Limited Evidence for Use of a Black Race Modifier in eGFR Calculations: A Systematic Review.

BACKGROUND: Commonly used estimated glomerular filtration rate (eGFR) equations include a Black race modifier (BRM) that was incorporated during equation derivation. Race is a social construct, and a poorly characterized variable that is applied inconsistently in clinical settings. The BRM results in higher eGFR for any creatinine concentration, implying fundamental differences in creatinine production or excretion in Black individuals compared to other populations. Equations without inclusion of the BRM have the potential to detect kidney disease earlier in patients at the greatest risk of chronic kidney disease (CKD), but also has the potential to over-diagnose CKD or impact downstream clinical interventions. The purpose of this study was to use an evidence-based approach to systematically evaluate the literature relevant to the performance of the eGFR equations with and without the BRM and to examine the clinical impact of the use or removal. CONTENT: PubMed and Embase databases were searched for studies comparing measured GFR to eGFR in racially diverse adult populations using the Modification of Diet in Renal Disease or the 2009-Chronic Kidney Disease Epidemiology Collaboration-creatinine equations based on standardized creatinine measurements. Additionally, we searched for studies comparing clinical use of eGFR calculated with and without the BRM. Here, 8632 unique publications were identified; an additional 3 studies were added post hoc. In total, 96 studies were subjected to further analysis and 44 studies were used to make a final assessment. SUMMARY: There is limited published evidence to support the use of a BRM in eGFR equations.

Provider Misinterpretation, Documentation, and Follow-Up of Definitive Urine Drug Testing Results.

BACKGROUND: Urine drug testing (UDT) is an essential tool to monitor opioid misuse among patients on chronic opioid therapy. Inaccurate interpretation of UDT can have deleterious consequences. Providers' ability to accurately interpret and document UDT, particularly definitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) results, has not been widely studied. OBJECTIVE: To examine whether providers correctly interpret, document, and communicate LC-MS/MS UDT results. DESIGN: This is a retrospective chart review of 160 UDT results (80 aberrant; 80 non-aberrant) between August 2017 and February 2018 from 5 ambulatory clinics (3 primary care, 1 oncology, 1 pain management). Aberrant results were classified into one or more of the following categories: illicit drug use, simulated compliance, not taking prescribed medication, and taking a medication not prescribed. Accurate result interpretation was defined as concordance between the provider's documented interpretation and an expert laboratory toxicologist's interpretation. Outcome measures were concordance between provider and laboratory interpretation of UDT results, documentation of UDT results, results acknowledgement in the electronic health record, communication of results to the patient, and rate of prescription refills. KEY RESULTS: Aberrant results were most frequently due to illicit drug use. Overall, only 88 of the 160 (55%) had any documented provider interpretations of which 25/88 (28%) were discordant with the laboratory toxicologist's interpretation. Thirty-six of the 160 (23%) documented communication of the results to the patient. Communicating results was more likely to be documented if the results were aberrant compared with non-aberrant (33/80 [41%] vs. 3/80 [4%], p < 0.001). In all cases where provider interpretations were discordant with the laboratory interpretation, prescriptions were refilled. CONCLUSIONS: Erroneous provider interpretation of UDT results, infrequent documentation of interpretation, lack of communication of results to patients, and prescription refills despite inaccurate interpretations are common. Expert assistance with urine toxicology interpretations may be needed to improve provider accuracy when interpreting toxicology results.

Electronic patient identification for sample labeling reduces wrong blood in tube errors.

BACKGROUND: Wrong blood in tube (WBIT) errors are a preventable cause of ABO-mismatched RBC transfusions. Electronic patient identification systems (e.g., scanning a patient's wristband barcode before pretransfusion sample collection) are thought to reduce WBIT errors, but the effectiveness of these systems is unclear. STUDY DESIGN AND METHODS: Part 1: Using retrospective data, we compared pretransfusion sample WBIT rates at hospitals using manual patient identification (n = 16 sites; >1.6 million samples) with WBIT rates at hospitals using electronic patient identification for some or all sample collections (n = 4 sites; >0.5 million samples). Also, we compared WBIT rates after implementation of electronic patient identification with preimplementation WBIT rates. Causes and frequencies of WBIT errors were evaluated at each site. Part 2: Transfusion service laboratories (n = 18) prospectively typed mislabeled (rejected) samples (n = 2844) to determine WBIT rates among samples with minor labeling errors. RESULTS: Part 1: The overall unadjusted WBIT rate at sites using manual patient identification was 1:10,110 versus 1:35,806 for sites using electronic identification (p < 0.0001). Correcting for repeat samples and silent WBIT errors yielded overall adjusted WBIT rates of 1:3046 for sites using manual identification and 1:14,606 for sites using electronic identification (p < 0.0001), with wide variation among individual sites. Part 2: The unadjusted WBIT rate among mislabeled (rejected) samples was 1:71 (adjusted WBIT rate, 1:28). CONCLUSION: In this study, using electronic patient identification at the time of pretransfusion sample collection was associated with approximately fivefold fewer WBIT errors compared with using manual patient identification. WBIT rates were high among mislabeled (rejected) samples, confirming that rejecting samples with even minor labeling errors helps mitigate the risk of ABO-incompatible transfusions.

The clinical impact of a false-positive urine cocaine screening result on a patient's pain management.

BACKGROUND: The urine of a patient admitted for chest and epigastric pain tested positive for cocaine using an immunoassay-based drug screening method (positive/negative cutoff concentration 150 ng/mL). Despite the patient's denial of recent cocaine use, this positive cocaine screening result in conjunction with a remote history of drug misuse impacted the patient's recommended pain therapy. Specifically, these factors prompted the clinical team to question the appropriateness of opioids and other potentially addictive therapeutics during the treatment of cancer pain from previously undetected advanced pancreatic carcinoma. OBJECTIVE: After pain management and clinical pathology consultation, it was decided that the positive cocaine screening result should be confirmed by gas chromatography-mass spectrometry (GC-MS) testing. RESULTS: This more sensitive and specific analytical technique revealed that both cocaine and its primary metabolite benzoylecgonine were undetectable (i.e., less than the assay detection limit of 50 ng/mL), thus indicating that the positive urine screening result was falsely positive. With this confirmation, the pain management service team was reassured in offering intrathecal pump (ITP) therapy for pain control. ITP implantation was well tolerated, and the patient eventually achieved excellent pain relief. However, ITP therapy most likely would not have been utilized without the GC-MS confirmation testing unless alternative options failed and extensive vigilant monitoring was initiated. CONCLUSION: As exemplified in this case, confirmatory drug testing should be performed on specimens with unexpected immunoassay-based drug screening results. To our knowledge, this is the first report of a false-positive urine cocaine screening result and its impact on patient management.

Clinical and financial impact of removing creatine kinase-MB from the routine testing menu in the emergency setting.

CONTEXT: Cardiac troponins T and I have replaced creatine kinase-MB (CK-MB) as the criterion standard for diagnosing myocardial injury. However, many laboratories still routinely perform a high volume of CK-MB testing in conjunction with troponin. PURPOSE: The purpose of this study is to study the clinical and financial impact of removing CK-MB from the routine emergency department (ED) test menu at a large academic medical center. METHODS: Creatine kinase-MB was removed from ED ordering templates and laboratory requisitions (ie, intervention), although the test could still be manually ordered. Data for creatine kinase (CK), CK-MB, and troponin T (TnT) specimens ordered during a 12-month period (6 months preintervention and 6 months postintervention) (n = 14571) was downloaded from our laboratory information system. All specimens with (1) normal TnT (ie, <0.01 ng/mL), (2) elevated CK-MB (ie, >6.6 ng/mL), and (3) elevated CK-MB index (ie, >5) were considered discrepant and independently reviewed by 2 ED clinicians for the presence of an acute coronary syndrome and for documentation of final diagnosis. Creatine kinase, CK-MB, and TnT ED volumes preintervention and postintervention were analyzed to assess laboratory cost savings. RESULTS: Of the 6444 cases included in the analysis, only 17 were discrepant. Of all 17 cases, no patients were diagnosed with acute coronary syndrome. After removing CK-MB from the templates and requisitions, CK-MB and CK volumes decreased by 80% and 76%, respectively, translating to annual reagent cost savings of approximately $47000. CONCLUSIONS: Creatine kinase-MB can be removed from the routine ED test menu without adversely affecting patient care. In addition, substantial cost savings can be achieved by reducing unnecessary CK-MB testing and associated CK orders.

Clinician Ordering and Management Patterns of Urine Toxicology Results at a Cancer Center.

CONTEXT: Opioid therapy is a cornerstone for treatment of cancer-related pain, but standardized management practices for patients with cancer and aberrant urine drug test (UDT) results are lacking. OBJECTIVES: To identify the prevalence of UDT ordering (both screening and definitive testing) in the oncology setting and to examine clinician management practices for patients with cancer on opioid therapy with aberrant definitive UDT results. METHODS: We conducted a retrospective chart review of patients with cancer on opioid therapy at an academic cancer center in the United States. Outcomes included UDT ordering patterns and clinician management practices in response to aberrant definitive UDT results. RESULTS: Our study revealed an overall UDT ordering rate of 3.7% among 10,371 patients with cancer on opioid therapy. Among 143 patients for whom definitive UDTs were ordered, oncologists only ordered 14 (9.8%) UDTs, while palliative care ordered the majority (n = 129; 90.2%). Fifty-five (38.5%) patients had aberrant results, and the most common aberrancy was presence of illicit drugs 22 [15.4%]. Clinicians rarely made medication changes (20 [36.4%]) when UDT results were aberrant, and in the setting of possible fentanyl use (n = 8), only 3 (37.5%) patients were started/switched to methadone, and none were started/switched to buprenorphine. CONCLUSION: Overall UDT ordering was infrequent for patients with cancer on opioid therapy, especially by oncologists, and clinicians rarely made prescribing changes when definitive UDT results were aberrant. More definitive guidance related to UDT ordering and opioid management are needed for patients with cancer and aberrant UDT results.

Performance of a Norfentanyl Immunoassay in Specimens with Low Concentrations of Fentanyl and/or Norfentanyl.

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.

Performance of Three Anti-SARS-CoV-2 Anti-S and One Anti-N Immunoassays for the Monitoring of Immune Status and Vaccine Response.

This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.

Large-Scale Scientific Study Led by a Professional Organization during the COVID-19 Pandemic: Operations, Best Practices, and Lessons Learned.

In 2021, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry [AACC]) developed a scientific study that aimed to contribute to the understanding of SARS-CoV-2 immunity during the evolving course of the pandemic. This study was led by a group of expert member volunteers and resulted in survey data from 975 individuals and blood collection from 698 of those participants. This paper describes the formulation and execution of this large-scale scientific study, encompassing best practices and insights gained throughout the endeavor.

Refrigeration is not necessary for measurement of uric acid in patients treated with rasburicase.

BACKGROUND: Rasburicase, used for hyperuricemia of tumor lysis syndrome, retains activity at room temperature (RT) in in vitro studies. Cold-temperature handling is recommended for uric acid measurements in patients receiving rasburicase: collection in prechilled tubes, transportation on ice, and 4°C centrifugation. We performed a prospective study of these requirements. METHODS: A total of 65 pairs of blood samples were collected from 34 patients, 12-24 h after receiving rasburicase. The effect of temperature on uric acid concentration was tested on paired samples handled either at RT or when cold: centrifugation (18 sample pairs), collection tube (14 pairs), transportation (24 pairs), and nine pairs were retested after 1 h at RT. RESULTS: No significant temperature effect was seen on the uric acid measurements for any of the cold-handling steps: proportional, absolute biases were -1.4%, -0.06 mg/dL (centrifugation), -1.5%, +0.02 mg/dL (tube temperature), and -2.2%, -0.01 mg/dL (transportation). A 20% negative bias was seen in samples retested after 1 h at RT. CONCLUSIONS: Cold handling (prechilled tubes, iced transportation, 4°C centrifugation) was equivalent to RT for immediate measurement. An additional 1 h delay at RT led to a 20% decrease in uric acid. The cold handling measures required by the manufacturer are not necessary for uric acid testing of patients receiving rasburicase treatment, if testing is performed without delay.

Optimizing urine drug testing for monitoring medication compliance in pain management.

BACKGROUND: It can be challenging to successfully monitor medication compliance in pain management. Clinicians and laboratorians need to collaborate to optimize patient care and maximize operational efficiency. The test menu, assay cutoffs, and testing algorithms utilized in the urine drug testing panels should be periodically reviewed and tailored to the patient population to effectively assess compliance and avoid unnecessary testing and cost to the patient. OBJECTIVE: Pain management and pathology collaborated on an important quality improvement initiative to optimize urine drug testing for monitoring medication compliance in pain management. METHODS: We retrospectively reviewed 18 months of data from our pain management center. We gathered data on test volumes, positivity rates, and the frequency of false positive results. We also reviewed the clinical utility of our testing algorithms, assay cutoffs, and adulterant panel. In addition, the cost of each component was calculated. RESULTS: The positivity rate for ethanol and 3,4-methylenedioxymethamphetamine were <1% so we eliminated this testing from our panel. We also lowered the screening cutoff for cocaine to meet the clinical needs of the pain management center. In addition, we changed our testing algorithm for 6-acetylmorphine, benzodiazepines, and methadone. For example, due the high rate of false negative results using our immunoassay-based benzodiazepine screen, we removed the screening portion of the algorithm and now perform benzodiazepine confirmation up front in all specimens by liquid chromatography-tandem mass spectrometry. CONCLUSION: Conducting an interdisciplinary quality improvement project allowed us to optimize our testing panel for monitoring medication compliance in pain management and reduce cost.

Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort Study.

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.

Robust Response of the Clinical Laboratory to the COVID-19 Pandemic despite Significant Challenges.

BACKGROUND: Clinical laboratories immediately provided rapid, reliable, and high-throughout diagnostic testing for COVID-19, which was an essential component in combating the pandemic. As the pandemic evolved, the clinical laboratory was faced with additional challenges. However, there are limited studies on the impact of the pandemic on the clinical laboratory over the past 3 years. METHODS: The American Association for Clinical Chemistry (AACC) sent 8 surveys over a 32-month time period to international clinical laboratory leadership asking questions about COVID-19 testing, supplies, staffing, and lessons learned. RESULTS: There were a total of 191 unique respondents: 133 laboratories in the US and 58 laboratories from 37 other countries participated. By May 2020, more than 70% of laboratories offered COVID-19 diagnostic testing with average turnaround times ranging from 1 to 24 h. Daily COVID-19 testing volumes peaked in January of 2022 at a median of 775 tests per day. Throughout the pandemic, supplies and staffing concerns increased. In most of the 8 surveys, 55% to 65% of laboratories reported they were unable to obtain supplies. Obtaining reagents and test kits was the most problematic. Staffing challenges continue to be a significant concern and most laboratories have struggled hiring testing personnel. CONCLUSIONS: Survey results were utilized to demonstrate the impact of the pandemic on the clinical laboratory community, and importantly, findings were presented to the White House Coronavirus Taskforce. Overall, the clinical laboratories had a robust response to the COVID-19 pandemic, and despite ongoing and evolving challenges, continue to provide rapid diagnostic testing.

T Cell Responses Correlate with Self-Reported Disease Severity and Neutralizing Antibody Responses Predict Protection against SARS-CoV-2 Breakthrough Infection.

OBJECTIVES: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. DESIGN AND METHODS: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. RESULTS: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. CONCLUSION: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection.

Lessons learned: A look back at the performance of nine COVID-19 serologic assays and their proposed utility.

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.

Cannabis positivity rates in 17 emergency departments across the United States with varying degrees of marijuana legalization.

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.