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Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic., Competing Interests: Declaration of conflicting interestThe authors declare the there are no conflicts of interest.

Introduction: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD)., Methods: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis., Results: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis., Conclusions: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: This study aimed to assess agreement between self-report and urine toxicology measures assessing use of 2 illicit simulants (methamphetamine and cocaine) during early pregnancy., Methods: This cross-sectional study of 203,053 pregnancies from 169,709 individuals receiving prenatal care at Kaiser Permanente Northern California between January 1, 2011, and December 31, 2019, assessed agreement ( κ , sensitivity, and specificity) between self-reported frequency and urine toxicology measures of methamphetamine and cocaine early in pregnancy., Results: Prenatal use of the illicit stimulants was rare according to toxicology (n = 244 [0.12%]) and self-report measures (n = 294 [0.14%]). Agreement between these measures was low ( κ < 0.20). Of the 498 positive pregnancies, 40 (8.03%) screened positive on both measures, 204 (40.96%) screened positive on toxicology tests only, and 254 (51.00%) screened positive by self-report only. Relative to toxicology tests, sensitivity of any self-reported use was poor with 16.39% (95% confidence interval [CI], 11.75%-21.04%) of pregnancies with a positive toxicology test self-reporting any use in pregnancy. Relative to self-report, sensitivity of toxicology tests was also poor with 13.61% (95% CI, 9.69%-17.52%) of pregnancies who self-reported any use having positive urine toxicology tests. The sensitivity improved slightly at higher frequencies of self-reported use: daily, 17.50% (95% CI, 5.72%-29.29%); weekly, 25.00% (95% CI, 11.58%-38.42%); and monthly or less, 11.06% (95% CI, 6.89%-15.23%). Specificity was high (>99%), reflecting the high negative rate of use., Conclusions: Findings suggest that using self-report and toxicology measures in combination likely provides the most accurate information on methamphetamine and cocaine use in early pregnancy. Findings also highlight the need to provide supportive nonstigmatizing environments in which pregnant individuals feel comfortable disclosing substance use without fear of punishment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Background: Detoxification is frequently recommended as a treatment for moderate to severe Cocaine Use Disorder (CUD). However, the response to detoxification varies among patients, and previous studies have focused mostly on patterns of drug use behavior to test associations with treatment outcomes, overlooking the potential impact of psychosocial factors, other clinical variables, and individual life experiences. In this study we comprehensively examined several variables aiming to find the most relevant predictors to classify patients with severe versus non-severe cocaine withdrawal symptoms at the end of detoxification., Methods: Data from 284 women with CUD who enrolled in a 3-week detoxification program was used in this longitudinal study. Psychosocial, clinical, and drug use behavior characteristics were evaluated, generating a dataset with 256 potential predictors. We tested six different machine learning classification algorithms., Results: The best classification algorithm achieved an average accuracy and ROC-AUC of approximately 70%. The 16 features selected as best predictors were the severity of psychiatric, family, and social problems and the level of exposure to childhood maltreatment. Features associated with drug-use behavior included days consuming drugs and having craving symptoms in the last month before treatment, number of previous drug/alcohol-related treatments, and a composite score of addiction severity. The level of cocaine withdrawal syndrome at the beginning of detoxification was also a key feature for classification. A network analysis revealed the pattern of association between predictors., Conclusion: These variables can be assessed in real-world clinical settings, potentially helping clinicians to identify individuals with severe cocaine withdrawal that is likely to be sustained over the course of detoxification., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest. The study was approved by the institutional review boards of included institutions, and it was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Studies indicate that cocaine abuse in Denmark is rising. The drug can damage the midface's nasal tissues, cartilage, and bone. Diagnosing the cocaine-induced midline destructive lesions condition is difficult as patients may not admit to drug use. Thus, this review finds that physicians should ask about cocaine abuse in younger patients who present with midline destructions of unknown origin. Mild symptoms are reversible with total abstinence, which is why it is important to involve addiction services early. Besides drug abstinence, comprehensive treatment involves assistance from GPs, physiatrists, rhinologists, and plastic surgeons., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: The "vices-paradox" describes the paradoxical association between illicit substance use and decreased mortality risk in trauma patients. Cocaine's vasoconstrictive effects may decrease hemorrhage but also increase the risk of thromboembolic complications. To clarify the effects of cocaine use on trauma patients, we compared the risk of mortality and thromboembolic complications in patients screening positive for cocaine with those screening negative., Methods: We searched the Trauma Quality Improvement Program database to identify patients 18 years and over who had presented with a drug and alcohol screen on admission between 2017 and 2019. After excluding all patients who had tested positive for alcohol and substances other than cocaine, we then compared the clinical outcomes of patients who were positive and negative for cocaine use., Results: Of the 312,553 patients identified, 11,942 (3.82%) had tested positive for cocaine. Cocaine users were significantly more likely to present with stab (8.0% vs 3.1%) or gunshot wounds (8.0% vs 3.0%) but had lower rates of mortality (3.6% vs 4.7%), myocardial infarction (0.1% vs 0.2%,) and cerebrovascular accident (0.3% vs 0.4%,). After controlling for covariates, the risk of death, myocardial infarction, and cerebrovascular accident did not significantly differ between cocaine and non-cocaine users., Conclusion: Trauma patients positive for cocaine have similar risks of death and thromboembolic complications and so have a similar prognosis to patients negative for all drugs or alcohol, indicating that the "vices-paradox" does not apply to cocaine use. However, these patients more commonly present after penetrating trauma, suggesting cocaine use in hazardous environments., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cocaine is a psychotropic tropane alkaloid and stimulant drug. Nasal insufflation of cocaine powder is a common route of administration. In Germany, cocaine is frequently adulterated with levamisole, an anthelminthic drug with immunomodulatory effects. Both substances are linked to various autoimmune conditions. Cocaine-induced midline destructive lesions cause a progressive destruction of osteocartilaginous structures within the upper respiratory tract and can mimic localized granulomatosis with polyangiitis. In addition, systemic vasculitis due to cocaine and levamisole has been reported. Differentiation of these conditions from primary vasculitis can be challenging because antineutrophil cytoplasmic antibodies (ANCA) are commonly detected. Early diagnosis of these conditions is crucial as clinical improvement is closely related to drug cessation., (© 2022. The Author(s).)

Background: Our group has established the feasibility of using on-body electrocardiographic (ECG) sensors to detect cocaine use in the human laboratory. The purpose of the current study was to test whether ECG sensors and features are capable of discriminating cocaine use from other non-cocaine sympathomimetics., Methods: Eleven subjects with cocaine use disorder wore the Zephyr BioHarness™ 3 chest band under six experimental (drug and non-drug) conditions, including 1) laboratory, intravenous cocaine self-administration, 2) after a single oral dose of methylphenidate, 3) during aerobic exercise, 4) during tobacco use (N=7 who smoked tobacco), and 5) during routine activities of daily inpatient living (unit activity). Three ECG-derived feature sets served as primary outcome measures, including 1) the RR interval (i.e., heart rate), 2) a group of ECG interval proxies (i.e., PR, QS, QT and QTc intervals), and 3) the full ECG waveform. Discriminatory power between cocaine and non-cocaine conditions for each of the three outcomes measures was expressed as the area under the receiver operating characteristics (AUROC) curve., Results: All three outcomes successfully discriminated cocaine use from unit activity, exercise, tobacco, and methylphenidate conditions with a mean AUROC values ranging from 0.66 to 0.99 and with least squares means values all statistically different/higher than 0.5 among all subjects [F(3, 99) = 3.38, p =0.02] and among those with tobacco use [F(4, 84) = 5.39, p = 0.0007]., Conclusions: These preliminary results support discriminatory power of wearable ECG sensors for detecting cocaine use., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: This retrospective study examined the prevalence of combined ethanol and cocaine use, which produces an enhanced psychoactive effect through formation of the active metabolite cocaethylene, compared to combined use of ethanol and two other common recreational drugs, cannabis and amphetamine, based on urine drug test results., Methods: The study was based on >30,000 consecutive samples from routine urine drug testing in 2020, and 2627 samples from acute poisonings in the STRIDA project (2010-2016), in Sweden. Drug testing for ethanol (i.e. ethyl glucuronide and ethyl sulfate), cocaine (benzoylecgonine), cannabis (Δ9-THC-COOH) and amphetamine was done by routine immunoassay screening and LC-MS/MS confirmatory methods. Seven samples testing positive for cocaine and ethyl glucuronide were also analyzed for cocaethylene by LC-HRMS/MS., Results: Among routine samples for which testing of ethanol and cocaine had been requested, 43% tested positive for both substances, compared with 24% for ethanol and cannabis and 19% for ethanol and amphetamine (P < 0.0001). Among the drug-related intoxications, 60% of cocaine-positive samples were also positive for ethanol, compared to 40% for cannabis and ethanol and 37% for amphetamine and ethanol. Cocaethylene was detected (range 1.3-150 μg/L) in all randomly selected samples testing positive for ethanol and cocaine use., Conclusions: These results, which were based on objective laboratory measures, indicated that combined ethanol and cocaine exposure was more prevalent than expected from drug use statistics. This may relate both to the common use of these substances in party and nightlife settings, and the amplified and prolonged pharmacological effect by the active metabolite cocaethylene., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press.)

The purpose of this study was to compare results from five commercial hair testing laboratories conducting workplace drug testing with regard to bias, precision, selectivity and decontamination efficiency. Nine blind hair specimens, including cocaine-positive drug user specimens (some contaminated with methamphetamine) and negative specimens contaminated with cocaine, were submitted in up to five replicates to five different laboratories. All laboratories correctly identified cocaine in all specimens from drug users. For an undamaged hair specimen from a cocaine user, within-laboratory Coefficients of Variation (CVs) of 5-22% (median 8%) were reported, showing that it is possible to produce a homogenous proficiency testing sample from drug user hair. Larger CVs were reported for specimens composed of blended hair (up to 29%) and curly/damaged hair (19-67%). Quantitative results appeared to be method-dependent, and the reported cocaine concentrations varied up to 5-fold between the laboratories, making interlaboratory comparisons difficult. All laboratories reported at least one positive result in specimens contaminated with cocaine powder, followed by sweat and shampoo treatments. Benzoylecgonine, norcocaine, cocaethylene and hydroxylated cocaine metabolites were all detected in cocaine powder-contaminated specimens. This indicates that current industry standards for analyzing and reporting positive cocaine results are not completely effective at identifying external contamination. Metabolite ratios between meta- or para-hydroxy-cocaine and cocaine were 6- and 10-fold lower in contaminated specimens compared to those observed in cocaine user specimens, supporting their potential use in distinguishing samples positive due to contamination and drug use., (Published by Oxford University Press 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen. In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments., (Copyright © 2022 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Chronic cocaine use may lead to widespread intranasal inflammation and necrosis. Cases of cocaine use affecting the orbit have been reported in the literature with a clinical spectrum ranging from inflammation-induced p-anti-cytoplasmic neutrophil autoantibodies positive vasculitis to severe midline destructive lesions resulting in orbital apex syndrome. Here, we present a case of chronic intranasal cocaine abuse with midline destruction that initially obscured diagnosis of, and is hypothesized to have exacerbated, underlying IgG4-Related Disease (IgG4-RD) of the orbit over a 2-year period., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: Intranasal cocaine is known to potentially lead to midline destructive lesions. The present systematic review was undertaken to systematically define the localization of cocaine-induced midline destructive lesions and their prevalence and to propose a practical classification of these lesions., Methods: A PRISMA-compliant systematic review was performed in multiple databases with criteria designed to include all studies published until March 2021 providing a precise definition of cocaine-induced midline lesions in humans. We selected all original studies except case reports. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for lesion localization, patients' demographics, exposure to cocaine, and relationship with external nose destruction., Results: Among 2593 unique citations, 17 studies were deemed eligible (127 patients). All studies were retrospective case series. The destructive process determined a septal perforation in 99.2% of patients. The distribution prevalence decreased from the inferior third of the sinonasal complex (nasal floor and inferolateral nasal wall, respectively, 59% and 29.9% of patients) to the middle third (middle turbinate and ethmoid, 22.8% of patients), and ultimately to neurocranial structures (7.9% of patients). Nasal deformities were inconsistently reported across reviewed studies. Cocaine use duration, frequency, and status were reported only occasionally., Conclusion: Based on the distribution prevalence observed, we propose a four-grade destruction location-based classification. Future prospective studies following the evolution of cocaine-induced lesions are needed to validate our classification, its relationship with lesion evolution, and whether it represents a reliable tool for homogeneous research results reporting., (© 2022. The Author(s).)

Cocaine abuse is widely increasing, especially in younger individuals. Cocaine is a major cause of chest pain and acute coronary syndrome and is the leading cause for drug abuse-related visits to emergency departments, most of which are due to cardiovascular complaints. Cocaine use, especially long-term, is associated with an increased risk of all-cause mortality, and with several significant, life-threatening cardiovascular diseases although the multifactorial underlying cellular and molecular pathophysiological mechanisms of acute and chronic cocaine cardiotoxicity are not well established due to limited studies. Current findings have important public health implications, reinforcing recommendations for substance use screening among young adults with heart diseases, and highlighting the need for education on its deleterious effects. Cocaine should be considered a cardiovascular risk factor, requiring attention to early detection of vascular disease in cocaine users.

Persons with dual severe opioid and cocaine use disorders are at risk of considerable morbidity, and the bidirectional relationship of escalation of mu-opioid agonists and cocaine use is not well understood. The aim of this study was to examine the bidirectional relationship between escalation of heroin and cocaine use in volunteers dually diagnosed with opioid and cocaine dependence (OD + CD). Volunteers from New York with OD + CD (total n = 295; male = 182, female = 113; age ≥ 18 years) were interviewed with the Structured Clinical Interview for the DSM-IV Axis I Disorders and Kreek-McHugh-Schluger-Kellogg scales for dimensional measures of drug exposure, which also collect ages of 1st use and onset of heaviest use. Time of escalation was defined as age of onset of heaviest use minus age of 1st use in whole years. Times of escalation of heroin and cocaine were positively correlated in both men (Spearman r = .34, 95% confidence interval [CI: .17, .48], p < .0001) and women (Spearman r = .51, [.27, .50], p < .0001) volunteers. After we adjusted for demographic variables, a Cox regression showed that time of cocaine escalation was a predictor of time of heroin escalation (hazard ratio [HR] = 0.97, 95% CI [0.95, 0.99], p = .003). Another Cox regression showed that this relationship is bidirectional, because time of heroin escalation was also a predictor of time of cocaine escalation (HR = 0.98, [0.96-0.99], p = .016). In these adjusted models, gender was not a significant predictor of time of escalation of either heroin or cocaine. Therefore, escalation did not differ robustly by gender when adjusting for demographics and other major variables. Overall, rapid escalation of cocaine use was a predictor of rapid escalation of heroin use, and vice versa, in persons with dual severe opioid and cocaine use disorders. These findings suggest a shared vulnerability to rapid escalation of these 2 drugs in persons with dual severe opioid and cocaine use disorders. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Competing Interests: The authors declare no conflict of interest.

Background: Assessment instruments commonly used in clinical trials to measure functional outcomes in substance users may lack sensitivity to detect change during treatment, potentially limiting findings regarding benefits of reduced drug use. This study evaluated the sensitivity of the Addiction Severity Index (ASI) to detect change in psychiatric functioning among cocaine users., Methods: Data were pooled across five clinical trials for cocaine use disorder (N = 492) that included a 12-week treatment period and 6-month follow-up. Within-person cohen's d' was used to evaluate effect size of change on the Psychiatric Composite Score of the ASI (ASI-Psych) and Global Severity Index (GSI) of the Brief Symptom Inventory, as well as cocaine use., Results: Effect sizes were larger for GSI than ASI-Psych from baseline to week 12 (GSI d' = 0.59; ASI-Psych d' = 0.16), and 6-month follow-up (GSI d' = 0.48; ASI-Psych d' = 0.10). For those with non-zero ASI-Psych at baseline (n = 252), medium effect sizes were found over the 12-week period (d' = 0.53) and 6-month follow-up (d' = 0.47). Effect sizes for change in days of cocaine use were most similar to GSI in either sample., Conclusions: The ASI Psychiatric Composite Score may have limited sensitivity to detect change in psychiatric functioning among clinical trial participants who reduce cocaine use. It may be useful for detecting change amongst those reporting some psychiatric problems at the start of treatment. Future research should consider an instrument's sensitivity to change when assessing the potential functional benefits of reducing cocaine use., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this work, we establish that cocaine binding to the Fab fragment of a recombinant humanized anti-cocaine mAb (h2E2) can be directly and easily quantitated using simple and inexpensive absorption and fluorescence measurements, employing dyes typically used for differential scanning fluorimetry, DASPMI and SYPRO Orange. For concentrated samples of the Fab fragment, absorbance spectroscopy employing these dyes reveals the number of cocaine sites present, using either DASPMI (by measuring the increase in dye absorbance) or SYPRO Orange (by measuring the change in dye maximal absorbance wavelength). Interestingly, we observed that cocaine binding to the Fab fragment had a much different effect on the SYPRO Orange dye absorbance than previously reported for the intact h2E2 mAb, resulting in a large decrease in the total dye absorbance for the Fab fragment, in contrast to previous results with the intact h2E2 mAb. For dilute samples of Fab fragment, a dye fluorescence emission spectroscopy assay was developed to quantitate the number of cocaine (and other high affinity cocaine metabolites) binding sites via the ligand-induced decrease in fluorescence emission of both of these extrinsic dyes. The difference in the cocaine titrations for the high affinity (Kd < 30 nM) ligands, cocaine, cocaethylene and benzoylecgonine and the low affinity (Kd > 30 μM) ligands, norcocaine, ecgonine methyl ester, and ecgonine were obvious using this assay. These simple, direct, and inexpensive techniques should prove useful for evaluation of other small molecule antigen binding Fab fragments, enabling quantitation and rapid biochemical assessments necessary for determining Fab fragment suitability for in vivo uses and other assays and experiments., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A highly discussed step in hair sample preparation for forensic analytics is the applied decontamination. The here presented investigations aim to gain insight and give recommendations on how to conduct this decontamination for the analysis of cocaine consumption in hair. Key insights were gained from the investigation of cocaine consumer hair, which was artificially contaminated in a humid atmosphere with 13C6 labelled cocaine and from cocaine powder contaminated hair. Several decontamination protocols were investigated, whereby the usage of a decontamination protocol consisting of multiple short repetitive washes allowed to visualize the wash out of (13C6-) cocaine. Multiple methanol washes proved to be an efficient and simple decontamination approach. Our findings showed that decontamination protocols can successfully wash out recent cocaine contaminations. They were observed to be rather quickly washed out, whereas cocaine from consumption or "older" cocaine contaminations were shown to eliminate both at a constant rate (from inner hair compartments). Thus, the usage of decontamination protocols to differentiate between consumption and contamination was shown to be limited. As contamination can happen any time at any level, only the application of elaborated decision trees, based on cocaine metabolite ratios and thresholds, can provide the distinction between consumption and contamination. Thus, the authors highly recommend the usage of such tools on all hair samples analyzed for cocaine consumption., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Cocaine use is a growing global health problem and patients with cocaine use disorders (CUD) present several complications, including high rates of major depression. These subjects present two types of major depressive disorder (MDD): primary major depressive disorder (P-MDD) and cocaine-induced major depressive disorder (CI-MDD). To improve treatment, it is necessary to distinguish between both types. The aim of this study was to assess the differences in depressive symptomatology criteria (P-MDD vs CI-MDD) in CUD patients., Methods: Secondary data analysis was carried out with a cross-sectional sample of 160 patients presenting CUD and MDD. Clinical assessment was performed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). A differential diagnosis was obtained between P-MDD and CI-MDD., Results: Men represented 80% of the sample, the mean age was 38.61 years, and 64.5% had elementary studies. CI-MDD diagnosis (61.3%) was more frequent than P-MDD (38.7%). There was a younger age of CUD onset in CI-MDD patients. In addition, 79.4% of the patients had another substance use disorder diagnosis. The criterion "Changes in weight or appetite" was more prevalent (57.1%) in P-MDD group., Conclusions: We found differences in the criterion "Changes in weight or appetite". Further research is needed in this field to establish a differential diagnosis and thus provide better treatment for CUD patients.

We are using real-life data in order to determine the prevalence of driving with the presence of cocaine and/or benzoylecgonine (BZE), their concentrations, and their use in combination with other drugs. This study assessed data on Spanish drivers with confirmed drug-positive results recorded by the Spanish National Traffic Agency from 2011-2016. Frequencies of positivity for cocaine and/or BZE and concentration of such substances were obtained. Comparisons and univariate and multivariate regression analyses were performed. Drivers who tested positive for cocaine and/or BZE accounted for 48.59% of the total positive results for drugs. In positive cases for both cocaine and BZE, other substances were detected in 81.74%: delta-9-tetrahydrocannabinol (THC) (68.19%), opioids (20.78%) and amphetamine-like substances (16.76%). In the multivariate logistic regression analysis, the frequency of cocaine and/or BZE positive cases decreased with age (OR:0.97) and were less likely among women (OR:0.63). Concentrations (ng/mL) of cocaine (249.30) and BZE (137.90) were higher when both substances were detected together than when detected alone. Positivity to cocaine represented an important proportion among Spanish drivers who tested positive for drugs, and polysubstance use was especially observed in more than 8 out of 10 positive cases for cocaine and/or BZE.

The use of illicit drugs across the world causes issues for users, healthcare workers and the public. Therefore, rapid and reliable onsite testing methods to detect these drugs are required. In this study, seven commercial surface-enhanced Raman spectroscopy (SERS) substrates A-G were compared for the analysis of cocaine. These substrates were compared using scanning electron microscopy to study the surface structure and Raman spectroscopy and to determine if there was any enhancement of the cocaine bands. Substrate B provided the best enhancement of known cocaine vibrational bands, allowing the detection down to concentrations of 1 ng/mL in standards and 10 ng/mL extracted from the oral fluid. The results showed that SERS is an ideal method for future rapid onsite analysis of illicit drugs in oral fluid. Commercial SERS substrates were compared for the analysis of cocaine. Substrate B provided the best result and was further tested with lower concentrations and extracts from the oral fluid. The application to oral fluid testing could prove useful for future onsite analysis., (© 2020 John Wiley & Sons, Ltd.)

Objectives: Cocaine use has been linked to stroke in several studies. However, few studies have considered the influence of cocaine use on stroke mechanisms such as small vessel disease (SVD). We conducted a study to assess associations between the toxicology-confirmed use of multiple drugs, including cocaine, and a marker of SVD, white matter hyperintensities (WMH)., Materials and Methods: We conducted a nested case-control study (n = 30) within a larger cohort study (N = 245) of homeless and unstably housed women recruited from San Francisco community venues. Participants completed six monthly study visits consisting of an interview, blood draw, vital sign assessment and baseline brain MRI. We examined associations between toxicology-confirmed use of multiple substances, including cocaine, methamphetamine, heroin, alcohol and tobacco, and WMH identified on MRI., Results: Mean study participant age was 53 years, 70% of participants were ethnic minority women and 86% had a history of cocaine use. Brain MRIs indicated the presence of WMH (i.e., Fazekas score>0) in 54% (18/30) of imaged participants. The odds of WMH were significantly higher in women who were toxicology-positive for cocaine (Odd Ratio=7.58, p=0.01), but not in women who were toxicology-positive for other drugs or had several other cerebrovascular risk factors., Conclusions: Over half of homeless and unstably housed women showed evidence of WMH. Cocaine use is highly prevalent and a significant correlate of WMH in this population, while several traditional CVD risk factors are not. Including cocaine use in cerebrovascular risk calculators may improve stroke risk prediction in high-risk populations and warrants further investigation., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest or disclosures, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively., Methods: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests., Results: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (β coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (β coefficient = 0.2%, P < .001, CI, 4-3)., Conclusions: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Hydroxycocaines in hair were investigated with many hundreds of head and body hair samples. All samples were washed by a published extensive aqueous method prior to confirmation by LC-MS/MS. Concentrations, percent of cocaine, and ratios of para- and meta-hydroxycocaines to ortho-hydroxycocaine are presented. Hydroxycocaines as percent of cocaine did not appear to be affected by cocaine concentrations, but were shown to increase with cocaethylene concentrations. Stability of hydroxycocaines over a year of ambient storage was demonstrated. Ortho-hydroxycocaine was shown to be formed by exposure of cocaine-positive hair to peroxide, while para- and meta-hydroxycocaines were not. Presence of para- or meta-hydroxycocaine at > 0.05% of cocaine is proposed as indicating ingestion of cocaine. This indicator prevents black hair from being more likely interpreted as positive for ingestion than lighter colored hair., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: Behavioral disturbances (BD) are prevalent in patients with substance use disorders (SUD)., Objectives: To test the hypothesis that chronic exposure to cocaine could favor the acquisition of BD that were not present in childhood., Methods: We used child and adult ADHD self-report screening scales (WURS-25 and ASRS-6, respectively, with their usual threshold) as assessment tools for significant BD. In a cross-sectional assessment of 382 patients with multiple SUD, we investigated BD and then "de novo" BD (i.e., by restricting the sample to patients below the threshold for childhood BD) (N = 214). We also tested for a gradient effect between patients' lifetime DSM IV cocaine and opioid dependence status and the prevalence of BD., Results: BD were found in 188/382 (42.9%) subjects and in 74/214 (34.6%) subjects. Three clinical factors were associated with BD in the whole sample: the number of cocaine dependence criteria (OR = 1.36 [1.14-1.64], p = 0.001), the number of opioid dependence criteria (OR = 0.69 [0.52-0.91], p = 0.010), and a personal history of using cocaine through rapid routes of administration (OR = 0.41 [0.19-0.88], p = 0.022). The same three factors were associated with "de novo" BD in the restricted sample: OR = 1.35 ([1.11-1.63], p = 0.002), OR = 0.83 ([0.70-0.99], p = 0.046), and OR 0.37 ([0.16-0.86], p = 0.022), respectively. There were significant gradients for BD according to the cocaine exposure categories in the whole (Mantel-Haenszel, p < 0.001) and in the restricted sample (Mantel-Haenszel, p = 0.002)., Conclusions: Cocaine exposure was positively associated with behavioral disturbances in a dose-dependent manner in this clinical sample, whilst opioid exposure showed a negative association.

Rationale: Many people being treated for opioid use disorder continue to use drugs during treatment. This use occurs in patterns that rarely conform to well-defined cycles of abstinence and relapse. Systematic identification and evaluation of these patterns could enhance analysis of clinical trials and provide insight into drug use., Objectives: To evaluate such an approach, we analyzed patterns of opioid and cocaine use from three randomized clinical trials of contingency management in methadone-treated participants., Methods: Sequences of drug test results were analyzed with unsupervised machine-learning techniques, including hierarchical clustering of categorical results (i.e., whether any samples were positive during each week) and K-means longitudinal clustering of quantitative results (i.e., the proportion positive each week). The sensitivity of cluster membership as an experimental outcome was assessed based on the effects of contingency management. External validation of clusters was based on drug craving and other symptoms of substance use disorder., Results: In each clinical trial, we identified four clusters of use patterns, which can be described as opioid use, cocaine use, dual use (opioid and cocaine), and partial/complete abstinence. Different clustering techniques produced substantially similar classifications of individual participants, with strong above-chance agreement. Contingency management increased membership in clusters with lower levels of drug use and fewer symptoms of substance use disorder., Conclusions: Cluster analysis provides person-level output that is more interpretable and actionable than traditional outcome measures, providing a concrete answer to the question of what clinicians can tell patients about the success rates of new treatments.

'Tree-in-bud' (TIB) appearance in computed tomography (CT) chest is most commonly a manifestation of infection. We here describe an unusual cause of TIB during the COVID-19 pandemic. A young male patient who had a history of fever, cough, and respiratory distress presented in the emergency department. As these symptoms matched with coronavirus infection, the COVID-19 test was done, which was found negative. He was then moved to the intensive care unit where he developed severe acute respiratory distress syndrome and was put on mechanical ventilation. Further workup did not reveal any source of infection, as all his cultures were negative, but his CT chest showed a tree-in-bud appearance. After obtaining a detailed history from his friends, the patient was found a chronic abuser of inhaled cocaine and treated with intravenous steroids. Subsequently, he was weaned from the ventilator and discharged from the intensive care unit after becoming asymptomatic.

Background: Requests for urine (UR) and oral fluid (OF) drug testing at our institutions are increasing. However, few studies have assessed the accuracy of each matrix using paired specimens and LC-MS/MS. We compared OF and UR for detection of cocaine (COC) abuse in addiction medicine-psychiatry (AMP) clinics., Methods: We measured COC and benzoylecgonine (BZE) in OF (limit of detection (LOD) 2.0 µg/L) and BZE in UR (LOD 5 µg/L) by LC-MS/MS in 258 paired samples, and compared the two matrices when higher UR cutoffs of 25, 50, and 150 µg/L were employed., Results: UR detected more COC abuse than OF at the LOD (5 µg/L). BZE was detected in 63 UR specimens and COC and/or BZE in 40 OF specimens (29 OF+UR+, 11 OF+UR-, 34 OF-UR+). UR creatinine was lower in OF+UR- specimens. COC and BZE were detected in 88% (35/40) and 75% (30/40) of OF specimens, respectively. OF was equivalent to UR at detecting COC abuse using a 25 µg/L cutoff, and detected more COC abuse than UR using 50 and 150 µg/L cutoffs. The ratio of OF COC/BZE increased with decreasing UR BZE concentrations., Conclusions: We demonstrate that OF detects more COC abuse in an AMP setting when UR BZE cutoffs ≥ 50 µg/L are utilized, and that UR creatinine concentrations are significantly lower in specimens positive for COC and/or BZE in OF and negative for BZE in UR. The presence of only COC in OF and low concentrations of UR BZE likely indicates remote use of COC., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Cocaine use is associated with multiple complications, some of which can mimic systemic diseases, especially Antineutrophil Cytoplasmic Antibody (ANCA) associated vasculitis. We report a case of Cocaine Induced Midline Destructive Lesions (CIMDL) for which a diagnosis of granulomatosis with polyangiitis (GPA) was discussed., Case Report: A 42-year-old male, cocaine consumer, was admitted in our department for a centrofacial destructive process. He had no extra ear, nose and throat (ENT) involvement. ANCA were positive with a perinuclear fluorescence pattern and an anti-Proteinase 3 specificity. Regarding this unusual immunologic pattern and in the absence of histological argument for a GPA, a diagnosis of CIMDL was made., Conclusion: CIMDL is a centrofacial destructive process due to intranasal cocaine use. It is frequently associated with the presence of p-ANCA with both anti-HNE and anti-PR3 specificity., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: Cocaine use is increasing. Comorbidities and diagnostic sequencing are needed among college students to inform treatment of cocaine use disorder (CUD). Method: Using electronic medical records from the psychiatric clinic at the student health care center of a large, public university from 2005 to 2015, patients diagnosed with CUD were identified. Their top mental health conditions were identified and assessed to see whether the first diagnosis of these conditions was made (1) before, (2) at the same time as, or (3) after the first diagnosis of CUD. Results: Among the 50 CUD patients, their most common mental health comorbidities were alcohol use disorder, anxiety, depression, and cannabis use disorder. Anxiety and depression were likely to be diagnosed before CUD; alcohol and cannabis use disorders were likely to be diagnosed concurrently with CUD. Conclusion : Diagnostic sequencing can be used to inform screening, workup, and treatment for patients with CUD.

Background: Although previous studies have shown that opioid agonist therapy (OAT) is linked to reductions in illicit opioid use, less is known about how OAT impacts the use of other psychoactive substances. We aimed to examine the changes in use of different substances by comparing patterns before and after initiating OAT., Methods: Data for this study was derived from three ongoing prospective cohorts involving people who use drugs in Vancouver, Canada from 1996 to 2018. We assessed use patterns for heroin, illicit prescription opioid, cocaine, crack cocaine, crystal methamphetamine, cannabis, daily alcohol use, and benzodiazepines. Segmented regression was conducted to compare the trends of substance use between pre-treatment and post-treatment periods., Results: The study included 1107 participants. After OAT engagement, we observed an immediate decline in the proportion as well as a decreasing trend for heroin (Adjusted Odds Ratio (AOR): 0.80, 95% confidence interval (CI): 0.77, 0.83), illicit prescription opioid (AOR: 0.87, 95% CI: 0.83, 0.90), and benzodiazepines (AOR: 0.73, 95 % CI: 0.67, 0.80). There was no significant difference comparing the pre-treatment and post-treatment trends for cocaine, crack cocaine, crystal methamphetamine, and cannabis. However, higher growth slope was noted during the post-treatment period for daily alcohol use (P = 0.016)., Conclusions: We observed significant reduction in illicit opioids use following OAT initiation, but not for stimulant and cannabis. The increasing problematic use of alcohol may pose challenges to the safety and effectiveness of OAT. Development of comprehensive and tailored treatment strategies is needed for poly-substance users accessing OAT., Competing Interests: Declaration of Competing Interest The University of British Columbia has received an unstructured gift from NG Biomed Ltd., a private firm seeking a license to produce medical cannabis, to support Dr. M.-J. Milloy. He is the Canopy Growth professor of cannabis science at the University of British Columbia, a position created using unstructured gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia’s Ministry of Mental Health and Addictions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A 35-year-old woman with a history of cocaine abuse presented with progressively worsening OS pain. Neuroimaging revealed a 3-cm ill-defined left orbital lesion involving the intraconal and extraconal spaces. The orbital mass was biopsied via an anterior orbitotomy approach. Pathology demonstrated prominent angiocentric granulomatous and lymphoplasmacytic inflammation consistent with vasculitis. Laboratory tests were significant for neutropenia, positive perinuclear antineutrophil cytoplasmic antibodies with high titer, and positive myeloperoxidase antibodies, consistent with levamisole-induced vasculitis. To the authors' knowledge, this is the first reported case of cocaine-levamisole-induced vasculitis presenting as orbitopathy.

Diffuse alveolar haemorrhage (DAH) is characterised by diffuse pulmonary opacities, respiratory failure, a falling haemoglobin level along with presence of hemosiderin-laden macrophages on bronchoalveolar lavage (BAL). Finding the underlying aetiology of DAH can be challenging but of importance as the treatment and prognosis are largely determined by it. We report a case of DAH with underlying cocaine abuse, a rare cause for the same.

The finding that drugs and metabolites can be detected from fingerprints is of potential relevance to forensic science and as well as toxicology and clinical testing. However, discriminating between dermal contact and ingestion of drugs has never been verified experimentally. The inability to interpret the result of finding a drug or metabolite in a fingerprint has prevented widespread adoption of fingerprints in drug testing and limits the probative value of detecting drugs in fingermarks. A commonly held belief is that the detection of metabolites of drugs of abuse in fingerprints can be used to confirm a drug has been ingested. However, we show here that cocaine and its primary metabolite, benzoylecgonine, can be detected in fingerprints of non-drug users after contact with cocaine. Additionally, cocaine was found to persist above environmental levels for up to 48 hours after contact. Therefore the detection of cocaine and benzoylecgonine (BZE) in fingermarks can be forensically significant, but do not demonstrate that a person has ingested the substance. In contrast, the data here shows that a drug test from a fingerprint (where hands can be washed prior to donating a sample) CAN distinguish between contact and ingestion of cocaine. If hands were washed prior to giving a fingerprint, BZE was detected only after the administration of cocaine. Therefore BZE can be used to distinguish cocaine contact from cocaine ingestion, provided donors wash their hands prior to sampling. A test based on the detection of BZE in at least one of two donated fingerprint samples has accuracy 95%, sensitivity 90% and specificity of 100% (n = 86).

Cocaine is a cardiotoxic drug which has been associated with morbi-mortality due to cardiovascular diseases (CVD). This study aims to: (1) analyze the hospitalizations due to cardiovascular processes and the presence of cocaine among the toxic habits of patients; and (2) discuss the forensic difficulties in sudden cardiac death (SCD) in the presence of cocaine. Hospital discharges due to CVD reporting cocaine consumption as a secondary diagnosis between 2003 and 2013 in Spain were analyzed. Subsequently, a review of judicial autopsies (SCD in cocaine users) was carried out to illustrate the forensic difficulties in the determination of the manner and underlying cause of death when cocaine use is involved. The average CVD morbidity rate was 1104.4 per 100,000 population. The most common main diagnoses of which cocaine use was recorded as a secondary diagnosis were rheumatic fever, ischemic heart disease and cerebrovascular disease in male patients between 15 and 44 years. The cardiovascular findings in the autopsies of cocaine users vary, and determining the mechanism that triggered the death in forensic practice is a challenge. The presence of cocaine among the toxic habits of young patients admitted for CVD in Spain is increasing. In our opinion, criteria must be unified to establish the manner and underlying cause of death in SCD and toxicological analysis can be a key part in the process.

Cocaine use by adolescents and young adults continues to be a significant public health issue and the cause of medical and psychological morbidity and mortality. Although use rates are lower than those seen with alcohol, tobacco, and other illicit substances such as marijuana, cocaine is highly addictive and presents significant acute and long-term medical and psychological effects. This article reviews the epidemiology of cocaine use among adolescents and young adults, discusses the pharmacology and neurobiology of cocaine use and dependence, provides information regarding acute intoxication and systemic effects seen with more chronic use, and describes current assessment and treatment approaches., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Despite calls for non-abstinence endpoints in randomized clinical trials (RCTs) for cocaine use disorder, there is a lack of data validating non-abstinence endpoints. We conducted a clinical validation of reduction in cocaine frequency level as a non-abstinence endpoint in RCTs for cocaine use disorder (CUD)., Methods: We utilized a pooled dataset (n = 716; 63.6 % male, 51.4 % non-Hispanic white) from seven RCTs for CUD. We specified three cocaine frequency levels at baseline and end of treatment (EOT): abstinence, low frequency (1-4 days/month), and high frequency (5+ days/month). Multiple regression analyses were conducted., Results: Among the sample, 38.3 % had at least a one-level reduction from baseline to EOT, whereas 61.7 % did not change/increased frequency level. At least a one-level reduction in cocaine frequency level from baseline to EOT versus no change/increase was significantly associated with better functioning up to one year following treatment on measures of cocaine use, as well as psychological, employment, legal, and other drug use problem severity domains of the Addiction Severity Index (ASI). We also conducted analyses only among those at the high frequency level at baseline and found those who reduced to low frequency use at EOT had similar outcomes at follow-up as those who reduced to abstinence., Conclusions: At least a one-level reduction in cocaine frequency level from pretreatment to EOT can be a clinically meaningful endpoint given its relation to sustained clinical benefit up to one-year following treatment. These data parallel recent findings regarding reduction in drinking risk level among individuals with alcohol use disorder., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Persons dually diagnosed with opioid and cocaine dependence (OD + CD) present a clinical challenge and are at risk of morbidity and mortality. The time of escalation of heroin and cocaine exposure in persons with OD + CD remain understudied, and the influence of gender and other variables have not been examined. This observational study focused on the time of escalation of heroin and cocaine in volunteers with OD + CD, examining gender and exposure to other drugs (e.g., cannabis or alcohol) as predictors. Ages of first use and of onset of heaviest use of each drug were collected (in whole years). Time of escalation was defined as the interval between age of first use and onset of heaviest use., Volunteers: sequentially ascertained adult volunteers recruited from the New York Metropolitan area, of which n = 297 were diagnosed with OD + CD., Methods: Instruments administered were the SCID-I diagnostic interview (DSM-IV criteria), BIS-11 impulsiveness scale, and KMSK scales, dimensional measures of maximal exposure to specific drugs., Results: In volunteers with OD + CD, ages of onset of heaviest use of cannabis (median age = 15) and alcohol (median age = 19) were in adolescence or emerging adulthood and preceded those for heroin and cocaine (median ages = 26 and 25, respectively). Maximal levels of cannabis and alcohol exposure were high, in volunteers with OD + CD. In adjusted Cox regressions, gender was not a significant predictor of time of heroin or cocaine escalation. However, more rapid time of alcohol escalation was a predictor of more rapid time of escalation of both heroin and cocaine, in volunteers with OD + CD., (Copyright © 2019 Elsevier B.V. All rights reserved.)