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INTRODUCTION AND OBJECTIVES: To investigate the epidemiological characteristics, clinic-pathological findings and recent use of substances of abuse and prescribed drugs in sexual activity-related sudden death (SArSD). METHODS: Multicenter population-based study on forensic autopsies conducted in 27 provinces of Spain over 12 years (2010-2021). RESULTS: Out of 18046 autopsied natural deaths, 64 cases (0.35 %) of SArSD were investigated (87 % males). Women were younger than males (50.5 ± 13.4 years vs 37.2 ± 14.2; p = 0.017). Sudden cardiac deaths (SCD) accounted for 87 % of cases. Ischemic heart disease was the predominant pathology (58 %), mainly affecting men ≥ 36 years of age. Cerebral haemorrhage (8 %) and asthma (5 %) were the leading non-cardiac causes. In young adults, SADS (36 %) and asthma (27 %) were the main causes The disease responsible of SCD was diagnosed in life in 7 subjects. In 64 % there were cardiovascular risk factors, mainly obesity. Toxicological analysis detected illicit drugs (23 %), mainly cocaine, medications for erectile dysfunction (9 %), and ethanol ≥ 0.5 g/L (8 %). Deaths occurred usually in the context of heterosexual intercourse and during or immediately after sexual activity. The most common location was at home (63 %). In 12 men the sexual partner was a sex worker. CONCLUSIONS: SArSD has a low incidence in the general population affecting middle-aged males during intercourse with a heterosexual partner. It is of cardiovascular origin, mainly due to ischemic heart disease that frequently remained silent during life. There is a frequent association with obesity, use of cocaine (and, to a lesser extent, medications for erectile dysfunction) and performing unconventional sexual practices. Forensic investigation is useful for developing prevention strategies.

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BACKGROUND: Self-discharge is a risk factor for readmission and excess mortality. We assess the rate of self-discharge from the emergency department (ED) among presentations for acute recreational drug toxicity and identify factors associated with self-discharge. METHODS: From the Euro-DEN Plus database of presentations to the ED with acute recreational drug toxicity, we extracted data from 11 centres in seven European countries from 2014 to 2017. Self-discharge was defined as taking one's own discharge or escaping from the ED before being medically cleared. We used multiple logistic regression analyses to look for factors associated with self-discharge. RESULTS: Among 15,135 included presentations, 1807 (11.9%) self-discharged. Self-discharge rates varied from 1.7 to 17.1% between centres. Synthetic cannabinoids were associated with self-discharge, adjusted odds ratio 1.44 (95% confidence interval 1.10-1.89), as were heroin, 1.44 (1.26-1.64), agitation, 1.27 (1.10-1.46), and naloxone treatment, 1.27 (1.07-1.51), while sedation protected from self-discharge, 0.38 (0.30-0.48). CONCLUSION: One in eight presentations self-discharged. There was a large variation in self-discharge rates across the participating centres, possibly partly reflecting different discharge procedures and practices. Measures to improve the management of agitation and cautious administration of naloxone to avoid opioid withdrawal symptoms may be approaches worth exploring to reduce self-discharge.

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Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations. TDM can be used to determine treatment efficacy and to prevent the occurrence or reduce the risk of drug-induced side effects, being, thus, a tool of personalized medicine. Drugs for which TDM is applied should have a narrow therapeutic range and exhibit both significant pharmacokinetic variability and a predefined target concentration range. The aim of our study was to assess the current status of TDM in Greek public hospitals and estimate its progress over the last 20 years. All Greek public hospitals were contacted to provide data and details on the clinical uptake of TDM in Greece for the years 2003 and 2021 through a structured questionnaire. Data from 113 out of 132 Greek hospitals were collected in 2003, whereas for 2021, we have collected data from 98 out of 122 hospitals. Among these, in 2003 and 2021, 64 and 51 hospitals, respectively, performed TDM. Antiepileptics and antibiotics were the most common drug categories monitored in both years. The total number of drug measurement assays decreased from 2003 to 2021 (153,313 ± 7794 vs. 90,065 ± 5698; p = 0.043). In direct comparisons between hospitals where TDM was performed both in 2003 and 2021 (n = 35), the mean number of measurements was found to decrease for most drugs, including carbamazepine (198.8 ± 46.6 vs. 46.6 ± 10.1, p < 0.001), phenytoin (253.6 ± 59 vs. 120 ± 34.3; p = 0.001), amikacin (147.3 ± 65.2 vs. 91.1 ± 71.4; p = 0.033), digoxin (783.2 ± 226.70 vs. 165.9 ± 28.9; p < 0.001), and theophylline (71.5 ± 28.7 vs. 11.9 ± 6.4; p = 0.004). Only for vancomycin, a significant increase in measurements was recorded (206.1 ± 96.1 vs. 789.1 ± 282.8; p = 0.012). In conclusion, our findings show that TDM clinical implementation is losing ground in Greek hospitals. Efforts and initiatives to reverse this trend are urgently needed.

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Wastewater analysis (WWA) has been used as a tool to monitor population drug use, both pharmaceutical and illicit, for over 15 years. Policymakers, law enforcement and treatment services may use WWA-derived data to seek an objective understanding of the extent of drug use in specific areas. Therefore, wastewater data should best be reported in a meaningful form to allow those that are not experts in the field to compare the scale within and between drug classes. Excreted drug loads quantified in wastewater describe the mass of drug present in the sewer. Normalisation for wastewater flow and population is standard practice and critical for comparing drug loads between different catchments and indicates a transition to an epidemiological approach (wastewater-based epidemiology (WBE)). A further consideration is necessary to accurately compare the measured level of one drug to another. The standard dose of a drug taken to elicit a therapeutic effect will vary, with some compounds requiring microgram amounts, while others are administered in the gram range. When WBE data is expressed with units representing excreted or consumed loads without considering dose amounts, the scale of drug use when comparing multiple compounds becomes distorted. To demonstrate the utility and significance of including known excretion rates, potency and typical dose amounts into back-calculations of the measured drug load, this paper compares the levels of 5 prescribed (codeine, morphine, oxycodone, fentanyl and methadone) and 1 illicit (heroin) opioid from South Australian wastewater. The data is presented at each stage of the back-calculation starting with the total mass load measured, to consumed amounts factoring in excretion rates and finally the number of doses the load equates to. This is the first paper to describe the levels of 6 opioids measured in wastewater over a 4-year period in South Australia that demonstrate the relative scale of use.

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The consumption patterns of five categories of psychoactive substances (PS), including "conventional" illicit drugs, new psychoactive substances (NPS), therapeutic opioids, alcohol and nicotine, were studied in the city of Split, Croatia, using wastewater-based epidemiology (WBE), with an emphasis on the impact of a large electronic music festival. The study involved the analysis of 57 urinary biomarkers of PS in raw municipal wastewater samples collected in three characteristic periods, including the festival week in the peak-tourist season (July) and reference weeks in the peak-tourist season (August) and the off-tourist season (November). Such a large number of biomarkers allowed the recognition of distinct patterns of PS use associated with the festival, but also revealed some subtle differences between summer and autumn seasons. The festival week was characterized by markedly increased use of illicit stimulants (MDMA: 30-fold increase; cocaine and amphetamine: 1.7-fold increase) and alcohol (1.7-fold increase), while consumption of other common illicit drugs (cannabis and heroin), major therapeutic opioids (morphine, codeine and tramadol) and nicotine remained rather constant. Interestingly, NPS and methamphetamine clearly contributed to the festival PS signature in wastewater, but their prevalence was rather low compared to that of common illicit drugs. Estimates of cocaine and cannabis use were largely consistent with prevalence data from national surveys, whereas differences were found for typical amphetamine-type recreational drugs, particularly MDMA, and for heroin. The WBE data suggest that the largest proportion of morphine came from heroin consumption and that the percentage of heroin users seeking treatment in Split is probably rather low. The prevalence of smoking calculated in this study (30.6 %) was consistent with national survey data for 2015 (27.5-31.5 %), while the average alcohol consumption per capita >15 years (5.2 L) was lower than sales statistics suggest (8.9 L).

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Mitochondria play a critical role in the regulation of several biological processes (e.g., programmed cell death, inflammation, neurotransmission, cell differentiation). In recent years, accumulating findings have evidenced that cannabinoids, a group of endogenous and exogenous (synthetic and plant-derived) psychoactive compounds that bind to cannabinoid receptors, may modulate mitochondrial function and dynamics. As such, mitochondria have gained increasing interest as central mediators in cannabinoids' pharmacological and toxicological signatures. Here, we review the mechanisms underlying the cannabinoids' modulation of mitochondrial activity and dynamics, as well as the potential implications of such mitochondrial processes' disruption on cell homeostasis and disease. Interestingly, cannabinoids may target different mitochondrial processes (e.g., regulation of intracellular calcium levels, bioenergetic metabolism, apoptosis, and mitochondrial dynamics, including mitochondrial fission and fusion, transport, mitophagy, and biogenesis), by modulating multiple and complex signaling pathways. Of note, the outcome may depend on the experimental models used, as well as the chemical structure, concentration, and exposure settings to the cannabinoid, originating equivocal data. Notably, this interaction seems to represent not only an important feature of cannabinoids' toxicological signatures, with potential implications for the onset of distinct pathological conditions (e.g., cancer, neurodegenerative diseases, metabolic syndromes), but also an opportunity to develop novel therapeutic strategies for such pathologies, which is also discussed in this review.

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Substances of abuse have the potential to cause addiction, habituation or altered consciousness. Most of the research on these substances focuses on addiction, and is carried out through observational and clinical studies on humans, or experimental studies on animals. The transposition of the EU Directive 2010/63 into Italian law in 2014 (IT Law 2014/26) includes a ban on the use of animals for research on substances of abuse. Since then, in Italy, public debate has continued on the topic, while the application of the Article prohibiting animal research in this area has been postponed every couple of years. In the light of this debate, we briefly review a range of methodologies - including animal and non-animal, as well as patient or population-based studies - that have been employed to address the biochemical, neurobiological, toxicological, clinical and behavioural effects of substances of abuse and their dependency. We then discuss the implications of the Italian ban on the use of animals for such research, proposing concrete and evidence-based solutions to allow scientists to pursue high-quality basic and translational studies within the boundaries of the regulatory and legislative framework.

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Substances of abuse (SoA), as well as smoking and alcohol consumption, are well known for their impact on male fertility status, erectile function, and ejaculation. We assessed SoA consumption habits in a cohort of men seeking medical attention for uro-andrological purposes. Data from 7447 men seeking medical attention for the first time for uro-andrological purposes were analyzed. A complete medical and sexual history was collected for each patient. Smoking, alcohol, and SoA consumption were investigated. Descriptive statistics was used to describe the whole cohort. The primary motivations for their evaluation were lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and infertility in 1912 (25.7%), 2944 (39.5%), and 2591 (34.8%) men, respectively. Previous use of SoA was reported by 378 (5.1%) men, and 190 (2.6%) individuals were current users. Patients seeking medical attention for infertility were more frequently current SoA users (107; 4.1%) than men with ED (66; 2.2%) and LUTS (17; 0.9%) (both P < 0.001). Current users of SoA were younger than those with past or no SoA history (P < 0.001). Current SoA users were more frequently smokers (P < 0.001) and alcohol consumers (P < 0.001) than those with a previous history or those who had never tried SoA. In conclusion, approximately 3% of men seeking medical attention for uro-andrological purposes were current SoA consumers. Infertile men reported a higher use of SoA than those with ED or LUTS. Current SoA users were younger and more frequently concomitant smokers and alcohol consumers compared to those who did or had never used SoA.

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There is a growing amount of evidence showing a reciprocal relation between the gut microbiota and the brain. Substance use disorders (SUD), which are a major cause of preventable morbidity and mortality worldwide, have an influence on the gut microbiota and on the gut-brain axis. The communication between the microbiota and the brain exists through different pathways: (1) the immune response elicited by bacterial products, coupled with alterations of the intestinal barrier allowing these products to enter the bloodstream, (2) the direct and indirect effects of bacterial metabolites such as short chain fatty acids (SCFAs) or tryptophan on the brain, (3) and the hypothalamic-pituitary-adrenal (HPA) axis, whose peripheral afferents can be influenced by the microbiota, and can in turn activate microglia. Among substances of abuse, alcohol has been the subject of the greatest number of studies in this field. In some but not all patients suffering from alcohol-use-disorder (AUD), alcohol alters the composition of the gut microbiota and the permeability of the intestinal barrier, directly and through dysbiosis. It has also been well demonstrated that alcohol induces a peripheral inflammation; it is still unclear whether it induces a central inflammation, as there are contradictory results in human studies. In animal studies, it has been shown that neuroinflammation increases during alcohol withdrawal. Literature on opioids and stimulants is less numerous. Chronic morphine intake induces dysbiosis, increased intestinal permeability and a probable neuroinflammation, which could explain symptoms such as tolerance, hyperalgesia and deficit in reward behavior. Cocaine induces a dysbiosis and conversely the microbiome can modulate the behavioral response to stimulant drugs. Tobacco cessation is associated with an increase in microbiota diversity. Taken together, the findings of our narrative literature review suggest a bidirectional influence in the pathogenesis of substance use disorders.

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Substances of abuse (SoA), as well as smoking and alcohol consumption, are well known for their impact on male fertility status, erectile function, and ejaculation. We assessed SoA consumption habits in a cohort of men seeking medical attention for uro-andrological purposes. Data from 7447 men seeking medical attention for the first time for uro-andrological purposes were analyzed. A complete medical and sexual history was collected for each patient. Smoking, alcohol, and SoA consumption were investigated. Descriptive statistics was used to describe the whole cohort. The primary motivations for their evaluation were lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and infertility in 1912 (25.7%), 2944 (39.5%), and 2591 (34.8%) men, respectively. Previous use of SoA was reported by 378 (5.1%) men, and 190 (2.6%) individuals were current users. Patients seeking medical attention for infertility were more frequently current SoA users (107; 4.1%) than men with ED (66; 2.2%) and LUTS (17; 0.9%) (both P < 0.001). Current users of SoA were younger than those with past or no SoA history (P < 0.001). Current SoA users were more frequently smokers (P < 0.001) and alcohol consumers (P < 0.001) than those with a previous history or those who had never tried SoA. In conclusion, approximately 3% of men seeking medical attention for uro-andrological purposes were current SoA consumers. Infertile men reported a higher use of SoA than those with ED or LUTS. Current SoA users were younger and more frequently concomitant smokers and alcohol consumers compared to those who did or had never used SoA.

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Introdução: A tuberculose é uma doença infectocontagiosa causada pelo Mycobacterium tuberculosis, que tem estreita relação com as desigualdades sociais, atingindo principalmente pessoas em exclusão social, e por vezes, em uso abusivo de álcool, tabaco e drogas ilícitas. Objetivo: Analisar a distribuição espacial e tendência temporal dos casos diagnosticados por tuberculose entre alcoolistas, tabagistas e usuários de drogas ilícitas no Estado do Paraná, Sul do Brasil. Métodos: Tratou-se de um estudo ecológico, desenvolvido nos 399 munícipios do Estado do Paraná. A população do estudo consistiu de casos diagnosticados de tuberculose no Sistema de Informação de Agravos de Notificação, entre o período de 2008 a 2018 com declaração de alcoolismo, tabagismo e uso de drogas ilícitas. Recorreu-se à análise exploratória dos dados por meio da estatística descritiva com o cálculo de medidas de frequências absolutas e relativas. Para a identificação de clusters, recorreu-se à técnica denominada Getis-Ord Gi*. Para a detecção dos aglomerados de risco espacial aplicou-se a Estatística de Varredura Puramente Espacial e o Spatial Variation in Temporal Trends. E nas séries temporais utilizou o método de autorregressão Prais-Winsten e a decomposição de séries temporais denominado Seasonal-Trend by Loess. O estudo foi aprovado pelo Comitê de Ética em Pesquisa da Escola de Enfermagem de Ribeirão Preto da Universidade de São Paulo. Resultados: Foram diagnosticados 29.499 casos de TB desses, 32,41% (n=9.529) faziam uso de algum tipo de substância psicoativa, sendo o alcoolismo o mais prevalente 20,4% (n=6.013), seguido do tabagismo 14,2% (n=4.185) e drogas ilícitas 9,8% (n=2.893). Quanto à detecção dos aglomerados de risco espacial, entre os que faziam uso do álcool, observou-se incidência de 5,4 casos/100 mil habitantes e um crescimento anual de 0,58%. Quanto ao tabagismo, verificou-se incidência de 3,8 casos por 100.000 habitantes, e um crescimento anual de 37,08% já as outras drogas, uma incidência de 2,6 casos/100.000 habitantes. Observou-se que 1.099 casos eram populações privadas de liberdade, sendo que a maioria era tabagista (n=460;41,8%), seguido por usuários de drogas ilícitas (n=451;41,0%) e alcoolistas (n=179;16,3%). Dentre esses casos, observou-se uma tendência temporal decrescente e hotspost para alcoolismo, tabagismo e drogas ilícitas nas quatro macrorregionais do Estado. Entre os casos de TB levantados, 560 eram de pessoas em situação de rua, tendo-se que a situação de alcoolismo foi a mais prevalente (n=420; 36,30%), seguido pelo tabagismo (n=382; 33,02%) e outras drogas ilícitas (n=355; 30,68%). Ao aplicar a tendência temporal também apresentou um cenário crescente no estado para todas as categorias analisadas. E ao identificar os hotspost entre a população nota-se que, houve associação espacial local apenas na macrorregional Leste na região metropolitana de Curitiba para alcoolismo, tabagismo e outras drogas ilícitas. Conclusão: O estudo avança no conhecimento ao evidenciar a problemática do uso de drogas entre pessoas com diagnóstico de TB, evidenciando uma tendência de crescimento desses eventos. Além disso, o estudo também evidenciou a problemática dessa situação em populações privadas de liberdade e em situação de rua. Apesar do Sul ser considerado região de grande riqueza, o estudo evidencia o contraste, da situação de desigualdade que aflige essa população, exprimindo a situação da TB, uso nocivo de drogas e da exclusão social. Os resultados advindos com o estudo evidenciam os desafios do país em se avançar no fim da TB, e serve de base de evidência para nutrir políticas publicas e desenvolvimento de ações estratégicas em territórios e grupos vulneráveis.

Introduction: Tuberculosis is an infectious and contagious disease caused by Mycobacterium tuberculosis, which is closely related to social inequalities, affecting mainly people in social exclusion, and sometimes in the abuse of alcohol, tobacco and illicit drugs. Objective: To analyze the spatial distribution and temporal trend of cases diagnosed with tuberculosis among alcoholics, smokers and illicit drug users in the state of Paraná, southern Brazil. Methods: This was an ecological study, developed in 399 municipalities in the state of Paraná. The study population consisted of diagnosed cases of tuberculosis in the Notifiable Diseases Information System, between 2008 and 2018, with declarations of alcoholism, smoking and use of illicit drugs. Exploratory data analysis was used through descriptive statistics with the calculation of absolute and relative frequency measures. For the identification of clusters, the technique called Getis-Ord Gi* was used. For the detection of spatial risk clusters, the Purely Spatial Scan Statistics and the Spatial Variation in Temporal Trends were applied. And in the time series used the Prais-Winsten autoregression method and the decomposition of time series called Seasonal-Trend by Loess. The study was approved by the Research Ethics Committee of the University of São Paulo at Ribeirão Preto College of Nursing. Results: Of these, 29,499 cases of TB were diagnosed, 32.41% (n=9,529) were using some type of psychoactive substance, with alcoholism being the most prevalent 20.4% (n=6,013), followed by smoking 14.2 % (n=4,185) and illegal drugs 9.8% (n=2,893). As for the detection of clusters of spatial risk, among those who used alcohol, there was an incidence of 5.4 cases/100 thousand inhabitants and an annual growth of 0.58%; As for smoking, there was an incidence of 3.8 cases per 100,000 inhabitants, and an annual growth of 37.08%, as for other drugs, an incidence of 2.6 cases/100,000 inhabitants. It was observed that 1,099 cases were populations deprived of liberty, with the majority being smokers (n=460;41.8%), followed by illicit drug users (n=451;41.0%) and alcoholics (n= 179;16.3%). Among these cases, there was a decreasing temporal trend and hotspot for alcoholism, smoking and illicit drugs in the four macro-regions of the state. Among the TB cases surveyed, 560 were homeless, with the situation of alcoholism being the most prevalent (n=420; 36.30%), followed by smoking (n=382; 33.02 %) and other illegal drugs (n=355; 30.68%). When applying the temporal trend, it also presented a growing scenario in the state for all categories analyzed. And when identifying the hotsposts among the population, it is noted that there was a local spatial association only in the East macro-region in the metropolitan region of Curitiba for alcoholism, smoking and other illicit drugs. Conclusion: The study advances in knowledge by highlighting the problem of drug use among people diagnosed with TB, showing a growing trend of these events. In addition, the study also highlighted the problem of this situation in populations deprived of liberty and on the streets. Although the South is considered a region of great wealth, the study highlights the contrast, the inequality that afflicts this population, expressing the situation of TB, harmful use of drugs and social exclusion. The results arising from the study highlight the country's challenges in moving towards the end of TB, and serve as an evidence base to nurture public policies and the development of strategic actions in territories and vulnerable groups.

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Substance use disorders pose a common medical, social and financial problem. Among the pathomechanisms of substance use disorders, the disruption and increased permeability of the blood-brain barrier has been recently revealed. Physical exercise appears to be a relatively inexpensive and feasible way to implement behavioral therapy counteracting the blood-brain barrier impairment. Concomitantly, there are also studies supporting a potential protective role of selected substances of abuse in maintaining the blood-brain barrier integrity. In this review, we aim to provide a summary on the modulatory influence of physical exercise, a non-pharmacological intervention, on the blood-brain barrier alterations caused by substances of abuse. Further studies are needed to understand the precise mechanisms that underlie various effects of physical exercise in substance use disorders.

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Recreational use of synthetic cannabinoids (SCs) before and during pregnancy poses a major public health risk, due to the potential onset of neurodevelopmental disorders in the offspring. Herein, we report the assessment of the neurotoxic potential of two commonly abused SCs, THJ-2201 and 5F-PB22, particularly focusing on how they affect neuronal differentiation in vitro. Differentiation ratios, total neurite length, and neuronal marker expression were assessed in NG108-15 neuroblastoma x glioma cells exposed to the SCs at non-toxic, biologically relevant concentrations (≤1 µM), either in acute or repeated exposure settings. Both SCs enhanced differentiation ratios and total neurite length of NG108-15 cells near two-fold compared to vehicle-treated cells, in a CB1R activation-dependent way, as the CB1R blockade with a specific antagonist (SR141718) abrogated SC-induced effects. Interestingly, repeated 5F-PB22 exposure was required to reach effects similar to a single THJ-2201 dose. Cell viability and proliferation, mitochondrial membrane potential, and intracellular ATP levels were also determined. The tested SCs increased mitochondrial tetramethyl rhodamine ethyl ester (TMRE) accumulation after 24 h at biologically relevant concentrations but did not affect any of the other toxicological parameters. Overall, we report firsthand the CB1R-mediated enhancement of neurodifferentiation by 5F-PB22 and THJ-2201 at biologically relevant concentrations.

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Approximately 37 million people worldwide are infected with human immunodeficiency virus (HIV). One highly significant complication of HIV infection is the development of HIV-associated neurocognitive disorders (HAND) in 15-55% of people living with HIV (PLWH), that persists even in the antiretroviral therapy (ART) era. The entry of HIV into the central nervous system (CNS) occurs within 4-8 days after peripheral infection. This establishes viral reservoirs that may persist even in the presence of ART. Once in the CNS, HIV infects resident macrophages, microglia, and at low levels, astrocytes. In response to chronic infection and cell activation within the CNS, viral proteins, inflammatory mediators, and host and viral neurotoxic factors produced over extended periods of time result in neuronal injury and loss, cognitive deficits and HAND. Substance abuse is a common comorbidity in PLWH and has been shown to increase neuroinflammation and cognitive disorders. Additionally, it has been associated with poor ART adherence, and increased viral load in the cerebrospinal fluid (CSF), that may also contribute to increased neuroinflammation and neuronal injury. Studies have examined mechanisms that contribute to neuroinflammation and neuronal damage in PLWH, and how substances of abuse exacerbate these effects. This review will focus on how substances of abuse, with an emphasis on methamphetamine (meth), cocaine, and opioids, impact blood brain barrier (BBB) integrity and transmigration of HIV-infected and uninfected monocytes across the BBB, as well as their effects on monocytes/macrophages, microglia, and astrocytes within the CNS. We will also address how these substances of abuse may contribute to HIV-mediated neuropathogenesis in the context of suppressive ART. Additionally, we will review the effects of extracellular dopamine, a neurotransmitter that is increased in the CNS by substances of abuse, on HIV neuropathogenesis and how this may contribute to neuroinflammation, neuronal insult, and HAND in PLWH with active substance use. Lastly, we will discuss some potential therapies to limit CNS inflammation and damage in HIV-infected substance abusers.

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Managing body packers and stuffers is a challenge to emergency physicians, stuffers in particular, as there is no systematic approach to their treatment. The aim of this study was therefore to review all available literature on body stuffing and propose a guide to manage these patients. We searched Medline/PubMed, Google Scholar, and Scopus for published work on body stuffers using key words "body stuffer", "body stuffing", "poisoning", "toxicity", and "treatment" without a time limit and retrieved 290 articles, of which 61 remained after exclusion of those on "body packers" and repetitive documents. This review article evaluates and summarises the information gathered from them. The main step in body stuffer management is observation to make sure that they have passed all the swallowed packages of drugs of abuse. In some cases, imaging can be quite useful. Diagnostic pitfalls may be avoided with abdominopelvic CT without contrast, which is probably the best diagnostic method to determine the presence and the number of packages in these patients. Treatment should be specific for each group of drugs, whether it is opioids, cocaine, or amphetamine. Surgical interventions are indicated for obstruction of the intestines or package rupture. Legal precautions should be taken because of the legal complexity of body stuffing cases.

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This study presents a new multi-residue analytical method for the simultaneous determination of 38 psychoactive drugs (including benzodiazepines, antidepressants and drugs of abuse) and related metabolites in raw wastewater. Potential analyte losses during sample filtration and stability in wastewater were evaluated. Analyte losses, especially for 12 compounds, were observed during filtration, indicating a strong sorption onto the filter material. In order to overcome this effect, filtered water samples were combined with methanolic washes of the corresponding filters and the resulting solutions were solid-phase extracted on mixed-mode (reverse-phase plus cation-exchange) sorbents. Extracts were analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. Quantification was performed by the internal standard method with isotopic labeled analogs. Recovery percentages varied between 65% and 137%; method quantification limits ranged between 0.2 and 22 ng/L in ultrapure water and between 0.3 and 30 ng/L in wastewater for all the analytes but three (for which they were ∼60-80 ng/L). The analysis of 24 h-composite samples collected during one week in the city of Santiago de Compostela demonstrated the ubiquity of 31 analytes, which were positively quantified in all samples. The highest concentrations were found for some of the antidepressants, with mean and maximum levels exceeding, in some cases, the levels previously reported in literature. This fact could be related to the additional washing step of the filters using methanol, which allowed to desorb retained analytes highlighting the importance of this step during the sample preparation protocol.

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We describe for the first time a method that utilizes microscale thermophoresis (MST) technology to determine polyclonal antibody affinities to small molecules. Using a novel type of heterologous MST, we have accurately measured a solution-based binding affinity of serum antibodies to heroin which was previously impossible with other currently available methods. Moreover, this mismatch approach (i.e., using a cross-reactive hapten tracer) has never been reported in the literature. When compared with equilibrium dialysis combined with ultra-performance liquid chromatography/tandem mass spectrometry (ED-UPLC/MS/MS), this novel MST method yields similar binding affinity values for polyclonal antibodies to the major heroin metabolites 6-AM and morphine. Additionally, we herein report the method of synthesis of this novel cross-reactive hapten, MorHap-acetamide-a useful analog for the study of heroin hapten-antibody interactions. Using heterologous MST, we were able to determine the affinities, down to nanomolar accuracies, of polyclonal antibodies to various abused opioids. While optimizing this method, we further discovered that heroin is protected from serum esterase degradation by the presence of these antibodies in a concentration-dependent manner. Lastly, using affinity data for a number of structurally different opioids, we were able to dissect the moieties that are crucial to antibody binding. The novel MST method that is presented herein can be extended to the analysis of any ligand that is prone to degradation and can be applied not only to the development of vaccines to substances of abuse but also to the analysis of small molecule/protein interactions in the presence of serum. Graphical abstract Strategy for the determination of hapten-induced antibody affinities using Microscale thermophoresis.

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Alcohol and drugs of abuse consumption in young adults, including women of childbearing age, has experienced significant increase over the past two decades. The use of questionnaires as the only measure to investigate prenatal alcohol and drugs of abuse exposure underestimates the real prevalence of exposure and could mislead to wrong conclusions. Therefore, the aim of this article was to compare reported rates of prenatal alcohol and drugs of abuse consumption with biomarkers of exposure by a comprehensive review of the available literature. We searched MEDLINE and EMBASE databases for articles catalogued between 1992 and 2015. We identified relevant published studies that assessed the comparison between prenatal exposure to alcohol and drugs of abuse assessed by self-reported questionnaire of consumption versus biomarkers of exposure. Thirteen studies were included regarding alcohol consumption, and seven of them about drugs of abuse. Women who admitted consumption during pregnancy by questionnaire varied from 0 to 37% for alcohol, from 0 to 4.3% for cocaine, and 2.9% for tetrahydrocannabinol (THC). Positive biomarkers results ranged from 16 to 44% for alcohol, 15.4% for cocaine, and from 4 to 12.4% for THC. Biomarkers should always complement questionnaires, as it has been shown that self-report may underestimate prenatal exposure to substances of abuse.

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BACKGROUND: Young patients with acute poisoning by substances of abuse have increased mortality rates in the long term. In Oslo, Norway, most of these patients are treated at the Oslo Accident and Emergency Outpatient Clinic. The majority were discharged without follow-up. In 2010, the clinic implemented an intervention program for patients under the age of 23 presenting with acute poisoning by substances of abuse. The intervention was a brief motivational interview with a social worker before discharge, followed by a telephone consultation. Patients in need of further follow-up were identified and referred. Our objective was to study short-term effects of the intervention program on referrals to follow-up and repetition rates of acute poisoning. METHODS: Comparative cohorts were derived from studies of acute poisoning at the Oslo Accident and Emergency Outpatient Clinic in 2003, 2008 and 2012. Two age groups of patients presenting with acute poisoning by substances of abuse were included: 16-22 years and 23-27 years. Patients in the pre-intervention cohorts of 2003 and 2008 were compared with patients of the same age in the post-intervention cohort of 2012. Repetition rates were estimated using survival analysis. In total, 1323 patients were included; 422 in the younger pre-intervention group, 366 in the younger post-intervention group, 288 in the older pre-intervention group, and 247 in the older post-intervention group. Overall, the major toxic agents were ethanol 823/1323 (62 %) and opioids 215/1323 (16 %). 719/1323 (54 %) patients were male. RESULTS: In the younger groups referrals to follow-up increased from 86/317 (27 %) to 156/366 (43 %) (p < 0.001) after the implementation of the program. Among the older patients, who were not included in the program, there was no significant change in referrals. There was no change in the repetition rate of acute poisoning in either age group. The program established contact with 225/366 (61 %) of the eligible patients. CONCLUSION: More patients were referred to follow-up after the intervention. We expect this to have a beneficial effect on their substance use and reduce excess morbidity and mortality in the long term. There was no change in the repetition rate of poisoning.

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Designer drugs are synthetic structural analogues/congeners of controlled substances with slightly modified chemical structures intended to mimic the pharmacological effects of known drugs of abuse so as to evade drug classification. Benzylpiperazine (BZP), a piperazine derivative, elevates synaptic dopamine and serotonin levels producing stimulatory and hallucinogenic effects, respectively, similar to the well-known drug of abuse, methylenedioxymethamphetamine (MDMA). Furthermore, BZP augments the release of norepinephrine by inhibiting presynaptic autoreceptors, therefore, BZP is a "messy drug" due to its multifaceted regulation of synaptic monoamine neurotransmitters. Initially, pharmaceutical companies used BZP as a therapeutic drug for the treatment of various disease states, but due to its contraindications and abuse potential it was withdrawn from the market. BZP imparts predominately sympathomimetic effects accompanied by serious cardiovascular implications. Addictive properties of BZP include behavioral sensitization, cross sensitization, conditioned place preference and repeated self-administration. Additional testing of piperazine derived drugs is needed due to a scarcity of toxicological data and widely abuse worldwide.

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