Challenges and future trends of forensic toxicology to keep a cut above the rest.

Forensic toxicology faces several challenges in research and daily practice, including new drugs and futuristic technologies requiring innovative testing methods and continuous education and training of professionals. One of the most pressing issues in recent years is the emergence of novel psychoactive substances, often created by modifying the chemical structure of existing drugs to produce compounds with similar effects that are not yet regulated and lack standardized references. To overcome this challenge, forensic toxicologists have employed a range of analytical methods, including qualitative and quantitative analysis using highly sensitive technologies such as liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), which are the most reliable and accurate methods for detecting drugs in biological samples. Liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is becoming the gold standard for detecting controlled substances, their derivatives and metabolites. Despite advancements in testing methods, challenges persist in forensic toxicology. As such, the field must invest in research and development to improve testing methods, utilize cutting-edge technologies, increase funding for training programs, and promote multidisciplinary interactions.

Trend differences over 20 years between two methadone maintenance clinics, one with and one without cannabis legalization.

BACKGROUND: Although methadone maintenance treatment (MMT) guidelines are well established, patients' characteristics and outcome change over time may be affected by the legality of cannabis. OBJECTIVE: To study trend changes between two clinics over 20 years from Las Vegas (LV) and 27 years from Tel Aviv (TA). METHODS: Patients' characteristics at admission, including drugs in urine at first and 13th month were obtained from their medical charts. Changes by year of admission and cumulative retention were analyzed. RESULTS: The LV MMT clinic (1724 patients) had a lower one-year retention rate compared to the TA MMT clinic (1014 patients) (46.4% vs. 74.4%, respectively, p < 0.0005), and a higher rate of opioid stop after one year (75.9% vs. 68.8%, respectively, p = 0.003). The age at MMT admission and the retention rates decreased in LV and increased in TA. The prevalence of cannabis and benzodiazepine misuse on MMT admission increased in LV with no change recorded in TA. Cocaine on MMT admission decreased in LV and increased in TA, while amphetamine use increased in LV and decreased in TA. Cox models multivariate analyses found cannabis on admission to predict shorter retention in LV (as younger age male and amphetamines), and cannabis after one year in TA (as did cocaine and opiates after one year and BDZ on admission). CONCLUSION: Although cannabis prevalence increased only in LV where it was legalized, it was associated with poor outcomes in both clinics. Younger age, a known poor outcome predictor, may be related to decreased retention in LV.

Marijuana and Nurses: Career Risks Remain.

As laws change, workplace rules often don't.

What the lab can and cannot do: clinical interpretation of drug testing results.

Urine drug testing is one of the objective tools available to assess adherence. To monitor adherence, quantitative urinary results can assist in differentiating "new" drug use from "previous" (historical) drug use. "Spikes" in urinary concentration can assist in identifying patterns of drug use. Coupled chromatographic-mass spectrometric methods are capable of identifying very small amounts of analyte and can make clinical interpretation rather challenging, specifically for drugs that have a longer half-life. Polypharmacy is common in treatment and rehabilitation programs because of co-morbidities. Medications prescribed for comorbidities can cause drug-drug interaction and phenoconversion of genotypic extensive metabolizers into phenotypic poor metabolizers of the treatment drug. This can have significant impact on both pharmacokinetic (PK) and pharmacodynamic properties of the treatment drug. Therapeutic drug monitoring (TDM) coupled with PKs can assist in interpreting the effects of phenoconversion. TDM-PKs reflects the cumulative effects of pathophysiological changes in the patient as well as drug-drug interactions and should be considered for treatment medications/drugs used to manage pain and treat substance abuse. Since only a few enzyme immunoassays for TDM are available, this is a unique opportunity for clinical laboratory scientists to develop TDM-PK protocols that can have a significant impact on patient care and personalized medicine. Interpretation of drug screening results should be done with caution while considering pharmacological properties and the presence or absence of the parent drug and its metabolites. The objective of this manuscript is to review and address the variables that influence interpretation of different drugs analyzed from a rehabilitation and treatment programs perspective.

A comparison of trends in wastewater-based data and traditional epidemiological indicators of stimulant consumption in three locations.

AIMS: To compare long-term trends in wastewater data with other indicators of stimulant use in three locations and to test the reliability of estimates based on 1 week of sampling. DESIGN: Comparison of trends in quantities ('loads') of stimulants or their metabolites in wastewater with trends in other indicators of stimulant use (e.g. treatment, police, population survey data). SETTING AND PARTICIPANTS: Populations in Oslo (Norway), South-East Queensland (Australia) and Eindhoven (the Netherlands). MEASUREMENTS: Wastewater data were modelled for MDMA (3,4-methyl​enedioxy​methamphetamine), benzoylecgonine (a metabolite of cocaine), amphetamine and methamphetamine in Oslo; benzoylecgonine in Eindhoven; and methamphetamine in South-East Queensland. Choice of stimulants modelled in each region was primarily determined by availability of useable data. FINDINGS: In Oslo, wastewater data, driving under the influence of drugs statistics and seizure data all suggested increasing MDMA use between 2009 and 2017. In South-East Queensland, there was an estimated 31.1% [95% confidence interval (CI) = 29.4-32.9%] annual increase in daily loads of methamphetamine in wastewater between 2009 and 2016, compared with a 14.1% (95% CI = 10.9-17.3%) annual increase in seizures. Some of the increase in wastewater can be explained by increased purity. In Eindhoven, there was no evidence of a change in cocaine consumption from wastewater, but a reduction was observed in numbers in treatment for cocaine use from 2012 to 2017. In approximately half the cases examined in Oslo, credible intervals around estimates of annual average loads from a regression model versus estimates based on a single week of sampling did not overlap. CONCLUSIONS: Long-term trends in loads of stimulants in wastewater appear to be broadly consistent with trends in other indicators of stimulant use in three locations. Wastewater data should be interpreted alongside epidemiological indicators and purity data. One week of wastewater sampling may not be sufficient for valid inference about drug consumption.

Seizures of illicit substances for personal use in two Italian provinces: analysis of trends by type and purity from 2008 to 2017.

BACKGROUND: The use of illicit substances represents one of the most difficult problems to confront in the health system. Drug use is a global problem but is not uniform throughout the world, within the same country and changes over time. Therefore, knowing the illicit substances that are used in a territory is essential to better organize health services in that specific geographical area. To this aim, we analysed 4200 samples confiscated from individuals who held them for personal use by police forces in the Italian provinces of Modena and Reggio Emilia from 2008 to 2017. METHODS: The suspected samples were screened by gas-chromatography-mass spectrometry (GC-MS) and by liquid chromatography-tandem mass spectrometry (LC-MS/MS); all samples were subsequently analysed by gas chromatography-flame ionization detector (GC-FID) for quantitative analyses. RESULTS: Cannabis was the most seized illicit substance (70.7%). Over the study period, the number of seizures of herb with a high content of Δ9-THC increased. The number of cocaine seizures remained stable (total 16.1%), but the median purity of seized cocaine increased to 75% in 2017. Heroin seizures decreased over time, but the median purity of seized heroin reached 16.8% in 2017. In almost all the years, heroin samples with a purity exceeding the 97.5 percentile were found. Especially from 2014, the range of seized substances increased and started to include synthetic cathinones, phenylethylamines, UR-144, LSD, psilocybe, prescription opioid and hypnotics. In two cases, tramadol together with tropicamide was seized. Most of the seizures involved male subjects and 82% of the seizures were from individuals younger than 35 years of age. CONCLUSIONS: The persistence of old illicit drugs and the rapid emergence of new psychoactive substances represented a serious challenge for public health in the studied Italian area. Some useful interventions might be: informing mainly young people about the possible complications of cannabis use; implementing standardized procedures to diagnose and treat cocaine-related emergencies in hospitals; increasing the distribution of naloxone to antagonize possible heroin overdoses; equipping laboratories to be able to identify the new psychoactive substances.

Toxicological oral fluid results among Spanish drivers testing positive on on-site drug controls from 2013 to 2015.

BACKGROUND: Driving under the influence of drugs (DUID) increases the risk of serious injury or death in traffic accidents. The aim of this study was to provide information about DUID in Spanish drivers. METHODS: 10,064 oral fluid samples were collected from Spanish drivers that tested positive on the roadside using the Dräger DrugTest 5000 (DDT5000) between 2013 and 2015. Samples were collected using Quantisal™ and analysed by LC-MS/MS at the Toxicology Laboratory of the Institute of Forensic Science of the University of Santiago de Compostela. RESULTS: Drivers were mainly young men (85.1% male, 29.7 ± 8.1 years old). In 98.5% of cases, LC-MS/MS results confirmed at least one of the positive results detected on the roadside. Cannabis (82.4%) and cocaine (42.1%) were the most commonly detected drugs. Poly-drug use was observed in 42.7% of drivers, mostly for all illicit drugs (>80%) except for cannabis (42.6%). Illicit drug and single-drug use was more frequent among drivers under 35 years old, and medicines and poly-drug use more common among drivers older than 35 years old. The on-site device performance was calculated using both the DDT5000 cut-offs and the LC-MS/MS method LOQs. Sensitivity (>73% vs >58%), specificity [>94% for all the compounds regardless the cut-offs used, except for cannabis (71%)] and accuracy (>87.5% with both cut-offs) fulfilled the DRUID Project requirements in all cases. CONCLUSION: LC-MS/MS confirmation result was negative in only 1.5% of the cases. The DUID driver profile was a young man, consuming cannabis or a combination of cannabis and cocaine.

Annual banned-substance review: Analytical approaches in human sports drug testing.

A number of high profile revelations concerning anti-doping rule violations over the past 12 months have outlined the importance of tackling prevailing challenges and reducing the limitations of the current anti-doping system. At this time, the necessity to enhance, expand, and improve analytical test methods in response to the substances outlined in the World Anti-Doping Agency (WADA) Prohibited List represents an increasingly crucial task for modern sports drug testing programs. The ability to improve analytical testing methods often relies on the expedient application of novel information regarding superior target analytes for sports drug testing assays, drug elimination profiles, and alternative sample matrices, together with recent advances in instrumental developments. This annual banned-substance review evaluates literature published between October 2017 and September 2018 offering an in-depth evaluation of developments in these arenas and their potential application to substances reported in WADA's 2018 Prohibited List.

Hair EtG: Alterations in segment levels accompanying hair growth.

Hair levels of the direct ethanol biomarker ethyl glucuronide (EtG) are used to evaluate history of alcohol intake. The proximal 3 cm of the hair sample is most often analyzed and this is assumed to represent the intake of ethanol over approximately the past three months. The aim of this study was to investigate change of EtG levels during hair growth in an ethanol-abstinent period. Twenty-seven patients were recruited from an alcohol treatment clinic. A hair sample was collected after hospitalization and EtG was analyzed in the 0-3 cm hair segment (T1). Another hair sample was collected after one month of abstinence and EtG was analyzed in the 1-4 cm hair segment (T2), discarding the proximal 1 cm (0-1 cm) of the segment. As a result of the segment choice and assuming a hair growth rate of 1 cm per month, T2 should represent roughly the same time of alcohol exposure as segment T1. The median concentration of EtG in T1 was 100 pg/mg (range 7.7-1320) and the median concentration in T2 was 53.4 pg/mg (range < LOQ-692). EtG concentrations decreased significantly from T1 to T2 (p = 0.003) and the median change in EtG from T1 to T2 was -46.0%. This study shows decreasing EtG concentrations in most subjects in a hair segment during growth when comparing two segments that is assumed to represent roughly the same period of alcohol intake. Further research is needed to confirm if this observed decline of EtG is a result of wash-out-effects of EtG or other factors.

Evidence of seasonal variation of ethyl glucuronide in hair: Modeling a seven-year data series.

The assessment of chronic excessive alcohol consumption by ethyl glucuronide (EtG) determination in hair is generally based on a cut-off value of 30 pg/mg recognized by regulatory authorities and scientific societies that guide the decision process. The ongoing debate about the risks connected with the straightforward application of this cut-off refers to the factors that may influence the detected EtG concentration. The present contribution to this debate evaluates the seasonal variation of the averaged EtG values along a seven-year period. Over 65 000 data points have been statistically analyzed to provide a mathematical model that interprets the data, gives insight into several influencing factors, and forecasts progressive data-points of the time series. This model shows that there is an annual pattern in the data exhibiting lower EtG concentrations during warm seasons and higher values in cold seasons. The estimated EtG cycles are characterized by the seasonal variation of ±2.78 pg/mg above and below the overall mean (with 5.56 pg/mg absolute difference overall). This seasonal factor associated with EtG quantification might result in a potential source of bias, at least in the regional/climatic conditions observed in the samples' collection area. Moreover, the EtG time series reveals that the change in the sample pre-treatment procedure has an effect on the modeled pattern as an abrupt increment (+38%) in the mean value of the EtG concentration. This change corresponds to the time when the former protocol of cutting hair into small segments before extraction was substituted by pulverization with a ball mill.

Implementing standardized substance use disorder screening in primary care.

OBJECTIVES: This quality improvement initiative aimed to develop and implement a protocol for an alcohol and substance use disorder screening for primary care. METHODS: The Two Item Conjoint Screen was selected and a process was piloted by care teams. Quality improvement tools were used to improve the protocol. Primary care providers (PCPs) were surveyed about their use of the screening protocol in the primary care setting. Data on total number of screenings were collected through the electronic health record. RESULTS: Implementation resulted in more than 30,000 screenings completed in 2016. PCP survey results indicated that PCPs felt screening was helpful in identifying potential substance use problems (100%) and that most providers (76%) felt that overall patient care improved after screening was initiated. CONCLUSIONS: Brief alcohol and substance use disorder screenings can be easily implemented and well integrated into primary care settings. PCPs found screenings to be valuable in caring for patients.

Racial disparities in discontinuation of long-term opioid therapy following illicit drug use among black and white patients.

BACKGROUND: Among patients prescribed long-term opioid therapy (LTOT) for chronic pain, no study has yet examined how clinicians respond to evidence of illicit drug use and whether the decision to discontinue opioids is influenced by a patient's race. METHODS: Among outpatients of black and white race initiating LTOT through the VA between 2000 and 2010, we reviewed electronic medical records to determine whether opioids were discontinued within 60 days of a positive urine drug test. Logistic regression was used to examine differences by race. RESULTS: Among 15,366 patients of black (48.1%) or white (51.9%) race initiating LTOT from 2000 to 2010, 20.5% (25.5% of blacks vs. 15.8% of whites, P <. 001) received a urine drug test within the first 6 months of treatment; 13.8% tested positive for cannabis and 17.4% for cocaine. LTOT was discontinued in 11.4% of patients who tested positive for cannabis and in 13.1% of those who tested positive for cocaine. Among patients testing positive for cannabis, blacks were 2.1 times more likely than whites to have LTOT discontinued (adjusted odds ratio [AOR] 2.06, 95% confidence interval [CI] 1.04-4.08). Among patients testing positive for cocaine, blacks were 3.3 times more likely than whites to have LTOT discontinued (AOR 3.30, CI 1.28-8.53). CONCLUSIONS: Among patients testing positive for illicit drug use while receiving LTOT, clinicians are substantially more likely to discontinue opioids when the patient is black. A more universal approach to administering and responding to urine drug testing is urgently needed.

Reducing the Incidence of Substance Use Disorders in Anesthesiology Residents: 13 Years of Comprehensive Urine Drug Screening.

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.

The Dangerous Pattern of Concurrent Use of Alcohol and Cocaine Among Drunk-Drivers of Northeast Italy.

AIM: To estimate the prevalence of drug and polydrug use among drunk-drivers during the driving license regranting program, in order to assess the inclusion of toxicological tests on hair and urine samples in the systematic methodology in this category of subjects. SHORT SUMMARY: A total of 2160 drunk-drivers were tested for alcohol and drugs during driving license regranting. Thirty-one subjects showed alcohol use, 212 illicit drug use and, among these, 131 were polydrug users. Nineteen different patterns of drug and polydrug use were found. Cocaine was detected in 165 subjects. METHODS: The study was performed on 2160 drunk-drivers examined at Legal Medicine and Toxicology Unit of the University of Padova, in a 3-year-period (2014-2017). The positivity for one or more illicit drugs in hair or urine samples was confirmed by LC/MS and GC/MS methods. Chi-square test, Fischer's exact test and Cochran-Armitage Trend test were used to study the correlation between general characteristics of the examined sample and the presence of drug/polydrug use. RESULTS: Thirty-one subjects showed alcohol use, 212 illicit drug use and, among these, 131 were polydrug users. Nineteen different patterns of drug and polydrug use were found. Cocaine was detected in 165 subjects in whom 122 showed a concurrent use of alcohol and cocaine, identified through the detection of cocaethylene in hair samples. No significant association and/or trends between drug/polydrug use and the general characteristics of the sample were detected. CONCLUSIONS: The results show that drug and polydrug use among drunk-drivers should be subjected to toxicological as well as alcohological monitoring, especially in the regranting procedure. The implementation of this procedure could improve the knowledge of dimensions of the issue, providing a powerful means for the reduction of phenomenon of driving under the influence of alcohol and drugs.

The impact of methamphetamines in patients with traumatic brain injury, a retrospective review.

OBJECTIVE: Both neurotoxic and neuroprotective effects of methamphetamines (METH) are being studied. There are few studies evaluating the effects of METH on patients with traumatic brain injury (TBI). The objective of this study is to compare clinical outcomes after TBI in METH users versus non-METH users. PATIENT AND METHODS: A retrospective review of 304 patients with severe traumatic head injury were performed. Patients were evaluated and stratified based on toxicology screening for methamphetamines (METH) or none. Of the patients reviewed with a full toxicology, 24 of those patients were positive for METH, and 60 patients were negative. Patients were evaluated based on demographics, type of injury, Glasgow Coma Scale (GCS), and Glasgow Outcome Scale (GOS). RESULTS: METH patients were younger upon presentation (43.5 versus 55.8, p = 0.003), with a larger improvement in GCS and GOS upon discharge (P = 0.012, 0.0001 respectively). There was no significant difference in length of hospital stay, initial presenting GCS and GOS, or discharge GCS and GOS. CONCLUSIONS: Our findings demonstrate an improved change in GCS and GOS for those positive with METH than those without. Surprisingly, substance positive patients did not have a worse outcome score. Further investigation is necessary to evaluate the potential neuro-protective effects of METH in TBI.

"Positive" urine testing for Cannabis is associated with increased risk of traffic crashes.

Although recent Cannabis use is widely reported to be associated with drug-related traffic accidents, the evidence that Cannabis users show an increased risk of being involved in road crashes is still not unequivocally proved. The purpose of the present work is to provide an objective assessment of this hypothesis, by comparing the frequency of occurrence of positive urine analyses in drivers involved in traffic accidents (n = 1406) with that observed in a control population undergoing mandatory urine drug testing (n = 1953). Urine analyses for drugs of abuse were performed by screening immunometric techniques followed by confirmation with UHPLC-QQQ MS, adopting a cut-off concentration for THC-COOH of 15 ng/mL. A case was classified as "positive" when a driver admitted to hospital for road traffic injuries showed urine concentrations of THC-COOH higher than the cut-off. All samples showing positive results for any other controlled drug in urine or blood alcohol concentrations >0.5 mg/mL were excluded from the study. Subjects positive to THC-COOH, and negative to all the other tested substances were 116 in Group 1 (8.2%) and 16 in Group 2 (0.8%). Subjects resulting negative to any tested substances were 1290 in Group 1 and 1937 in Group 2. The frequency of THC-COOH detection in the two groups was compared by using the "chi square" test, which resulted = 119.57, i.e. highly significant (P <<< 0.01). The Odds Ratio of the two groups was =10.88, showing a high degree of association between the presence of THC-COOH in urine and the occurrence of traffic accidents (P < 0.0001). The presented data, proving a high degree of association between Cannabis use and the occurrence of traffic accidents with injuries of the driver, support the use of urine testing for Cannabis in the procedures for the issuing of the driving licence, particularly in the case of subjects formerly or presently using Cannabis. This finding looks even more relevant in the present times, because of the increasing success of the policies of legalization of Cannabis for medical and non-medical purposes.