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Introduction: 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., Conclusion: 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

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., (© 2024. The Author(s).)

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., (© Association for Diagnostics & Laboratory Medicine 2024.)

Introduction: There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine among the general population of Danish pregnant women., Material and Methods: In this anonymous, national, cross-sectional, descriptive study, pregnant women were invited when attending an ultrasound scan between November 2019 and December 2020 at nine Danish hospitals. Women submitted a urine sample and filled out a questionnaire. Urine samples were screened on-site with a qualitative urine dipstick for 15 substances including alcohol, nicotine, opioids, amphetamines, cannabis, and benzodiazepines. All screen-positive urine samples underwent secondary quantitative analyses with gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results were compared to questionnaire information to analyze the validity of self-reporting and to examine possible cross-reactions., Results: A total of 1903 of 2154 invited pregnant women participated (88.3%). The prevalence of dipstick-positive urine samples was 25.0%. 44.0% of these were confirmed positive, resulting in a total confirmed prevalence of 10.8%. The prevalence of nicotine use was 10.1%-and for all other substances, <0.5%. Nicotine use was more prevalent among younger pregnant women, while other substance use appeared evenly distributed over age groups. Self-reporting of use of nicotine products was high (71.1%), but low for cannabis and alcohol intake (0% and 33.3%, respectively). Prescription medication explained almost all cases of oxycodone, methylphenidate, and benzodiazepine use., Conclusions: Substance use among pregnant women consisted mainly of nicotine. Dipstick screening involved risks of false negatives and false positives. Except for alcohol intake and cannabis use, dipstick analyses did not seem to provide further information than self-reporting. LC-MS/MS analyses remain gold standard, and future role of dipstick screenings should be discussed., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Valid measurement of drug use in patients enrolled in clinical trials that treat substance use disorder is vital to determine the trial's outcome. Self-reports are often used but their validity has been studied with mixed results. Urinalysis may sometimes be employed as an alternative or supplement to self-reports. Objectives: This study examined how estimating drug use by either method would affect the results from a randomized clinical trial conducted in a methadone treatment program. At the initial Baseline interview and four follow-up interviews, participants were asked about their drug use history and provided a urine specimen for drug testing. Results: In most cases, the urinalyses detected more drugs than the patients had reported using. A major exception was heroin, whose use was an eligibility criterion for enrollment in the study and methadone treatment. Conclusions: The patients' self-reports would have led us to conclude that the use of heroin and fentanyl had declined from the initial Baseline interview to the final follow-up interview, while the urinalysis results indicated no change in exposure to heroin and an increase in exposure to fentanyl. Clinical trials would be well served to employ the use of biological tests in addition to self-reports to measure recent drug use and to accurately estimate the efficacy of the experimental protocols and patients' exposure to drugs.

Objective: To measure racial inequities in drug testing among pregnant people during the first prenatal visit based on their drug use disclosure pattern., Methods: We used data from a cohort study of patient-clinician communication patterns regarding substance use in first prenatal visits from February 2011 to August 2014. We assessed racial differences (Black-White) in the receipt of urine toxicology testing, stratifying on patients' drug use disclosure to the clinician., Results: Among 341 study participants (205 Black [60.1%] and 136 White [39.9%] participants), 70 participants (33 Black [47.1%] and 37 White [52.9%] participants) disclosed drug use, and 271 participants (172 Black [63.5%] and 99 White [36.5%] participants) did not disclose drug use during their first obstetric visit. Of 70 participants who disclosed drug use, 50 (28 Black [56.0%] and 22 White [44.0%] White) had urine drug testing conducted. Black pregnant patients who disclosed drug use were more likely to be tested for drugs than their White counterparts in the adjusted regression analysis (adjusted odds ratio [aOR] 8.9, 95% CI 1.3-58.6). Among the 271 participants who did not disclose drug use, 38 (18 Black [47.4%] and 20 White [52.6%] participants) had urine drug testing conducted. For those who did not disclose drug use, the adjusted model showed no statistically significant differences in urine drug testing by patients' race (aOR 0.7, 95% CI 0.3-1.6)., Conclusion: When pregnant people disclosed drug use, clinicians were more likely to order urine drug testing for Black pregnant people compared with their White counterparts, suggesting clinician racial bias. Current practice patterns and protocols such as urine drug testing in pregnancy care deserve review to identify and mitigate areas of potential clinician discrimination., Competing Interests: Financial Disclosure Judy C. Chang disclosed that she is completing her last term on the Executive Committee and Board of the Academy of Communication in Healthcare (since 2015 in various roles) and she serves on the Board of the Pennsylvania Coalition Against Domestic Violence. One of Dr. Chang's clinical responsibilities is serving as a prescribing physician in the Pregnancy and Women's Recovery Center at Magee-Womens Hospital. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to determine the factors associated with positive infant drug screen and create a shortened screen and a prediction model., Study Design: This is a retrospective cohort study of all infants who were tested for drugs of abuse from May 2012 through May 2014. The primary outcome was positive infant urine or meconium drug test. Multivariable logistic regression was used to identify independent risk factors. A combined screen was created, and test characteristics were analyzed., Results: Among the 3,861 live births, a total of 804 infants underwent drug tests. Variables associated with having a positive infant test were (1) positive maternal urine test, (2) substance use during pregnancy, (3) ≤ one prenatal visit, and (4) remote substance abuse; each p -value was less than 0.0001. A model with an indicator for having at least one of these four predictors had a sensitivity of 94% and a specificity of 69%. Application of this screen to our population would have decreased drug testing by 57%. No infants had a positive urine drug test when their mother's urine drug test was negative., Conclusion: This simplified screen can guide clinical decision making for determining which infants should undergo drug testing. Infant urine drug tests may not be needed when a maternal drug test result is negative., Key Points: · Many common drug screening criteria are not predictive.. · Four criteria predicted positive infant drug tests.. · No infant urine drug test is needed if the mother tests negative.., Competing Interests: None declared., (Thieme. All rights reserved.)

This study aims to investigate the association between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and methylation status of MB-COMT (membrane-bound catechol-O-methyltransferase) promotor or DRD2 gene considering gene variants and clinical parameters. Based on the DSM-5 criteria, 218 CUD/SCUD patients' diagnoses were confirmed with a positive urine test, and a control group consisting of 102 participants without substance use disorders was included. Methylation-specific PCR was used to identify the methylation of the MB-COMT promotor and DRD2 gene. DRD2-141C Ins/Del and COMT Val158Met gene variants were evaluated by using PCR-RFLP. When the DRD2 and MB-COMT promoter methylation of CUD/SCUD patients were compared with the control group, there was a significant difference between the MB-COMT promoter methylation status of the two groups. When comparing DRD2 gene methylation due to clinical parameters and DRD2 genotype distribution in patients, the methylation status was significantly different between the groups due to the family history. Again, comparing the MB-COMT promotor methylation due to the COMT Val158Met genotype distribution and clinical parameters in patients, the MB-COMT promoter methylation status was significantly different between the groups due to the presence of alcohol usage. In summary, whereas the MB-COMT promoter methylation may be associated with the CUD/SCUD, the methylation of the DRD2 gene was not related to CUD/SCUD.

Objective: Validation of a non-targeted method for urine drug screening (UDS) by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), and comparison to an established GC-MS method in a hospital setting., Methods: 217 UDS specimens sent to a quaternary hospital pathology department, were analysed by a CEDIA® immunoassay screen (six drug panels; amphetamines, barbiturates, benzodiazepines, cocaine metabolites, cannabinoids and opiates) on an Abbott Architect instrument. Specimens were subsequently analysed by an established non-targeted qualitative GC-MS method and results compared with a general unknown screening method by LC-QTOF that was under evaluation as a replacement method., Results: 42 selected drugs were evaluated; limits of identification ranged from 2 to 100 µg/L and most drugs (n = 39) were stabile for 24 h after preparation. Matrix effects greater than 25% were observed in seven of the selected drugs. 87% of the specimens tested positive to 1 or more drug panels in a CEDIA® screen. A total of 537 positive drug findings were identified by GC-MS compared to 1,267 positive findings by LC-QTOF. On average, each GC-MS screen identified 2.5 ± 1.8 drugs and the LC-QTOF screen identified 5.8 ± 3.2 drugs. No drugs were identified in 11.3% of the GC-MS screens, whereas drugs were detected in 99% of these by the LC-QTOF. In almost all instances, the LC-QTOF screen could provide mass spectrometric confirmatory results of positive immunoassay screens and was able to identify a wider range of additional drugs and drug metabolites., Conclusions: The described general unknown screening (non-targeted, qualitative) LC-QTOF method can detect a larger range of drugs encountered in a hospital setting. The method has been shown to be suitable for comprehensive toxicology screening in a clinical toxicology laboratory., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Many illicit drug users attempt to manipulate urine drug testing; dilution is one of the methods. In screening tests, false-negative results below the cut-off values can create positive results after creatinine normalization. This study aimed to evaluate the impact of a creatinine reference value on the normalization of the drug concentration in diluted urine. The study focused on 25 630 cases and the following information: gender, age, urine collection time, drug screening test results, creatinine concentration (CR), and confirmation analysis result. Mean CR value was 143.71 ± 83.68 mg/dl. There was a significant difference between CR and gender (p = 0.03). The mean CR for women was lower than that for men. The correlation between age and CR was not significant (r = -0.08, p = 0.00). However, after grouping the sample into age groups of 10 years, there was a significant difference between age groups and mean CR (p = 0.00). The mean CR was significantly lower in the 0-9 year age group (n = 34) than in the 20-29 year age group (n = 10 943). According to the urine specimen collection time, CR levels during the early hours of the day (06:00-06:59) were lower than those during the remaining hours (p = 0.00). The highest converted drug-negative to drug-positive results were obtained from 153.23 mg/dl CR reference value. Reference CR values were evaluated according to gender, age, and urine collection time. Different rates of positive results were obtained for each reference value. There is no published local creatinine value for spot urine samples in many countries, including Turkey. This will be useful to develop appropriate normalization models when reporting drug test results., (© 2021 American Academy of Forensic Sciences.)

Chronic ketamine abuse is associated with bladder dysfunction and cystitis. However, the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Here, we recruited 56 ketamine abusers (KA) and 40 age-matched healthy controls (HC) and applied the iTRAQ-based proteomics approach to unravel quantitative changes in the urine proteome profile between the two groups. Many of the differentially regulated proteins are involved in the complement and coagulation cascades and/or fibrotic disease. Among them, a significant increase in APOA1 levels in KA relative to control samples (392.1 ± 59.9 ng/ml vs. 13.7 ± 32.6 ng/ml, p < 0.0001) was detected via ELISA. Moreover, urinary ketamine, norketamine and dehydronorketamine contents (measured via LC-SRM-MS) were found to be positively correlated with overactive bladder syndrome score (OABSS) and APOA1 levels with urinary RBC, WBC, OABSS and numeric pain rating scale in KA. Collectively, our results may aid in developing new molecular tool(s) for management of ketamine-induced bladder dysfunction. Moreover, information regarding the differentially regulated proteins in urine of KA provides valuable clues to establish the molecular mechanisms underlying ketamine-induced cystitis.

Background: Currently, there are no national guidelines for antenatal drug testing. At Colchester Hospital, we use a strategy of screen-only using point-of-care testing to detect illicit drug use in pregnancy. To determine the suitability of this approach, we have compared the results of urine analysis by point-of-care testing with another NHS specialist clinical toxicology service that uses confirmation mass spectrometry., Methods: A total of 482 anonymized random urine specimens from antenatal clinics were tested for six drug classes: amphetamine, benzodiazepines, buprenorphine, cocaine, methadone and opiates using the Alere™ Drug Screen Urine Test Cup. The manufacturer's claims for positive cut-off and result stability were verified using spiked blank urine. Confirmatory testing was performed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for detection of 26 individual drugs., Results: Of 473 urine samples with adequate volume for point-of-care screening, 4.4% tested positive: 19 opiate and 2 cocaine. Concordance between point-of-care screening and UPLC-MS/MS confirmation was 97.9% for all drugs and 78.9% for opiates. Using spiked urine, only positive results for opiates were stable when read up to the manufacturer's recommended time of 60 min., Conclusions: The key advantages of using point-of-care devices to detect drug use in pregnancy are that is convenient and cheap. However, the clinical utility of point-of-care testing is limited by its poor sensitivity. Best practice is to confirm results using a more specific and sensitive method. As a result of this study, we are now reviewing our own procedures to consider introducing routine confirmation by mass spectrometry.

The use of the new psychoactive substances is continuously growing and the implementation of accurate and sensible analysis in biological matrices of users is relevant and fundamental for clinical and forensic purposes. Two different analytical technologies, high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) were used for a screening analysis of classic drugs and new psychoactive substances and their metabolites in urine of formed heroin addicts under methadone maintenance therapy. Sample preparation involved a liquid-liquid extraction. The UHPLC-HRMS method included Accucore™ phenyl Hexyl (100 × 2.1 mm, 2.6 μm, Thermo, USA) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2 mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2 mM in methanol/acetonitrile 50:50 ( v / v ), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode for substances identification (mass range 100-1000 m / z ). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m, 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40-550 m / z ). Urine samples from 296 patients with a history of opioid use disorder were examined. Around 80 different psychoactive substances and/or metabolites were identified, being methadone and metabolites the most prevalent ones. The possibility to screen for a huge number of psychotropic substances can be useful in suspected drug related fatalities or acute intoxication/exposure occurring in emergency departments and drug addiction services.

Drug of abuse (DOA) screening in urine is often performed in the clinical emergency setting. However, there is considerable evidence that questions the usefulness of this screening in the acute management of patients with suspected intoxications. The used method is an immunoassay, in which cross reactivity with false positive results may occur. A positive result does not always indicate current toxicity, a negative result does not exclude drug use or a current intoxication. Therefore, DOA screening has limited value in the acute clinical management of patients with intoxications.

Background and Objectives: Opioid overdose-related deaths increased from approximately 18 000 deaths in 2007 to 46 802 deaths in 2018. Fentanyl is primarily responsible for the increase in opioid overdose deaths from 2011 through 2017. The primary aim of this study is to determine the rates of fentanyl in the urine drug screens of all patients who presented to the psychiatric emergency room at VA Connecticut, over 7 months in 2018., Methods: Data were collected for all patient presentations between June 2018 and December 2018. There were 746 total patient presentations, with 497 being unique. Collected data included basic demographic information, psychiatric diagnosis, and urine drug screen for various illicit substances, including fentanyl., Results: Over 15% of patients screened positive for fentanyl. Patients who tested positive for fentanyl were further classified based on positive urine drug screening results for other opioids, cocaine, or both. Twenty percent of patients who screened positive for fentanyl and cocaine tested negative for other opioids. This category suggests that some veterans might be consuming fentanyl with cocaine., Discussion and Conclusions: Fentanyl was found at a high rate, even in the absence of other opioids, which suggests that some veterans might be consuming fentanyl with cocaine. Consequently, harm reduction strategies should be broadened to include all patients at risk of fentanyl overdose, including patients who use substances (eg, cocaine) that are potentially adulterated with fentanyl., Scientific Significance: This study is the first one of its kind that looked at rates of fentanyl use in all presentations to a psychiatric emergency room. While it is well-known that fentanyl is highly prevalent, these findings extend the current state of knowledge by replication in a psychiatric emergency population. (Am J Addict 2021;30:92-95)., (© 2020 American Academy of Addiction Psychiatry.)

Background: The objective of the current study is to determine how alcohol and illicit substance use contributes to motorcycle crash fatalities by examining the relationship between toxicology levels found postmortem and the behavior of riders and passengers in fatal motorcycle crashes., Materials and Methods: All motorcycle fatalities in Miami-Dade County, FL, from 2009 to 2014 were reviewed using the Miami-Dade County Medical Examiner's toxicology reports and the corresponding crash reports., Results: Positive alcohol/illicit substance detection was found in 44% of our population of 227 fatalities. When compared with those with a negative alcohol/illicit substance detection, those with a positive alcohol/illicit substance detection were more likely to be found at fault of the crash (77% versus 50%, P < 0.001), more likely to be in a single-vehicle crash (47% versus 21%, P < 0.001) and less likely to wear a helmet (44% versus 64%, P = 0.002). However, there was no significant relationship between speeding and alcohol/illicit substance detection (29% versus 33%, P = 0.748). In addition, a regression analysis demonstrated that there was less helmet use and more single-vehicle crashes with higher blood alcohol concentration., Conclusions: In fatal motorcycle crashes, alcohol and illicit substance use had a significantly negative impact on the risk aversion of motorcycle fatalities in regard to fault, helmet use, and single-vehicle crashes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Our goal was to assess the diagnostic utility and temporal kinetics of serum creatine kinase (CK) measurement as a predictor of acute kidney injury (AKI) in emergency department (ED) patients who present with possible substance-use related conditions., Methods: This was a retrospective chart review of ED patients with a urine drug screen (UDS) ordered and resulted between 2009-2013. Data was extracted electronically from EPIC Systems electronic health records, populated into a Microsoft Excel file, and includes demographics, chief complaint, vital signs, neuro-psychiatric physical examination findings, laboratory findings, psychiatric consult order time, ED medications given, orders, disposition and its time, and diagnosis., Results: Of 74,970 patients with an ED UDS, 22,101 (29%) had at least one CK measured. After inclusion and exclusion criteria, 2858 (13%) remained. Mean (standard deviation [SD]) age was 43.3 (12.5) years, 73% were male, 61% Black, 22% White, and 17% Hispanic. Mean (SD) ED length of stay was 10.4 (5.8) hours, and 56.7% were hospitalized. On average, CK was higher at 6-12 hours (p<0.001) and 12-18 hours (p=0.016) compared to 6 hours. CK was lower at 42-56 hours (p = 0.011), 72 hours (p<0.001), and over 72 hours (p<0.001), compared to 6 hours. Maximum CK was determined in those with >2 CK measures. We defined AKI risk as a creatinine of >1.4 milligrams per deciliter based on RIFLE criteria. AKI risk was calculated among those with at least two creatinine values in 522 patients. We identified five (1%) patients as having AKI risk. The odds of AKI risk were not associated with increase in CK over time., Conclusion: In 74,970 ED patients undergoing UDS testing for potential substance abuse, there was no identifiable CK level associated with AKI risk. In patients with possible substance-use conditions, CK continued to trend up even after six hours from door time and began to decrease after 42 hours. We found no value in repeated ED CK measures. Disposition should not be based solely on CK levels.

Purpose/background: The number of patients with acute synthetic cannabinoid intoxication (SCI) has increased in recent years although the prohibition of its legal sale and use in Turkey despite other countries allowing to some extent sale and use. The reported clinical findings of acute SCI are similar to the symptoms of several diseases. The first case of acute SCI seen in our hospital was in 2014. The aim of this study was to share the data of synthetic cannabinoid use in a research hospital in Turkey and to contribute the epidemiologic data globally betwen 2014 and 2017., Methods/procedures: A retrospective evaluation was made of patients who presented at emergency department (ED) because of SCI between January 2014 and December 2017. The initial diagnosis of the patients was done either via their self-report or clinician's clinical observation (family history with hallucination, lethargy, convulsions, dizziness, etc.). Totally, 352 patients were included to the study whose cannabioid use was proven with their urine drug analysis., Findings/results: Men were predominantly high (93.8%). Nearly all patients (93.5%) were followed up and discharged in 24 hours. Among them, 21 (5.9%) patients were admitted for hospitalization, and mortality was seen in 2 (0.6%). The mean number of previous presentations at ED with a similar diagnosis was 8.6 ± 10.31., Implications/conclusions: Great care must be taken in respect of complications related to SCI, which can even result in death. Patients have a tendency to not disclose the substance they have taken because it is illegal. Patients presenting at ED with recurrent symptoms must be referred to relevant legal authorities. For patients presenting with different clinical effects, SCI must be considered.

Objective : This case series describes and illustrates the effective use of a trauma-informed approach, GLAPE, to provide drug screens for individuals in substance use treatment programs. The GLAPE approach recognizes that individuals who have experienced traumatic events and are recovering from substance use difficulties may also face unique challenges when engaging in mental health treatment. The nature of drug screening procedures in practice may feel invasive and triggering for clients with trauma histories. Finding ways to decrease barriers to treatment and increase engagement and retention are important components of effective substance use treatment. Methods: This case series involved three veteran cisgender men with posttraumatic stress disorder (PTSD) and co-occurring substance use conditions in an outpatient addiction recovery program in a Veterans' hospital. The cases illustrate how recovery can be aided by trauma-informed approaches for urine drug screens. The treatment team evaluated various monitoring modalities and collaborated with each client to form a treatment plan that implemented the GLAPE approach to bolster their recovery. The GLAPE approach includes five components: Giving detailed instructions prior to the urine screen procedure, listening to and eliciting questions and concerns of the client, articulating options and exhibiting flexibility in the procedure to accommodate the needs of the individual client, giving permission to the client to voice concerns at any point during the procedure, and evaluating the process in collaboration with the client, including what could be improved for next time. Results: Use of the GLAPE approach effectively helped to engage and retain military veterans with co-occurring PTSD and substance use disorder within a trauma informed outpatient program. Preliminary evidence from three cases provides that this approach may be useful for use in substance use treatment with clients who have trauma histories. Conclusions: Given widespread use of observed urine drug screens in substance use treatment programs, and prominent co-occurrence of substance use disorder and PTSD, it is essential that staff approach this procedure in a trauma-informed way. This case series illustrates an approach that can improve client experience, aid clients in treatment engagement, and assist staff in the provision of effective care.

New psychoactive substances (NPS) emerge continually, amongst which is a growing class of ketamine analogues with an arylcyclohexylamine backbone. Recently we reported a poisoning outbreak associated with 2-oxo-PCE (deschloro-N-ethyl-ketamine). The present report describes the emergence of another ketamine analogue, 2-fluorodeschloroketamine (2F-DCK). The compound was first detected in a patient's urine, its identity confirmed by accurate mass analysis and comparison with reference standard. Four putative metabolites were identified, including nor-2F-DCK, dehydronor-2F-DCK (major metabolite) and two hydroxylated derivatives of nor-2F-DCK. Between January and July 2019, 20 cases of analytically confirmed 2F-DCK exposure were encountered. In 19 out of 20 cases, at least one more ketamine-type drug was detected concurrently with 2F-DCK, including ketamine (90%), deschloroketamine (DCK, 50%), 2-oxo-PCE (45%) and tiletamine (10%). In particular, six of the cases showed the presence of 4 ketamine-type drugs in the same urine sample. The clinical effects observed in patients exposed to 2F-DCK are predominantly neurological (impaired consciousness, agitation, abnormal behaviour) and cardiovascular (hypertension, tachycardia); five patients had loss of consciousness or convulsion. Management was mainly supportive; all patients recovered uneventfully. This is the first clinical case series involving 2F-DCK and frontline medical personnel are urged to be aware of this rapidly expanding class of NPS, in particular the co-ingestion of multiple ketamine analogues., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Acceptance of organs from acute chemical intoxicated donors remains controversial and outcomes are insufficiently explored., Methods: This is a single-center retrospective cohort analysis of 484 patients undergoing deceased donor kidney transplantation (DDKT). We assessed the association of positive urine drug screen before transplantation with cohort statistics, delayed graft function (DGF), and graft outcomes at 2 years. Multiple logistical regression (MLR) analysis was used to assess the odds ratio for DGF., Results: Of 484 random DDKTs performed at our institution between January 2010 and October 2015, 280 deceased kidney donors were current drug users. Mean age was 35.4 (15) years, 39% male, 61% were African Americans, and 38.2% had more than one test positive. The main chemical toxins detectable in donor urine were alcohol, heroin, opioid/methadone, cocaine, marijuana, benzodiazepines, methamphetamine, ecstasy, and LSD. Single and multiple urine chemical toxicology of kidney donors did not have a significant effect on KT outcomes of DGF and graft failure during a median follow-up (P for odds ratios > 0.05)., Conclusions: The use of deceased donor kidney grafts from donors with positive urine chemical toxicology may be a worthwhile method of increasing the availability of scarce donor kidney organs as such exposure to illicit drug(s) is not associated with major adverse transplant outcomes.

Unfortunately, risk-based testing introduces physician bias into decisionmaking, and can disproportionately target low-income, minority, and immigrant women. Simultaneously, physicians can overlook screening patients who are white and higher income, placing their infants at risk for drug withdrawal and birth defects. Universal screening has been touted by many physicians and providers because it eliminates risk for discriminatory practices, provides a basis for early detection and education of pregnant women, and directs physicians to provide resources for pregnant women to quit drug use during pregnancy.

Purpose: The dried urine spots (DUSs) technique is increasing continuously as an easy sampling method for monitoring substance abuse due to its advantages of stability and convenience regarding transport and storage. 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a new type of tryptamine hallucinogen, the use of which has been banned in many countries. And according to the previous research, 5-MeO-DIPT is not stable in urine. In order to improve its stability, an LC-MS/MS method for determining 5-MeO-DIPT in DUSs was developed., Method: 10 μl urine was spotted on Whatman FTA TM classic card, then extracted with 200 μl methanol, and liquid chromatography-tandem mass spectrometry in positive ion multiple reaction monitoring mode was utilized for analysis., Results: The LOD and LLOQ of the method were 0.1 ng/ml and 0.2 ng/ml, respectively. The accuracy and precision were 98.2%-103.9% and 2.7%-8.5%, respectively. It was found that the stability of 5-MeO-DIPT in DUSs was better than the stability of 5-MeO-DIPT in urine stored at 25 °C. Moreover, this method was also applied to detect 5-MeO-DIPT in the urine of individuals known to have used 5-MeO-DIPT. It was found that the concentrations of 5-MeO-DIPT were 0.3-2.3 ng/ml, which were lower than those obtained via GC-Orbitrap-MS. The small volume of urine required (10 μl), combined with the simplicity of the analytical technique, makes this an useful procedure for the screening of drug of abuse., Competing Interests: Declaration of competing interest The authors declare that they have no confict of interest., (Copyright © 2020 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Illicit drugs consumption can be back-calculated based on the analysis of drug residues in wastewater using the wastewater-based epidemiology method. The Music Day, held on June 21 in France since 1982, has grown to global proportions and is now celebrated as World Music Day. This large outdoor event takes place in many cities with people allowed to play music in the streets. As psychotropic drugs are often associated with music events, the goal of this study is to investigate the use of illicit drugs on this day in Bordeaux, the fifth largest urban area in France. Daily sampling campaigns of composite wastewater were carried out for seven days in two wastewater treatment plants in Bordeaux in 2017 (Music Day) and 2018. World Music Day in Bordeaux has no observable effect on illicit drug consumption even if this event has massive public participation: this is the first report of the absence of an illicit drug consumption increase in a festival of such magnitude, corroborating the effect of others' views and opinions, because this event takes place publicly in the street and not among peers. Different hypothesizes are put forward to explain this fact: inappropriate type of event for drug consumption, effect of other festivals, and influence of the event's timing on a weekday., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The rise in opioid use among pregnant women has resulted in an increase in the incidence of neonatal abstinence syndrome (NAS). Despite the focus on opioid use, prenatal polysubstance exposure is often associated with NAS diagnosis and severity. Drug toxicology screens such as urine drug screens and umbilical cord toxicology are dependent upon the substance, timing, frequency, and dose to detect substances present and can underestimate the neonatal exposure. The aim of this study was to identify the predictability of the consequences of prenatal polysubstance exposure versus opioid only exposure based on toxicology and toxicology plus self-report., Methods: Neonates > 35 weeks gestation with prenatal opioid exposure were included in this retrospective data analysis. NAS was identified using maternal urine drug screen (UDS) toxicology, self-reported exposure during pregnancy, and neonatal toxicology. Analysis was conducted using Stata 15.1 utilizing McNemar's test, chi-square for categorical outcomes, and Wilcoxon test for numerical outcomes., Results: A statistically significant difference in length of stay and length of treatment with poly-exposed neonates was observed when maternal self-report was considered with toxicology, but not with toxicology alone. This trend was observed for cumulative hospital length of stay as well as length and dose of treatment., Conclusions for Practice: The findings in this report demonstrate that self-report is important for identifying substance of exposure. Three substances in particular that often require a change in treatment paradigm went undetected by toxicology were Gabapentin (20.9% of the population), Heroin (20.5% of the population), and Benzodiazepines (8.5% of the population). A healthy rapport with patients is often critical to effective clinical practice. Women with substance use disorder anticipate negative reactions from healthcare providers. Empathetic interview techniques to facilitate accurate disclosure may be more important to the treatment of the exposed neonate.

Nonalcohol substance use is a robust correlate of suicide risk. However, few data exist regarding the degree to which nonalcohol substance use, as measured by objective indicators (e.g., urinalysis toxicology screen), is related to suicide risk. This study examined the associations of a multimodal assessment of nonalcohol substance use and multiple indicators of suicide risk. Overall, 168 acute care psychiatric inpatients participated and provided data spanning urinalysis toxicology screen and self-report instruments. Substance use per urinalysis toxicology screen and self-report was not related to current suicidal ideation severity. However, substance use per urinalysis toxicology screen was significantly associated with a suicide attempt history and suicidality as a primary reason for admission. Substance use is an important variable to consider in suicide risk conceptualization. Findings underscore the importance of leveraging, when possible, objective indicators of substance use (e.g., urinalysis toxicology screen) in suicide risk formulations.

Background: Drug use during pregnancy is associated with adverse perinatal outcomes. This study was conducted to assess the prevalence of consumption of drugs of abuse in pregnant women at the end of gestation., Methods: Cross-sectional study of all consecutive pregnant women in labor admitted to a regional hospital in Calella (Barcelona, Spain) in labor over one year (2014-2015). Women who gave written consent to take part in the study provided a urine sample on admission and completed a questionnaire with toxic-habit-related questions., Results: The study population included 862 women, 721 (83.6%) of which agreed to participate. Of the 721 urine samples obtained, 719 (99.7%) were valid for analysis. The prevalence of drugs of abuse was 5.4% (N.=39). Cannabis was the most frequently detected substance. No participant tested positive for opioids. In the multivariate analysis, predictors of illicit drug use were history of more than two abortions, premature delivery, self-reporting of consumption during pregnancy, poor obstetric control during gestation, and consideration of vulnerable pregnant woman. Based on the β coefficients of these five factors, a scoring system for discriminating positivity or negativity of drugs of abuse in urine testing was calculated (area under the ROC 0.84)., Conclusions: The prevalence of consumption of drugs of abuse at the end of pregnancy was 5.4%. A simple test based on five anamnestic variables is useful to discriminate women with positive and negative results of urine testing for drugs of abuse tested in this study.

Data on the detection of joint presence of pregabalin and lorazepam in the biological objects and material evidence. Aim of this study is to develop a method of the detection of pregabalin and lorazepam in urine. The proposed approach to sample preparation of a biological object and the detection of lorazepam and pregabalin allows the detection of toxicants in cases of their joint presence. It can be used in the analysis of urine in cases of acute poisoning for detoxification therapy or chemical toxicological analysis as a preliminary and confirmatory study for the presence of abuse of these drugs.

Background: Dried specimens have been proposed in multiple environments to minimize costs associated with specimen storage and shipping in clinical studies. This report describes the development and validation of an automated method for qualitative toxicology screening of dried urine samples using LC-MS/MS., Methods: Urine standards containing 41 compounds were prepared and applied to filter paper cards. Dried urine was eluted from the cards using a Dried Blood Spot (DBS) autosampler from Spark Holland, which was plumbed inline with a Thermo Scientific Turboflow chromatography system for subsequent MS/MS detection with selected reaction monitoring. Limits of detection, precision of peak areas, repeatability, and carryover studies were conducted. Concordance with a reference LC-MS/MS method using liquid samples was evaluated using remnant discarded specimens., Results: The limit of detection ranged from 5 to 75 ng/mL for most compounds. At the LOD for each analyte, the peak area precision ranged from 8 to 29%. For 20 repeat injections of samples spiked at ±25% of the LOD, there was a 4% false positive rate for the 75% × LOD samples, and a 0.4% false negative rate for the +125% × LOD samples. In comparing 40 known positive specimens analyzed with the DUS method and a liquid urine reference method, there was 88% agreement. Analysis of 10 known negative specimens yielded negative results. There was no significant carryover detected up to 2000 ng/mL for any of the analytes in the assay., Conclusion: Using a robotic DUS sampling an inline HTLC-MS/MS system, we have developed and validated a fully-automated and robust method for multi-analyte detection of drugs of abuse in dried urine specimens., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Substance use during pregnancy has been linked to adverse birth and other outcomes. Screening and intervention in the prenatal clinic are recommended, and reliance on patient reports or selective urine drug screening is inadequate. The aim of this prospective project was to determine substance use identification rates associated with common screening practices, compared to universal screening, among pregnant women seeking care at an urban, academic obstetric clinic., Methods: Women attending their first prenatal visit (N = 275) completed a self-report questionnaire on lifetime and current substance use. A urine drug screening was also conducted, the results of which were not reported to providers. Participants' charts were reviewed to obtain the results of provider-ordered screens., Results: The sample was primarily African-American and Latino, with Medicaid insurance. Ten women (4.6%) reported current marijuana use, while more than double that number (n = 27; 11.6%) screened positive for marijuana via universal screening. The majority of women who screened positive via universal screening did not have a provider-ordered urine drug screening, and less than one-third (29.3%) of clinician-ordered screens were positive for at least one substance. Finally, 90% of women who reported they were using marijuana were not selected by providers for a screen., Discussion: Data demonstrate the high proportion of women using marijuana and the limitations of patient self-report and selective, nonroutine screening to identify substance use during pregnancy. Effective, standardized, clinic-wide strategies are needed to support providers in identifying pregnant women who use substances in order to increase the frequency of education and intervention., (© 2019 Wiley Periodicals, Inc.)

Background: Substance use during pregnancy is a major medical and public health concern. Determination of the most appropriate screening protocol remains a clinical conundrum. Interviews and/or laboratory drug screens may be costly, inaccurate, and are frequently inadequate to identify patterns of substance use for a given population or geographic area. We compared commercially available urine "dip cup" toxicology screens obtained in the clinic to university hospital drug toxicology results., Methods: 267 observed urine samples were collected from pregnant women with known substance use disorders enrolled in a specialized treatment program that included access to buprenorphine medication-assisted treatment. Each urine sample was tested by commercial dip cup with temperature confirmation and then sent to the university hospital laboratory for analyses. The number of substances detected and cost for each screening method were compared., Results: Uniformly, the dip cup had comparable detection of amphetamines, barbiturates, cocaine, methadone, opiates, and tetrahydrocannabinol to the university hospital laboratory with the exception of benzodiazepines. In addition, the dip cup detected use of buprenorphine (a commonly misused opiate receptor ligand not included in the hospital screen) and was significantly less expensive., Conclusions: Commercially available urine dip cups are cost-effective, equally comparable to hospital based screening, and provide 'real time' results germane to clinical care and treatment planning., (Copyright © 2019. Published by Elsevier B.V.)

A rapid lateral flow immunoassay is presented that uses carboxyl-modified superparamagnetic nanoparticles as labels that can be quantified by highly sensitive multi-channel electronic readers. The approach is generic in that it is likely to be applicable to numerous small molecules. The method permits both single- and multiplex assays at a point-of-need without sample pretreatment. It is user-friendly and offers attractive characteristics demonstrated here for detection of morphine, fentanyl and methamphetamine in urine. The competitive immunoassay uses commercially available reagents that do not require special permissions. After migration of sample, the lateral flow test strips are subjected to an alternating magnetic field at two frequencies. The response from the nanolabels is readout at a combinatorial frequency from the entire volume of a porous immunochromatographic membrane by the magnetic particle quantification technique. Even trace concentrations can be quantified within ≤20 min with the limits of detection (LOD) of 0.20 ng·mL -1 , 0.36 ng·mL -1 and 1.30 ng·mL -1 for morphine, fentanyl and methamphetamine, respectively. The second variant presented here features highly sensitive quantification of haptens (LOD for fentanyl - 0.05 ng·mL -1 ). This is due to high-affinity trapping of magnetic nanolabels in a universal streptavidin-based test strip, which can be also used for detection of virtually any other small molecule. The third variant is of the multiplexed type and intended for rapid and simultaneous detection of the drugs of abuse in human urine with LODs equal to 0.60 ng·mL -1 and 3.0 ng·mL -1 for morphine and methamphetamine, respectively. In addition to the low LODs, the RSDs did not exceed 7%, 9%, and 11% for methamphetamine, morphine and fentanyl, respectively. Graphical abstract Three variants of small molecule detection in competitive format at a point-of-need. Single-plex variants feature antibody and high-affinity streptavidin test lines, while multiplex variant - several antibody test lines. Magnetic nanolabels are quantified from the whole volume of test strip.

The study investigates the prevalence of drugs of abuse detected from 2011 to 2015 through (i) forensic drug testing of illicit drug seizures from law enforcement agencies; and (ii) analysis of common drugs of abuse in urine samples obtained from offenders/probationers under mandatory drug-use surveillance programmes. Under the selected drug testing groups, there were an average of 5334 cases/year of illicit drug seizures examined and 28,438 samples/year requiring drugs of abuse analysis in urine, from 2011 to 2015. The drug positive rates for urinalysis in the selected population group (i.e., offenders/probationers requiring mandatory drug testing) were steady with an average of about 22%. The ratio of single drug use to more than one drug was about 4:1, showing predominant use of single drug. Ketamine, methamphetamine (MA) and heroin were the three most commonly encountered abused drugs through laboratory testing. During the period, identification of ketamine was shown to decline continuously in both illicit drug testing and urinalysis while there was substantial increase in detection of MA. A rising trend was noted for cases identified with new psychotropic substances (NPS) in illicit drug seizures although NPS cases contributed to a small proportion of overall drug seizure cases examined (<5%) in the study period. A total of 47 substances classified as NPS were encountered with cathinones, either synthetic or plant-based, contributed to the majority of NPS cases (˜77%) followed by synthetic cannabinoids and phenethylamines., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In 2013, the Centers for Disease Control and Prevention released a warning regarding a new recreational drug, acetyl fentanyl. Acetyl fentanyl is a μ-opioid receptor agonist, and its pharmacological effects include euphoria, altered mood, miosis and central nervous system depression. The objective of this report was to develop a sensitive and specific method for the quantitation of acetyl fentanyl by gas chromatography-mass spectrometry in postmortem casework. Acetyl fentanyl was isolated from biological matrices using solid-phase extraction and acetyl fentanyl-13C6 was employed as an internal standard. The method was validated utilizing the Scientific Working Group for Forensic Toxicology's published method validation parameters, and the biological matrices used for analysis were postmortem blood and urine. In addition to the quantitation of acetyl fentanyl, a demographic study of cases obtained from the Rhode Island Office of State Medical Examiners and the University of Florida Health Pathology Laboratories-Forensic Toxicology Laboratory was performed to examine potential risk factors for acetyl fentanyl use. The results from this study found that the blood concentrations in these individuals ranged from 17 to 945 ng/mL. This suggests acetyl fentanyl is less potent than its prototype drug, fentanyl and requires an increased dose to achieve its desired effects. The demographic analysis indicated white males aged 21-40 years and individuals with a previous history of drug use have the highest risk for acetyl fentanyl abuse., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Data examining usefulness of urine drug testing in addiction settings for accurately establishing diagnoses and informing treatment is limited. In this retrospective-cohort study we examined the utility of performing urine drug testing in patients presenting for an outpatient addiction assessment., Methods: Urine drug testing and patient-reported substance use history were obtained from the medical record of patients who presented for an outpatient addiction evaluation. Patients who denied use of a substance within the window of detection but tested positive were considered to have misrepresented their use. Differences between patients accurately representing versus misrepresenting their use were evaluated. Sensitivity/specificity of drug tests were calculated from self-report and changes to treatment recommendations and diagnoses assessed., Results: One hundred and seventy-four patients (mean age = 43.35 ± 15.68 years) were included and the sample was majority male (67%). Ninety-four (54%) patients reported use of a substance within the window of detection. Of 80 patients denying recent use, 14 tested positive (8%). There were no differences in sex (P = 0.78) or age (P = 0.12); referral sources differed significantly between correct and incorrect responders (P = 0.01). Specificity varied between 96% and 99%, while sensitivity had a wider range (17%-87%). Treatment recommendations and diagnoses were altered after review of drug testing results in 1 patient (0.5%). However, in the remainder, all patients were already diagnosed with a severe substance use disorder and had received recommendations to initiate residential/outpatient substance use treatment., Conclusions: Among patients completing urine drug testing during outpatient substance use disorder evaluation positive screens alerted providers to undisclosed persistent substance use and potential withdrawal in 8% of the cohort and resulted in a change in diagnoses and/or treatment in 1 patient.

Background: Ayahausca is an ethnobotanical drink of South America and the compound dimethyltryptamine (DMT) is primarily responsible for the hallucinogenic effects. DMT has a short half-life and its detection in urinary drug screens is challenging. We investigate a simple alternate approach to detect ayahuasca consumption by relying on other constituents of the drink, the β-carboline harmala alkaloids., Methods: Three commercially sourced harmala alkaloids were characterized and added to a non-targeted high-resolution mass spectrometry urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof, in positive electrospray ionization mode. The mass detector was operated in MSE mode and data processed with UNIFI™ software. A urine specimen from a patient suspected to have consumed ayahuasca was analyzed by a non-targeted drug screen., Results: The harmala alkaloids: harmine, harmaline and tetrohydroharmaline (THH) were characterized and their detection data added to the toxicology screening library. Harmaline and THH were detected in the patient's urine specimen., Conclusion: The inclusion of the harmala alkaloids into the drug screen method library may enable the detection of ayahuasca use in patients that undergo non-targeted drug screen., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

New analytical methods are urgently needed to enable high-throughput, yet comprehensive drug screening, given an alarming opioid and prescription drug crisis in public health. Conventional urine drug testing based on a two-tier immunoassay screen followed by a gas chromatography-tandem mass spectrometry (GC-MS/MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) method are expensive and prone to bias while being limited to targeted panels of known drugs of abuse (DoA). Herein, we outline an improved method for drug surveillance that allows for the resolution and detection of an expanded panel of DoA and their metabolites when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). Multiplexed separations of ten urine samples with a quality control by CE (< 3 min/sample) in conjunction with full-scan data acquisition using a time-of-flight mass spectrometer (TOF-MS) under positive ion mode detection allows for the identification and quantification of DoA above recommended cut-off levels. An excellent resolution of drug isomers and isobars, including background interferences, are achieved when using MSI-CE-MS with an electrokinetic spacer between sample segments, where accurate mass/molecular formula together with the comigration of a matching deuterated internal standard and the detection of one or more bio-transformed metabolites facilitate DoA identification over a wider detection window. Additionally, urine samples can be analyzed directly without enzyme deconjugation for the rapid screening without complicated sample workup. MSI-CE-MS enables the surveillance of a broad spectrum of DoA that is required for the treatment monitoring of high-risk patients, including confirming prescribed drug adherence, revealing illicit drug use/substitution, and evaluating optimal dosage regimes as required for new advances in precision medicine.

Introduction: γ-Hydroxybutyric acid is an endogenous substance, a therapeutic agent, and a recreational drug of abuse. This psychoactive substance acts as a depressant of the central nervous system and is commonly encountered in clinical and forensic practice, including impaired drivers, poisoned patients, and drug-related intoxication deaths., Objective: The aim of this review is to assist clinical and forensic practitioners with the interpretation of γ-hydroxybutyric acid concentrations in blood, urine, and alternative biological specimens from living and deceased persons., Methods: The information sources used to prepare this review were PubMed, Scopus, and Web-of-Science. These databases were searched using keywords γ-hydroxybutyrate (GHB), blood, urine, alternative specimens, non-conventional biological matrices, saliva, oral fluid, sweat, hair, vitreous humor (VH), brain, cerebrospinal fluid (CSF), dried blood spots (DBS), breast milk, and various combinations thereof. The resulting 4228 references were screened to exclude duplicates, which left 1980 articles for further consideration. These publications were carefully evaluated by taking into account the main aims of the review and 143 scientific papers were considered relevant. Analytical methods: The analytical methods used to determine γ-hydroxybutyric acid in blood and other biological specimens make use of gas- or liquid-chromatography coupled to mass spectrometry. These hyphenated techniques are accurate, precise, and specific for their intended purposes and the lower limit of quantitation in blood and other specimens is 0.5 mg/L or less. Human pharmacokinetics: GHB is rapidly absorbed from the gut and distributes into the total body water compartment. Only a small fraction of the dose (1-2%) is excreted unchanged in the urine. The plasma elimination half-life of γ-hydroxybutyric acid is short, being only about 0.5-0.9 h, which requires timely sampling of blood and other biological specimens for clinical and forensic analysis. Endogenous concentrations of GHB in blood: GHB is both an endogenous metabolite and a drug of abuse, which complicates interpretation of the laboratory results of analysis. Moreover, the concentrations of GHB in blood and other specimens tend to increase after sampling, especially in autopsy cases. This requires the use of practical "cut-off" concentrations to avoid reporting false positive results. These cut-offs are different for different biological specimen types. Concentrations of GHB in clinical and forensic practice: As a recreational drug GHB is predominantly used by young males (94%) with a mean age of 27.1 years. The mean (median) and range of concentrations in blood from apprehended drivers was 90 mg/L (82 mg/L) and 8-600 mg/L, respectively. The concentration distributions in blood taken from living and deceased persons overlapped, although the mean (median) and range of concentrations were higher in intoxication deaths; 640 mg/L (280 mg/L) and 30-9200 mg/L, respectively. Analysis of GHB in alternative specimens: All biological fluids and tissue containing water are suitable for the analysis of GHB. Examples of alternative specimens discussed in this review are CSF, saliva, hair strands, breast milk, DBS, VH, and brain tissue., Conclusions: Body fluids for the analysis of GHB must be obtained as quickly as possible after a poisoned patient is admitted to hospital or after a person is arrested for a drug-related crime to enhance chances of detecting the drug. The sampling of urine lengthens the window of detection by 3-4 h compared with blood samples, but with longer delays between last intake of GHB and obtaining specimens, hair strands, and/or nails might be the only option. In postmortem toxicology, the concentrations of drugs tend to be more stable in bladder urine, VH, and CSF compared with blood, because these sampling sites are protected from the spread of bacteria from the gut. Accordingly, the relationship between blood and urine concentrations of GHB furnishes useful information when drug intoxication deaths are investigated.

The abuse of new psychoactive substances (NPS) has been dramatically increasing all around the world since the late 2000s. The availability of hundreds of NPS in the past decade is challenging for both public health and global drug policies. A 39-year-old woman, known as a multidrug addict, was murdered by her partner by ligature strangulation. A comprehensive toxicological screening by gas chromatography and ultra-high performance liquid chromatography with tandem mass spectrometry revealed the simultaneous presence of ethanol (1.37 g/L), diazepam (157 ng/mL) and nordiazepam (204 ng/mL), cocaine (25 ng/mL) and benzoylecgonine (544 ng/mL), and (3-methoxy-(1-(1-phenylcyclohexyl)piperidine) or 3-MeO-PCP, a dissociative hallucinogen anesthetic drug. Concentrations of 3-MeO-PCP were 63, 64, and 94 ng/mL in femoral blood, bile, and urine, respectively. Hair tested also positive for 3-MeO-PCP on 3 × 2-cm segments at 731, 893, and 846 pg/mg, indicating long-term abuse of the drug. This seems to be the first ever reported hair concentrations. Major impairment of the victim, including visual hallucinations and alteration of behavior, was attributed to the mixture of all the drugs, with a major contribution of 3-MeO-PCP. The toxicological findings were compared to the few reports available in the medical literature.

Urine drug testing is an essential component of monitoring patients who are receiving long-term opioid therapy, and it has been suggested for patients receiving long-term benzodiazepine or stimulant therapy. Family physicians should be familiar with the characteristics and capabilities of screening and confirmatory drug tests. Immunoassays are qualitative tests used for initial screening of urine samples. They can give false-positive and false-negative results, so all results are considered presumptive until confirmatory testing is performed. Immunoassays for opioids may not detect commonly prescribed semisynthetic and synthetic opioids such as methadone and fentanyl; similarly, immunoassays for benzodiazepines may not detect alprazolam or clonazepam. Immunoassays can cross-react with other medications and give false-positive results, which have important implications for a patient's pain treatment plan. False-negative results can cause missed opportunities to detect misuse. Urine samples can be adulterated with other substances to mask positive results on urine drug testing. Family physicians must be familiar with these substances, the methods to detect them, and their effects on urine drug testing.

It is unknown if estimates of illicit drug use among young men who have sex with men and transgender women (YMSM/TW) may be biased due to historical distrust of research or reliable due to more accepting norms for use. Research is needed to examine the validity of drug use self-reports among YMSM/TW. Data came from an ongoing longitudinal study of YMSM/TW aged 16-29 living in Chicago (analytic N = 1029). Baseline urinalysis screens for marijuana, ecstasy, amphetamine, methamphetamine, cocaine, benzodiazepine, and opiate metabolites were compared to self-reported use within different recall periods using measures of concordance. Generalized estimating equations logistic regressions were conducted on three waves of data to identify predictors of disclosing past-6-month use of marijuana and non-marijuana drugs. Past-6-month self-reported use of all non-marijuana substances was <15%. There was excellent agreement between self-reported and drug-tested marijuana use. For other substances, sensitivities within the urinalysis detection window were <0.5 but increased with longer recall periods. Black participants had lower odds of disclosing non-marijuana drug use. Gender minority participants had lower odds of disclosing marijuana use. Participants with a history of arrest had higher odds of disclosing both marijuana and non-marijuana drug use. Wave and year of first research participation were non-significant, suggesting no systematic bias or increasing honesty associated with longer research participation. Programs that rely on self-identification of non-marijuana illicit substance use may be missing a substantial portion of drug-using YMSM/TW. Future epidemiological studies should work to reduce social desirability biases and include biomarker-based drug screenings to increase validity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Self-reported data are commonly used when investigating illicit substance use. However, self-reports have well-known limitations such as limited recall and socially desirable responding. Mislabeling or adulteration of drugs on the illicit market may also cause incorrect reporting. Objectives: We aimed to examine what could be gained in terms of illicit drug use findings among music festival attendees when including biological sample test results in the assessment. Methods: We included 651 attendees at three music festivals in Norway from June to August 2016. Self-reported drug use was recorded using questionnaires, and samples of oral fluid were analyzed to detect use of illicit drugs. In addition, we analyzed samples of pooled urine from portable toilets at each festival. Results: All methods identified cannabis, MDMA, and cocaine as the most commonly used drugs. Overall, 6.6% of respondents reported use of illicit substances during the previous 48 hours. Oral fluid testing identified a larger number of drug users as 12.6% tested positive for illicit drugs. In oral fluid testing, we identified ketamine and three new psychoactive substances (NPS) that had not been reported on the questionnaire. In pooled urine testing, we identified amphetamine and three additional NPS that were neither reported used nor found in oral fluid samples. Conclusions/Importance: Drug testing of biological samples proved to be an important supplement to self-reports as a larger number of illicit substances could be detected.

Objective In the management of patients with suspected acute drug poisoning, a screening test using the patient's urine is usually performed. The Triage DOA ® and INSTANT-VIEW M-1 ® kits are two commonly used point-of-care screening kits in Japan. However, the relationship between the results of these screening kits and the blood concentration of the poisoning drug is not clear. In this study, we evaluated which kit is more useful for acute drug poisoning screening based on a comparison of their results with the results of a serum drug analysis. Methods This prospective cross-sectional study investigated all patients with acute drug poisoning admitted to a general hospital in Tokyo, Japan, over a nine-month period. The Triage DOA ® and INSTANT-VIEW M-1 ® screening kits were used, and a qualitative serum analysis was conducted simultaneously in all cases. We compared the kits for use in screening patients with acute drug poisoning and evaluated the utility of the kits. Results For the 117 patients enrolled in this study, the 2 kits showed different sensitivities to benzodiazepines (Triage ® , 78.6%; INSTANT-VIEW ® , 90.5%). Both kits showed high sensitivity to barbiturates (Triage ® , 87.0%; INSTANT-VIEW ® , 91.3%) but low sensitivity to tricyclic antidepressants (Triage ® , 25.0%; INSTANT-VIEW ® , 45.8%). Conclusion Because the sensitivity varies depending on the kind of drug, it is difficult to discuss the superiority of these kits. However, this study compared the results of two types of urinary drug screening kits with the results of qualitative analysis of drugs in serum as a gold standard, providing important reference data.

Background: The technical advantages of direct-to-definitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) urine testing for monitoring patient compliance in pain management are well known. However, the design and implementation of LC-MS/MS methods are more controversial, including factors such as determining appropriate cutoffs, specimen processing (e.g., specimen hydrolysis), reporting of qualitative and/or quantitative results, and test menu., Objectives: The objective of the research was to compare the clinical performance of our previous urine pain toxicology panel, a combination of immunoassay (IA) screens and LC-MS/MS, to our current pain toxicology panel, which features direct-to-definitive LC-MS/MS for 34 drugs and metabolites., Study Design: Six months of results from our previous pain toxicology panel were compared to 5.5 months of results from our current pain toxicology panel, enabling us to make conclusions regarding clinical performance., Setting: The research took place at Brigham and Women's Hospital in Boston, MA., Methods: The percentage of false positive IA results was evaluated for our previous pain toxicology panel. The positivity rates for each drug and/or metabolite were calculated for both the previous and current panels, including rates of detection of both prescribed and illicit drugs. The turnaround time (TAT), direct and send-out costs associated with each approach, as well as projected cost savings were also determined., Results: False positive rates with IA ranged from 0% to 29%; the highest false positive rate was seen for 6-acetylmorphine (6-AM). The elimination of IA, addition of metabolites, and/or lowering of cutoffs increased the detection rate of 6-AM, benzoylecgonine (cocaine metabolite), fentanyl, morphine, and oxycodone. The ability to differentiate compliance from simulated compliance improved after eliminating specimen hydrolysis. The TAT improved significantly and projected yearly cost savings with the current panel was $95,003 (USD). In our opinion, qualitative results appeared sufficient to assess compliance in the majority of cases., Limitations: Our study was performed in a single academic center in a specific geographic region; therefore, our results may not be generalizable to other types of centers or regions., Conclusion: Direct-to-definitive LC-MS/MS testing has several clinical benefits, including reduction of false positive results, improved assessment of patient compliance, decreased TAT, and increased detection of drug use and abuse. Cost savings were also realized using this approach., Key Words: Direct-to-definitive, LC-MS/MS, immunoassay, sensitivity, cost, pain management, turnaround time, patient compliance.

In this work, an alternative LC-MS-MS strategy for the analysis of urinary creatinine in abstinence control was presented and discussed. The two-way electrospray ionization consisted of two different precursor ions in which fragmentation was used in multiple reaction monitoring experiments. A creatinine adduct ion with sodium and sodium acetate together with the conventional analyte protonation was investigated. Adduct formation and fragmentation was explored by appropriate infusion experiments performed with analyte solutions prepared in different concentrations. The analytical signal was compensated by the application of appropriate isotopically labeled internal standard. The advantages of information carried by precursor ions separated in the mass spectra were pointed out. Sample preparation based solely on sample dilution performed in the final HPLC vial directly. A Luna 5 μm C18 (2) 100 A, 150 mm × 2 mm analytical column together with a mobile phase consisted of H2O/methanol = 3%/97% (v/v) with 10 mmol/L ammonium acetate and 0.1% acetic acid (flow = 0.4 mL/min) were used for the separation performed during a run of 5 min. The linearity was examined in the range of 100-3,000 mg/L. The limit of detection (13 mg/L), limit of quantification (43 mg/L) together with method precision/accuracy, selectivity, stability and matrix effect were tested to be appropriate for forensic applications. The applicability of water as surrogate matrix for method calibration was also examined successfully. The presented strategy was used in the analysis of real samples. No interferences with the creatinine peak eluted at about 1.0 min could be recorded.

Substance use disorder remains a pervasive problem in the U.S. and elsewhere. Recent scholarship has explored therapist characteristics and evidence based intervention implementation in an attempt to improve client outcomes. One such construct that has received considerable attention is grit. People with high levels of grit tend to remain determined despite setbacks. This study sought to elucidate the relationship of grit to therapeutic alliance and attitudes towards evidence-based interventions in a sample of front-line therapist (n = 240). Grit was found to be positively associated with therapeutic alliance and correlated with favorable attitudes towards using proven practice. Findings suggest that gritty therapists may sustain the use of evidence based interventions in their usual services and have better client outcomes.

Introduction: Paper spray mass spectrometry has provided a rapid, quantitative ambient ionization method for xenobiotic and biomolecule analysis. As an alternative to traditional sample preparation and chromatography, paper spray demonstrates the sampling ionization of a wide range of molecules and significant sensitivity from complex biofluids. The amenability of paper spray with dried blood spots and other sampling types shows strong potential for rapid, point-of-care (POC) analysis without time-consuming separation procedures. Areas covered: This special report summarizes the current state and advances in paper spray mass spectrometry that relate to its applicability for clinical analysis. It also provides our perspectives on the future development of paper spray mass spectrometry and its potential roles in clinical settings. Expert commentary: Paper spray has provided the fundamental aspects of ambient ionization needed for implementation at the POC. With further clinical management and standardization, paper spray has the potential to replace traditional complex analysis procedure for rapid quantitative detection of illicit drugs, therapeutic drugs and metabolites. Surface and substrate modifications also offer significant improvement in desorption and ionization efficiencies, resulting in enhanced sensitivity. Comprehensive analysis of metabolites and lipids will further extend the implementation of paper spray ionization mass spectrometry into clinical applications.

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The incidence of substance use disorders in the United States among residents in anesthesiology is between 1% and 2%. A recent study reported that the incidence of substance use disorders in U.S. anesthesiology residents has been increasing. There are no reports of effective methods to prevent substance use disorder in residents. A comprehensive drug testing program including a random component may reduce the incidence of substance use disorders., Methods: The authors initiated a comprehensive urine drug screening program of residents, fellows, faculty physicians, and certified nurse anesthetists. The authors performed 3,190 tests over 13 yr. The authors determined the incidence of substance use disorders among residents in our large anesthesiology residency program during the decade before (January 1, 1994, to December 31, 2003) and for the 13 yr after (January 1, 2004 to December 31, 2016) instituting a random urine drug testing program. A total of 628 residents trained in the program over these 23 yr; they contributed a total of 1,721 resident years for analysis. Fewer faculty and certified nurse anesthetists were studied, so we do not include them in our analysis., Results: The incidence of substance use disorders among trainees in our department during the 10 yr before initiation of urine drug screening was four incidents in 719 resident years or 0.0056 incidents per resident-year. In the 13 yr after the introduction of urine drug screening, there have been zero incidents in 1,002 resident years in our residency program (P = 0.0305)., Conclusions: This single-center, comprehensive program including preplacement and random drug testing was associated with a reduction of the incidence of substance use disorders among our residents in anesthesiology. There were no instances of substance use disorders in our residents over the recent 13 yr. A large, multicenter trial of a more diverse sample of academic, government, and community institutions is needed to determine if such a program can predictably reduce the incidence of substance use disorders in a larger group of anesthesiology residents.