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Objectives: Selection of autoimmune/paraneoplastic antibody panels remains challenging because health-care professionals often lack familiarity with panel contents, recommended specimen types, and antibody combinations for a given patient. Inappropriate use adds cost, prompts unnecessary additional workup, and delays the identification of the true cause of patient symptoms. In this study, we assessed whether order-entry clinical decision support can improve autoimmune/paraneoplastic antibody panel utilization., Methods: An order-entry clinical decision support tool was embedded in the electronic health record system. Using a nested panel structure, the decision support tool prompted clinicians to identify their patient's clinical presentation and guided selection of the appropriate tests. In addition, the tool featured a duplicate checking function to alert clinicians when placing multiple orders with substantially similar antibody content within a 3-month period. Panel ordering practices were assessed during the 12 months before implementation and compared with the 6 months immediately following implementation., Results: Clinical decision support significantly reduced the monthly test volume of all orderables from 75.8 per month before implementation to 54.5 per month after implementation (incident rate ratio [IRR], 0.72; 95% CI, 0.63-0.81; P < .001). Placement of multiple orders for panels with substantially overlapping antibody content also decreased significantly, from 7.0 per month to 1.2 per month (IRR, 0.17; 95% CI, 0.07-0.33; P < .001). The number of neural-specific antibodies detected remained unchanged, but the reduction in total test volume increased the neural-specific antibody positivity rate from 4.2% to 6.8% (IRR, 1.61; 95% CI, 0.94-2.70; P = .075)., Conclusions: Order-entry clinical decision support offers an efficient and effective approach to improve the utilization of autoimmune/paraneoplastic antibody panels., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. 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.)

Context: The Roche prolactin immunoassay is used throughout the world. It reports higher values than the Siemens immunoassay but the manufacturer-defined reference intervals are similar. Patient results are often above the Roche upper limit but within the Siemens interval, causing diagnostic confusion., Objective: Establish new reference intervals for the Roche and Siemens prolactin immunoassays., Methods: We established new reference intervals for the Roche and Siemens immunoassays using 374 specimens from healthy outpatients. We performed chart review for unnecessary testing and treatment for 298 patients in a 6-month period with at least 1 Roche prolactin value above the manufacturer-defined upper limit and below our new upper limit., Results: The new upper limit for the Roche assay was 37.8 ng/mL (females) and 22.8 ng/mL (males). The manufacturer-defined limits were 23.3 ng/mL and 15.2 ng/mL, respectively. New intervals for the Siemens assay matched the manufacturer. No cases of clinically significant pathophysiologic prolactin excess were identified in patients with values between the manufacturer-defined upper reference limit and our new Roche upper limit. Unnecessary further evaluation in these patients included 459 repeat prolactin measurements, 57 macroprolactin measurements, 39 magnetic resonance imaging studies, and 28 endocrine referrals. Eleven patients received dopamine agonists. The minimum cost of excess care using Medicare reimbursement rates was $34 134, with substantially higher amounts billed to patients and their insurance providers., Conclusion: Adoption of new upper reference limits for the Roche prolactin assay of 37.8 ng/mL (females) and 22.8 ng/mL (males) would not delay diagnosis or necessary intervention in patients with clinically significant pituitary tumors but would reduce unnecessary evaluation in patients without pathophysiologic prolactin excess., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

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.

Background: In the US adverse drug reactions (ADRs) are estimated to cause 100 000 fatalities and cost over $136 billion annually. A patient's genes play a significant role in their response to a drug. Pharmacogenomics aims to optimize drug choice and dose for individual patients by characterizing patients' pharmacologically relevant genes to identify variants of known impact., Methods: DNA was extracted from randomly selected remnant whole blood samples from Caucasian patients with previously performed complete blood counts. Samples were genotyped by mass spectrometry using a customized pharmacogenomics panel. A third-party result interpretation service used genotypic results to predict likely individual responses to frequently prescribed drugs., Results: Complete genotypic and phenotypic calls for all tested Cytochrome P450 isoenzymes and other genes were obtained from 152 DNA samples. Of these 152 unique genomic DNA samples, 140 had genetic variants suggesting dose adjustment for at least one drug. Cardiovascular and psychiatry drugs had the highest number of recommendations, which included United States Food and Drug Administration warnings for highly prescribed drugs metabolized by CYP2C19, CYP2C9, CYP2D6, HLA-A, and VKORC1., Conclusions: Risk for each drug:gene pairing primarily depends upon the degree of predicted enzyme impairment or activation, width of the therapeutic window, and whether parent compound or metabolite is pharmacologically active. The resulting metabolic variations range from risk of toxicity to therapeutic failure. Pharmacogenomic profiling likely reduces ADR potential by allowing up front drug/dose selection to fit a patient's unique drug-response profile., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Disclosure The authors have nothing to disclose.

Thyroid hormones are primarily responsible for regulating the basal metabolic rate but also make important contributions to reproductive function and fetal development. Both hyper- and hypothyroidism in pregnancy have been associated with increased risks of complications that include preeclampsia and low birth weight, among others. Furthermore, thyroid hormone deficiency in the developing fetus results in neurodevelopmental delay. As the fetus is exclusively reliant on maternal thyroid hormone for most of the first trimester and requires continued maternal supply until birth, identifying maternal thyroid dysfunction is critically important. However, evaluating thyroid function in pregnancy is challenging because of the many physiological changes that affect concentrations of thyroid-related analytes. Increasing plasma human chorionic gonadotropin (hCG) concentrations in the second half of the first trimester elicit a corresponding transient decrease in thyroid-stimulating hormone (TSH), and continually increasing estradiol concentrations throughout pregnancy cause substantial increases in thyroxine-binding globulin (TBG) and total thyroxine (T4) relative to the nonpregnant state. Lastly, free T4 concentrations gradually decrease with increasing gestational age. For these reasons, it is essential to interpret thyroid function test results in the context of trimester-specific reference intervals to avoid misclassification of thyroid status. This review summarizes the effects of thyroid dysfunction prior to conception and during pregnancy and describes considerations for the laboratory assessment of thyroid function in pregnant women.

Background: Loperamide (Imodium®), a commonly used anti-diarrheal, is a mu opioid receptor agonist that, like all opioids, reduces gastrointestinal tract peristalsis. Loperamide is considered to have low abuse potential as it does not produce an analgesic or euphoric effect due to low bioavailability and first-pass metabolism. However, reports of individuals misusing loperamide through the use of super-therapeutic doses, alone or in combination with P-glycoprotein and/or CYP450 enzyme inhibitors, is increasing. We hypothesized that loperamide could potentially cross-react with laboratory immunoassay drug screens., Methods: Drug-free urine was spiked with loperamide or its principal metabolite, N-desmethyl loperamide (dLop), and assayed on multiple fentanyl and buprenorphine assays. Fentanyl immunoassay screen-positive results at one institution were examined by high-resolution mass spectrometry (MS) for the presence of loperamide and quantified by liquid chromatography- tandem MS when positive., Results: Loperamide produced positive results on the Thermo DRI Fentanyl and Immunalysis Fentanyl assays at concentrations greater than 5.72 mg/L and 23.7 mg/L. dLop generated positive results for the Thermo DRI and Immunalysis fentanyl assays at concentrations exceeding 6.9 mg/L and 35.7 mg/L. dLop also produced positive buprenorphine results on the Thermo CEDIA buprenorphine assay at concentrations exceeding 12.2 mg/L. High-resolution MS analysis of 225 fentanyl immunoassay positives (Thermo DRI) yielded 5 specimens containing loperamide and/or dLop, 4 of which contained measurable quantities of fentanyl in addition to loperamide/dLop., Conclusions: Laboratories using these assays should be aware of the potential for false-positive screening results due to the presence of high concentrations of loperamide and its metabolite dLop., Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: P.J. Jannetto, Secretary for the AACC Board of Directors. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: None declared. Expert Testimony: None declared. Patents: None declared., (© American Association for Clinical Chemistry, 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A longitudinal study was performed to determine the breadth, kinetics, and correlations of systemic and mucosal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: Twenty-six unvaccinated adults with confirmed coronavirus disease 2019 (COVID-19) were followed for 6 months with 3 collections of blood, nasal secretions, and stool. Control samples were obtained from 16 unvaccinated uninfected individuals. SARS-CoV-2 neutralizing and binding antibody responses were respectively evaluated by pseudovirus assays and multiplex bead arrays., Results: Neutralizing antibody responses to SARS-CoV-2 were detected in serum and respiratory samples for 96% (25/26) and 54% (14/26), respectively, of infected participants. Robust binding antibody responses against SARS-CoV-2 spike protein and S1, S2, and receptor binding (RBD) domains occurred in serum and respiratory nasal secretions, but not in stool samples. Serum neutralization correlated with RBD-specific immunoglobulin (Ig)G, IgM, and IgA in serum (Spearman ρ = 0.74, 0.66, and 0.57, respectively), RBD-specific IgG in respiratory secretions (ρ = 0.52), disease severity (ρ = 0.59), and age (ρ = 0.40). Respiratory mucosal neutralization correlated with RBD-specific IgM (ρ = 0.42) and IgA (ρ = 0.63)., Conclusions: Sustained antibody responses occurred after SARS-CoV-2 infection. Notably, there was independent induction of IgM and IgA binding antibody and neutralizing responses in systemic and respiratory compartments. These observations have implications for current vaccine strategies and understanding SARS-CoV-2 reinfection and transmission., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The aim of this study was to redefine the icterus index cutoff for the Roche Jaffé creatinine method using both conjugated and unconjugated bilirubin on 3 Roche cobas modules (c311, c501, and c701/c702) at laboratories across our hospital network., Methods: Interference was evaluated by adding conjugated bilirubin (as bilirubin conjugate, ditaurate) and unconjugated bilirubin to pooled remnant plasma. The effects of conjugated and unconjugated bilirubin were tested separately to assess the contribution of each species. The magnitude of interference was calculated as both absolute and percentage error with total allowable error limits set at 0.1 mg/dL (8 µmol/L or 8%)., Results: Analysis of interference data across the 3 Roche modules did not show bias exceeding our total allowable error limits for plasma creatinine up to a conjugated bilirubin icterus index of 16.2 (approximately 16.2 mg/dL or 277 μmol/L) or an unconjugated bilirubin icterus index of 18.5 (approximately 18.5 mg/dL or 316 μmol/L), the highest concentrations tested., Conclusions: Our results demonstrate that the Roche Jaffé method exhibits acceptable performance in the presence of icterus at icterus indexes above the manufacturer's current recommendations of 5 (approximately 5 mg/dL or 86 μmol/L) and 10 (approximately 10 mg/dL or 171 μmol/L) for conjugated and unconjugated bilirubin, respectively. We have updated the icterus index in our hospital system to 16 for conjugated bilirubin and 18 for unconjugated bilirubin., Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Mark A. Cervinski has disclosed that he has previously received compensation from Roche Diagnostics following participation in an advisory board not related to the topic of this manuscript. Disclosures and/or potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: M.A. Cervinski has previously received compensation from Roche Diagnostics following participation in an advisory board. Stock Ownership: None declared. Honoraria: None declared. Research Funding: None declared. Expert Testimony: None declared. Patents: None declared., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

Background: The AACC Academy revised the reproductive testing section of the Laboratory Medicine Practice Guidelines: Evidence-Based Practice for Point-of-Care Testing (POCT) published in 2007., Methods: A panel of Academy members with expertise in POCT and laboratory medicine was formed to develop guidance for the use of POCT in reproductive health, specifically ovulation, pregnancy, premature rupture of membranes (PROM), and high-risk deliveries. The committee was supplemented with clinicians having Emergency Medicine and Obstetrics/Gynecology training., Results: Key recommendations include the following. First, urine luteinizing hormone (LH) tests are accurate and reliable predictors of ovulation. Studies have shown that the use of ovulation predicting kits may improve the likelihood of conception among healthy fertile women seeking pregnancy. Urinary LH point-of-care testing demonstrates a comparable performance among other ovulation monitoring methods for timing intrauterine insemination and confirming sufficient ovulation induction before oocyte retrieval during in vitro fertilization. Second, pregnancy POCT should be considered in clinical situations where rapid diagnosis of pregnancy is needed for treatment decisions, and laboratory analysis cannot meet the required turnaround time. Third, PROM testing using commercial kits alone is not recommended without clinical signs of rupture of membranes, such as leakage of amniotic fluid from the cervical opening. Finally, fetal scalp lactate is used more than fetal scalp pH for fetal acidosis due to higher success rate and low volume of sample required., Conclusions: This revision of the AACC Academy POCT guidelines provides recommendations for best practice use of POCT in fertility and reproduction., Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: J.H. Nichols, The Journal of Applied Laboratory Medicine, AACC; Z. Shajani-Yi, labcorp. Consultant or Advisory Role: J.H. Nichols, IL/Werfen, Diabetes Technology Society, Abbott. Stock Ownership: Z. Shajani-Yi, labcorp. Honoraria: J.H. Nichols, IL/Werfen, Siemens, BioRad. Research Funding: J.H. Nichols, Roche Diagnostics, IL Werfen, Abbott Diagnostics. Expert Testimony: None declared. Patents: None declared. Other Remuneration: J.H. Nichols, support for attending meetings and/or travel from IFCC, CLSI, AACC, CAP., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context.—: Moderna (mRNA-1272) and Pfizer (BNT162b2) SARS-CoV-2 vaccines demonstrate favorable safety and efficacy profiles, but direct comparison data are lacking., Objective.—: To determine the vaccines' side effect profiles and expected antibody responses. These data may help personalize vaccine selection and identify individuals with a suboptimal vaccine response., Design.—: One hundred forty-nine healthy, largely seronegative adults were assigned Moderna (n = 79) or Pfizer (n = 70). Following the second dose, participants completed a survey documenting their side effects. Serum was collected 0 to 4 days prior to dose 2, and 14 ± 4 days, 30 ± 4 days, 90 ± 10 days, and 180 ± 20 days after dose 2. Convalescent serum specimens were collected 32 to 54 days from donors after a polymerase chain reaction-confirmed SARS-CoV-2 infection (n = 20). Anti-spike antibodies were measured using the Roche Diagnostics Elecys Anti-SARS-CoV-2 S assay on a Roche cobas e801 instrument., Results.—: Participants receiving the Moderna vaccine experienced side effects with greater frequency and severity. Both vaccines elicited a robust antibody response, but median signal was higher in Moderna recipients. Symptom severity decreased with age. Antibody response in Pfizer recipients negatively correlated with age. Antibody response decreased after 6 months (84% reduction in Moderna, 79% Pfizer), but values remained greater than for convalescent donors. Antibody response did not correlate with gender or symptom severity., Conclusions.—: Moderna may be preferred in individuals in need of greater immune stimulation (eg, older individuals), whereas Pfizer may be preferred in those concerned about vaccine reactions. Anti-spike antibody signal varies by vaccine, so specific reference intervals will be needed to identify individuals with a suboptimal response.

SARS-CoV-2 viral RNA is shed in the stool of 55-70% of infected individuals and can be detected in community wastewater up to 7 days before people present with COVID-19 symptoms. The detection of SARS-CoV-2 RNA in wastewater may serve as a lead indicator of increased community transmission. Here, we monitored viral concentrations in samples collected from nine municipal wastewater facilities in New Hampshire (NH) and Vermont (VT).Twenty-four-h composite primary influent wastewater samples were collected from nine municipal wastewater treatment facilities twice per week for 5 months (late September 2020 to early February 2021). Wastewater was centrifuged for 30 min at 4600 ×  g , then the supernatant was frozen until further analysis. Once thawed, samples were concentrated, extracted, and tested for SARS-CoV-2 RNA using reverse transcriptase-quantitative PCR (RT-qPCR) and reverse transcriptase-droplet digital PCR (RT-ddPCR) detection methods. Active case counts for each municipality were tracked from the NH and VT state COVID-19 dashboards. We received a total of 283 wastewater samples from all sites during the study period. Viral RNA was detected in 175/283 (61.8%) samples using RT-qPCR and in 195/283 (68.9%) samples using RT-ddPCR. All nine sites showed positivity in the wastewater, with 8/9 (88.8%) sites having over 50% of their samples test positive over the course of the study. Larger municipalities, such as Nashua, Concord, and Lebanon, NH, showed that SARS-CoV-2 positivity in the wastewater can precede spikes in active COVID-19 case counts by as much as 7 days. Smaller municipalities, such as Woodsville, NH and Hartford, VT, showed sporadic SARS-COV-2 detection and did not always precede a rise in active case counts. We detected SARS-CoV-2 RNA in samples from all 9 municipalities tested, including cities and small towns within this region, and showed wastewater positivity as an early indicator of active case count increases in some regions. Some of the smaller rural municipalities with low case counts may require more frequent sampling to detect SARS-CoV-2 in wastewater before a case surge. With timely collection and analysis of wastewater samples, a community could potentially respond to results by increasing public health initiatives, such as tightening mask mandates and banning large indoor gatherings, to mitigate community transmission of SARS-CoV-2. IMPORTANCE Despite vaccination efforts, the delta and omicron variants of SARS-CoV-2 have caused global surges of COVID-19. As the COVID-19 pandemic continues, it is important to find new ways of tracking early signs of SARS-CoV-2 outbreaks. The manuscript outlines how to collect wastewater from treatment facilities, concentrate the virus in a dilute wastewater sample, and detect it using two sensitive PCR-based methods. It also describes important trends in SARS-CoV-2 concentration in wastewater of a rural region of the United States from Fall 2020 - Winter 2021 and demonstrates the utility of wastewater monitoring as a leading indicator of active SARS-CoV-2 cases. Monitoring changes in concentration of SARS-CoV-2 virus in wastewater may offer an early indicator of increased case counts and enable appropriate public health actions to be taken.

Background: Autoimmune encephalitis (AE) is a rare collection of disorders that present with a diverse and often nebulous set of clinical symptoms. Indiscriminate use of multi-antibody panels decreases their overall utility and predictive value. Application of a standardized scoring system may help reduce the number of specimens that generate misleading or uninformative results., Methods: The results of autoimmune encephalopathy, epilepsy, or dementia autoantibody panels performed on serum (n = 251) or cerebrospinal fluid (CSF) (n = 235) specimens from October 9th, 2016 to October 11th, 2019 were collected. Retrospective chart review was performed to calculate the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score for patients with an antibody above the assay-specific reference interval and to classify results as true or false positive., Results: Of the 486 specimens, 60 (12.3%) generated positive results for any AE antibody (6 CSF and 54 serum). After removing 2 duplicate specimens collected from a single patient, 10 of the remaining 58 were determined to be true positives and 8 contained neural-specific antibodies. Application of the APE2 score revealed that 89% of all true positives and 86% of specimens with neural-specific antibodies had a score ≥4. In contrast, 76% of false positives, 74% of clinically nonspecific antibodies, and 85% of the negative specimens had an APE2 score <4., Conclusion: The APE2 score can improve the diagnostic utility of autoimmune encephalopathy evaluation panels., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: As part of an ongoing effort to improve healthcare value for patients, laboratories increasingly implement test utilization review. Alkaline phosphatase (ALP) isoenzymes (hereafter: isoenzymes) testing distinguishes the various ALP isoforms to explain elevations in total serum ALP. Gamma glutamyl transferase activity (GGT) has served as a proxy for total ALP elevations attributable to the hepatic isoform given that both are membrane-bound proteins with a shared mechanism of release. We assessed the utility of GGT in evaluating isoenzymes requests., Methods: We obtained 8 years of isoenzymes results and identified same-patient GGT measurements obtained within 7 days. We assessed the ability of GGT to predict elevations in hepatic, bone, intestinal, and nonhepatic ALP isoforms overall. We generated ROC curves and calculated sensitivity and specificity using our in-house reference limits for GGT., Results: GGT as a predictor of hepatic isoform elevation had an area under the ROC curve (AUC) of 0.68, and GGT activity above the upper reference limit was 46.6% sensitive and 85.0% specific for hepatic ALP elevation. GGT activity as a predictor of nonhepatic isoform elevation had an AUC of 0.52, and GGT within reference limits was 59.8% sensitive and 46.4% specific for elevation in a nonhepatic ALP isoform. In 133 individuals with hepatic isoform elevations, 93 had a concurrent elevation in a nonhepatic ALP isoform., Conclusion: GGT was reasonably specific but insensitive for hepatic ALP isoform elevation and was a poor predictor of ALP isoform elevation overall, suggesting that its usefulness in evaluating isoenzymes orders is limited., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Commercially available serological assays for SARS-CoV-2 detect antibodies to either the nucleocapsid or spike protein. Here we compare the performance of the Beckman-Coulter SARS-CoV-2 spike IgG assay to that of the Abbott SARS-CoV-2 nucleocapsid IgG and Roche Anti-SARS-CoV-2 nucleocapsid total antibody assays. In addition, we document the trend in nucleocapsid and spike antibodies in sequential samples collected from convalescent plasma donors., Methods: Plasma or serum samples from 20 individual SARS-CoV-2 RT-PCR-positive inpatients (n = 172), 20 individual convalescent donors with a previous RT-PCR-confirmed SARS-CoV-2 infection (n = 20), were deemed positive SARS-CoV-2 samples. RT-PCR-negative inpatients (n = 24), and 109 pre-SARS-CoV-2 samples were determined to be SARS-CoV-2 negative. Samples were assayed by the Abbott, Roche, and Beckman assays., Results: All three assays demonstrated 100% specificity. Abbott, Beckman, and Roche platforms had sensitivities of 98%, 93%, and 90% respectively, with the difference in sensitivity attributed primarily to samples from immunocompromised patients. After the exclusion of samples immunocompromised patients, all assays exhibited ≥ 95% sensitivity. In sequential samples collected from the same individuals, the Roche nucleocapsid antibody assay demonstrated continually increasing signal intensity, with maximal values observed at the last time point examined. In contrast, the Beckman spike IgG antibody signal peaked between 14 and 28 days post positive SARS-CoV-2 PCR and steadily declined in subsequent samples. Subsequent collections 51-200 days (median of 139 days) post positive SARS-CoV-2 RT-PCR from five inpatients and five convalescent donors revealed that spike and nucleocapsid antibodies remained detectable for several months after confirmed infection., Conclusions: The three assays are sensitive and specific for SARS-CoV-2 antibodies. Nucleocapsid and spike antibodies were detectable for up to 200 days post-positive SARS-CoV-2 PCR but demonstrated markedly different trends in signal intensity., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Identifying women with preterm labor who will go on to deliver prematurely is crucial to improving outcomes for mother and baby and for saving healthcare resources. Even among those with symptoms, the number of women who deliver preterm is low, and thus the low positive predictive value (PPV) and high negative predictive value (NPV) associated with available biomarkers does not substantially reduce the uncertainty of the clinical diagnosis. While there is some promise in the use of fetal fibronectin (fFN), interleukin 6 (IL-6), or placental alpha microglobulin 1 (PAMG-1) for predicting preterm birth (PTB), their use is unlikely to provide considerable clinical value in populations with a low prevalence. To provide real clinical benefit, a biomarker must demonstrate a high PPV to allow identification of the minority of symptomatic women who will deliver prematurely. As none of the currently available biomarkers exhibit this performance characteristic, we do not recommend their routine clinical use in populations with a pre-test probability of PTB of <5%. Limiting biomarker testing to only high-risk women identified on the basis of cervical length or other characteristics will increase the pre-testprobability in the tested population, thereby improving PPV. PAMG-1 is associated with a higher PPV than fFN and may show clinical utility in populations with a higher pre-test probability, but further work is required to conclusively demonstrate improved outcomes in this patient group., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated., Methods: After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas® platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed., Results: FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer's reference interval., Conclusions: Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel member of the coronavirus family that caused the global coronavirus 2019 (COVID-19) pandemic. The prevalence remains largely unknown because of early testing supply shortages. Although it cannot currently be used to determine level of immunity, antibody testing can contribute to epidemiological studies, identify convalescent plasma donors, or satisfy curiosity about previous exposure to the virus., Methods: 407 samples collected from hospitalized inpatients with and without a confirmed SARS-CoV-2 infection, 170 remnant clinical specimens collected and frozen prior to the COVID-19 outbreak, and paired serum and plasma samples from 23 convalescent plasma donors were used to determine performance characteristics of the Abbott SARS-CoV-2 IgG and Roche Elecsys Anti-SARS-CoV-2 assays. The sensitivity, specificity, imprecision, interferences, and sample stability were determined. These assays were then used to characterize the antibody response in serial samples from 20 SARS-CoV-2 positive inpatients., Results: Both assays exhibited 100% specificity (95% CI; 99.05-100.00), giving no positive results in 170 specimens collected before July 2019 and 215 specimens from patients without a confirmed SARS-CoV-2 infection. Differences between platforms were most notable in SARS-CoV-2 positive samples. Roche offered higher sensitivity in convalescent plasma donors at 95.7% (95% CI; 78.1-99.9) versus 91.3% (95% CI; 72.0-98.9) but Abbott detected antibodies in 2 immunocompromised patients whereas Roche did not. The Roche and Abbott platforms also exhibited different trends in antibody signal for a subset of patients., Conclusions: Both the Abbott and Roche platforms offer excellent specificity but different trends in antibody signal may reflect qualitative differences in the types of antibodies recognized by the 2 assays. Negative serologic results do not exclude previous SARS-CoV-2 infection., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Background: Laboratorians have the opportunity to help minimize the frequency of adverse drug reactions by implementing pharmacogenomic testing and alerting care providers to possible patient/drug incompatibilities before drug treatment is initiated. Methods combining PCR with MALDI-ToF MS have allowed for sensitive, economical, and multiplexed pharmacogenomic testing results to be delivered in a timely fashion., Method: This study evaluated the analytical performance of the Agena Biosciences iPLEX® PGx 74 panel and a custom iPLEX panel on a MassARRAY MALDI-TOF MS instrument in a clinical laboratory setting. Collectively, these panels evaluate 112 SNVs across 34 genes implicated in drug response. Using commercially available samples (Coriell Biorepository) and in-house extracted DNA, we determined ideal reaction conditions and assessed accuracy, precision, and robustness., Results: Following protocol optimization, the Agena PGx74 and custom panels demonstrated 100% concordance with the 1000 Genomes Project Database and clinically validated hydrolysis probe genotyping assays. 100% concordance was also observed in all assessments of assay precision when appropriate QC metrics were applied., Conclusions: Significant development time was required to optimize sample preparation and instrumental analysis and 3 assays were removed due to inconsistent performance. Following modification of the manufacturer's protocol and instituting manual review of each assay plate, the Agena PGx74 and custom panel constitute a cost-effective, robust, and accurate method for clinical identification of 106 SNVs involved in drug response., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Introduction: Several reports describe high anion gap metabolic acidosis with 5-oxoproline (5-OP) after acetaminophen exposure, including therapeutic use of acetaminophen. The mechanism may involve disordered glutathione metabolism. It is unknown whether acute acetaminophen overdose consistently causes elevations in 5-oxoproline concentration. Methods: We enrolled 23 consecutive adult and adolescent patients with measureable plasma APAP after acute APAP overdose. We used plasma left over in the laboratory after blood tests obtained in clinical care of the patients. We measured plasma [5-OP] by GC/MS. We compared the [5-OP] to laboratory results obtained in the care of these patients to search for correlations. The study had IRB approval. Results: Eighteen patients had non-detectable or normal (<100 μmol/L) 5-oxoproline concentrations. Six more patients had concentrations between 100 μmol/L and 300 μmol/L. There was no significant correlation of 5-OP with APAP, AST, ALT, creatinine, anion gap, INR, or total bilirubin. Discussion: Limitations of the study include small sample size and treatment with IV N-acetylcysteine for all patients with APAP concentrations above the 150 line of the Rumack Matthew nomogram or with hepatotoxicity. We believe that inherited enzyme deficiencies more likely explain cases of 5-oxoprolinemia. Conclusion: Acetaminophen overdose generally results in normal 5-oxoproline concentrations with some patients having slightly elevated 5-oxoproline concentrations.

Biotin is commonly used as a dietary supplement for the claimed benefits of promoting healthy hair and nail growth and is available without a prescription at doses up to 10mg/capsule. Biotin-mediated interference in immunoassay testing is an emerging issue for clinical laboratories and previous studies have indicated that biotin at regularly encountered doses may interfere with these assays. In this study, we evaluated the effect of supplemental biotin on seven POC urine hCG test devices using purified biotin and urine collected from four volunteers consuming 10mg biotin/day. Six of the seven devices showed no evidence of biotin interference as each device's control line remained clearly detectable at all biotin concentrations tested. However, the QuickVue device control line demonstrated a marked decrease in intensity when used to test solutions containing >5μg/mL biotin. The absence of a control line during patient testing has the potential to delay care due to the generation of an invalid test result and lead to additional unnecessary testing. It is not realistic to measure urinary biotin concentrations in every patient undergoing qualitative urine hCG testing but biotin supplementation should be considered if repeat testing on a patient sample generates an invalid test result., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Opioid analgesics are frequently prescribed to manage acute and chronic pain, but individual differences in opioid response make effective pain control in all patients an elusive goal. Furthermore, the risk of addiction following opioid consumption varies among individual patients. Although many psychosocial factors contribute to an individual's opioid response and risk for addiction, a strong genetic component has also been demonstrated., Content: Opioids undergo substantial enzymatic modification that can generate metabolites with either increased or decreased opioid activity relative to the parent compound. To elicit their analgesic effect, parent compounds and active metabolites must be transported into the central nervous system where they bind to opioid receptors and inhibit neurotransmission. Inherited genetic variants that alter the function of proteins involved in these processes have been associated with differences in opioid response and risk for addiction. Detection of these variants can help guide opioid selection, inform dosing decisions, or encourage use of a nonopioid analgesic., Summary: Whereas some genetic variants are clearly associated with differences in opioid response and have been included in consensus clinical practice guidelines, the impact of other variants on opioid response remains unclear. Studies performed to date have generated promising results, but inconsistent findings, reimbursement challenges, and the lack of robust decision support tools have hampered widespread adoption of pharmacogenetic testing to guide pain management treatment decisions. Future work involving the simultaneous evaluation of large numbers of variants and demonstration of a clear clinical benefit provided by pharmacogenetic testing will be required to overcome these obstacles., (© 2017 American Association for Clinical Chemistry.)

Background: Graves disease is caused by autoantibodies that target the thyroid-stimulating hormone receptor (TSHR). Anti-TSHR autoantibody measurement is routinely performed to differentiate between Graves disease and other causes of hyperthyroidism. We evaluated the clinical performance of a reference laboratory bioassay [the Thyretain thyroid-stimulating immunoglobulin (TSI) Bioassay by Diagnostic Hybrids] and 2 commercially available immunoassays: the TSI Bridge immunoassay by Siemens and the thyroid-stimulating hormone receptor antibody (TRAb) immunoassay by Roche. We further evaluated the analytical performance of the Siemens TSI and Roche TRAb assays., Methods: We performed method comparisons using 125 patient specimens submitted for TSI testing for clinical purposes. Concordance of patient results was assessed between the 3 methods, and chart review was performed to further evaluate samples that generated discordant results. All 3 methods were also evaluated for potential interference caused by human chorionic gonadotropin (hCG)., Results: The Roche and Siemens assays demonstrated acceptable day-to-day precision, within-run precision, and precision at the clinical decision cutoffs. Despite manufacturer-defined analytical measuring ranges up to 40 IU/L, the Roche and Siemens assays were linear to 20 IU/L and 15 IU/L, respectively. hCG concentrations up to 150000 IU/L did not interfere with any of the methods evaluated. Moderate agreement between methods was observed when testing patient specimens that generated negative (≤1.3) or weakly positive (1.4-3.8) results by the Thyretain assay. One hundred percent agreement was observed when the Thyretain assay was strongly positive (≥3.9)., Conclusions: The 3 commercially available anti-TSHR autoantibody measurement methods demonstrated equivalent performance in patients with untreated Graves disease. Discordant results were observed when testing specimens collected from patients undergoing treatment for Graves disease. In these patients, the Siemens TSI assay more frequently generated results consistent with clinical history, results of other laboratory tests, and imaging studies than the Thyretain Bioassay and Roche TRAb assay., (© 2017 American Association for Clinical Chemistry.)

Objective: Elevated concentrations of hCG beta core fragment (hCGβcf) are known to cause false-negative results in qualitative urine pregnancy test devices, but the pattern of urinary hCGβcf during normal pregnancy has not been well characterized. Here, we evaluate the relationship between urine hCG, hCGβcf, and hCG free β subunit (hCGβ) during pregnancy., Design and Methods: Banked second trimester urine specimens from 100 pregnant women were screened for high concentrations of hCGβcf using a qualitative point-of-care device known to demonstrate false-negative results in the presence of elevated hCGβcf concentrations. Additional first and third trimester specimens from the same pregnancy were obtained from 10 women who generated negative/faint positive results, 5 women who generated intermediate positive results, and 10 women who generated strong positive results on the point-of-care device. Intact hCG, hCGβcf, hCGβ, and specific gravity were quantified in these 75 specimens., Results: Urinary hCGβcf concentrations were greater than intact hCG concentrations at all times. A strong correlation (r(2)=0.70) was observed between urine intact hCG and hCGβcf concentrations. A poor correlation was observed between specific gravity and intact hCG (r(2)=0.32), hCGβ (r(2)=0.32), and hCGβcf (r(2)=0.32). The highest hCGβcf concentrations were observed between 10 and 16weeks gestation but individual women demonstrated very different patterns of hCGβcf excretion., Conclusions: Urine specimens with elevated hCGβcf are frequently encountered during pregnancy but hCGβcf excretion patterns are unpredictable. Manufacturers and clinicians must appreciate that hCGβcf is the major immunoreactive component in urine during pregnancy and must design and interpret qualitative urine hCG test results accordingly., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Point-of-care (POC) urine qualitative human chorionic gonadotropin (hCG) devices are used to rapidly assess pregnancy status, but many of these devices are susceptible to false-negative results caused by increased concentrations of hCG β core fragment (hCGβcf) that does not contain hCGβcf., Methods: Purified hCG was added to hCG-negative heparinized whole blood to generate samples with known hCG concentrations, and the resulting samples were used to evaluate device sensitivity, low-end reproducibility, high-dose hook effect, intermediate range performance, acceptable sample volume, acceptable hematocrit range, and lot-to-lot variation. Device performance was also prospectively evaluated in 40 pregnant and 40 nonpregnant women aged 18-44 years in a hospital-based clinic or an academic hospital emergency department., Results: All device observations were positive using a whole blood sample containing a plasma hCG concentration of 2.2 × 106 IU/L, and all device observations were positive from18 IU/L to 1.2 × 103 IU/L and from 2.5 × 104 IU/L to 2.2 × 106 IU/L. Three invalid results were observed in the intermediate range because of decreased control line intensity. The minimum sample volume was 30 μL, and maximum hematocrit was 46%. In 40 pregnant and 40 nonpregnant women aged 18-44 years, the device generated 100% concordance with urine qualitative and plasma quantitative test results., Conclusions: The ADEXUSDx™ hCG test demonstrates acceptable performance for the determination of pregnancy status using capillary fingerstick samples., (© 2016 by American Association for Clinical Chemistry.)

Objective: Elevated urine concentrations of hCG beta core fragment (hCGβcf) are known to cause false negative qualitative point-of-care hCG test results, but limited information is available regarding urine hCGβcf. In this study, we evaluate the relationship between serum and urine hCG concentrations and the frequency of elevated urine hCGβcf concentrations., Design and Methods: Paired serum and urine specimens were obtained from 60 women at various stages of pregnancy and hCG was measured using the Abbott Architect and Roche Cobas e602 assays. Urine specimens with the greatest difference in urine hCG concentrations between these two instruments were tested using a qualitative point-of-care device and hCGβcf was quantified using LC-MS/MS., Results: Urine hCG concentrations were lower than serum and the magnitude of the difference depended on whether the hCG assay detected hCGβcf. Elevated hCGβcf concentrations (>280,000pmol/L) were observed in 12% of specimens from an unselected patient population. There was a significant correlation (r=0.97; p<0.0001) between the difference (Roche hCG-Abbott hCG) and the hCGβcf concentration as measured by LC-MS/MS (Roche-Abbott difference IU/L=(hCGβcf (pmol/L)∗0.131+656))., Conclusions: A correlation exists between serum and urine hCG concentrations but this correlation is variable. hCGβcf concentrations can be estimated using two automated assay reagent platforms that differ in their recognition of hCGβcf., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Treatment for many infertile couples often consists of in vitro fertilization (IVF) but an estimated 70% of IVF cycles fail to produce a live birth. In an attempt to improve the live birth rate, the vast majority of IVF cycles performed in the United States involve the transfer of multiple embryos, a practice that increases the risk of multiple gestation pregnancy. This is a concern because multiple gestation pregnancies are associated with an increased incidence of maternal and fetal complications and significant cost associated with the care of preterm infants. As the ideal outcome of each IVF cycle is the birth of a single healthy baby, significant effort has focused on identifying embryos with the greatest developmental potential. To date, selection of euploid embryos using comprehensive chromosome screening (CCS) is the most promising approach while metabolomic and proteomic assessment of spent culture medium have the potential to noninvasively assess embryo viability. Endometrial gene expression profiling may help determine the optimal time to perform embryo transfer. While CCS has been implemented in some clinics, further development and optimization will be required before analysis of spent culture medium and endometrial gene expression profiling make the transition to clinical use. This review will describe efforts to identify embryos with the greatest potential to result in a healthy, live birth, with a particular emphasis on detection of embryo aneuploidy and metabolic profiling of spent embryo culture medium. Assessment of endometrial receptivity to identify the optimal time to perform embryo transfer will also be discussed., (© 2016 Elsevier Inc. All rights reserved.)

Objective: Previous work has documented the ability of the Clearblue Advanced Test with Weeks Estimator, a new over-the-counter (OTC) urine hCG device, to accurately estimate weeks since ovulation in early pregnancy. In this study, the performance of this device in more advanced pregnancy was assessed., Methods: The Clearblue Advanced Test with Weeks Estimator device was used to test solutions containing purified intact hCG and hCGβcf at concentrations consistent with early, middle and late pregnancy. Urine samples from three normal pregnant patients 9-13 weeks of gestation and from a patient 12 weeks of gestation known to generate false negative results on qualitative urine test devices due to excess hCGβcf were also evaluated., Results: The Clearblue Weeks Estimator device gave expected results using solutions containing purified intact hCG and hCGβcf at concentrations observed throughout pregnancy. The device generated expected results using urine from three of four patients tested between 9 and 13 weeks of gestation. However, when urine from a patient with elevated concentrations of hCGβcf was used, the device correctly indicated pregnancy although the estimate for the date was incorrect., Conclusion: This device gave expected "pregnant" results using all samples tested. However, the "Weeks Estimator" should be interpreted with caution when used by patients after seven weeks of pregnancy., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: The ability to perform quantitative hCG testing in whole blood at the point-of-care is desirable. The purpose of this study was to perform an analytical validation of the Abbott i-STAT Total β-hCG test., Methods: Whole blood, plasma, and serum samples were prepared by the addition of hCG and were used to evaluate precision, linearity, analytical sensitivity, accuracy, the high-dose hook effect, and dilution recovery., Results: Imprecision was highest with whole blood (CV = 16.0% and 6.7% at 10 and 1184 IU/l, respectively) and lowest in serum (CV = 8.1% and 4.3% at 11 and 1305 IU/l, respectively). The limits-of-quantitation were 8 and <5 IU/l for whole blood and both plasma and serum, respectively. The assay was linear between 5 and 2000 IU/l in all sample types (R(2) ≥ 0.998). i-STAT results agreed most closely with the Architect Total β-hCG assay and with greater differences observed with Beckman DxI Total βhCG and Roche Cobas e601 hCG+β assays (mean differences across all sample types were 9.3% and 12.3%, respectively). A high-dose hook effect was observed at concentrations > 400,000 IU/l. Accuracy was achieved in samples diluted with serum but not saline., Conclusions: The i-STAT Total β-hCG test demonstrates acceptable performance for quantifying hCG in whole blood, plasma and serum., (Copyright © 2015 Elsevier B.V. All rights reserved.)