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Background: Cocaine use disorder (CUD) is a debilitating condition with no NICE-recommended medication or specific psychosocial interventions. In the United Kingdom (UK), general counselling (treatment-as-usual; TAU) is widely delivered, but has limited effectiveness. We tested the feasibility, safety and preliminary efficacy of a novel, adjunctive psychosocial intervention for CUD, called 'memory-focused cognitive therapy' (MFCT)., Methods: We did a two-arm, external pilot randomised controlled trial at a specialist community National Health Service addictions clinic in London, UK. 30 adults (≥18years), voluntarily seeking treatment for CUD (enrolled ≥14days; all with moderate-to-severe DSM5 CUD), were individually randomised (1:1) to a control group (ongoing TAU; 3×90min CUD cognitive conceptualisation assessments; 2×30min cocaine-related cue-induction procedures; and 3×30min research follow-ups); or to an intervention group (ongoing TAU; 3×90min cognitive conceptualisation assessments; 2×30min cocaine-related cue-induction procedures; 5×120min, one-to-one, MFCT sessions [in 1week]; and 3×60min research follow-ups and MFCT-relapse prevention). The primary outcome was the total percentage score on the frequency version of the Craving Experiences Questionnaire (CEQ-F) at 1-month follow-up after the intensive intervention week (clinical endpoint; recall period past 2weeks; higher score indicating greater craving). Secondary outcomes at the 1-month follow-up were percentage days abstinent (PDA) from cocaine, and longest period (days) of continuous abstinence (LPA) in the prior 28days. Outcomes were analysed as an unadjusted group mean difference (with Hedge's g effect size [ES]) and a 95% Confidence Interval [CI] for the primary outcome and a 90% CI for the secondary outcomes. Exploratory, multivariable linear (primary outcome) and Poisson regression models (secondary outcomes), with sex, age, months of regular cocaine use, baseline outcome score, and group estimated the effectiveness of the intervention. The trial is registered with the ISCRTN (ISRCTN16462783)., Findings: Between July 15, 2015, and November 27, 2016, 58 patients were assessed for eligibility and 30 participants were randomised (14 to the control group and 16 to the intervention). With outcome data collected for all participants at the endpoint, the intervention group mean CEQ-F score (14·77; SD 21·47) was lower than the control group mean (51·75; SD 22·72); ES -1·62; 95% CI -2·45 to -0·80. MFCT was associated with more cocaine abstinence in the intervention group (PDA 85·94; SD 18·96) than the control group (PDA 54·59; SD 30·29); ES 1·19; 90% CI 0·54 to 1·84. There was also greater maximum abstinence in the intervention group (LPA 15·69; SD 10·10) than the control group (6·00; SD 7·36); ES 1·06; 90% CI 0·41 to 1·70. Exploratory, confounder-adjusted regression models for this preliminary effect supported the treatment association for reduced craving experiences (CEQ-F Coef. -28·25; 95% CI -45·15 to -11·35); more abstinence (PDA Incidence Rate Ratio [IRR] 1·56; 95% CI 1·31 to 1·88); and greater maximum abstinence (LPA IRR 2·56; 95% CI 1·96 to 3·35), although relative weak unmeasured confounding could overturn these model-adjusted exposure-outcome associations. There were four serious adverse events (among three participants). None were judged related to study procedures or interventions., Interpretation: In this first external pilot randomised controlled trial of MFCT for CUD, we have shown that the intervention and control procedures and acceptable feasible and safe, and report preliminary evidence that MFCT is associated with reduced craving and increased abstinence. These findings support progression to a substantive trial., Funding Source: UK National Institute for Health Research, Biomedical Research Centre., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The κ-opioid receptor (KOP-r) system and its endogenous ligands, the dynorphins, are involved in the neurobiological regulation of addictive states, and of mood. There are limited data on the impact of selective KOP-r antagonism in humans on basic biobehavioral functions, or on addictive diseases and mood disorders. Previously studied selective KOP-r antagonists have unusual pharmacodynamic and pharmacokinetic properties (slow development of KOP-r selectivity, extremely long duration of action) that limit translation to human studies. A recently developed selective KOP-r-antagonist, Opra Kappa (LY2456302; CERC-501), has medication-like duration of action, oral bioavailability, and target engagement. The current study is the first investigation of the effects of a KOP-r-antagonist in cocaine-dependent persons in comparison with normal volunteers. In a stress-minimized inpatient setting, we determined the neuroendocrine and neurobehavioral effects of repeated administration of an active dose of Opra Kappa (10 mg p.o. daily, four consecutive days in comparison with an initial baseline day). Healthy volunteers (n=40), persons diagnosed with cocaine dependence in early abstinence (<2 months, EACD) (n=23), and drug-free former cocaine-dependent persons (7-month to 25-year abstinence, DFFCD) (n=7) were studied, with measurements including circulating neuroendocrine hormones, affect, and, in cocaine-dependent persons, cocaine craving. Modest adverse events related to Opra Kappa included pruritus, observed in a subset of individuals. No significant change was observed in serum prolactin levels following Opra Kappa administration, but modest increases in circulating adrenocorticotropic hormone and cortisol were observed. No significant changes were noted in measures of depression or cocaine craving in this stress-minimized setting. Overall, these studies demonstrate that effects of 10 mg Opra Kappa are largely consistent with those predicted for a selective KOP-r antagonist. This medication regimen was tolerable, and is therefore feasible for further studies in cocaine-dependent persons.

Background: Most recent research on adolescent drug use has focused on alcohol, tobacco, and marijuana. Less is known about the recent epidemiology of adolescent cocaine use, which has serious health consequences., Purpose: To describe recent trends in cocaine use by U.S. high school students, and identify differences in lifetime and repeated use across sex and racial/ethnic groups., Methods: We used data from the national Youth Risk Behavior Surveys (YRBS) from 1999 to 2015. We estimated the prevalence of lifetime cocaine use (LCU) and repeated lifetime cocaine use (RLCU) across years by race/ethnicity and sex and tested for linear and quadratic trends., Results: The prevalence of LCU decreased from 1999 to 2015 (9.54%-5.19%). RLCU also decreased (5.13%-2.84%). Despite the overall decline, LCU and RLCU both rose between 2009-2015 (LCU:2.78%-5.19%, RLCU:1.58%-2.84%). Boys had higher rates of LCU and RLCU than girls (LCU:6.42% vs 4.65%; RLCU:3.69% vs 2.18%). American Indian/Alaskan Native, Native Hawaiian/Pacific Islander, and Hispanic adolescents had the highest overall prevalence of LCU. Black adolescents' LCU patterns differed from other racial/ethnic groups. The prevalence of LCU among Black boys increased over time, while the prevalence for Black girls remained consistently low., Conclusions: Adolescent cocaine use is less common today than in the 1990s. However, rates of adolescent cocaine use have risen across all racial/ethnic groups in the past few years. Public health efforts should address at risk groups with particularly high or rising rates of cocaine use., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A 50-year-old man presented with acute onset dyspnea following cocaine use. He had severe aortic stenosis (AS), mild mitral regurgitation (MR) due to mitral valve prolapse, and no coronary artery disease on recent coronary angiography. He was in acute heart failure with signs of impending cardiogenic shock. Urgent bedside echocardiography revealed hyperdynamic left ventricular systolic function with acute severe MR from a ruptured chordae tendineae. The acute cocaine-induced spike of his already elevated left ventricular systolic pressure from severe AS likely precipitated chordal rupture of his vulnerable mitral valve. This patient underwent emergent mitral and aortic valve replacements. Although cocaine use has been associated with a myriad of cardiovascular complications, acute MR due to chordal rupture has not, to our knowledge, been previously reported in this setting. Prompt diagnosis with echocardiography and surgical intervention are of paramount importance in the management of acute MR., Competing Interests: Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

Substance use disorders (SUD) and personality disorders co-occur frequently. This relationship might be understood by studying schema modes (a key concept in Schema therapy), which explain the dysfunctions characterizing personality disorder patients. In the present study, we compared the schema modes and personality disorder symptoms between alcohol-dependent patients, cocaine-dependent patients and healthy controls. We found indications that specific schema modes are specific for SUD patients. However, no differences between specific subtypes of SUD patients (alcohol- vs. cocaine-dependent patients) could be found regarding schema modes. Further, it is suggested that borderline personality disorder symptoms are highly relevant for SUD patients. A first step is made in understanding the relationship between schema modes and SUD, which may contribute to the understanding of the problematic behaviour seen in patients with personality disorders and SUD (and may possibly contribute to the improvement of the treatment of this group of patients)., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: Adverse reactions to local anesthetics (LAs), especially esters, are not uncommon, but true allergy is rarely diagnosed. To our knowledge, currently there is no reliable method of determining IgE-mediated hypersensitivity to LAs and cocaine., Objective: To assess the clinical value of allergy tests (prick, IgE, challenges, and arrays) in people suffering hypersensitivity reactions (asthma and anaphylaxis) during local anesthesia with cocaine derivatives and drug abusers with allergic symptoms after cocaine inhalation., Methods: We selected cocaine-dependent patients and allergic patients who suffered severe reactions during local anesthesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity, and predictive value) of allergy tests using cocaine and coca leaf extracts in determining cocaine allergy was assessed, taking a positive challenge as the criterion standard., Results: After prick tests, specific IgE, and challenge with cocaine extract, 41 of 211 patients (19.4%) were diagnosed as sensitized to cocaine. Prick tests and IgE to coca leaves (coca tea) had a good sensitivity (95.1% and 92.7%, respectively) and specificity (92.3 and 98.8%, respectively) for the diagnosis of cocaine allergy and LA-derived allergy., Conclusions: Cocaine may be an important allergen. Drug abusers and patients sensitized to local anesthesia and tobacco are at risk. Both prick tests and specific IgE against coca leaf extract detected sensitization to cocaine. The highest levels were related to severe clinical profiles., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Attentional bias towards substance-related stimuli has shown to be involved in the development and maintenance of cocaine dependence. The relationship between alcohol use and cocaine dependence shown in literature justify the need of study these two substances jointly., Methods: This paper analyzes patterns of attentional bias in 71 patients with cocaine dependence and compares these patterns according to whether occasional or problematic concurrent alcohol use is taken into account. It also analyzes whether attentional bias towards alcohol and cocaine-related stimuli predicts treatment retention. Attentional bias was evaluated with a visual probe task between 15 and 20days after admission to treatment. Treatment status was recorded at a three-month follow-up. Severity of dependence and cocaine and alcohol craving were also measured., Results: Results show that patients with cocaine dependence and problematic alcohol use show a pattern of approach towards alcohol stimuli (M=8.32, SD=27.01). In contrast, patients with cocaine dependence with occasional consumption of alcohol exhibit a pattern of avoidance of such stimuli (M=-7.23, SD=19.20) (t=2.79, p=0.007). Logistic regression indicates that alcohol attentional bias is the only variable with predictive capacity (OR=1.05, 95% CI=[1.01, 1.09]). It should also be noted that there is a pattern of avoidance of alcohol stimuli in patients who drop out of treatment., Conclusion: The results of this study suggest the need to delve into whether therapeutic strategies involving deeper emotional processing or avoidance strategies are more suitable for preventing relapse., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to compare sociodemographic characteristics, patterns of drug use, and risky sexual behaviour among female and male users of crack cocaine., Methods: Between 2012 and 2013, we conducted a cross-sectional study of 919 crack cocaine users (783 men and 136 women) in Central Brazil using face-to-face interviews. Blood samples were collected to test for syphilis. The Chi-Square Automatic Interaction Detector (CHAID) was used to explore the differences between genders. We implemented two models: the first model included previous incarceration and variables related to patterns of drug use, and the second model included variables related to sexual risky behaviours and syphilis exposure., Results: Women consumed more crack cocaine than men on a regular basis; however, poly-drug use was more common among men. More women than men reported exchanging sex for money and/or drugs and inconsistent condom use during sexual intercourse; women also reported more sexual partners. In addition, the frequency of sexual violence was higher for women than men. A higher proportion of women than men were positive for syphilis (27.2% vs. 9.2%; p < 0.001). The CHAID decision tree analysis identified seven variables that differentiated the genders: previous incarceration, marijuana use, daily crack cocaine consumption, age at first illicit drug use, sexual violence, exchange of sex for money and/or drugs, and syphilis exposure., Conclusion: Our findings demonstrate a difference in patterns of crack cocaine consumption and sexual risky behaviours between genders, thus indicating a need for gender-specific interventions in this population.

Cocaine is a widely used illicit substance and has previously been described as a risk factor for aortic dissection. We present a case of a young recreational cocaine user with uncontrolled hypertension who presented to hospital with acute chest pain and was diagnosed with an acute aortic dissection. The patient's last use of powdered cocaine was 3 days prior. A workup for secondary hypertension was negative and no other risk factors for aortic dissection were determined. In hospital, the patient was medically managed with multiple antihypertensive agents, was provided with education regarding the risk of ongoing stimulant use and resources to support his goal of abstinence. This case highlights the importance of considering a diagnosis of aortic dissection in a young patient presenting with acute chest pain, underscores the need for a thorough substance use history and provides a novel example of the potential danger of even recreational cocaine use., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The use of semi-quantitative assays such as the enzyme-linked immunosorbent assay (ELISA) requires stringent quality control of the data. However, such quality control is often lacking in academic settings due to unavailability of software and knowledge. Therefore, our aim was to develop methods to easily implement Levey-Jennings quality control methods. For this purpose, we created a program written in Python (a programming language with an open-source license) and tested it using a training set of ELISA standard curves quantifying the Fab fragment of an anti-cocaine monoclonal antibody in mouse blood. A colorimetric ELISA was developed using a goat anti-human anti-Fab capture method. Mouse blood samples spiked with the Fab fragment were tested against a standard curve of known concentrations of Fab fragment in buffer over a period of 133days stored at 4°C to assess stability of the Fab fragment and to generate a test dataset to assess the program. All standard curves were analyzed using our program to batch process the data and to generate Levey-Jennings control charts and statistics regarding the datasets. The program was able to identify values outside of two standard deviations, and this identification of outliers was consistent with the results of a two-way ANOVA. This program is freely available, which will help laboratories implement quality control methods, thus improving reproducibility within and between labs. We report here successful testing of the program with our training set and development of a method for quantification of the Fab fragment in mouse blood., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Sexually transmitted disease (STD) clinics provide critical public health services for screening and treatment of sexually transmitted infections throughout the United States. These settings serve high-risk populations, often on a walk-in basis, and may be promising venues for integrating substance use disorder (SUD) services., Methods: We report findings from 2 pilot studies conducted at Baltimore City Health Department's STD clinics. The screening study characterized rates of SUDs among STD clinic patients. Patients waiting for services completed a diagnostic interview mapping to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition SUD criteria (n = 100). The Treatment Linkage Feasibility study examined the feasibility of linking STD clinic patients with opioid and/or cocaine use disorders to SUD treatment in the community (n = 21), using SUD-focused Patient Navigation services for 1 month after the STD clinic visit. Assessments were conducted at baseline and 1-month follow-up., Results: In the screening study, the majority of STD clinic patients met diagnostic criteria for alcohol and/or drug SUD (57%). Substance-specific SUD rates among patients were 35% for alcohol, 31% for cannabis, 11% for opioids, and 8% for stimulants (cocaine/amphetamines). In the Treatment Linkage Feasibility study, 57% (12/21) of participants attended at least 1 SUD service, and 38% (8/21) were actively enrolled in SUD treatment by 1-month follow-up. The sample reported significant reductions in past 30-day cocaine use from baseline to follow-up (P = 0.01)., Conclusions: SUD rates are high among STD clinic patients. STD clinics are viable settings for initiating SUD treatment linkage services. Larger-scale research on integrating SUD services in these settings is needed.

A lab-on-valve miniaturized system integrating on-line disposable micro-solid phase extraction has been interfaced with ion mobility spectrometry for the accurate and sensitive determination of cocaine and ecgonine methyl ester in oral fluids. The method is based on the automatic loading of 500μL of oral fluid along with the retention of target analytes and matrix clean-up by mixed-mode cationic/reversed-phase solid phase beads, followed by elution with 100μL of 2-propanol containing (3% v/v) ammonia, which are online injected into the IMS. The sorptive particles are automatically discarded after every individual assay inasmuch as the sorptive capacity of the sorbent material is proven to be dramatically deteriorated with reuse. The method provided a limit of detection of 0.3 and 0.14μgL -1 for cocaine and ecgonine methyl ester, respectively, with relative standard deviation values from 8 till 14% with a total analysis time per sample of 7.5min. Method trueness was evaluated by analyzing oral fluid samples spiked with cocaine at different concentration levels (1, 5 and 25μgL -1 ) affording relative recoveries within the range of 85±24%. Fifteen saliva samples were collected from volunteers and analysed following the proposed automatic procedure, showing a 40% cocaine occurrence with concentrations ranging from 1.3 to 97μgL -1 . Field saliva samples were also analysed by reference methods based on lateral flow immunoassay and gas chromatography-mass spectrometry. The application of this procedure to the control of oral fluids of cocaine consumers represents a step forward towards the development of a point-of-care cocaine abuse sensing system., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis., Methods: Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis., Results: Robust regression analyses showed that (1) duration of protease inhibitor (PI) use was independently associated with myocardial and hepatic triglyceride contents, (2) duration of PI use was independently associated with myocardial triglyceride in cocaine users (p=0.025), but not in cocaine never-users (p=0.84), and (3) duration of PI use was independently associated with hepatic triglyceride in cocaine users, but not in cocaine never-users (p=0.52)., Conclusions: Cocaine use may trigger/exacerbate the toxicity of PI in ART-associated myocardial and hepatic steatosis, suggesting that cocaine abstinence/reduced use may retard these ART-associated comorbidities. Clinical trials should be conducted to examine whether reduced cocaine use improves HIV/AIDS-associated myocardial and hepatic steatosis., (Copyright © 2017. Published by Elsevier B.V.)

Introduction: A single LC-MS equipment was used to validate three methods for simultaneously analyzing cocaine (COC), benzoylecgonine (BZE), cocaethylene (CE), anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC) in oral fluid (OF), urine and plasma., Methods: The methods were carried out using a Kinetex HILIC column for polar compounds at 30°C. Mobile phase with isocratic condition of acetonitrile: 13mM ammonium acetate pH 6.0: methanol (55:35:10 v/v/v) at 0.8mL/min flow rate was used., Results: After buffer dilution (OF) and protein precipitation (urine and plasma), calibration curve ranges were 4.25-544ng/mL for oral fluid and 5-320ng/mL for urine and plasma with correlation coefficients (r) between 0.9947 and 0.9992. The lowest concentration of the calibration curves were the lower limit of quantification. No major matrix effect could be noted, demonstrating the efficiency of the cleaning procedure., Discussion: The methods were fully validated and proved to be suitable for analysis of 124 cocaine and/or crack cocaine users. Among the subjects, 56.5% reported daily use of cocaine in the previous three months. Results show a high prevalence of the analytes, with BZE as the most prevalent (94 cases), followed by COC (93 cases), AEC (70 cases), CE (33 cases) and AEME (13 cases). In addition, the concentration of BZE in urine was higher compared to OF and plasma found in the real samples, showing the facility of accumulation in chronic users in matrices with a large detection window., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: The psychostimulant drugs cocaine and methamphetamine are potent indirect dopamine receptor agonists which act through similar but not identical mechanisms. Studies in humans have observed that a large proportion of those who chronically use these drugs experience psychotic symptoms. However, direct comparisons of psychotic symptom severity between cocaine and methamphetamine users are lacking., Objectives: The goal of the present study was to directly compare severity of psychotic symptoms between cocaine- and methamphetamine-dependent individuals. Additionally, we sought to determine how concurrent cocaine + methamphetamine dependence would influence psychotic symptoms., Methods: We recruited 153 polysubstance-using subjects meeting DSM-IV-TR criteria for cocaine dependence, 38 with methamphetamine dependence, and 32 with cocaine + methamphetamine dependence. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) and analyzed using a five-factor model. All participants were also assessed for physical and mental illnesses as well as recent substance use. Most subjects completed a comprehensive neurocognitive battery., Results: While all three groups exhibited high total PANSS scores, the positive symptom subscale was significantly higher in the methamphetamine-dependent (17.03 ± 6.3) than the cocaine-dependent group (13.51 ± 4.12) and non-significantly higher (p = 0.08) than the cocaine + methamphetamine group (14.44 ± 5.50). Groups also differed on demographic variables, viral infection, and other indices of substance use, which were unlikely to account for the difference in positive symptoms. There were only modest differences between groups in neurocognitive function., Conclusions: Methamphetamine dependence was associated with more severe positive symptoms of psychosis than cocaine dependence. Concurrent cocaine + methamphetamine dependence did not increase psychosis severity.

Hair testing is a recognized approach when it comes to accessing historical drug use. According to the World Drug Report of United Nations Office on Drugs and Crime (UNODC) 2015, Brazil is the largest cocaine (COC) market in South America. New analytical methodologies to detect crack/cocaine analytes in hair samples are highly desirable. Here, a method consisting of a liquid-phase microextraction (LPME) as a clean-up step, followed by gas chromatography-mass spectrometry (GC-MS) analysis has been proposed. The new validated method consisted of a washing step; an overnight incubation with methanol and a quick derivatization with butylchloroformate. Once derivatized, the samples were then submitted to the LPME procedure. Limits of detection (LoD) and quantitation (LoQ) obtained were of 0.1 and 0.5ng/mg for COC 0.4 and 0.5ng/mg for anhydroecgonine methyl ester (AEME); 0.03 and 0.05 for cocaethylene (CE), respectively and 0.05ng/mg for both LoD and LoQ for benzoylecgonine (BZE). All calibration curves were linear over the scope applied, from LoQ up to 20ng/mg, with a r 2 >0.99. Precision and accuracy assays showed acceptable %RSD values, according to international guidelines. Twelve postmortem head hair samples stemming from the Institute of Legal Medicine of Sao Paulo (IML-SP) have been analyzed, from which seven have shown to be positive for COC (0.75->20ng/mg) and BZE (0.1->20ng/mg). Apart from COC's main metabolite, four samples were also positive for CE (0.1-3.9ng/mg) and three samples for AEME (0.5-4.9ng/mg). To conclude, the LPME technique together with GC-MS analysis have shown promising results and were able to meet the demand of the laboratory of analyzing postmortem hair samples to look for all four analytes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Levamisole is an antihelminthic drug with immunomod- ulatory properties. Recent estimates suggest the majority of the cocaine in the United States is adulterated with levamisole. Le- vamisole-induced necrosis syndrome (LINES) is characterized by vasculitis, neutropenia, and purpura that progresses to skin necro- sis. Diagnosis relies on physical examination ndings and history of previous cocaine use. The purpose of this case series is to describe the pathophysiology, diagnosis, and management of LINES. The au- thors' institutional database was reviewed from 2008 to 2015, and they found 3 patients with LINES. Subsequent management and outcomes data are discussed. Patients had a variety of outcomes ranging from local wound care to necrosis and amputation of pha- langes. Patients with LINES can have a wide variety of outcomes; thus, this syndrome must be aggressively managed. Psychotherapy should also be utilized to help patients with further cocaine use. Levamisole-induced necrosis syndrome incidence is expected to in- crease, and all providers should be aware of this patient population.

Even though hair analysis often seems to be the best choice for retrospective monitoring of cocaine intake, differentiating between incorporated cocaine and external contamination is widely debated. In this study we report results obtained in 90 hair samples from addicts. All samples were analyzed for cocaine, benzoylecgonine, norcocaine, cocaethylene, and tropococaine by gas chromatography-mass spectrometry (GC-MS) techniques coupled with direct immersion solid-phase micro-extraction. Cocaine concentrations were stratified into three classes of usage: light (0.5-3 ng/mg), moderate (3.1-10 ng/mg) and heavy (10.1-40 ng/mg). The Substance Abuse and Mental Health Services Administration cut-off criteria for establishing active cocaine use were applied to the results. For all samples criteria were cocaine levels above 0.5 ng/mg (ranging from 1.63 to 39.29 ng/mg, mean 9.49 ng/mg), benzoylecgonine concentrations ≥ 0.05 ng/mg (ranging from 0.19 to 5.77 ng/mg, mean 1.40), and benzoylecgonine to cocaine % ratio ≥5% (from 6.43 to 26.09%). Norcocaine was present in 58.9% of samples (concentration range: 0.22-3.14 ng/mg) and was strongly predictive only of heavy cocaine use (sensitivity 100% for cocaine concentrations above 9.58 ng/mg). Twenty hair samples from moderate and heavy users tested positive for cocaethylene (concentration range: 0.22-1.98 ng/mg, mean 0.73 ng/mg). This study on hair samples with no chance of false positive cases highlights the very limited applications of testing minor cocaine metabolites for definitive proof of active cocaine consumption. © 2015 The Authors. Drug Testing and Analysis Published by John Wiley & Sons, Ltd., (© 2015 The Authors. Drug Testing and Analysis Published by John Wiley & Sons, Ltd.)

Hygrine (HYG) and cuscohygrine (CUS) are natural alkaloids of coca leaves but are not found in illicit cocaine seizures. Therefore, they were proposed as markers for coca chewing in contrast to cocaine abuse in urine and hair testing. In order to examine at which step of the illegal cocaine production these compounds are lost, coca leaves were processed according to an authentic procedure by extraction with lime and kerosene, re-extraction with sulphuric acid, and precipitation of coca paste with ammonia. Non-extracted and extracted coca leaves, acidic extract and coca paste were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for cocaine, ecgonine methyl ester (EME), cinnamoylcocaine (CIN), HYG, and CUS. It follows from the results that under these conditions, HYG and CUS are extracted only to a minor extent by kerosene and are not precipitated from the acidic re-extract in the coca paste. Due to this behaviour in illegal cocaine production, they fulfil the conditions as markers for coca chewing in an optimal way. However, for unambiguous discrimination between coca chewing and cocaine abuse in human samples, additional markers of manufactured cocaine are required. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

A cocaine-based molecular imprinted polymer (MIP) has been produced by bulk polymerization and employed as selective solid-phase extraction support for the determination of cocaine in saliva samples by ion mobility spectrometry (IMS). The most appropriate conditions for washing and elution of cocaine from MIPs were studied and MIPs were characterized in terms of analyte binding capacity, reusability in water and saliva analysis, imprinting factor and selectivity were established and compared with non-imprinted polymers. The proposed MIP-IMS method provided a LOD of 18μgL -1 and quantitative recoveries for blank saliva samples spiked from 75 to 500μgL -1 cocaine. Oral fluid samples were collected from cocaine consumers and analysed by the proposed MIP-IMS methodology. Results, ranging from below the LOD to 51±2mgL -1 , were statistically comparable to those obtained by a confirmatory gas chromatography-mass spectrometry method. Moreover, results were compared to a qualitative lateral flow immunoassay procedure providing similar classification of the samples. Thus, MIP-IMS can be considered an useful alternative that provided fast, selective and sensitive results with a cost affordable instrumentation that does not require skilled operators., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The Scott test, widely used as the field test for cocaine, is performed in three steps. If a sample contains cocaine, blue precipitates appear in step 1, the precipitates are dissolved and the solution turns pink in step 2, and the lower layer turns blue in step 3. However, some pyrrolidine-type cathinones produce cocaine-like results when tested, necessitating modification of the test procedure. Filtration of the second-step mixture weakened the blue color in step 3; however, the blue color did not completely disappear. Adding the Chen-Kao reagent to the test procedure enhanced the differentiation: when the reagent was added to cocaine, the solution was initially turbid, but then became clear over time; its addition to cathinones resulted in turquoise or light sky-blue precipitation. These results indicated that the Chen-Kao test was useful for exclusion of cathinones. A combination of the modified Scott test and the Chen-Kao test was successfully applied to the forensic samples containing cocaine or pyrrolidine-type cathinones. In conclusion, a combination of these tests will be the useful field-test procedure for cocaine., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study is to compare the features of two groups of cocaine dependent patients in treatment, one of them with co-morbid diagnosis of antisocial personality disorder and the other not. Cross-sectional design, with 143 cocaine-dependent patients attending a drug unit, distributed in two groups: patients with and without Antisocial Personality Disorder. As results, we found that the 15.38% of the sample were diagnosed with an Antisocial Personality Disorder. In relation to socio-demographic variables, Antisocial Personality Disorder patients have less probability of being working or studying (9.1% vs. 47.9%). After multivariate analysis it was found that significantly Antisocial Personality Disorder patients have more opiates dependence (OR: 0.219; 95% IC 0.072-0.660), sedative dependence (OR: 0.203; 95% IC 0.062-0.644) and in more cases show Borderline Personality Disorder (OR: 0.239; 95% IC 0.077-0.746). This study highlights significant differences between cocaine addicts with or without an Antisocial Personality Disorder. All these differences are good indicators of the complexity of the patients with this personality disorder. Better knowledge of their profile will help us to improve the design of specific treatment programs., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

: Cocaine is the most commonly used recreational drug among young adults with levels reaching epidemics proportions. This accelerated rate of use is due mainly to easy access and administration, reduced cost, and, importantly, underestimation of the drug risks. Cocaine, instead, is responsible of endothelial dysfunction and accelerated atherosclerosis with consequent organ damage. Cocaine abuse is not only associated with central necrotizing vasculitis, but it is also appeared to play a role in the development of peripheral vasoconstriction with symptoms similar to Buerger's disease. The current study reports a middle-aged man addicted to cocaine for 20 years. The patient presents several cardiovascular disease risk factors and manifestations, including diabetes mellitus and hypertension. Additionally, arteriography showed complete left posterior tibial artery obstruction with distal collateral vessels and severe leftfoot ischemia. For clinical worsening 1 month later, the patient underwent another arteriography. Although angioplasty of posterior tibial artery showed recovery of blood flow, immediately after treatment (selective percutaneous transluminal angioplasty of posterior tibial artery, dilation with balloon without stenting), a return to pretreatment blood flow 2 min later was observed. This transient change was mediated by severe vasospasm resulting in a complete re-obstruction of the vessel. The poor vascular manifestations are most probably due to cocaine-necrotizing vasculitis subsequent to endothelial dysfunction and accelerated atherosclerosis usually associated with cardiovascular risk factors. Therefore, treatments of young cocaine addicts presenting many cardiovascular risk factors and manifestations should always be carefully investigated and cautiously approached, especially in those with poor outcomes.

Objective: To describe the clinical characteristics of adolescents with crack cocaine dependence and possible predictors of transition from drug experimentation to crack cocaine dependence., Methods: This cross-sectional study enrolled a consecutive sample of 90 adolescents admitted to a psychiatric inpatient unit in the city of Porto Alegre in southern Brazil for crack cocaine detoxification between May 2011 and November 2012. Comorbid psychological conditions were assessed using the Kiddie-SADS-Present and Lifetime Version, and severity of drug use was assessed using the Teen Addiction Severity Index (T-ASI). Comorbidities were compared with those in a community sample of non-drug using controls (n = 81)., Results: Patients' mean age was 15.6 years (85.6% boys, 14.4% girls). Seventy-nine (93.2%) met criteria for cocaine dependence (DSM-IV-TR), while 78 (91.8%) had symptoms consistent with cocaine abuse. All patients had experimented with at least 1 other addictive substance before crack cocaine: 61.4%, tobacco (mean age at first use = 11.61 years); 44.3%, alcohol (age at first use = 12.43 years); and 54.5%, cannabis (age at first use = 12.15 years). Patients had used crack cocaine 23.2 days in the last month, and the mean age at first use of crack cocaine was 13.38 years. The most common psychiatric comorbidity was conduct disorder (81.8%), followed by oppositional defiant disorder (52.3%) and attention-deficit/hyperactivity disorder (44.3%), all of which were more prevalent in the patient population than in controls (P < .001). The T-ASI questionnaire showed severe consequences of drug use in most areas of life assessed. The mean time between onset of drug experimentation and crack cocaine dependence was 2.53 (SD = 1.96) years. When Cox regression models were applied, we found that predictors of earlier progression to using crack cocaine were age at first use of any drug (hazard ratio [HR] = 0.79 [95% CI, 0.71-0.88]; P < .001) and age at admission (HR = 0.7 [95% CI, 0.57-0.87]; P = .001)., Conclusions: Patients were found to have a multitude of comorbid conditions, which supports the idea of treatment by a multidisciplinary health care team. For each year of delay in the age at first drug use, the chance of crack cocaine initiation is reduced by 18%. Prevention programs aimed at delaying experimentation with addictive substances, especially "gateway" drugs, could delay the progression to crack cocaine dependence., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Objective: We assessed cross-sectional and longitudinal associations of 3 nontraditional cardiovascular disease risk factors-HIV, cocaine use, and chronic hepatitis C virus infection-with 3 validated markers of subclinical cardiovascular disease: carotid artery plaque, albuminuria, and aortic pulse wave velocity in a well-characterized cohort., Approach and Results: We measured carotid plaque at baseline and after 24 months, urine albumin/creatinine ratio every 6 months, and pulse wave velocity annually for up to 36 months in a predominantly black cohort of 292 participants (100 HIV negative and 192 HIV positive). Thirty-nine percent had chronic hepatitis C virus infection and 20%, 28%, and 52% were never, past, and current cocaine users, respectively. Sixteen percent, 47%, and 64% of those with none, 1 or 2, or all 3 nontraditional risk factors had ≥2 abnormal cardiovascular disease risk markers (P=0.001). In fully adjusted models that included all 3 nontraditional risk factors, HIV infection was independently associated with carotid plaque progression (increase in the number of anatomic segments with plaque), albuminuria (albumin-creatinine ratio >30 mg/g), albuminuria progression (doubling of albumin-creatinine ratio from baseline to a value >30 mg/g), and pulse wave velocity. Cocaine use was associated with an ≈3-fold higher odds of carotid plaque at baseline, and hepatitis C virus infection was significantly associated with a higher risk of carotid plaque progression., Conclusions: These results suggest that HIV infection, cocaine use, and hepatitis C virus infection are important nontraditional risk factors for cardiovascular disease and highlight the need to understand the distinct and overlapping mechanisms of the associations., (© 2016 American Heart Association, Inc.)

Due to the complexity of crack -cocaine addiction treatment, the identification of biological markers that could help determining the impact or outcome of drug use has become a major subject of study. Therefore, we aim to evaluate the association of Brain-Derived Neurotrophic Factor (BDNF) and Thiobarbituric Acid Reactive Substances (TBARS) levels in crack -cocaine users with treatment adherence and with drug addiction severity. A sample of 47 male inpatient crack- cocaine users were recruited in a treatment unit, and blood samples were collected at admission and discharge in order to measure BDNF and TBARS serum levels. Subjects were split into 2 groups: treatment non-completers (n=23) and treatment completers (n=24). The completer group had a tendency of higher levels of BDNF than non-completers at admission (16.85±3.24 vs. 14.65±5.45, p=0.10), and significant higher levels at discharge (18.10±4.88 vs. 13.91±4.77, p=0.001). A negative correlation between BDNF levels at admission and years of crack use was observed. We did not find significant changes in TBARS levels during inpatient treatment, although the completer group tended to decrease these levels while non-completers tend to increase it. These findings suggest an association between higher levels of BDNF and better clinical outcomes in crack- cocaine users after detoxification. We believe that the variation in BDNF and TBARS found here add evidence to literature data that propose that such biomarkers could be used to better understand the physiopathology of crack- cocaine addiction., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Altered sensitivity to positive and negative outcomes may be linked to the maladaptive choices characteristic of substance use disorders. Few studies have determined the distinct roles that positive and negative outcomes play in stimulus-response learning in cocaine users. The purpose of the present study was to investigate sensitivity to learning from positive and negative outcomes on a probabilistic learning task in cocaine users employing human laboratory and crowdsourcing techniques., Methods: Individuals who reported cocaine use were recruited for a laboratory study (Experiment 1) or an online study on Amazon.com's Mechanical Turk (mTurk) (Experiment 2). All participants completed a feedback-based probabilistic learning task in which images were classified into categories (A versus B). Positive and negative outcomes were provided in a probabilistic manner on separate trials. Proportion of optimal responses and response times were recorded., Results: Active cocaine users were less sensitive to learning from positive relative to negative outcomes. These effects were consistent across image type and session in the laboratory sample. Similarly, reduced sensitivity to learning from positive outcomes was observed in cocaine users on mTurk. Control participants did not show suboptimal performance following positive or negative outcomes., Conclusions: This study extends the limited research on feedback-based learning in drug users by demonstrating reduced sensitivity to positive outcomes in cocaine users recruited in the human laboratory and online. Future studies on the clinical significance and mechanisms underlying this bias are needed to understand its relevance as a target for intervention development., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Abusive use of drugs is a public health problem worldwide. The use of these substances by pregnant or lactating women can have many serious side effects in newborns. Among the commonest causes of addiction in drug users is cocaine in powdered form, inhaled, intravenously injected or smoked form (crack). Fast screening and a confirmation test using high specificity and sensitivity instruments such as LC-MS or GC/MS, can provide data to qualify and quantify chemical substances present in biological samples such as breast milk or meconium. Cocaine and/or crack can be detected through biomarkers or the unchanged molecule, enabling the form of cocaine use to be distinguished through the analytes. These methods must be carefully developed and validated according to internationally recognized guidelines. Thus, the study of biological matrices in which it can be detected through the development of simple and quick analytical methods can help prevent intoxication and diagnose the symptoms of dependency such as seizures, especially in babies, providing appropriate medical care., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: TV-1380 (AlbuChE) is a novel recombinant fusion protein of mutated butyrylcholinesterase (BChE) that has increased catalytic efficiency for cocaine metabolism compared to wild-type BChE., Methods: Intra-muscular injections of TV-1380 (150mg or 300mg) or placebo were administered once weekly to participants (n=66-69 per group) in a randomized, double-blind study to evaluate the ability of TV-1380 to facilitate abstinence in treatment-seeking, cocaine-dependent individuals. The primary endpoint was the proportion of participants achieving abstinence from cocaine during the last three weeks of the 12 week treatment phase, based on daily self-report of "no use" confirmed by urine testing., Results: Although there were no significant differences between the TV-1380 treatment groups and placebo for the primary endpoint, 6% of participants in the 150mg and 300mg TV-1380 groups and no participants in the placebo group achieved abstinence. For the only declared secondary endpoint, there was a dose-dependent increase in the group mean percentage of urine samples testing negative for cocaine metabolites during weeks 5-12 (8.1% and 14.6% for the 150mg and 300mg TV-1380 groups, respectively, compared to 4.7% for the placebo group; p=0.0056 for 300mg vs. placebo). No meaningful differences in adverse events were seen between treatment groups., Conclusions: While the apparent reduction in cocaine use may be of insufficient magnitude to justify further trials of TV-1380 in cocaine dependence, the results argue for development of improved enzymes with greater catalytic activity., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: In rodents, cholinesterase inhibitors can cause sustained decreases in the reinforcing effects of cocaine. Nonetheless, cocaine is metabolized by butyrylcholinesterase (BuChE), raising concerns that cholinesterase inhibition could increase its peripheral concentrations, perhaps augmenting toxicity. Although donepezil is approved for use in patients and selective for inhibiting acetylcholinesterase over BuChE, no studies have reported cocaine bioavailability in human subjects receiving donepezil., Methods: Twelve cocaine-dependent veterans received three days of treatment with either oral placebo or 5 mg daily of donepezil, followed by cross-over to the opposite treatment. During both oral treatments, double-blind intravenous cocaine was administered at .0, .18, and .36 mg/kg in a laboratory setting, followed by determinations of heart rate, blood pressure, and plasma concentrations of cocaine and major metabolites., Results: Intravenous cocaine produced dose-related increases in systolic blood pressure that were most pronounced over the initial 30 minutes after treatment. Oral donepezil attenuated drug-induced elevations of systolic blood pressure following low-dose cocaine (.18 mg/kg). No significant difference in blood pressure following treatment with placebo or donepezil after high-dose cocaine (.36 mg/kg). Peak values of blood pressure and heart rate were unaffected by donepezil. Plasma concentrations of cocaine and metabolites did not differ in donepezil- and placebo-treated participants., Conclusions and Scientific Significance: We conclude that donepezil can attenuate drug-induced increases in systolic blood pressure following low-dose cocaine, but does not otherwise modify the cardiovascular effects of intravenous cocaine. Clinically significant changes in cocaine bioavailability and cardiovascular effects do not occur following this dose of donepezil. (Am J Addict 2016;25:392-399)., (© 2016 American Academy of Addiction Psychiatry.)

Adulteration of cocaine with levamisole is common and can induce serious medical complications. Levamisole is an antihelminthic agent originally approved as an immunomodulator in the treatment of autoimmune disorders and as a chemotherapy adjunct. It was withdrawn from the US market in 2000 but is available in veterinary medicine. Cocaine-using patients may present with nonspecific constitutional symptoms, cutaneous eruptions, leukopenia, vasculitis, and organ damage. Skin manifestations may include severe necrosis, especially of the ear lobes. Here, a case of levamisole toxicity is presented and treatment options are discussed., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

We report a case of bilateral infero-medial orbital wall destruction, associated with loss of sinonasal architecture. The patient presented with intermittent horizontal diplopia following an acute on chronic infective sinusitis. Eight months previously the patient had developed a midline hard palate fistula for which a palatine prosthesis had been fitted. The broad differential diagnosis is discussed, though in this patient chronic cocaine abuse was identified as the underlying aetiology. Eye movement restriction worsened progressively with bilateral inflammation around the medial and inferior rectus muscles. Attempts to resolve the recurring cycle of sinus infection and inflammation by palatal fistula closure failed despite augmented techniques mobilising flaps from both nasal and palatal sides.

Background: The online study presented surveyed occasional users, high-risk users and non-consumers of psychotropic substances for relationships between consumer type and emotion regulation (ER), health-related quality of life (HRQOL) and coping strategies., Methods: A total of 199 people participated in the survey. The sample was split into three groups depending on a substance list and a detailed questionnaire regarding the consumption habits: 28 individuals had no illicit drug experience, 127 were occasional users and 44 frequent (high-risk) users. The sample set was tested using the (1) emotion regulation inventory, (2) the coping inventory for stressful situations and (3) the medical outcomes study (MOS) 36-item short-form health survey., Results: Regarding ER the occasional users showed no significant differences to the two reference groups, except for the scale of re-evaluation where the high-risk consumers scored higher than the occasional users. Regarding HRQOL no significant differences were observed between the three groups; however, significant differences were observed between persons with strong and weak physical and mental HRQOL scores and satisfaction with own emotion regulation. The search for predictors showed a significant predictive value for gender, the number of inhabitants at the place of residence and the ER strategy of re-evaluation in negative emotions for the allocation to a consumer type. Neither substance consumption as an ER strategy nor a relationship between consumer type and coping strategy and/or HRQOL could be observed., Discussion: With respect to ER the only significant difference observed was that of high-risk users employing the strategy of re-evaluation more often than occasional users. A possible explanation is reality embellishment and a down-playing function of this strategy associated with drug consumption. Therefore, the assumed relationship between affective dysfunction and drug addiction could not be observed.

Background: Substance use is common in Brazil. In order to improve availability of substance misuse care services, over 400 Psycho-Social Care Centres for Alcohol and Drugs (CAPS-AD) - providing community-based care - have been established following mental health care reform (2001). Information on CAPS-AD clients and outcomes is limited. The present study examined select characteristics of local CAPS-AD clients., Methods: N=143 adult CAPS-AD clients in Ceilândia (suburb of Brasília, Federal District) participated in a 1-week 'snapshot' assessment of service users (February 2015). Following consent, descriptive data were collected by a brief, anonymous interviewer-administered questionnaire that included socio-demographic, drug use, treatment history and needs/barriers information., Results: Participants were predominantly male; middle-aged; unemployed; married; with middle-school education; primary problem drugs indicated were alcohol and cocaine/crack; half had prior treatment histories and indicated that treatment was externally motivated; 60% reported ways to improve treatment and possible reasons for treatment discontinuation; in multi-variate analyses, the latter was associated with employment and education status (both p<.05)., Conclusion: CAPS-AD services appear to have increased low-barrier substance misuse treatment availability in Brazil, as well as attract individuals new to the treatment system. Various potential barriers to continuing in treatment should be addressed and more research on CAPS-AD clients and outcomes is needed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Research on the progression from substance use to dependence typically relies on lifetime retrospective reports of dependence among ever users. We sought to evaluate probability and correlates of dependence among recent (past-year) weekly users of alcohol, nicotine, cannabis, and cocaine through cross-sectional and prospective analyses., Methods: Data on substance use (assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV) and DSM-IV psychiatric disorders were assessed in 2 waves (Wave 1, N = 43,093; Wave 2, N = 34,653) through the National Epidemiologic Survey on Alcohol and Related Conditions., Results: Conditional risk of dependence varied by frequency of substance use, although it was relatively stable for nicotine use. Among weekly past-year substance users at Wave 1, rates of dependence when rates of past-year dependence at Wave 1 were combined with new cases of dependence reported at Wave 2 were 15.6% for alcohol, 25.0% for cannabis, and 67.3% for nicotine. For past-year weekly users of cocaine at Wave 1, 49.9% met criteria for past-year dependence. Multiple demographic characteristics and past-year psychiatric disorders were correlated with past-year dependence, even among daily users. Men were generally more likely than women to be dependent on alcohol, cannabis, and cocaine, although women were more likely to be dependent on nicotine. Prospective analyses indicated that depressive disorders at Wave 1 predicted subsequent development of alcohol dependence (odds ratio [OR] = 1.40; 95% CI, 1.19-1.65; P < .05). Further, 33.5% of weekly tobacco smokers who were nondependent at Wave 1 developed dependence later on., Conclusions: The present findings highlight the importance of frequency of use when determining the addictiveness of substances and suggest that certain demographic variables and psychiatric disorders are associated with substance dependence even among regular substance users., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Background: The key objectives of this study were to examine whether HIV infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies (ARTs) to subclinical coronary artery disease (CAD) in HIV-infected persons., Methods and Results: Between June 2004 and February 2015, 1429 African American (AA) adults with/without HIV infection in Baltimore, Maryland, were enrolled in an observational study of the effects of HIV infection, exposure to ART, and cocaine use on subclinical CAD. The prevalence of subclinical coronary atherosclerosis was 30.0% in HIV-uninfected and 33.7% in HIV-infected (P=0.17). Stratified analyses revealed that compared to HIV-uninfected, HIV-infected ART naïve were at significantly lower risk for subclinical coronary atherosclerosis, whereas HIV-infected long-term ART users (≥36 months) were at significantly higher risk. Thus, an overall nonsignificant association between subclinical coronary atherosclerosis and HIV was found. Furthermore, compared to those who were ART naïve, long-term ART users (≥36 months) were at significantly higher risk for subclinical coronary atherosclerosis in chronic cocaine users, but not in those who never used cocaine. Cocaine use was independently associated with subclinical coronary atherosclerosis., Conclusions: Overall, HIV infection, per se, was not associated with subclinical coronary atherosclerosis in this population. Cocaine use was prevalent in both HIV-infected and -uninfected individuals and itself was associated with subclinical disease. In addition, cocaine significantly elevated the risk for ART-associated subclinical coronary atherosclerosis. Treating cocaine addiction must be a high priority for managing HIV disease and preventing HIV/ART-associated subclinical and clinical CAD in individuals with HIV infection., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

We report a case of recurrent spontaneous pneumothorax in a patient with cocaine abuse through inhalation alone. He underwent thoracoscopic apical lung resection with mechanical pleurodesis. Despite the lack of significant radiological features of talc induced pulmonary granulomatosis, pathological findings showed granulomas with foreign materials suggestive of being talc. Electronic microscopy showed that the size of talc particles were <4.0 µm and thus small enough to reach the alveoli.

The identification of behavioral traits that could predict an individual's susceptibility to engage in cocaine addiction is relevant for understanding and preventing this disorder, but investigations of cocaine addicts rarely allow us to determinate whether their behavioral attributes are a cause or a consequence of drug use. To study the behaviors that predict cocaine vulnerability, male C57BL/6J mice were examined in a battery of tests (the elevated plus maze, hole-board, novelty preference in the Y-Maze, episodic-like object recognition and forced swimming) prior to training in a cocaine-conditioned place preference (CPP) paradigm to assess the reinforcing value of the drug. In a second study, the anatomical basis of high and low CPP in the mouse brain was investigated by studying the number of neurons (neuronal nuclei-positive) in two addiction-related limbic regions (the medial prefrontal cortex and the basolateral amygdala) and the number of dopaminergic neurons (tyrosine hydroxylase-positive) in the ventral tegmental area by immunohistochemistry and stereology. Correlational analyses revealed that CPP behavior was successfully predicted by anxiety-like measures in the elevated plus maze (i.e., the more anxious mice showed more preference for the cocaine-paired compartment) but not by the other behaviors analyzed. In addition, increased numbers of neurons were found in the basolateral amygdala of the high CPP mice, a key brain center for anxiety and fear responses. The results support the theory that anxiety is a relevant factor for cocaine vulnerability, and the basolateral amygdala is a potential neurobiological substrate where both anxiety and cocaine vulnerability could overlap., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Researchers compared 12-lead ECGs from 97 treatment-seeking cocaine-dependent patients, with ECG parameters from 8,513 non-cocaine-using control patients from the Atherosclerosis Risk in Communities study. After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use.