Chemistry.)

Background: Accuracy of serum neuron-specific enolase (NSE) measurement is paramount, particularly in the context of neurological outcome prognostication. However, NSE measurements are compromised by even slight hemolysis, as it is abundant in red blood cells (RBCs). We derived and validated an individualized hemolysis correction equation in an attempt to reduce the current rejection rate of 14% at our institution., Methods: Intracellular NSE was measured in RBC lysates to determine concentration variability. A correction equation was derived, accounting for both RBC-derived NSE false-elevation and hemoglobin-derived signal quenching. The performance of this individualized correction was evaluated in intentionally hemolyzed samples and accuracy was compared to a generalized correction., Results: Significant inter-individual variability of RBC NSE was observed, with an almost two-fold range (15.7-28.5 ng NSE/mg Hb, p<0.001); intra-individual variability was insignificant. The individualized hemolysis correction equation derived: NSE(corr)=NSE(meas)-(Hb(serum))(NSE(RBCs/Hb))+0.0844(Hb(serum))+1.1 corrected 95% of the intentionally hemolyzed samples to within ±5 ng/ml of corresponding baseline NSE concentrations, compared to 74% using a generalized formula., Conclusions: The individualized hemolysis correction provides increased accuracy in the estimation of true serum NSE concentrations for hemolyzed samples, compared to a generalized approach, by accounting for inter-individual RBC NSE variability. Incorporating this correction should reduce sample rejection rates and overall health care costs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: Tumor marker analysis in ascites has been proposed as a measure to aid in the diagnosis of malignancy. The objectives of this study were to establish tumor marker cut-offs and determine the diagnostic performance of measuring CEA, CA 19-9 and AFP in ascites for differentiating between non-malignant and malignant etiologies., Design and Methods: Ascites from 137 patients (83 non-malignant, 54 malignant) was assayed for CEA, CA 19-9 and AFP concentrations by immunoassay. Diagnostic cut-offs were established via ROC curve analysis. Performance was compared to cytology findings and patient history following medical chart review. Analysis based on cytological findings in combination with tumor marker testing, as well as subset analysis by tumor marker secretion was also performed., Results: Concentrations of CEA, CA 19-9 and AFP were significantly higher in patients with malignant ascites versus non-malignant etiologies. The diagnostic cut-off, sensitivity and specificity for CEA were 3.5 ng/mL, 31% and 95%, respectively; for CA 19-9 were 72 U/mL, 30% and 95%; and for AFP were 5 ng/mL, 17% and 95%. Using cytological findings in conjunction with tumor marker results improved the sensitivity of CEA, CA 19-9 and AFP to 57.4%, 64.8%, and 59.3%, respectively. Improvement in sensitivity was seen when subset analysis by causative malignancy was performed., Conclusions: Tumor marker analysis in ascites, especially in subset analysis by type of malignancy, demonstrated utility for differentiating non-malignant from malignant etiologies. This analysis should not replace cytology, but offers potential for differentiation in situations where cytology is inconclusive, or in patients with suspected malignancies known to secrete these markers., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Model substrates presenting biochemical cues immobilized in a controlled and well-defined manner are of great interest for their applications in biointerface studies that elucidate the molecular basis of cell receptor-ligand interactions. Herein, we describe a direct, photochemical method to generate surface-immobilized biomolecular gradients that are applied to the study of selectin-mediated leukocyte rolling. The technique employs benzophenone-modified glass substrates, which upon controlled exposure to UV light (350-365 nm) in the presence of protein-containing solutions facilitate the generation of covalently immobilized protein gradients. Conditions were optimized to generate gradient substrates presenting P-selectin and PSGL-1 (P-selectin glycoprotein ligand-1) immobilized at site densities over a 5- to 10-fold range (from as low as ∼200 molecules μm(-2) to as high as 6000 molecules μm(-2)). The resulting substrates were quantitatively characterized via fluorescence analysis and radioimmunoassays before their use in the leukocyte rolling assays. HL-60 promyelocytes and Jurkat T lymphocytes were assessed for their ability to tether to and roll on substrates presenting immobilized P-selectin and PSGL-1 under conditions of physiologically relevant shear stress. The results of these flow assays reveal the combined effect of immobilized protein site density and applied wall shear stress on cell rolling behavior. Two-component substrates presenting P-selectin and ICAM-1 (intercellular adhesion molecule-1) were also generated to assess the interplay between these two proteins and their effect on cell rolling and adhesion. These proof-of-principle studies verify that the described gradient generation approach yields well-defined gradient substrates that present immobilized proteins over a large range of site densities that are applicable for investigation of cell-materials interactions, including multi-parameter leukocyte flow studies. Future applications of this enabling methodology may lead to new insights into the biophysical phenomena and molecular mechanism underlying complex biological processes such as leukocyte recruitment and the inflammatory response., (This journal is © The Royal Society of Chemistry 2011)

The metabolic syndrome is often described as a group of risk factors associated with diabetes. These risk factors include, but are not limited to, such conditions as insulin resistance, obesity, high blood pressure, and oxidant stress. Here, we report on a tool that may provide some clarity on the relationship between some of these associated risk factors, especially oxidant stress and hypertension. Specifically, we describe the ability to simultaneously monitor nicotinamide dinucleotide phosphate (NADPH), reduced glutathione (GSH), and shear-induced adenosine triphosphate (ATP) release from erythrocytes using luminescence detection on a microfabricated device. The measurements are performed by delivering erythrocyte lysate (for the NADPH and GSH measurements, two analytes indicative of oxidative stress) or whole red blood cells (RBCs) (for the determination of ATP release from the cells) to an array of wells that contain the necessary reagents to generate a luminescence emission that is proportional to analyte concentration. A fluorescence macrostereomicroscope enables whole-chip imaging of the resultant emission. The concentrations of each NADPH and GSH contained within a 0.7% erythrocyte solution were determined to be 31.06 +/- 4.12 and 22.55 +/- 2.47 microM, respectively, and the average ATP released from a nonlysed 7% erythrocyte solution was determined to be 0.54 +/- 0.04 microM. Collectively, the device represents a precursor to subsequent merging of microfluidics and microtiter-plate technology for high-throughput assessment of metabolite profiles in the diabetic erythrocyte.

Detecting multiple components from a single red blood cell (RBC) sample within a flow-based system and in less than 20 minutes will enable improved in vitro determinations of drug efficacy and cellular response to administered drugs. Here, an example of an improved in vitro measurement involving iloprost, a pharmaceutical reported to improve blood flow, has been determined by incorporating multiple cell types onto a single device. The method allows fluid flow to address individual rows of wells contained within an 18-well microfluidic array that serves as a precursor to a 96-well micro-titre plate device. The ability to better mimic the in vivo circulation by incorporating the flow of blood components, coupled with simultaneous detection and laboratory automation in place for micro-titre plates, suggests that the microfluidic array presented here will allow for improved mechanistic drug research studies. Utilizing fluorescence microscopy, concentrations of multiple metabolites present within the RBC can also be determined using the microfluidic array. The current progress towards using this device for personalized medicine is presented here.