- Predictive Value of Positive Drug Screening Results in an Urban Outpatient Population. [JOURNAL ARTICLE]
- J Anal Toxicol 2016 Aug 22.
Urine drug testing (UDT) has become an essential component in the management of patients prescribed opioid analgesics for the treatment of chronic non-malignant pain. Several laboratory methods are available to monitor adherence with the pharmacological regimen and abstinence from illicit or unauthorized medications. Immunochemical screening methods are rapid and economical, but they have limitations, including lack of specificity, and confirmatory methods are often necessary to verify presumptive positive results. We analyzed the results of confirmatory assays in an outpatient setting to determine the predictive value of presumptive positive urine drug screen results using an automated immunoassay for eight common drugs or drug classes. Positive predictive values (PPVs), in descending order, were as follows: cannabinoids (100%), cocaine (100%), opiates (86.8%), benzodiazepines (74.6%), oxycodone (67.6%), methadone (44.1%) and amphetamines (9.3%). The number of positive barbiturate results was too small to be included in the statistical analysis.
- Management of Narcolepsy. [Journal Article, Review]
- Curr Treat Options Neurol 2016 Oct; 18(10):43.
Narcolepsy type 1 (NT1) and type 2 (NT2) are two rare neurological diseases, classified as central disorders of hypersomnolence. The pathophysiology of NT1 is well known; it is caused by the selective destruction of hypocretin (Hcrt) neurons, by a highly suspected autoimmune process. On the contrary, little is known about NT2 etiology, sharing with NT1 somnolence and signs of dysregulation of rapid eye movement (REM) sleep, but not cataplexy. Management strategies are rather codified, at least in adults, with a lifelong treatment required in NT1, whereas no pharmacological study focused only on NT2 patients, with sometimes spontaneous improvement or disappearance of their symptoms. We recommend that medications and guidelines in NT2 should be the same as for NT1 (except for cataplexy), but the benefit risk ratio should be reassessed regularly. The main symptom in both diseases is a disabling excessive daytime sleepiness (EDS). First-line medications should be stimulants such as modafinil, armodafinil, or sodium oxybate, second-line methylphenidate and pitolisant, where available, and amphetamines as third-line therapy. Sodium oxybate has the advantage to be also effective to manage the fragmented nocturnal sleep, another common symptom in NT1. We advise to wait a few weeks with a stimulant drug before starting an anticataplectic treatment in NT1, except for severe cataplexy. Furthermore, cataplexy treatment should not be systematic. First-line strategy is the use of sodium oxybate, the only drug approved for cataplexy and EDS in adults. However, antidepressant agents such as venlafaxine are also commonly used, with few adverse effects and a good efficacy, although based on expert consensus only. A clinically relevant tool is required to quantify the severity of narcolepsy, subjective symptoms, and their consequences, to monitor the treatment efficacy, and to finally optimize narcolepsy management. In the future, Hcrt replacement or Hcrt agonists will certainly be options to treat NT1, but for now the different peptides do not cross easily the blood brain barrier. Immune-based therapies are other possibilities in NT1, at disease onset, with already some successful attempts to slow down or stop the autoimmune process.
- Psychosis associated with acute recreational drug toxicity: a European case series. [JOURNAL ARTICLE]
- BMC Psychiatry 2016; 16(1):293.
Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs.The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset.Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations.The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators.
- The impact of pre-injury controlled substance use on clinical outcomes following trauma. [JOURNAL ARTICLE]
- J Trauma Acute Care Surg 2016 Aug 18.
A disproportionately high percentage of trauma patients use controlled substances, and they often co-ingest multiple drugs. Previous studies have evaluated the effect of individual drugs on clinical outcomes following trauma. However, the impact of all drugs included in a comprehensive screening panel has not yet been compared in a single cohort of patients.All trauma patients who underwent urine drug screens following admission to the LAC+USC Medical Center (01/2008-06/2015) were identified retrospectively. Univariable and multivariable regression analyses determined the significance of all drugs tested in the hospital's standard toxicology screen (amphetamine, barbiturate, benzodiazepine, cocaine, opiate, phencyclidine) on clinical outcomes.A total of 10,288 patients who underwent admission toxicology screening were identified. While 5,661 patients had completely negative screens, 3,370 patients tested positive for only one drug and 1,257 patients tested for multiple drugs. Univariable analysis indicated that patients who tested positive for multiple drugs had higher rates of operative intervention (p<0.001), longer hospital stay (p<0.001), and longer ICU stays (p<0.001). Multivariable analysis indicated that phencyclidine was associated with higher rates of mortality (p=0.028) while amphetamine was associated with lower rates of mortality (p=0.008). Higher rates of operative intervention were observed in patients testing positive for amphetamine (p<0.001), benzodiazepine (p<0.001), or opiate (p<0.001). Benzodiazepine use was associated with higher rates of mechanical ventilation (p<0.001), but use of amphetamines (p=0.030) or opiates (p<0.001) was associated with lower rates.Pre-injury use of amphetamine, barbiturate, benzodiazepine, cocaine, opiate, and PCP have significant and variable impact on clinical outcomes following trauma. Comparing the relative effect of each drug class can help clinicians risk-stratify all trauma patients, including those who test positive for multiple substances.Epidemiologic study, level III.
- Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse. [JOURNAL ARTICLE]
- Am J Drug Alcohol Abuse 2016 Aug 17.:1-15.
Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.
- The Difference Between Random and Postaccident Urine Drug Test Concentrations Among Southern Indiana, Western Kentucky, and Eastern Illinois Workers. [JOURNAL ARTICLE]
- J Addict Med 2016 Aug 11.
If employee drug use plays a significant part in the incidence of workplace accidents, one would anticipate the positivity rates of postaccident drug tests to be higher than the positivity rates for random tests. Past studies examined the difference of a dichotomous outcome between 2 groups. Dichotomous (positive or negative) categorization may have been a source of systemic error, which minimized the difference between random and postaccident groups.This is a study exploring the difference of urine drug concentrations between random and postaccident groups. The population consists of employees from various industries in Southern Indiana, Western Kentucky, and Eastern Illinois. Normalization of drug excretion to urinary creatinine concentration was carried out. Preliminary assumption testing was done. Logarithmic transformation was completed. One-way between-groups analysis of variance was performed to investigate random and postaccident drug test differences in urine drug concentrations.There was a statistically significant difference between test groups on the combined dependent variables. The only dependent variables to reach statistical significance, to an alpha level of 0.025, were urine opiate and urine amphetamine concentrations. Higher mean concentration of both drugs was found in the postaccident group. However, the proportion of variances explained by the reason for testing was quite small.The results of this study are consistent with studies using dichotomous dependent variables, which demonstrated a significantly higher prevalence for positive postaccident urine opiate tests. The study also identified a similar result for postaccident urine amphetamine tests which was not previously known.
- Frontal traumatic brain injury in rats causes long-lasting impairments in impulse control that are differentially sensitive to pharmacotherapeutics and associated with chronic neuroinflammation. [JOURNAL ARTICLE]
- ACS Chem Neurosci 2016 Aug 15.
Traumatic brain injury (TBI) affects millions yearly, and is increasingly associated with chronic neuropsychiatric symptoms. We assessed the long-term effects of different bilateral frontal controlled cortical impact injury severities (mild, moderate, severe) on the five-choice serial reaction time task, a paradigm with relatively independent measurements of attention, motor impulsivity and motivation. Moderately- and severely-injured animals exhibited impairments across all cognitive domains that were still evident 14 weeks post-injury, while mild-injured animals only demonstrated persistent deficits in impulse control. However, recovery of function varied considerably between subjects such that some showed no impairment ("TBI-resilient"), some demonstrated initial deficits that recovered ("TBI-vulnerable") and some never recovered ("chronically-impaired"). Three clinically-relevant treatments for impulse-control or TBI, amphetamine, atomoxetine, and amantadine, were assessed for efficacy in treating injury-induced deficits. Susceptibility to TBI affected the response to pharmacological challenge with amphetamine. Whereas sham and TBI-resilient animals showed characteristic impairments in impulse control at higher doses, amphetamine had the opposite effect in chronically-impaired rats, improving task performance. In contrast, atomoxetine and amantadine reduced premature responding but increased omissions, suggesting psychomotor slowing. Analysis of brain tissue revealed that generalized neuroinflammation was associated with impulsivity even when accounting for the degree of brain damage. This is one of the first studies to characterize psychiatric-like symptoms in experimental TBI. Our data highlight the importance of testing pharmacotherapies in TBI models in order to predict efficacy, and suggest that neuroinflammation may represent a treatment target for impulse control problems following injury.
- Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia. [JOURNAL ARTICLE]
- Cell Rep 2016 Aug 10.
Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.
- Prenatal Substance Exposure and Reporting of Child Maltreatment by Race and Ethnicity. [JOURNAL ARTICLE]
- Pediatrics 2016 Aug 12.
Substance exposure is thought to contribute to reports of suspected maltreatment made to child protective services (CPS) at or shortly after birth. There are limited data, however, on whether clinicians are more likely to report black and Hispanic substance-exposed infants compared with white infants.We examined racial differences in diagnosed substance exposure and subsequent maltreatment reports by using linked birth, hospital discharge, and CPS records. Diagnostic codes were used to document substance exposure; CPS records provided information on maltreatment reports. Prevalence of infant exposure was calculated by race or ethnicity, substance type, and sociodemographic covariates. We estimated racial differences in maltreatment reporting among substance-exposed infants using multivariable models.In a 2006 population-based California birth cohort of 474 071 black, Hispanic, and white infants, substance exposure diagnoses were identified for 1.6% of infants (n = 7428). Exposure varied significantly across racial groups (P < .001), with the highest prevalence observed among black infants (4.1%) and the lowest among Hispanic infants (1.0%). Among white and Hispanic infants, the most frequently observed substances were amphetamine and cannabis; for black infants, cannabis was the most common, followed by cocaine. After adjusting for sociodemographic and pregnancy factors, we found that substance-exposed black and Hispanic infants were reported at significantly lower or statistically comparable rates to substance-exposed white infants.Although we were unable to address potential racial and ethnic disparities in screening for substances at birth, we found no evidence that racial disparities in infant CPS reports arise from variable responses to prenatal substance exposure.
- Method Validation and Determination of Lisdexamfetamine and Amphetamine in Oral Fluid, Plasma and Urine by LC-MS/MS. [JOURNAL ARTICLE]
- Biomed Chromatogr 2016 Aug 12.
Lisdexamfetamine (LDX) is a long-acting prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder and binge-eating disorder symptoms. In vivo hydrolysis of LDX amide bond releases the therapeutically active d-amphetamine (d-AMPH). Since toxicological tests in biological samples can detect AMPH due to the use of some medications, efficient methods are needed in order to correctly interpret the results. The aim of this study was to develop and validate a LC-MS/MS method for the simultaneous quantification of LDX and its main biotransformation product AMPH in human oral fluid, plasma and urine. Calibration curve range for both analytes was 1 to 128 ng/mL in oral fluid and plasma and 4 to 256 ng/mL in urine, being the lowest concentration the limit of quantification. Accuracy of the determined values of the target analytes for the five control levels ranged from 94.8-111.7% for oral fluid, 91.3-100.2% for plasma and 94.8-109.8% for urine. Imprecision for the five control levels did not exceeded 12.8% for oral fluid, 16.2% for plasma and 17.1% for urine. The method developed for the three matrices was validated and was also successfully applied to assess real samples, showing for the first time the detection of lisdexamfetamine in oral fluid.