Urine Drug Testing Research Articles

Urinalysis and perceived effects following 2-week use of a commercial broad-spectrum cannabidiol product.

A growing number of hemp-derived cannabidiol (CBD) products are available with negligible amounts (< 100 ppm) of delta-9-tetrahydrocannabinol (THC) due in part to consumer concerns regarding the risk of positive drug screens. There are, however, no published studies that report whether repeated use of these products may lead to positive urine drug tests for THC. There is also scant research on the effects of these products on physical and mental well-being. Twenty healthy adults consumed a hemp-derived broad-spectrum CBD product every day for 2 weeks. Participants attended study visits at the beginning and end of the 2-week period. At each visit, participants underwent urinalysis testing for CBD, THC, and metabolites (analyzed via liquid chromatography with tandem mass spectrometry) and completed a validated assessment of physical and mental well-being. Participants reported using an average of 1.09 ± 0.51 ml (34.20 ± 16.00 mg CBD) of study product per day. Neither tetrahydrocannabinol nor its metabolites were detectable in urine following the 2-week period of use. Ingestion of the broad-spectrum product was associated with a significant reduction in sleep disturbance and pain intensity symptoms (p < .05), which remained significant after correcting for possible confounds (i.e., age, sex, dosage). No adverse events were reported. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Consensus Statement on Pain Management for Pregnant Patients with Opioid-Use Disorder from the Society for Obstetric Anesthesia and Perinatology, Society for Maternal-Fetal Medicine, and American Society of Regional Anesthesia and Pain Medicine.

Pain management in pregnant and postpartum people with an opioid-use disorder (OUD) requires a balance between risks associated with opioid tolerance, including withdrawal or return to opioid use, considerations around social needs of the maternal-infant dyad, and the provision of adequate pain relief for the birth episode that is often characterized as the worst pain a person will experience in their lifetime. This multidisciplinary consensus statement between the Society for Obstetric Anesthesia and Perinatology (SOAP), Society for Maternal-Fetal Medicine (SMFM), and American Society of Regional Anesthesia and Pain Medicine (ASRA) provides a framework for pain management in obstetric patients with OUD. The purpose of this consensus statement is to provide practical and evidence-based recommendations and is targeted to health care providers in obstetrics and anesthesiology. The statement is focused on prenatal optimization of pain management, labor analgesia, and postvaginal delivery pain management, and postcesarean delivery pain management. Topics include a discussion of nonpharmacologic and pharmacologic options for pain management, medication management for OUD (eg, buprenorphine, methadone), considerations regarding urine drug testing, and other social aspects of care for maternal-infant dyads, as well as a review of current practices. The authors provide evidence-based recommendations to optimize pain management while reducing risks and complications associated with OUD in the peripartum period. Ultimately, this multidisciplinary consensus statement provides practical and concise clinical guidance to optimize pain management for people with OUD in the context of pregnancy to improve maternal and perinatal outcomes.

Nighttime blood pressure reductions after radiofrequency renal denervation through 24 months in patients with uncontrolled hypertension: pooled analysis from the SPYRAL HTN trials

Abstract Introduction Studies have shown that elevated nighttime and early morning systolic blood pressure (SBP) are associated with the highest risk for cardiovascular (CV) events. Radiofrequency renal denervation (RF RDN) is an interventional therapy to reduce BP in patients with uncontrolled hypertension (HTN). Although sustained, durable reductions in office and 24-h ambulatory systolic BP (SBP) after RDN have been observed, whether the therapy produces similar, durable nighttime and early morning SBP reductions requires further evaluation. Objective To assess whether RF RDN significantly reduces nighttime SBP through long-term follow-up, in addition to other times of the day. Methods We pooled data from patients with uncontrolled HTN undergoing RF RDN using the latest-generation Symplicity SpyralTM multi-electrode catheter from the published SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-h ambulatory SBP were evaluated from baseline through 24 months. We also assessed BP changes during specific, diurnal time ranges including nighttime (1am-6am), early morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urine and plasma drug testing were tabulated from baseline through 24 months. Results Outcomes from 388 patients undergoing RF RDN were pooled for this analysis. Patients were on average 54±10yrs old, 26.8% female, mean BMI was 31.3±6.0, 45.1% with &amp;gt;10yrs diagnosis of hypertension, 7.7% with type 2 diabetes, 9.8% with obstructive sleep apnea, 47.7% with a history of smoking. The baseline nighttime SBP was 139±11mmHg, morning SBP was 154±15mmHg, and daytime SBP was 156±9mmHg. At baseline, 92.5% of patients had nocturnal hypertension (BP ≥120/70 mmHg) and took 1.0±1.2 antihypertensive drugs. 12 months after RF RDN, 30.6% of patients no longer had nocturnal hypertension (p&amp;lt;0.0001). The mean nighttime SBP change at 12 months was -10.8±15.4mmHg, morning changed was -12.8±20.4mmHg, and daytime changed was -12.2±13.6mmHg (Figure). The mean 24-h ambulatory SBP change at 12 months was -11.9±12.4mmHg, and the office SBP change was -17.7±15.4mmHg . Patients took 1.8±1.1 antihypertensive drugs at 12 months. Results from 24 months, not currently available, will also be presented for the first time. Conclusions In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. Clinically meaningful reductions at 12 months throughout the 24-hr circadian cycle, including at nighttime and early morning SBP, are consistent with the "always on" effect of RDN. Results from 24 months will also be presented for the first time at ESC. As an adjunctive therapy to pharmacotherapy, RDN may help to reduce CV risk by lowering nighttime and morning SBP.

Socio-demographic, clinical variables and pain among Egyptian patients of opioid use disorder with and without comorbid gabapentin use

IntroductionThere is increased clinical use of gabapentin, these trends appear to chronologically align with the opioid overdose crisis and particularly with the increased restrictions on opioid prescription.ObjectivesThe study aimed to assess the clinical variables, pain quality, and severity among patients with opioid use disorder as the main substance with and without gabapentin comorbid use.MethodsThe research involved 60 patients diagnosed with substance use disorder, divided into two groups: opioid use as the main substance and opioid use with comorbid gabapentin. All participants were assessed using a semi-structured clinical addiction interview, the structured clinical interview for diagnostic and statistical manual of mental disorders, the Addiction Severity Index, urine drug test, McGill Pain Questionnaire, and Douleur Neuropathique en 4 Questionnaire, in one interview setting.ResultsThe study showed that pain relief was the main desirable effect in the gabapentin group, with 66.2% of the group experiencing it. Euphoria was the desirable effect in the opioid group, while overdose was more common in the gabapentin group. Respiratory complications were also more common in the Gabapentin group.ConclusionThe study concluded that patients with comorbid gabapentin use disorder had a higher frequency of overdose, history of pain, and significant neuropathic pain, while less abstinence.

Evaluation of a Point of Care Urine Drug Test System for Application in Outpatient Pain Management Clinics

Abstract Introduction/Objective Most states require testing for illicit and controlled substances in ambulatory, non-terminal pain management populations to ensure prescription compliance. Point of care (POC) urine drug testing (UDT) is a widely adopted testing method that assists with clinical decision making within minutes. However, these immunoassays may lack the sensitivity and specificity needed for potent medications such as fentanyl. This study compares the performance characteristics of a POC UDT to an in-house, high throughput, automated chemistry analyzer and the reference method, gas chromatography-mass spectrometry (GC-MS). Providers should be aware of the limitations of each methodology given the rise of synthetic opioid misuse, and the need to quantify multiple substances and metabolites within the same drug class. Methods/Case Report 100 residual deidentified patient urine samples from an ambulatory pain management population were analyzed using GC-MS, Profile®-V MEDTOX Scan® POCT device (Burlington, NC), and a Beckman Coulter AU480® Chemistry Analyzer using EMIT® II Plus reagents (Beckman Coulter; Brea, CA). Drug classes on the Profile®-V included: amphetamines, barbiturates, benzodiazepines, buprenorphine, cocaine metabolite, methamphetamine, methadone, opiates, oxycodone, cannabinoids and phencyclidine. Drug classes on the AU480® included the same except without a methamphetamine-specific immunoassay. Results (if a Case Study enter NA) The results from GC-MS showed that 99% (99/100) of the samples were positive for one or more of the drug classes. Overall, the AU480® was 90% sensitive and 98% specific while the MEDTOX Scan® was 87% sensitive and 98% specific. Both devices exhibited variable performance across drug classes. Neither the AU480® nor the MEDTOX Scan® detected fentanyl in five specimens. Conclusion POCT-UDS systems like the Profile®-V MEDTOX Scan® can provide good accuracy and may offer a time and cost benefit when compared to higher throughput analyzers like the AU-480®. Due to the low reference values of immunoassays, definitive testing such as GC-MS is recommended for use in the pain management population.

Clinical implications of opioid parent-metabolite ratios

BackgroundThe opioid epidemic has underscored the importance of urine drug testing in the management of chronic pain. However, interpreting test results can be challenging, especially in scenarios where medications may have been directly added to urine samples to simulate compliance. MethodsWe conducted a retrospective analysis of 9,690 opioid testing results using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study aimed to define the expected ratios between parent drugs and metabolites for eight commonly prescribed opioids. Cases with a parent-metabolite ratio above the 95th percentile were subjected to chart review. ResultsA total of 13 cases appeared likely consistent with simulated compliance with buprenorphine, 2 with methadone, 14 with oxycodone, and one with hydrocodone. The unusual patterns of parent-metabolite ratio can also be associated with hyperacute drug exposures/use, pharmaceutical impurity, or underlying liver enzyme deficiency. Furthermore, patients who failed the decision limits could exhibit other illicit use or aberrant behaviors. ConclusionLaboratories conducting LC-MS/MS-based opioid testing can more objectively identify anomalies by analyzing parent-metabolite ratios. When in consultation with providers, laboratories can point to these data when suggesting the possibility of simulated compliance and help identify cases warranting further investigation.

B-275 Trends of urine drug testing findings in a pediatric hospital from 2019 to 2023

Abstract Background Semi-quantitative immunoassays (IA) are commonly used as the initial urine drug screen (UDS), with positive results confirmed by additional testing. However, substantial false negative (FN) rates have been reported in the classes of opioids and amphetamines. In our pediatric hospital, a semi-quantitative comprehensive urine drug testing by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF) MS (referred as QTOF) is offered as either a direct order or a reflexive order following positive IA UDS. The lab also reflexes to run an IA UDS with every direct QTOF order. This study presents paired urine drug IA and QTOF results in the classes of opiate, synthetic opioid, and amphetamine/methamphetamine between 2019 and 2023 to understand trends and to evaluate assay accuracy. Methods Paired results from IA (Siemens Atellica) and QTOF (Sciex 4600) were analyzed with reporting cutoff concentrations from representative drugs in each class listed in Figure 1. The opiate class reported on QTOF includes 6-monoacetylmorphine, morphine, hydrocodone, codeine and metabolites. The synthetic opioid class includes buprenorphine, fentanyl, levorphanol, methadone, naloxone, oxycodone, tramadol and metabolites. Simultaneous findings of opiate and synthetic opioid were counted as the opiate class. FN rate of IA was calculated using QTOF as the reference. Results As shown in Figure 1, QTOF testing nearly doubled from 2019 to 2023, with an expected high FN rate in the synthetic opioid class and alarmingly rising FN rates in opiate and amphetamine classes. Within the synthetic opioid class, percentage of positive fentanyl results increased from 37.6% to 59.0% in 5 years, and ∼10% are only positive for norfentanyl, which is detected in very few commercial fentanyl IAs. Conclusions Our study clearly demonstrates the gap in pediatric toxicology investigation, reporting high FN rates in common drug classes by urine IA, calling for more comprehensive and sensitive UDS to be broadly adopted.

B-262 Validation of a point-of-care lateral flow immunoassay for urine drug testing prior to application in an outpatient rapid access addiction medicine clinic

Abstract Background Point-of-care (POC) urine drug testing is a useful adjunct to self-reporting in rapid access addiction medicine settings to immediately guide patient management. However, available POC immunoassays have limitations including cross-reactivity with unrelated compounds or low sensitivity that may cause false results. Here, we assessed the performance of a multi-drug test panel by comparing against gold-standard liquid chromatography tandem mass spectrometry (LC-MS/MS) testing. Methods 102 residual urine specimens were assayed using a competitive lateral flow immunoassay (LFA) for 10 drugs: 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP, methadone metabolite), buprenorphine, morphine, hydromorphone, oxycodone, fentanyl, cocaine, methamphetamine, amphetamine, and benzodiazepines (BTNX Rapid ResponseTM Multi-Drug Panel). Results were compared to those obtained by LC-MS/MS (n=67, 66%) or kinetic interaction of microparticles in solution automated immunoassay (KIMS) (Roche Diagnostics, n=35, 33%). Broad spectrum LC-MS/MS results were reviewed in entirety for discordant cases, particularly in false positives to identify the presence of any known cross-reacting compounds. Results Of 10 drugs evaluated, four demonstrated ≥95% agreement with LC-MS/MS or KIMS immunoassay (EDDP, buprenorphine, oxycodone, methamphetamine). Fentanyl demonstrated the highest false negative rate of 44% (LFA cut-off: 10 ng/mL) followed by amphetamines (22%, cut-off: 1000 ng/mL). Morphine and hydromorphone demonstrated false positive rates of 14% and 18%, respectively, with most cases likely due to cross-reacting opiate or opioid metabolites. Benzodiazepines (target: Oxazepam) demonstrated false positive and negative rates of 13% and 24%, respectively. Conclusions To our knowledge, this is the first study to evaluate the performance of the BTNX multi-drug test panel against definitive testing in urine samples. While good concordance was observed for most drugs, high rates of discordant results for fentanyl and others emphasize the need for confirmatory testing by methods with higher sensitivity and specificity. Careful consideration prior to implementation would be essential, including physician education, interpretative comments, and training resources.

B-276 Evaluation of the Roche Benzodiazepines II Immunoassay for Urine Drug Testing in Clinical Specimens

Abstract Background Benzodiazepines are one of the most commonly prescribed medications in the United States and are frequently linked to instances of abuse and overdose. Historically, FDA-cleared benzodiazepine urine immunoassays cross-react poorly with glucuronidated metabolites excreted in urine. False negative results are especially prevalent with lorazepam, which is almost exclusively excreted as lorazepam glucuronide. Some clinical laboratories have addressed this problem with the addition of beta-glucuronidase to enhance assay sensitivity as a laboratory developed test (LDT). Roche Diagnostics recently received FDA clearance to offer a benzodiazepine immunoassay that includes beta-glucuronidase. Methods Performance characteristics of two FDA-cleared benzodiazepine urine immunoassays (Benzodiazepines Plus, no glucuronidase and Benzodiazepines II, with glucuronidase; Roche Diagnostics) and a benzodiazepine immunoassay LDT (with glucuronidase) were evaluated using 258 urine specimens. These immunoassays were directly compared to an LC-MS/MS benzodiazepine LDT to determine clinical sensitivity and specificity. Cross-reactivity of all three immunoassays were compared and evaluated based on the measured benzodiazepine concentrations determined by the LC-MS/MS LDT. Cross-reactivity for 7-aminoclonazepam, lorazepam, and lorazepam glucuronide were assessed using drug-free urine spiked with reference materials (Cerilliant) at concentrations ranging from 100 to 1000 ng/mL. The cutoff for positive results was set at 1000 mAbs, corresponding to 200 ng/mL of the nordiazepam calibrator. Results The Benzodiazepines II and LDT immunoassays exhibited greater clinical sensitivity (100% and 95.2%) compared to the Benzodiazepines Plus assay (66.7%). Clinical specificity of 100% was observed for all three assays. Cross-reactivity of the Benzodiazepines II assay was greater across the range of benzodiazepine concentrations tested in comparison to the other immunoassays. In particular, the Benzodiazepines II assay was the most sensitive for 7-aminoclonazepam, as it was the only immunoassay out of the three that detected the presence of specimens containing this metabolite alone. Cross-reactivity analysis shows that both 7-aminoclonazepam and lorazepam yielded positive results when tested using the Benzodiazepines II assay at a concentration of 300 ng/ml. 7-aminoclonazepam tested positive at 800 ng/ml with the LDT and Benzodiazepines Plus assays, whereas lorazepam tested positive at 600 ng/ml with these assays. Additionally, the LDT and Benzodiazepines II assays detected lorazepam glucuronide at concentrations of 400 ng/ml and 250 ng/ml, respectively. However, the Benzodiazepines Plus assay yielded negative results for all concentrations of lorazepam glucuronide tested (up to 1000 ng/mL). Conclusions A comprehensive evaluation of these three immunoassays demonstrates that the Benzodiazepines II immunoassay has increased clinical and analytical sensitivity compared to the Benzodiazepines Plus and LDT immunoassays. The inclusion of a beta-glucuronidase greatly improved the sensitivity of the Benzodiazepines II and LDT immunoassays for lorazepam, which is primarily excreted as a glucuronide metabolite in urine.

Fentanyl, Heroin, Methamphetamine, and Cocaine Analyte Concentrations in Urine Drug Testing Specimens

The US is experiencing a protracted drug overdose crisis primarily associated with exposure to illicitly manufactured fentanyl (IMF), methamphetamine, and cocaine. Overdose risk and treatment responses may be directly affected by absolute drug exposure concentrations and drug use prevalence. To quantify changes in absolute drug exposure concentrations from 2013 to 2023. This cross-sectional study analyzed urine drug testing (UDT) results from urine specimens collected between January 1, 2013, and August 22, 2023, in 49 states and the District of Columbia. Urine specimens were obtained from patients aged 18 years or older who presented to substance use disorder treatment clinics. The UDT was ordered by clinicians based on medical necessity. Urine specimens were analyzed for the following drugs or metabolites (analytes tested in parentheses): fentanyl (fentanyl), heroin (6-monoacetylmorphine), cocaine (benzoylecgonine), and methamphetamine (methamphetamine) using liquid chromatography with tandem mass spectrometry. Relative concentrations of fentanyl, heroin, cocaine, and methamphetamine. Creatinine-normalized drug concentration values were log-transformed prior to visualization and statistical analyses. The Mann-Kendall trend test was performed to examine trends over time. To estimate the geospatial and temporal patterns of drug concentration, a second series of models (1 for each drug) with an interaction effect for clinic location and collection year were fit. A total of 921 931 unique UDT samples were collected from patients (549 042 males [59.6%]; median [IQR] age, 34 [27-44] years). The adjusted fentanyl concentration in urine specimens was 38.23 (95% CI, 35.93-40.67) ng/mg creatinine in 2023 and 4.61 (95% CI, 3.59-5.91) ng/mg creatinine in 2013. The adjusted methamphetamine concentration was 3461.59 (95% CI, 3271.88-3662.30) ng/mg creatinine in 2023 and 665.27 (95% CI, 608.51-727.32) ng/mg creatinine in 2013. The adjusted cocaine concentration was 1122.23 (95% CI, 1032.41-1219.87) ng/mg creatinine in 2023 and 559.71 (95% CI, 524.69-597.06) ng/mg creatinine in 2013. The adjusted heroin concentration was 58.36 (95% CI, 48.26-70.58) ng/mg creatinine in 2023 and 146.59 (95% CI, 136.06-157.92) ng/mg creatinine in 2013. Drug concentrations varied across US Census divisions. This cross-sectional study found that absolute concentrations of fentanyl, methamphetamine, and cocaine in urine specimens increased from 2013 to 2023, with a decrease in heroin concentration during that period. The findings suggest that exposure to these substances, as well as the illicit drug supply, has fundamentally changed in many parts of the US, highlighting the need to reinforce surveillance initiatives and accelerate efforts to treat individuals with IMF and/or stimulant exposure.

Opioids and Cannabinoids in Neurology Practice.

Opioid and cannabinoid therapies for chronic pain conditions including neuropathic pain are controversial. Understanding patient and prescribing factors contributing to risks and implementing risk mitigation strategies optimizes outcomes. The ongoing transformation from a biomedical model of pain care toward a biopsychosocial model has been accompanied by a shift away from opioid therapy for pain, in particular for chronic pain. Opioid overdose deaths and opioid use disorder have greatly increased in the last several decades, initially because of increases in opioid prescribing and more recently associated with illicit drug use, in particular fentanyl derivatives. Opioid risk mitigation strategies may reduce risks related to opioid prescribing and tapering or discontinuation. Opioid therapy guidelines from the Centers for Disease Control and Prevention have become the consensus best practice for opioid therapy. Regulatory agencies and licensing medical boards have implemented restrictions and other mandates regarding opioid therapy. Meanwhile, interest in and use of cannabinoids for chronic pain has grown in the United States. Opioid therapy is generally not recommended for the chronic treatment of neuropathic pain conditions. Opioids may be considered for temporary use in patients with severe pain related to selected neuropathic pain conditions (such as postherpetic neuralgia), and only as part of a multimodal treatment regimen. Opioid risk mitigation strategies include careful patient selection and evaluation, patient education and informed consent, querying the state prescription drug monitoring programs, urine drug testing, and issuance of naloxone as potential rescue medication. Close follow-up when initiating or adjusting opioid therapy and frequent reevaluation during long-term opioid therapy is required. There is evidence for the efficacy of cannabinoids for neuropathic pain, with meaningful response rates in select patient populations.

Impaction-Based Exhaled Breath Sampling for Substance Monitoring: A Prospective Pilot Study (DrugXhale).

For decades, intake monitoring of drugs using urine as the matrix of choice is the gold standard in drug treatment centers. A properly conducted urine drug test can identify recent use of prescribed, non-prescribed and illicit drugs. However, issues like adulteration, substitution and privacy issues have driven the search for alternative matrices. This prospective pilot study evaluates the use of an impaction-based breath sampling device, Breath Explor®, as an alternative to traditional urine-based drug monitoring. Breath samples were analyzed using a validated 32-component liquid chromatography-tandem mass spectrometry (LC-MSMS) method. Recovery data represent the efficiency of extracting the analytes from the breath devices. Both automated and manual processing of the Breath Explor® devices showed mean recovery rates ranging from 39.5% to 55.4% for the 32 analytes. Despite the small number of subjects, breath analysis proved to be a convenient and easy-to-use methodology. An overall kappa-values of 0.5 indicated a moderate level of agreement with urine analysis, underscoring its potential as a complementary diagnostic tool. All participants tested positive in their breath sample for methadone (70% methadone and 100% EDDP), while a significant portion (90%) tested positive for 6-monoacetylmorphine (6-MAM). This innovative approach offers several advantages, including non-invasiveness, reduced risk of adulteration, and the ability to perfom repeated automated sampling and confirmation testing. These findings suggest that breath-based substance monitoring could complement or even replace traditional urine-based methods in clinical practice.

"We're Checking a Box and, You Know, Covering Our Own": Health Professionals' Descriptions of Hospital-Policy Making Regarding Child Welfare Reporting Related to Birthing People's Drug Use.

Hospital policies play a role in healthcare providers' decision-making about reporting birthing people who use drugs to child welfare. This study sought to understand how these specific hospital policies are made. We conducted semi-structured interviews with healthcare professionals involved in developing or revising hospital policies related to child welfare reporting for birthing people who use drugs. The interview guide was informed by an implementation science framework and focused on participants' experiences developing or revising these policies. We coded transcripts inductively, focusing on themes that emerged in the interviews themselves, and deductively, focusing on pre-determined aspects of the policy development process. Participants (N = 16) were physicians (69%), registered nurses (19%), and social workers (12%). The sample was drawn from all regions of the United States. Two themes emerged in data analysis. The first theme was that urine drug testing policies for pregnant and birthing individuals are seen as part of hospital child welfare reporting policies. Specifically, participants often described child welfare reporting policies as including criteria for urine drug testing and explained that the connection between urine drug testing and child welfare reporting policies was by design. The second theme was that the content of hospital child welfare reporting policies is a result of hospital politics and a focus on legal compliance. They described the legal compliance aspects of the hospital policies as serving to protect the institution and, occasionally, individual employees from legal consequences. The content of hospital policies regarding birthing people who use drugs appears influenced by political and legal considerations more than considerations of patient or public health.

Repeated lyophilization: A neo-method for urine-based reference materials preparation

In urine drug testing, a cut-off value is often imposed to determine whether the sample is negative or positive. A matrix containing a reference substance helps counteract the adverse effects of the urine matrix across different laboratories to improve the consistency of final results. However, as a biological matrix, urine is prone to corruption and other problems that make it difficult to use as a reference sample. In this study, morphine, nitrazepam, lorazepam, buprenorphine, zolpidem, midazolam, diazepam, and clozapine commonly used in clinical practice were selected as target analytes, and the preparation process was further optimized to repeated lyophilization, in order to obtain more effective, stable, and accurate urine matrix reference materials (mRMs). The appropriate urine density (1.010–1.017 kg/m3) for preparing lyophilized samples was investigated through density determination. Conducting repeated lyophilizations resulted in a denser powder with reduced susceptibility to collapse and improved the quality of lyophilized urine samples. Lyophilized urine mRMs could be stored at room temperature for one month or under refrigeration conditions (4 ℃) for six months.

How substance use preferences and practices relate to fentanyl exposure among people who use drugs in Rhode Island, USA

BackgroundOver 107,000 people died in the United States (U.S.) from drug overdose in 2022, with over one million overdose deaths since 1999. The U.S. drug market is characterized by a highly toxic, unregulated, and rapidly changing supply. Understanding the extent of exposure to fentanyl among people who use drugs (PWUD) will guide public health interventions aimed to decrease overdose. MethodsWe utilized baseline data from the Rhode Island Prescription and Illicit Drug Study, a randomized controlled trial of harm reduction-oriented interventions for PWUD in Rhode Island from 2020 to 2023. We evaluated sociodemographic and drug use-related covariates and examined fentanyl presence in urine drug testing (UDT). We built a classification and regression tree (CART) model to identify subpopulations with the highest likelihood of fentanyl presence in UDT. ResultsAmong 446 participants, those with fentanyl present in UDT tended to be younger, non-Hispanic white, and had recently injected drugs (p<0.05 for all). The CART analysis demonstrated a large variation in sample sub-groups’ likelihood of fentanyl presence in UDT, from an estimated probability of 0.09 to 0.90. Expected recent fentanyl exposure was the most important predictor of fentanyl in UDT. ConclusionsUnivariate analyses and CART modeling showed substantial variation in the presence of fentanyl in UDT among PWUD. Harm reduction services for people actively injecting drugs and drug checking programs based on capacity-building, empowerment, and targeted towards those not yet engaged in services are urgently needed to support PWUD in navigating the current volatile drug supply.

Orlando Veterans Affairs stratification tool for opioid risk mitigation (STORM) very high risk interdisciplinary team review: A brief report

BackgroundCompared to the general population, Veterans Health Administration (VHA) patients have higher rates of mental illness, chronic pain, and substance use disorders (SUD), conditions that increase risk for opioid-related adverse events. VHA developed the Stratification Tool for Opioid Risk Mitigation (STORM) and mandated case reviews by an interdisciplinary team (IDT) for patients identified as very high risk, a process implemented and led by clinical pharmacist practitioners at the Orlando Veterans Affairs Healthcare System (OVAHCS) in 2018. ObjectiveTo evaluate and describe the implementation and process for IDT reviews of patients identified as very high risk by the STORM clinical decision support tool at OVAHCS. MethodsA single center, retrospective, observational chart review was conducted. Veterans reviewed by the STORM IDT between January and September 2018 were reviewed for change in Morphine Equivalent Daily Dose (MEDD), naloxone, nonopioid analgesics, medications for SUD, benzodiazepines, engagement with clinical services (e.g., mental health, SUD, and pain clinic), and overdose or suicide attempts in the year prior versus the year after IDT review. The frequency of follow-up IDT reviews was evaluated. ResultsSeventeen patients were identified. Four were excluded due to nonopioid related death within 12 months after review. The average baseline MEDD was 82.2 mg (range 10–496 mg) and average 12 months after review was 7.5 mg (range 0 – 67.5 mg), a decrease of 74.7 mg, or 90.9% reduction. An increase in medications for SUD (3 patients; 23%), SUD engagement (3 to 6 patients), and urine drug tests was observed (79% increase). Benzodiazepine use decreased by 50%. ConclusionThis report provides insight on the IDT case review process at OVAHCS, a process that may vary widely across facilities. A reduction in MEDD, increase in SUD treatment, and improved risk mitigation was observed. The central role of clinical pharmacy and expanded process for continued follow-up warrants further study.

O91 SIGNIFICANT NIGHTTIME BLOOD PRESSURE REDUCTIONS FOLLOWING RENAL DENERVATION IN PATIENTS WITH UNCONTROLLED HYPERTENSION: POOLED ANALYSIS FROM THE SPYRAL HTN TRIALS

Objective: Elevated nighttime systolic blood pressure (SBP) is more strongly associated with risk for cardiovascular events than daytime or office SBP. We assessed whether radiofrequency renal denervation (RF RDN) reduces nighttime SBP, in addition to other times of the day. Design and Method: We pooled data from patients with uncontrolled hypertension undergoing RF RDN using the latest-generation SpyralTM multi-electrode catheter, from the published, SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-ambulatory SBP were evaluated at baseline and at 12 months. Different time ranges were evaluated including nighttime (1am-6am), morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urinary drug testing, where available, was assessed at baseline and at 12 months. Results: Data from 388 patients undergoing RDN were pooled. Patients were 54±10yrs old, 26.8% female, BMI 31.3±6.0, 45.1% with &gt;10yrs diagnosis of hypertension, 7.7% type 2 diabetes, 9.8% obstructive sleep apnea, 47.7% history of smoking. The baseline nighttime SBP was 139±11mmHg, and 92.5% had nocturnal hypertension (BP ≥120/70 mmHg). Patients took 1.0±1.2 antihypertensive drugs with drug burden of 1.6±3.1 at baseline. 12 months after RDN, 30.6% of patients no longer had nocturnal hypertension (p&lt;0.0001). The overall 24-h ambulatory SBP reduced by -11.9±12.4mmHg, nighttime -10.8±15.4mmHg, morning -12.8±20.4mmHg, daytime -12.2±13.6mmHg, and office -17.7±15.4mmHg (Figure). Patients took 1.8±1.1 antihypertensive drugs with drug burden of 2.9±3.0 at 12 months. Results from 24 months, not currently available, will also be presented. Conclusions: In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. RF RDN achieved clinically meaningful reductions throughout the 24-hr circadian cycle including the nighttime SBP, when CV risk is highest. RF RDN, in addition to pharmacotherapy, may help to reduce this risk.

Evaluation of a Benzodiazepine Immunoassay for Urine Drug Testing in Clinical Specimens.

Benzodiazepines are commonly prescribed medications frequently linked to instances of abuse and overdose. Historically, FDA-cleared benzodiazepine urine immunoassays cross-react poorly with glucuronidated benzodiazepine metabolites, leading to false negatives. Clinical laboratories have addressed this deficiency by creating laboratory-developed tests (LDTs) that incorporate a beta-glucuronidase hydrolysis step to increase the clinical sensitivity of these assays. Performance characteristics of 2 FDA-cleared benzodiazepine urine immunoassays (Benzodiazepines Plus, no glucuronidase and Benzodiazepines II, with glucuronidase; Roche Diagnostics) and a previously described benzodiazepine immunoassay LDT (with glucuronidase) were evaluated using 258 clinical urine specimens. The positive immunoassay cutoff was set at 200 ng/mL of nordiazepam and results were compared to an LC-MS/MS benzodiazepine LDT. Clinical sensitivity, specificity, precision, and immunoassay cross-reactivity were determined for all 3 immunoassays. The Benzodiazepines II and LDT immunoassays exhibited greater clinical sensitivity (100% and 95.2%) compared to the Benzodiazepines Plus assay (66.7%). Clinical specificity of 100% was observed for all 3 assays. Immunoassay response of the Benzodiazepines II assay was greater across the range of concentrations tested (100-1000 ng/mL) relative to the other immunoassays and was the most sensitive immunoassay for the detection of lorazepam glucuronide. The Benzodiazepines II immunoassay demonstrated the greatest clinical and analytical sensitivity compared to the Benzodiazepines Plus and LDT immunoassays. The incorporation of beta-glucuronidase was crucial, as the Benzodiazepines II and LDT immunoassays demonstrated superior clinical sensitivity when compared to the Benzodiazepines Plus immunoassay that does not incorporate a beta-glucuronidase hydrolysis step.

Δ9-tetrahydrocannabinol and 11-hydroxy-Δ9-tetrahydrocannabinol as markers of cannabis use in urinary drug testing.

With some exceptions, California Assembly Bill 2188 will preclude the use of ∆9-tetrahydrocannabinol-9-carboxylic acid (Δ9-THC-COOH) as a marker of cannabis use in urinary workplace drug testing. The bill allows for the use of psychoactive cannabis markers, which include Δ9-tetrahydrocannabinol (Δ9-THC) and the metabolite 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC). Both analytes are present in urine mainly as conjugated metabolites and will require hydrolysis prior to analysis, but very little is known about expected concentrations in urine. The aim of this study was to report concentrations from two large data sets comprising 1,411 workplace drug testing urine specimens positive by immunoassay (50 ng/mL cutoff) and discuss strategies for using 11-OH-Δ9-THC and/or Δ9-THC to detect cannabis use. Median 11-OH-Δ9-THC and Δ9-THC concentrations were 28-35% and 1.1-1.6% of those of Δ9-THC-COOH and correlations between analytes were observed. To avoid the risk of positives from passive exposure, laboratories could use a cutoff with equivalent sensitivity to cannabis exposure. A 5 ng/mL cutoff for 11-OH-Δ9-THC showed 92% agreement with a 15 ng/mL cutoff for Δ9-THC-COOH, with only 0.9% of specimens being positive only for 11-OH-Δ9-THC. It was not possible to propose an estimated cutoff for Δ9-THC, due to the constraints of the limit of detection used in this study.

Opioid agonist treatment outcomes among individuals with a history of nonfatal overdose: Findings from a pragmatic, pan-Canadian, randomized control trial.

History of nonfatal overdose (NFO) is common among people who use opioids, but little is known about opioid agonist treatment (OAT) outcomes for this high-risk subpopulation. The objective of this study was to investigate the relative effectiveness of buprenorphine/naloxone and methadone on retention and suppression of opioid use among individuals with opioid use disorder (OUD) and history of NFO. Secondary analysis of a pan-Canadian pragmatic trial comparing flexible take-home buprenorphine/naloxone and supervised methadone for people with OUD and history of NFO. Logistic regression was used to examine the impact of OAT on retention in the assigned or in any OAT at 24 weeks and analysis of covariance was used to examine the mean difference in opioid use between treatment arms. Of the 272 randomized participants, 155 (57%) reported at least one NFO at baseline. Retention rates in the assigned treatment were 17.7% in the buprenorphine/naloxone group and 18.4% in the methadone group (adjusted odds ratio [AOR] = 0.54, 95% CI: 0.17-1.54). Rates of retention in any OAT were 28% and 20% in the buprenorphine/naloxone and methadone arms, respectively (AOR = 1.55, 95% CI: 0.65-3.78). There was an 11.9% adjusted mean difference in opioid-free urine drug tests, favoring the buprenorphine/naloxone arm (95% CI: 3.5-20.3; p = .0057). Among adults with OUD and a history of overdose, overall retention rates were low but improved when retention in any treatment was considered. These findings highlight the importance of flexibility and patient-centered care to improve retention and other treatment outcomes in this population.