Toxicology testing for drugs associated with scenarios such as recreational use or substance use disorder can be performed in support of the emergency department (ED) for specific patient populations such as pediatrics and trauma. These compounds were historically referred to as drugs of abuse (DOA); although the word "abuse" is recognized as potentially stigmatizing, no replacement terminology for DOA has emerged in current guidelines. This document refers to these compounds as drugs or substances of misuse, and acknowledges the need for less-stigmatizing language that more fully encompasses the range of uses for these drugs. This literature-driven, consensus guidance document provides recommendations primarily targeted to US hospital-based laboratories performing urine drug testing (UDT) in support of the ED. Indications for ordering UDT and related testing in both pediatric and adult populations are summarized. Further, recommendations are made for testing that should be available at all facilities with rapid turnaround, and how to perform and report testing. The advantages and disadvantages of immunoassays and mass spectrometry, as well as common challenges, are reviewed. Indications for mass-spectrometry assays and more extensive testing (e.g., novel psychoactive substances) are also provided. Future directions for improvements in laboratory technology to improve the utility of this testing are outlined. All laboratories should collaborate with ED leadership, medical toxicologists and poison control centers to optimize and update test menus to reflect local drug use patterns, ensure test methodologies and results meet clinical needs, and educate clinical staff regarding assay limitations and accurate test interpretation.

This Clinical Insights describes the process for initiating feminizing gender-affirmative hormone therapy for transgender women or nonbinary people.

Electronic medical records (EMRs) allow for the creation of “fictional” and unknown patients within the EMR production environment. Surprisingly, there is sparse literature regarding the use cases for these patients or the challenges associated with their existence in the EMR. Here, we identified three classes of patients in regular use at our institution: true fictional patients with medical record numbers (MRNs) used to test EMR functions in the production environment, “confidential patients” used to store sensitive data, and “unknown” patients that are assigned temporary MRNs in emergency situations until additional information can be acquired. A further layer of complexity involving the merging of records for unknown patients once they are identified is also explored. Each class of patients, real or fictional, poses a variety of challenges from a clinical laboratory standpoint, which are often dealt with on a case-by-case basis. Here, we present a series of instructional cases adapted from actual patient safety events at our institution involving fictional, confidential, and unknown patient records. These illustrative cases highlight the utility of these fictional and unknown patients, as well as the challenges they pose on an institutional and individual level, including issues that arise from merging clinical data from temporary MRNs to identified patient charts. Lastly, we provide recommendations on how best to manage similar scenarios that may arise.

center dot Context.-Accurate interpretation of drug test results is key to appropriate patient care in numerous settings, including pain management. Despite recommendations that providers should consult laboratory professionals for guidance when necessary, literature demonstrating laboratorian expertise in drug test interpretation is lacking. Objective.-To evaluate participating laboratories' performance on the case-based, interpretive ("dry") challenge included with each Drug Monitoring for Pain Management proficiency testing program from 2012-2023. Design.-All challenges (n = 23) required participants to identify if drug test results were consistent or inconsistent with prescribed medications in the case history. Relevant medications, presumptive and confirmatory drug test results, and participant responses were extracted from program summary reports and examined for performance and common themes. Results.-Overall, 91.8% (6821 of 7431) of participant responses correctly identified whether drug testing was consistent with medications. There were 8 challenges with participant scores less than 91.8% (range, 59.8% [49 of 82 responses] to 88.9% [193 of 217 responses]). Common knowledge gaps identified in these challenges included false-positive presumptive (screening) results, minor metabolism of opiates, and recognizing that presence of a nonprescribed drug is inconsistent with prescribed medications. Although some participants repeatedly responded incorrectly, there were no associations between laboratory type, personnel responding, or analytical performance and incorrect responses to interpretative challenges. Conclusions.-Program participants performed well overall, but several concerning educational gaps were identified. Laboratorians have a role in providing interpretative guidance for drug testing and should emphasize ongoing education to ensure competence in the setting of constantly changing prescribed and nonprescribed drug use. (Arch Pathol Lab Med. 2024;148:1292-1298; doi: 10.5858/arpa.2023-0310-CP)

Journal Article Uncertainty in Hormone Monitoring of Transgender and Non-Binary People Get access Dina N Greene, Dina N Greene Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States Address correspondence to this author at: Laboratory Medicine, University of Washington, Campus Box 357110, Seattle, WA 98195-7110, United States. E-mail dngreene@uw.edu. https://orcid.org/0000-0002-6966-9904 Search for other works by this author on: Oxford Academic Google Scholar Zil Goldstein, Zil Goldstein Callen-Lorde Community Health Center, New York, NY, United StatesCity University of New York, Graduate School of Public Health & Health Policy, New York, NY, United States Search for other works by this author on: Oxford Academic Google Scholar Matthew D Krasowski Matthew D Krasowski Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States https://orcid.org/0000-0003-0856-8402 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Applied Laboratory Medicine, Volume 9, Issue 3, May 2024, Pages 426–429, https://doi.org/10.1093/jalm/jfae013 Published: 07 March 2024 Article history Received: 17 January 2024 Accepted: 24 January 2024 Published: 07 March 2024

The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.

BACKGROUND:Substance use during pregnancy is common, as is biological testing that is intended to help identify prenatal exposures. However, there is no standardized requirement for biological testing with either maternal or newborn specimens, nor is there standardization related to when testing occurs, how frequently testing occurs, what specimen(s) to test, what substances to test for, or how to perform testing. CONTENT:We review common specimen types tested to detect maternal and newborn substance exposure with a focus on urine, meconium, and umbilical cord tissue. We also review common analytical methods used to perform testing, including immunoassay, and mass spectrometry platforms. Considerations regarding the utilization of testing relative to the purpose of testing, the drug analyte(s) of interest, the specific testing employed, and the interpretation of results are emphasized to help guide decisions about clinical utilization of testing. We also highlight specific examples of unexpected results that can be used to guide interpretation and appropriate next steps. SUMMARY:There are strengths and limitations associated with all approaches to detecting substance exposure in pregnant persons as well as biological testing to evaluate a newborn with possible substance exposure. Standardization is needed to better inform decisions surrounding evaluation of substance exposures in pregnant people and newborns. If biological sampling is pursued, testing options and results must be reviewed in clinical context, acknowledging that false-positive and -negative results can and do occur.

This chapter provides an overview of therapeutic drug monitoring of selected antifungal drugs. The antifungal drugs with the strongest evidence for routine drug monitoring are the triazoles (particularly itraconazole, posaconazole, and voriconazole) and the antimetabolite 5-flucytosine. Justifications for drug monitoring include immunocompromized patients, variable pharmacokinetics, clearly defined correlation between drug concentration and therapeutic efficacy, and avoidance of toxicity. The benefit of drug monitoring is less certain for amphotericin B and the echinocandins such as caspofungin. Future areas for research include drug monitoring of antifungal agents in specialized populations such as young children (especially neonates in infants) and for combination antifungal therapy.

Background:Gender-affirming hormone therapy with either estradiol or testosterone for transgender persons can significantly impact chemistry and hematology laboratory tests. The sex used for assignment of reference intervals (RIs) in the electronic health record (EHR) will influence normal/abnormal flagging of test results.Objective:To analyze common non-hormonal laboratory tests with sex-specific RIs ordered in patients with sexual orientation/gender identify (SOGI) field differences (one or more differences between legal sex, sex assigned at birth, and gender identity) in the EHR at an academic medical center in midwestern United States.Methods:We utilized a previously characterized data set of patients at our institution that included chart review information on gender identity and gender-affirming therapy. We focused on the subset of these patients that had orders for 18 common laboratory tests in calendar year 2021.Results:A total of 1336 patients with SOGI field differences (1218 or 91.2% identifying as gender-expansive; 892 or 66.8% receiving estradiol or testosterone as gender-affirming therapy) had a total of 9374 orders for 18 laboratory tests with sex-specific RIs. Hemoglobin, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and high-density lipoprotein were the most frequently ordered tests. For patients taking estradiol, 128 of 970 (13.2%) creatinine and 39 of 193 (20.2%) hemoglobin measurements were within the RI for one sex but not the other. For those taking testosterone, 119 of 531 (22.4%) creatinine and 49 of 120 (40.8%) hemoglobin measurements were within the RI for one sex but not the other. Values above the cisgender female RI but within the cisgender male RI were common for hemoglobin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in patients taking testosterone.Conclusions:Clinicians should be aware of the potential impact of gender-affirming therapy on laboratory tests and what sex/gender is being used in the EHR to assign RIs.

CONTEXT.—:Accurate interpretation of drug test results is key to appropriate patient care in numerous settings, including pain management. Despite recommendations that providers should consult laboratory professionals for guidance when necessary, literature demonstrating laboratorian expertise in drug test interpretation is lacking. OBJECTIVE.—:To evaluate participating laboratories' performance on the case-based, interpretive ("dry") challenge included with each Drug Monitoring for Pain Management proficiency testing program from 2012-2023. DESIGN.—:All challenges (n = 23) required participants to identify if drug test results were consistent or inconsistent with prescribed medications in the case history. Relevant medications, presumptive and confirmatory drug test results, and participant responses were extracted from program summary reports and examined for performance and common themes. RESULTS.—:Overall, 91.8% (6821 of 7431) of participant responses correctly identified whether drug testing was consistent with medications. There were 8 challenges with participant scores less than 91.8% (range, 59.8% [49 of 82 responses] to 88.9% [193 of 217 responses]). Common knowledge gaps identified in these challenges included false-positive presumptive (screening) results, minor metabolism of opiates, and recognizing that presence of a nonprescribed drug is inconsistent with prescribed medications. Although some participants repeatedly responded incorrectly, there were no associations between laboratory type, personnel responding, or analytical performance and incorrect responses to interpretative challenges. CONCLUSIONS.—:Program participants performed well overall, but several concerning educational gaps were identified. Laboratorians have a role in providing interpretative guidance for drug testing and should emphasize ongoing education to ensure competence in the setting of constantly changing prescribed and nonprescribed drug use.

Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are some rare congenital causes of methemoglobinemia, most cases are acquired from the effects of specific drugs or environmental exposures. In this retrospective study, we analyzed a large data set of whole blood samples analyzed for methemoglobin at an academic medical center in Midwestern United States that provides both pediatric and adult services. For a 14 year timeframe (May 2009- June 2023), we performed detailed chart analysis of all patients with a methemoglobin concentration of 3.1% or higher. For an earlier 13 year timeframe (January 1996-April 2009), we performed chart review for all patients with a methemoglobin concentration of 10.0% or higher. For the 2009-2023 data, dapsone was the most frequent cause of methemoglobinemia (methemoglobin 3.1% or higher) in both pediatric (73.3%, 115 clinical encounters, 105 unique patients) and adult (65.3%, 195 clinical encounters, 190 unique patients) populations. Inhaled nitric oxide as medical therapy was the next most frequent cause in both pediatric (18.1%) and adult (13.2%) populations. Causes associated with two or more unique episodes with methemoglobin concentrations of 10.0% and higher included the following: dapsone (n=40 episodes), benzocaine (n=10), recreational use of amyl or isobutyl nitrite (n=3), suicide attempt with sodium nitrite (n=3 with 1 fatality; all 3 cases within last 3 years), food contaminated with nitrates (n=2), and sepsis (n=2). A total of 18 patients received treatment with methylene blue including 5 cases associated with benzocaine and all of the cases associated with amyl nitrite, isobutyl nitrite, sodium nitrite, and contaminated food. Only 3 patients with dapsone-associated methemoglobinemia received methylene blue, reflecting primary management by dose reduction or discontinuation of drug. Overall, our data reinforce previous studies showing dapsone, inhaled nitric oxide, and nitrites as common agents causing methemoglobinemia in a patient population seen at a medical center. Our data also are consistent with recent epidemiology trends showing increase in suicide attempts using sodium nitrite.

Point-of-care testing is widely used in a variety of clinical settings. While this testing provides immediate and actionable clinical information, it is prone to error in both the interpretation and reporting of results. Point-of-care urinalysis presents unique opportunities for errors, ranging from variation in visual interpretation to input of results. The data included here represent the results from 63,279 urinalyses from 36,780 unique patients performed over a span of three years at an academic medical center and its associated clinics. The data include the patient age/legal sex, methodology (instrument and test strip used), and the available test results (color, clarity, glucose, bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrite, and leukocyte esterase). Additionally, we include the method of interface between the testing instrumentation and our electronic medical record (EMR). These fell into one of three broad categories: "Interfaced" (results directly transmitted from the urinalysis instrument to the EMR via specialized data interface), "Manual" (results input by selecting from a drop-down menu in the laboratory information system), and "Enter/Edit" (results typed freely into a text field in the EMR). Analysis of this data was primarily a direct comparison of detectable errors (typos, uninterpretable results, and results outside the reportable range) as a function of the method of entry into the EMR. Secondary analysis comparing the impact of restricting drop-down menu options for urine color and clarity was also performed. These data are of use to others as they are diverse in terms of the test performed and the method of interface. Others may wish to analyze these data when making decisions as to how to perform and report these tests and when estimating risks of error with various methods of data entry.

Patient portals allow patients to access their personal health information. The 21st Century Cures Act in the United States sought to eliminate ‘information blocking’, requiring timely release upon request of electronic health information including diagnostic test results. Some health systems, including the one in the present study, chose a systematic switch to immediate release of all or nearly all diagnostic test results to patient portals as part of compliance with the Cures Act. Our primary objective was to study changes in the time to view test results by patients before and after implementation of Cures Act-related changes. This retrospective pre-post study included data from two 10-month time periods before and after implementation of Cures Act-related changes at an academic medical center. The study included all patients (adult and pediatric) with diagnostic testing (laboratory and imaging) performed in the outpatient, inpatient, or emergency department settings. Between February 9, 2020 and December 9, 2021, there was a total of 3 809 397 diagnostic tests from 204 605 unique patients (3 320 423 tests for adult patients; 488 974 for pediatric patients). Overall, 56.5% (115 627) of patients were female, 84.1% (172 048) white, and 96.5% (197 517) preferred English as primary language. The odds of viewing test results within 1 and 30 days after portal release increased monthly throughout both time periods before and after the Cures Act for all patients. The rate of increase was significantly higher after implementation only in the subgroup of tests belonging to adult patients with active MyChart accounts. Immediate release shifted a higher proportion of result/report release to weekends (3.2% pre-Cures vs 15.3% post-Cures), although patient viewing patterns by day of week and time of day were similar before and after immediate release changes. The switch to immediate release of diagnostic test results to the patient portal resulted in a higher fraction of results viewed within 1 day across outpatient, inpatient, and emergency department settings.

Testosterone as replacement therapy for male hypogonadism or as gender-affirming hormone therapy for transgender and non-binary patients has increased worldwide. Commonly used formulations of testosterone include intramuscular, transdermal patch, and topical gel, each of which has differing pharmacokinetics and practical challenges. In monitoring testosterone serum concentrations, contamination of the phlebotomy site by testosterone topical gel can lead to supraphysiologic (>1000 ng/dL or 34.7 nmol/L) serum concentrations of testosterone, as demonstrated in a few published case reports. The frequency of this issue is currently not known. The present study involves a retrospective search over a 13-year period across all clinical sites at an academic medical center. Out of 578 unique patients using testosterone topical gel, a total of 48 patients had at least 1 testosterone serum concentration exceed 1000 ng/dL. Documentation in the electronic health record revealed 7 patients where contamination of the phlebotomy site by topical gel was strongly supported as the cause of supraphysiologic testosterone serum concentrations. These included 5 males with primary hypogonadism, 1 male with panhypopituitarism, and a non-binary patient with gender dysphoria. The high testosterone concentrations prompted further work-up, including retesting and endocrinology consultation. There were additional cases of high testosterone serum concentration that may have been falsely elevated due to gel contamination but without sufficient supporting evidence available in the health record. Overall, we present 7 cases of spuriously high testosterone concentrations strongly suspected to be due to venipuncture performed near or at the location of prior testosterone gel application. Gel contamination should be considered as a possible cause of otherwise unexplained high testosterone serum concentration in patients receiving topical testosterone gel formulations. Patient counseling and provider awareness of this potential cause of spuriously high testosterone serum concentrations is important.

Context.— Consequences related to nicotine (NIC) use remain a major health concern, leading to demand for testing to detect NIC, metabolites such as cotinine (COT), and related tobacco alkaloids, including anabasine (ANAB). NIC-related testing is not standardized among laboratories, nor are there clinical or regulatory guidelines to inform decisions such as appropriate screening cutoffs or limits of quantitation. Objective.— To evaluate analytical performance and reporting practices of laboratories that perform NIC-related testing by reviewing participant responses to the Nicotine and Tobacco Alkaloid (NTA) Proficiency Testing Survey. Design.— NTA results were retrieved from 2017 (the first year of the survey) through 2020. Survey participants, methodologies, and results were evaluated for all analytes, and simulated grading was performed for COT. Additional data, including limits of quantitation, qualitative cutoffs, and reasons for testing, were reviewed. Results.— Participant growth was steady for qualitative COT testing. Participation was stable for NIC, ANAB, and quantitative COT testing. Overall, participants performed well on survey challenges. However, reporting thresholds were widely divergent, ranging from 10 to 3000 ng/mL and 0.5 to 300 ng/mL, respectively, for qualitative and quantitative COT testing. Screening cutoffs were as high as 100 ng/mL for ANAB and 1000 ng/mL for NIC. Conclusions.— Although participating laboratories performed well on the NTA Survey, the wide diversity of qualitative and quantitative reporting thresholds creates substantial risk for misinterpretation of results, and could lead to analytical concerns such as excessively high false-negative or false-positive rates. NIC-related testing would benefit from evidence-based guidelines to drive standardization of reporting.

Abstract Electronic medical records (EMRs) allow for the creation of "test" patients that can be used for training new users, testing changes before they go "live", simulating the placement of orders, or for a range of similar applications. Test patients are commonly utilized in EMR validation, support, or “playground” environments that might use a copy of the production EMR database but do not connect to the official medical record to prevent billing errors or patient harm. However, there are a variety of cases where it is useful to have test or anonymous patients within the EMR production environment as well. One example of this is infectious disease testing for employee blood-borne pathogen exposure (e.g., needlestick injury) that may need to be stored in a de-identified or restricted manner to comply with workplace privacy regulations. There are also instances, generally in emergency situations, where a medical record is created for a patient about whom little identifying information is known. In this example, these so-called "anonymous" patients are assigned random or arbitrarily pre-determined birthdates (e.g., 1/1/1900) and on occasion have no sex assigned in their chart. This poses a variety of challenges from a laboratory standpoint as it can be difficult to provide accurate normal ranges for laboratory results that are age and/or gender specific. Additionally, this has on occasion resulted in an inability to identify appropriate blood products as these recommendations are similarly based on age and gender. Another layer of complexity comes as additional information regarding the patient is made available, and health care information services merges data from a previously anonymous account to a specific patient record. Such mergers can result in cancellation of pending orders, errors in reporting laboratory results, or other complications depending on the specific process utilized. Surprisingly, there is little to no literature regarding the use cases for these “test” and “anonymous” patients or the challenges associated with their existence in the EMR. To explore this topic, we identified three classes of patients in our institutional EMR: true virtual “test” patients, “anonymous” patients that were subsequently identified, and “anonymous” patients that were never identified. Basic characteristics of these patients (sex and date of birth) and available laboratory results were compiled. Along with this, we present a series of instructional cases adapted from actual patient safety events at our institution involving anonymous patient records. These illustrative cases highlight the utility of these “test” and “anonymous” patients, as well as the challenges these pose on an institutional and individual level. Lastly, we provide recommendations on how best to manage similar scenarios that may arise.

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.

INTRODUCTION:Screening for hepatitis C virus (HCV) is performed by testing for anti-HCV antibodies, which may yield false-positive results leading to additional testing and other downstream consequences for the patient. We report our experience in a low prevalence population (<0.05%) using a two-assay algorithm aimed at testing specimens with borderline or weak positive anti-HCV reactivity in the screening assay by a second anti-HCV assay prior to confirming positive anti-HCV results with RT-PCR.MATERIALS AND METHODS:Retrospective analysis of 58,908 plasma samples was obtained over a 5-year period. Samples were initially tested using the Elecsys Anti-HCV II assay (Roche Diagnostics), with borderline or weakly positive results (defined in our algorithm as a Roche cutoff index of 0.9-19.99) reflexively analyzed using the Architect Anti-HCV assay (Abbott Diagnostics). The Abbott anti-HCV results dictated the final anti-HCV interpretation for reflexed samples.RESULTS:Our testing algorithm resulted in 180 samples requiring second-line testing, with final anti-HCV results interpreted as 9% positive, 87% negative, and 4% indeterminate. The positive predictive value (PPV) of a weakly positive Roche result was 12%, which was significantly lower than the PPV using our two-assay approach (65%).CONCLUSIONS:The incorporation of a two-assay serological testing algorithm in a low prevalence population provides a cost-effective method of improving the PPV of HCV screening in specimens with borderline or weakly positive anti-HCV results.