BACKGROUND: The benefits of methadone maintenance treatment (MMT) may be compromised by the continued use of other substances during treatment. Polysubstance use has been identified as a major contributing factor to treatment discontinuation, a known risk factor for drug overdose. We examined trends in immunoassay drug positivity rates for amphetamines, benzodiazepines, cannabis, cocaine and opioids, and (2) trends in polysubstance positivity rates for drug combinations associated with increased risk of drug overdose among patients attending the national drug treatment centre in Ireland for MMT between 2010 and 2020.
METHODS: Repeated cross-sectional study of patients attending the national drug treatment centre (NDTC) for MMT (total N = 1942) between 2010 and 2020, focused on urine drug samples provided for testing to the NDTC clinical testing laboratory (n = 221,564). Samples were analysed using immunoassay during the study period. Mixed-effects logistic regression models evaluate time trends in drug positivity. A random intercept accounts for repeat testing of individual patients. The study reports Adjusted Odds Ratios (AOR) for time (per year) with 95 % Confidence Intervals (95 % CI).
RESULTS: Drug positivity rates increased over time for benzodiazepines (AOR 1.02, 95 % CI 1.01-1.03, p < .0001), cannabis (AOR 1.06, 95 % CI 1.05-1.08, p < .0001) and cocaine (AOR 1.28, 95 % CI 1.27-1.29, p < .0001), with decreasing trends for opioids (AOR 0.91, 95 % CI 0.91-0.92, p < .0001). Methadone and benzodiazepines were co-detected in over two-thirds of all samples during the study period. Co-detection of methadone and benzodiazepines with cocaine was also found to be increasing (AOR 1.24, 95 % CI 1.23-1.25, p < .0001), with weighted polysubstance positivity rates reaching 29.2 % in 2020. The co-detection of methadone and benzodiazepines with opioids decreased over the study period (AOR 0.92, 95 % CI 0.91-0.92, p < .0001), ranging from 36.7 % in 2010 to 26.9 % in 2020.
CONCLUSIONS: Interventions are needed to target the persistently high use of benzodiazepines among patients in receipt of methadone due to their synergistic effects with opioids on respiratory depression, enhancing the risk of overdose. The growing use of cocaine among people in MMT also needs to be addressed.

The production and use of New Psychoactive Substances (NPS) has skyrocketed over the last decade, causing major challenges for government authorities, public health agencies, and laboratories across the world. NPS are designed to mimic the psychoactive effects of unregulated or controlled drugs, while constantly being modified to evade drug control regulation. Hence, they are referred to as \"legal highs\", as they are technically legal to sell, possess, and use. NPS can be classified by their pharmacological mechanism of action and include cannabimimetic, depressants, dissociatives, hallucinogens, opioids, and stimulants. There is significant structural diversity within each NPS class, leading to variable detection using traditional clinical laboratory testing and complicating the interpretation of results. In this article, we review each of the NPS classes and summarize their associated mechanism of action, common structures, and metabolic pathways, and provide examples of recent drugs and emerging threats with a focus on Canadian drug trends. We also explore the current analytical advantages and limitations commonly faced by the clinical laboratory and provide insight on how toxicosurveillance can improve detection of NPS in the ever-changing NPS landscape.

The purpose of this study was to evaluate disparities in urine drug testing (UDT) during perinatal care at a single academic medical center. This retrospective cohort study included patients who had a live birth and received prenatal care at our institution between 10/1/2015 and 9/30/2020. The primary outcomes were maternal UDT during pregnancy (UDTPN) and UDT only at delivery (UDTDEL). Secondary outcomes included the number of UDTs (UDTNUM) and the association between a positive UDT test result and race/ethnicity. Mixed model logistic regression and negative binomial regression with clustering based on prenatal care locations were used to control for confounders. Of 6,240 live births, 2,265 (36.3%) and 167 (2.7%) received UDTPN and UDTDEL, respectively. Black (OR 2.09, 95% CI 1.54-2.84) and individuals of Other races (OR 1.64, 95% CI 1.03-2.64) had greater odds of UDTPN compared to non-Hispanic White individuals. Black (beta = 1.12, p < 0.001) and Hispanic individuals (beta = 0.78, p < 0.001) also had a positive relationship with UDTNUM. Compared to individuals with non-Medicaid insurance, those insured by Medicaid had greater odds of UDTPN (OR 1.66, 95% CI 1.11-2.49) and had a positive relationship with UDTNUM (beta = 0.89, p < 0.001). No significant associations were found for UDTDEL and race/ethnicity. Despite receiving more UDT, Black individuals were not more likely to have a positive test result compared to non-Hispanic White individuals (OR 0.95, 95% CI 0.72-1.25). Our findings demonstrate persistent disparities in substance use testing during the perinatal period.

BACKGROUND: 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.
OBJECTIVE: 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.
CONCLUSIONS: 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.

Background: Opioid misuse is a persistent concern, heightened by the COVID-19 pandemic. This study examines the risk factors contributing to elevated rates of abnormal urine drug tests (UDTs) in the cancer pain patient population during COVID-19. Materials & methods: A retrospective chart review of 500 patient encounters involving UDTs at a comprehensive cancer center. Results: Medication adherence rates increase when UDTs are incorporated into a chronic cancer pain management protocol. Higher positive tests for illicit or nonprescribed substances in patients with specific risk factors: current smokers (tobacco), no active cancer and concurrent benzodiazepine use. Conclusion: This research emphasizes the increased risk of opioid misuse during COVID-19 among cancer pain patients with specific risk factors outlined in the results.
This study looked at how the COVID-19 pandemic has affected opioid use among people with cancer-related pain. The researchers checked the records of 500 patients who had had tests to see if they used opioids correctly. They found that when these tests were part of the treatment plan, patients were more likely to take their medicines correctly. However, they also noticed that certain patients, such as those who smoke, do not have active cancer or are taking another type of medication (i.e., benzodiazepines), are more likely to use opioids or other drugs in ways that deviated from the original intention. This study shows that during the pandemic, which continues to exist, it is even more important to watch how these patients use their painkillers and help them avoid misuse.

Regular monitoring of pain management and substance use disorder patients through urine drug screening is important for assessing patient compliance with prescribed drugs and abstinence from non-prescribed drugs. Sample analysis is commonly performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as multiple drugs and metabolites can be monitored from one sample. However, challenges faced in developing an LC-MS/MS method for multiple analytes in urine include variability in matrix and concentration from sample to sample and variable chemistry of many pain management drugs and associated metabolites affecting accuracy and precision of results. We describe here an LC-MS/MS method for analysis of 41 drugs and metabolites commonly prescribed for pain management patients. The developed method uses enzymatic hydrolysis followed by cation exchange solid phase extraction. Resorufin-glucuronide is used as an internal hydrolysis control to monitor hydrolysis in each patient sample and minimize false negatives. Analysis was performed using an Agilent 6470 mass spectrometer in dynamic multiple reaction monitoring mode.

BACKGROUND: In response to the opioid crisis, U.S. states have passed laws requiring urine drug testing (UDT) when opioid analgesics are prescribed for chronic pain. We sought to identify state law UDT requirements.
METHODS: We searched NexisUni legal database using terms related to UDT, chronic pain, and opioids. We included laws effective during spring 2022 that required UDT when opioids were prescribed for chronic pain. We performed deductive content analysis, coding laws for mandated UDT frequency, type of clinician and type of payer to whom the law applied, and circumstances under which UDT was mandated.
RESULTS: We found 32 laws across 13 states that met our inclusion criteria. UDT requirements varied substantially by state, including with regard to the type of clinician to whom the law applied, the mandated frequency of UDT (eg, at initiation/assessment, at least annually, more than once per year), and the circumstances in which UDT was mandated (eg, patient had substance use disorder; dosage/day threshold).
CONCLUSIONS: Relatively few states have UDT mandates associated with prescribing opioids as chronic pain treatment. When developing policy indicators for empirical studies, researchers evaluating how UDT policy affects health outcomes must consider the complexity and lack of uniformity of UDT requirements. In addition, even if states mandate UDT, it is unclear whether clinicians understand the best way to use the test results.

Patients in methadone medication treatment for opioid use disorder (M-MOUD) typically have a complex history of opioid use, often in combination with other drugs. It is unknown how frequently M-MOUD patients experience persistent substance or polysubstance use. We measured trends in illicit substance use in a large, multistate population of M-MOUD patients and persistence of substance use in the first year of treatment.
Retrospective cohort study of United States (US) M-MOUD patients from 2017 to 2021, focused on urine drug specimens provided for testing to Millennium Health, a third-party laboratory. Specimens were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Generalized estimating equations (GEE) were used to estimate the average trends in positivity during time in treatment.
Specimens were obtained from clinics in 10 US states that provided at least 300 unique patients during the study period (Alaska, Arizona, Florida, Illinois, Kentucky, Minnesota, New Mexico, Ohio, Virginia and Washington).
Patients with opioid use disorder receiving M-MOUD (n = 16 386).
Positivity rates for heroin, fentanyl, methamphetamine and cocaine.
From 2017 to 2021, yearly crude positivity rates for first collected specimens increased for fentanyl (13.1%-53.0%, P < 0.001), methamphetamine (10.6%-27.2%, P < 0.001) and cocaine (13.8%-19.5%, P < 0.001); for heroin positivity did not significantly change (6.9%-6.5%, P = 0.74). In regression models estimating patient trajectories from week 1 to week 52, marginal fentanyl positivity declined from 21.8% to 17.1% (incidence rate ratio [IRR] = 0.78, P < 0.001) and heroin positivity declined from 8.4% to 4.3% (IRR = 0.51, P < 0.001), but positivity for methamphetamine and cocaine did not significantly change, remaining at an average of 17.7% (IRR = 0.98, P = 0.53) and 9.2% (IRR = 0.96, P = 0.36), respectively.
Between 2017 and 2021, United States patients presenting to opioid treatment programs increasingly tested positive for fentanyl, methamphetamine and cocaine. Methadone medication treatment for opioid use disorder appears to remain an effective intervention for reducing illicit opioid use.

Urine drug testing (UDT) is an important feature of outpatient treatment for opioid use disorder, but associations with patient characteristics among adolescent and young adult patients are unknown. This study assessed UDT results in office-based opioid treatment and characteristics associated with treatment compliance.
This was a retrospective study of adolescent and young adult patients enrolled in office-based opioid treatment between January 1, 2009, and December 31, 2020. UDT results were described as positive results or expected and unexpected results. Expected results were negative UDTs for opioids, marijuana (THC [tetrahydrocannabinol]), or cocaine/methamphetamine, or a positive UDT for buprenorphine. Unexpected results were positive UDTs for opioids, THC, or cocaine/methamphetamine, or a negative UDT for buprenorphine. Treatment compliance was defined as ≥75% of UDTs provided being expected results. Counts and percentages described UDT results. Regressions evaluated associations between patient characteristics (retention time, age, sex, race/ethnicity, insurance, and comorbid mental health diagnoses) with treatment compliance, and assessed change of positivity rates for UDTs over time.
A total of 407 patients were included. Overall, 305 patients (74.9%) demonstrated treatment compliance. Rates of expected UDT results increased with longer retention time (p <.001), except for methamphetamine. Buprenorphine expected results ranged from 77.0% to 96.5%. Diagnosis of stimulant use disorder was associated with decreased compliance (p = .04), while diagnoses of depression, anxiety, nicotine use disorder, and post-traumatic stress disorder were associated with increased compliance (p ≤.04).
Proportion of expected UDT results increased with retention time. Diagnosis of specific mental health conditions affected treatment compliance. Further research regarding long-term health outcomes is needed.

BACKGROUND: Urine drug testing (UDT) monitors prescription compliance and/or drug abuse. However, interpretation of UDT results obtained by liquid chromatography-tandem mass spectrometry (LC-MS-MS) can be complicated by the presence of drug impurities that are detected by highly sensitive methods. Hydrocodone is a drug impurity that can be found as high as 1% in oxycodone pills.
OBJECTIVE: We evaluated the frequency and concentration of hydrocodone and its metabolite, hydromorphone, in patients taking oxycodone to check if the ratio of hydrocodone or hydromorphone to oxycodone could distinguish between oxycodone only use from those consuming additional opiates.
METHODS: We correlated LC-MS/MS results with medication records of 319 patients with positive oxycodone results over 7 months (4/2021-11/2021).
RESULTS: Fifteen of 319 patients with positive oxycodone results were taking oxycodone only. For these 15 patients, the mean ratio of hydrocodone to oxycodone was 0.57% (range 0.05%-3.35%), and the mean ratio of hydromorphone to oxycodone was 0.81% (range 0.18-3.51%).
CONCLUSIONS: Hydrocodone and/or hydromorphone are detectable in patients taking only oxycodone and can likely be identified as an impurity if their calculated ratio to oxycodone is <1 %. Further validation of the ratios in a larger sample size is recommended.