Clinical and Toxicological Profile of NBOMes: A Systematic Review.

BACKGROUND: NBOMes are a new class of potent hallucinogens widely present in illicit drugs. Little is known about this class of drugs, regarding its detection and clinical manifestations of intoxication. OBJECTIVE: This study aims to enhance care involving NBOMes by reviewing the literature on their clinical manifestations and laboratorydetection. METHODS: A systematic review was performed on the clinical manifestations and laboratory tests of NBOMEs ingestion. Embase, Pubmed, PsycINFO, and Cochrane databases were employed in this analysis. RESULTS: Forty-five articles met the inclusion criteria out of the 2814 nonduplicated studies on the theme. Seventy case reports of intoxication were found in the analyzed articles (64.3% were men and 11.4% were women, mean age of 22.5). The technique most employed for NBOMes identification was chromatography of blood, urine, and oral fluids. Moreover, the studies identified 13 chemical structures differentfrom the NBOMes on their toxicological analyses.According to these studies, most of these drugs were ingested orally-nasal use was the second preferred administration route, followed by intravenous administration. CONCLUSION: Better identification of the clinicalmanifestations and laboratory profile of NBOMes is crucial to the recognition of intoxication as well as to its effective treatment.

Re-traumatization Cycle: Sexual Abuse, Post-Traumatic Stress Disorder and Sexual Risk Behaviors among Club Drug Users.

Background: Club drug users are high risk and vulnerable population for adverse drug-related consequences and sexual risk behaviors. Few investigations have addressed the possible interrelationship between early trauma and PTSD among young club drug using populations. Objective: Exposure to traumatic experiences - especially in childhood, has been linked to risk behaviors exposure and substance use disorder. This study aimed to assess and compare drug use patterns and the presence of childhood sexual abuse (CSA) experiences among ecstasy and LSD users with and without Posttraumatic Stress Disorder (PTSD). Method: This cross-sectional study employed targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals. The Global Appraisal of Individual Needs questionnaire was used as the primary assessment instrument. Participants were from 18 to 39 years of age, had used ecstasy and/or LSD in the 90 days prior to the interview, and were not in treatment for alcohol and other drug problems. Results: Out of the 240 participants, 123 (51.2%) presented PTSD symptoms. Those presenting PTSD were younger, less educated, with lower income, and presented higher drug use severity than those without PTSD symptoms. Moreover, a higher prevalence of sexual risk behavior was verified among those with PTSD. There was an association between PTSD symptoms and CSA history, where 64.2% of individuals with PTSD also presented CSA, compared to 47% among those without PTSD (p = .028). Individuals with co-occurring history of CSA and PTSD symptoms reported earlier use of ecstasy, LSD, and cocaine compared to individuals with a history of CSA but without PTSD. Conclusions: In the present study, participants with a history of PTSD demonstrate a history of CSA, as well as pronounced severity in several areas - precocity of use, severity of addiction, and greater exposure to situations of sexual risk. Thus, a cycle of traumatization may be established through early potential trauma, which can remain unprocessed and contribute to earlier and more severe substance use and sexual risk behaviors. Identification of PTSD symptoms and risk for HIV and other STIs among young club drug users is critical to address focused treatment approaches for this vulnerable population.

Markers for Severity of Problems in Interpersonal Relationships of Crack Cocaine Users from a Brazilian Multicenter Study.

Crack cocaine users frequently report difficulties regarding having healthy and rewarding relationships. Factors other than the use of crack cocaine itself may be at play when it comes to being able to develop healthier connections with partners, adult relatives and close friends. To verify which factors, including demographics, substance abuse related factors and psychiatric comorbidities could be markers for a higher severity of problems in interpersonal relationships of crack cocaine users seeking for treatment. This was a cross-sectional study, conducted between April 2011 and November 2012. Participants were 407 crack cocaine users seeking treatment in specialized public facilities of six Brazilian capitals. The relationship of severity of problems in the family/social area and the prevalence of psychiatric disorders, exposure to stressful events, substance use related factors and practice of illicit activities were explored through multivariate analyses. Number of days using crack cocaine in the last 30 days, age of first time using alcohol and feeling its effects, a diagnosis of alcohol abuse, posttraumatic stress disorder, antisocial personality disorder and attention-deficit/hyperactivity disorder were significantly associated with a higher severity of problems in interpersonal relationships with partners, adult relatives and friends. Problems in interpersonal relationships are strongly related to specific psychiatric comorbidities and the frequency of crack cocaine use. Factors identified by this study can make the paths to recovery more challenging. These results support psychosocial interventions that focus in the improvement of interpersonal relationships of crack cocaine users.

Hematological inflammatory biomarkers in patients with alcohol and cocaine use disorders.

BACKGROUND: Neutrophil-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelets-lymphocyte ratio (PLR) are biomarkers easy-to-obtain and could be used in clinical practice to verify an inflammatory status and are associated with alcohol use disorder (AUD) and cocaine use disorder (CUD). Our aim was to compare NLR, MLR and PLR among men with AUD and CUD and to assess the relationship between these biomarkers and addiction-related outcomes. METHODS: This is a cross-sectional study comprising 979 inpatient men diagnosed with substance use disorder (391 with AUD and 588 with CUD) under hospital treatment for drug addiction. RESULTS: Individuals with AUD had higher NLR and MLR (p=0.041, p<0.001 respectively) compared to individuals with CUD. In the AUD group, positive correlations between age and MLR (r=0.111; p=0.029), NLR and liver enzymes ALT and AST (r=0.103, p=0.043; r=0.155, p=0.002; respectively), and MLR and ALT, AST and GGT levels were observed (r=0.173, p=0.001; r=0.242, p<0.001; r=0.167, p=0.001, respectively). Individuals with CUD showed a positive correlation between age and NLR (r=0.113; p=0.006). The presence of clinical comorbidities, HIV, HCV and syphilis were not associated with NLR, MLR, and PLR (p>0.05). CONCLUSION: These biomarkers are a rapid and inexpensive way to assess the effects of substance use on the inflammatory profile. Our findings contribute with valuable insights into the distinctive inflammatory profiles associated with AUD and CUD. These insights could guide further research and the development of more studies, which could include control groups, in order to refine the clinical applicability of these biomarkers.

Reliability of roadside oral fluid testing devices for ∆9 -tetrahydrocannabinol (∆9 -THC) detection.

Driving under the influence of cannabis (DUIC) is increasing worldwide, and cannabis is the most prevalent drug after alcohol in impaired driving cases, emphasizing the need for a reliable traffic enforcement strategy. ∆9 -tetrahydrocannabinol (THC) detection in oral fluid has great potential for identifying recent cannabis use; however, additional data are needed on the sensitivities, specificities, and efficiencies of different oral fluid devices for detecting cannabinoids at the roadside by police during routine traffic safety enforcement efforts. At the roadside, 8945 oral fluid THC screening tests were performed with four devices: AquilaScan®, Dräger DrugTest®, WipeAlyser Reader®, and Druglizer®. A total of 530 samples screened positive for THC (5.9%) and were analyzed by liquid chromatography-tandem mass spectrometry at multiple cutoff concentrations (2 ng/mL, 10 ng/mL, and manufacturers' recommended device cutoffs) to investigate device performance. Results varied substantially, with sensitivities of 0%-96.8%, specificities of 89.8%-98.5%, and efficiencies of 84.3%-97.8%. The Dräger DrugTest® outperformed the other devices with a 96.8% sensitivity, 97.1% specificity, and 97.0% efficiency at a 5-ng/mL LC-MS/MS confirmation cutoff. The WipeAlyser Reader® had good performance with a 91.4% sensitivity, 97.2% specificity, and 96.4% efficiency. AquilaScan® and Druglizer® had unacceptable performance for cannabinoid detection, highlighted by sensitivity <13%. The choice of roadside oral fluid testing device must offer good analytical performance for cannabinoids because of its high prevalence of use and impact on road safety.

A rapid review of machine learning approaches for telemedicine in the scope of COVID-19.

The COVID-19 pandemic has rapidly spread around the world. The rapid transmission of the virus is a threat that hinders the ability to contain the disease propagation. The pandemic forced widespread conversion of in-person to virtual care delivery through telemedicine. Given this gap, this article aims at providing a literature review of machine learning-based telemedicine applications to mitigate COVID-19. A rapid review of the literature was conducted in six electronic databases published from 2015 through 2020. The process of data extraction was documented using a PRISMA flowchart for inclusion and exclusion of studies. As a result, the literature search identified 1.733 articles, from which 16 articles were included in the review. We developed an updated taxonomy and identified challenges, open questions, and current data types. Our taxonomy and discussion contribute with a significant degree of coverage from subjects related to the use of machine learning to improve telemedicine in response to the COVID-19 pandemic. The evidence identified by this rapid review suggests that machine learning, in combination with telemedicine, can provide a strategy to control outbreaks by providing smart triage of patients and remote monitoring. Also, the use of telemedicine during future outbreaks could be further explored and refined.

Differential impact on suicide mortality during the COVID-19 pandemic in Brazil.

OBJECTIVES: To compare suicide rates observed in Brazil after the onset of the COVID-19 pandemic with the estimated rate based on suicide deaths between 2010 and 2020, and identify sociodemographic variables associated with this outcome. METHODS: Ecological time-series study. Data were obtained from Brazilian Unified Health System Department of Information Technology (DATASUS), with the structural break of the data set in March 2020. The number of actual suicides observed and the number of expected suicides if there were no COVID-19 pandemic were analyzed through bayesian structural time series modeling. RESULTS: The overall incidence of suicides in Brazil remained stable after the start of the COVID-19 pandemic compared to what would be expected. However, there was a significant increase in suicide deaths among women (6.9%) and older adult (9.1%). Analysis by macro-regions of the country showed significant increases in suicide deaths in the Center-West (7.4%), Northeast (5.7%), and Southeast (10%). Stratified analyses revealed differences according to age, sex, education, and skin color. CONCLUSIONS: Despite stability in the overall number of suicides, this phenomenon occurs heterogeneously among different population groups and regions of Brazil. Rates have increased in populations with a history of poor access to health, which may have been more severely impacted by the pandemic.

Increase in serum brain-derived neurotrophic factor levels during early withdrawal in severe alcohol users.

INTRODUCTION: Changes in brain-derived neurotrophic factor (BDNF) have been linked to the neuroadaptative consequences of chronic alcohol use and associated with disease severity and prognosis. Few studies have evaluated the influence of drug withdrawal and clinical and sociodemographic data on BDNF levels in severe alcohol users. OBJECTIVES: Our goals were (1) to evaluate variation in BDNF levels during alcohol withdrawal and, (2) to assess the influence of putative confounding factors on BDNF levels. METHODS: Our sample consists of 62 men with alcohol use disorder undergoing a detoxification process. Serum BDNF levels were measured using a commercial sandwich-ELISA kit, at two points: before and after the detoxification period. RESULTS: We found an increase in BDNF levels during alcohol withdrawal (25.4±9.6 at admission vs. 29.8±10.2 ng/ml at discharge; p < 0.001), even after controlling for potential confounders (positive family history, number of days between blood sample collections, and age) (Generalized Estimating Equation: coefficient = -4.37, 95% confidence interval [95%CI] -6.3; -2.4; p < 0.001). Moreover, individuals who had first-degree relative with alcohol dependence had smaller increases in BDNF levels than individuals with no family history (14.8 [95%CI -5.3; 35.6] vs. 35.3 [95%CI 15.4; 74.8]; p = 0.005). CONCLUSIONS: In summary, variation in BDNF levels seems to be influenced by withdrawal in severe alcohol users. A positive family history of alcohol dependence could also be a factor that influences variation in this biomarker.

First and second COVID-19 waves in Brazil: A cross-sectional study of patients' characteristics related to hospitalization and in-hospital mortality.

BACKGROUND: Background The second wave of the COVID-19 pandemic was more aggressive in Brazil compared to other countries around the globe. Considering the Brazilian peculiarities, we analyze the in-hospital mortality concerning socio-epidemiological characteristics of patients and the health system of all states during the first and second waves of COVID-19. METHODS: We performed a cross-sectional study of hospitalized patients with positive RT-PCR for SARS-CoV-2 in Brazil. Data was obtained from the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) and comprised the period from February 25, 2020, to April 30, 2021, separated in two waves on November 5, 2020. We performed a descriptive study of patients analyzing socio-demographic characteristics, symptoms, comorbidities, and risk factors stratified by age. In addition, we analyzed in-hospital and intensive care unit (ICU) mortality in both waves and how it varies in each Brazilian state. FINDINGS: Between February 25, 2020 and April 30, 2021, 678 235 patients were admitted with a positive RT-PCR for SARS-CoV-2, with 325 903 and 352 332 patients for the first and second wave, respectively. The mean age of patients was 59 · 65 (IQR 48 · 0 - 72 · 0). In total, 379 817 (56 · 00%) patients had a risk factor or comorbidity. In-hospital mortality increased from 34 · 81% in the first to 39 · 30% in the second wave. In the second wave, there were more ICU admissions, use of non-invasive and invasive ventilation, and increased mortality for younger age groups. The southern and southeastern regions of Brazil had the highest hospitalization rates per 100 000 inhabitants. However, the in-hospital mortality rate was higher in the northern and northeastern states of the country. Racial differences were observed in clinical outcomes, with White being the most prevalent hospitalized population, but with Blacks/Browns (Pardos) having higher mortality rates. Younger age groups had more considerable differences in mortality as compared to groups with and without comorbidities in both waves. INTERPRETATION: We observed a more considerable burden on the Brazilian hospital system throughout the second wave. Furthermore, the north and northeast of Brazil, which present lower Human Development Indexes, concentrated the worst in-hospital mortality rates. The highest mortality rates are also shown among vulnerable social groups. Finally, we believe that the results can help to understand the behavior of the COVID-19 pandemic in Brazil, helping to define public policies, allocate resources, and improve strategies for vaccination of priority groups. FUNDING: Coordinating Agency for Advanced Training of Graduate Personnel (CAPES) (C.F. 001), and National Council for Scientific and Technological Development (CNPq) (No. 309537/2020-7).

Making the COVID-19 Pandemic a Driver for Digital Health: Brazilian Strategies.

The COVID-19 outbreak exposed several problems faced by health systems worldwide, especially concerning the safe and rapid generation and sharing of health data. However, this pandemic scenario has also facilitated the rapid implementation and monitoring of technologies in the health field. In view of the occurrence of the public emergency caused by SARS-CoV-2 in Brazil, the Department of Informatics of the Brazilian Unified Health System created a contingency plan. In this paper, we aim to report the digital health strategies applied in Brazil and the first results obtained during the fight against COVID-19. Conecte SUS, a platform created to store all the health data of an individual throughout their life, is the center point of the Brazilian digital strategy. Access to the platform can be obtained through an app by the patient and the health professionals involved in the case. Health data sharing became possible due to the creation of the National Health Data Network (Rede Nacional de Dados em Saúde, RNDS). A mobile app was developed to guide citizens regarding the need to go to a health facility and to assist in disseminating official news about the virus. The mobile app can also alert the user if they have had contact with an infected person. The official numbers of cases and available hospital beds are updated and published daily on a website containing interactive graphs. These data are obtained due to creating a web-based notification system that uses the RNDS to share information about the cases. Preclinical care through telemedicine has become essential to prevent overload in health facilities. The exchange of experiences between medical teams from large centers and small hospitals was made possible using telehealth. Brazil took a giant step toward digital health adoption, creating and implementing important initiatives; however, these initiatives do not yet cover the entire health system. It is expected that the sharing of health data that are maintained and authorized by the patient will become a reality in the near future. The intention is to obtain better clinical outcomes, cost reduction, and faster and better services in the public health network.

Obsessive-compulsive disorder reinforcement during the COVID-19 pandemic.

The COVID-19 pandemic is unquestionably impacting on the mental health of the population worldwide. Fear of contamination can both increase levels of stress in healthy individuals and intensify psychiatric symptoms in patients with pre-existing conditions, especially obsessive-compulsive disorder (OCD). During the COVID-19 pandemic, the imminent risk of contamination creates a logical need for self-surveillance and hygiene habits. However, this kind of information can have drastic implications for subjects with OCD, since cognitive distortions and compensatory strategies (cleansing rituals) are no longer irrational or oversized - rather, these ideas become legitimate and socially accepted, generating plausible validation for the intensification of compulsive cleaning rituals. Patients who presented remission of OCD symptoms would be more likely to have a relapse, and subclinical patients may scale up and ultimately be diagnosed with OCD due to the reinforcement of their habits, emotions and thoughts.

The next pandemic: impact of COVID-19 in mental healthcare assistance in a nationwide epidemiological study.

BACKGROUND: Studies have reported the worsening of psychiatric symptoms during the COVID-19 pandemic. However, few studies have evaluated the impact on the access to mental health services during COVID-19. Our aim was to analyze temporal trends and prediction of appointments held in Brazil's public health system, to compare the observed and expected number of mental healthcare appointments during the COVID-19 pandemics. METHODS: An ecological time-series study was performed, analyzing mental health appointments before and during the pandemic (from 2016 and 2020) from the Brazilian governmental database. The structural break in the data series was assessed using the Chow test, with the break considered in March 2020. Bayesian structural time-series models were used to estimate current average appointments and the predicted expectation if there was no pandemic. FINDINGS: Compared to the expected, between March and August 2020 about 28% less outpatient appointments in mental health were observed, totaling 471,448 individuals with suspended assistance. Group appointments and psychiatric hospitalizations were also severely impacted by the pandemic (decreased of 68% and 33%, respectively). On the other hand, mental health emergency consultations and home care increased during this period (36% and 52%, respectively). INTERPRETATION: Our findings demonstrate a dramatic change in mental health assistance during the COVID-19 pandemic, which corroborates a recent WHO survey. This phenomenon can aggravate the mental health crisis and generate a parallel pandemic that may last for a longer time than the COVID-19 pandemic. FUNDING: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.

From phone use to speeding and driving under influence: Identifying clusters of driving risk behaviors as an opportunity for targeted interventions.

Identifying the profile of risky behaviors among drivers is central to propose effective interventions. Due to the multidimensional and overlapping aspects of risky driving behaviors, cluster analysis can provide additional insights in order to identify specific subgroups of risk. This study aimed to identify clusters of driving risk behavior (DRB) among car drivers, and to verify intra-cluster differences concerning clinical and sociodemographic variables. We approached a total of 12,231 drivers and we included 6392 car drivers. A cluster algorithm was used to identify groups of car drivers in relation to the DRB: driving without a seat belt (SB), exceeding the speed limit (SPD), using a cell phone while driving (CELL), and driving after drinking alcohol (DUI). The algorithm classified drivers within five different DRB profiles. In cluster 1 (20.1%), subjects with a history of CELL. In cluster 2 (41.4%), drivers presented no DRB. In cluster 3 (9.3%), all drivers presented SPD. In cluster 4 (12.5%), drivers presented all DRB. In cluster 5 (16.6%), all drivers presented DUI. Clusters with DUI-related offenses (4 and 5) comprised more men (81.9 and 78.8%, respectively) than the overall sample (63.4%), with more binge drinking (50.9 and 45.7%) and drug use in the previous year (13.5 and 8.6%). Cluster 1 had a high years of education (14.4 ± 3.4) and the highest personal income (Md = 3000 IQR [2000-5000]). Cluster 2 had older drivers (46.6 ± 15), and fewer bingers (10.9%). Cluster 4 had the youngest drivers (34.4 ± 11.4) of all groups. Besides reinforcing previous literature data, our study identified five unprecedented clusters with different profiles of drivers regarding DRB. We identified an original and heterogeneous group of drivers with only CELL misuse, as well as other significant differences among clusters. Hence, our findings show that targeted interventions must be developed for each subgroup in order to effectively produce safe behavior in traffic.

The COVID-19 pandemic and its impact on substance use: Implications for prevention and treatment.

The COVID-19 pandemic has brought major challenges to healthcare systems and public health policies globally, as it requires novel treatment and prevention strategies to adapt for the impact of the pandemic. Individuals with substance user disorders (SUD) are at risk population for contamination due to multiple factors-attributable to their clinical, psychological and psychosocial conditions. Moreover, social and economic changes caused by the pandemic, along with the traditional difficulties regarding treatment access and adherence-will certainly worsen during this period, therefore aggravate their condition. In addition, this population are potential vectors of transmission. In that sense, specific strategies for prevention and treatment must be discussed. health care professionals dealing with SUD must be aware of the risks and challenges they will meet during and after the COVID-19 outbreak. Addiction care must be reinforced, instead of postponed, in order to avoid complications of both SUD and COVID-19 and to prevent the transmission of coronavirus.

Prediction of attempted suicide in men and women with crack-cocaine use disorder in Brazil.

BACKGROUND: Suicide is a severe health problem, with high rates in individuals with addiction. Considering the lack of studies exploring suicide predictors in this population, we aimed to investigate factors associated with attempted suicide in inpatients diagnosed with cocaine use disorder using two analytical approaches. METHODS: This is a cross-sectional study using a secondary database with 247 men and 442 women hospitalized for cocaine use disorder. Clinical assessment included the Addiction Severity Index, the Childhood Trauma Questionnaire, and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, totalling 58 variables. Descriptive Poisson regression and predictive Random Forest algorithm were used complementarily to estimate prevalence ratios and to build prediction models, respectively. All analyses were stratified by gender. RESULTS: The prevalence of attempted suicide was 34% for men and 50% for women. In both genders, depression (PRM = 1.56, PRW = 1.27) and hallucinations (PRM = 1.80, PRW = 1.39) were factors associated with attempted suicide. Other specific factors were found for men and women, such as childhood trauma, aggression, and drug use severity. The men's predictive model had prediction statistics of AUC = 0.68, Acc. = 0.66, Sens. = 0.82, Spec. = 0.50, PPV = 0.47 and NPV = 0.84. This model identified several variables as important predictors, mainly related to drug use severity. The women's model had higher predictive power (AUC = 0.73 and all other statistics were equal to 0.71) and was parsimonious. CONCLUSIONS: Our findings indicate that attempted suicide is associated with depression, hallucinations and childhood trauma in both genders. Also, it suggests that severity of drug use may be a moderator between predictors and suicide among men, while psychiatric issues shown to be more important for women.

User experience and operational feasibility of four point-of-collection oral fluid drug-testing devices according to Brazilian traffic agents.

OBJECTIVE: Traffic fatalities in Brazil still rank among the highest worldwide, with an overall rate of 23.4 deaths/100,000 inhabitants/year. Although alcohol and drug use play an important role in traffic accidents, national data about their relative influence are scarce. Drug screening is not routinely performed by traffic agents because alcohol is the only substance regularly investigated in roadblocks. Therefore, we aimed to describe the initial traffic agent user experience for 4 handheld point-of-collection oral fluid drug testing devices used in routine roadblocks in Brazil, focusing on usage perceptions in hopes of generalizing this approach for other developing countries. METHODS: Four different oral fluid collection devices were evaluated: The DDS2, the DOA MultiScreen, the Dräger DrugTest 5000, and the Multi-Drug Multi-Line Twist Screen Device. Fourteen trained traffic agents obtained oral fluid from 164 drivers and performed 37 qualitative evaluations of the devices. Traffic agents filled out a questionnaire focusing on 9 feasibility criteria: Overall simplicity for roadside operation; operational success; saliva sample collection time; sample analysis time; ease of sample preparation and analysis; agreement with observed clinical signs; overall hygiene and safety; sufficient operating instructions; and hygiene of saliva collection. These were weighted based on an expert panel and yielded an overall composite device experience score that ranged from 1 (poor) to 100 (excellent). RESULTS: Ease of use, operational success, and acceptable collection and analysis time were considered the most important criteria by the expert panel. The results ranged from 27.3 to 88.9% for simplicity of use; 45.5 to 100.0% for operational success; 27.3 to 100% for acceptable collection time; and 36.4 to 100.0% for acceptable analysis time. The final device scores, based on the agents' user experiences, ranked as follows: DOA MultiScreen: 49.3/100; Dräger DrugTest 5000: 82.4/100; Multi-Drug Multi-Line Twist Screen Device: 84.3/100; DDS2: 88.4/100. CONCLUSION: Based on the selected criteria, 3 of the 4 devices were considered useful by traffic agents in routine roadblock operations. The weighted evaluations suggest that their ease of use (handling, sampling analysis, and reliability), as well as their agreement with findings obtained by other means, defined their utility to traffic agents, although such appraisals must be further analyzed in future studies.

Comparison of Cocaine/Crack Biomarkers Concentrations in Oral Fluid, Urine and Plasma Simultaneously Collected From Drug Users.

The use of oral fluid (OF) as an alternative specimen for drug analysis has become very popular in forensic toxicology. Many clinical studies have evaluated the correlations between concentrations of cocaine and its metabolites in OF and other matrices, but results have shown high variability. In addition, there are no data available regarding the correlations between biomarkers of crack-cocaine use in different matrices. This study evaluated the relationship between concentrations of cocaine/crack-cocaine biomarkers in OF, urine and plasma samples collected from cocaine users. All samples were analyzed for the presence of cocaine (COC), benzoylecgonine (BZE) and anhydroecgonine (AEC) by a validated liquid chromatography-mass spectrometry method. Median COC, BZE and AEC concentrations ranged from 4.20 to 33.26 ng/mL, from 13.03 to 3,615.86 ng/mL and from 7.40 to 1,892.5 ng/mL across matrices, respectively. The relationship between drug concentrations in OF versus plasma (OF/P) and OF versus urine (OF/U) was evaluated by their coefficients of determination (R2). Least-squares regression analyses demonstrated significant correlations between OF/P and OF/U for cocaine and BE (P < 0.05), with R2 = 0.17, 0.07 for cocaine and R2 = 0.73, 0.45 for BE, respectively. The correlation coefficients (r) found for BZE, COC and AEC in OF/P and OF/U were 0.85 and 0.67 (P < 0.05); 0.41 and 0.26 (P < 0.05); and 0.30 and -0.37 (P > 0.05), respectively. Many factors contribute to the variability of drug correlation ratios in studies involving random samples, including uncertainty about the time of last administration and dosage. Overall, we found significant R2 values for COC and BZE in OF/P and OF/U, but not for AEC. Despite the good correlations found in some cases, especially for BZE, the large variation in drug concentrations seen in this work suggests that OF concentrations should not be used to estimate concentrations of COC, BZE or AEC in plasma and/or urine.

Leptin levels and its correlation with crack-cocaine use severity: A preliminary study.

BACKGROUND: Crack-cocaine is an important public health problem in Brazil and worldwide. It is a potent form of cocaine which results in rapid and damaging stimulating effects on the central nervous system through inhibition of the dopamine transporter. Some studies have suggested that both food and drugs - including crack, can act on the same brain reward mechanisms, altering the dopamine pathways that modulate behavioral responses. Our hypothesis was that leptin, a well-known peptide that modulates energy metabolism and appetite, can be used as a biomarker for drug use. METHODS: Anthropometric data, drug use profiles, and leptin serum levels were evaluated in a cross-sectional study of 40 crack-cocaine users. RESULTS: Leptin showed an inverse correlation with the severity of crack use, and this correlation remained when corrected by body mass index (BMI) and body composition by bioimpedance (BIA). The majority of subjects were eutrophic or overweight/obese considering BMI and BIA, and these variables were not significantly associated with the severity of crack use, but positively correlated with leptin levels. CONCLUSIONS: Our preliminary findings suggest that leptin could be involved in drug use severity, perhaps through pathways similar to those whereby it modulates food intake. Considering the anthropometric parameters, these findings provide additional evidence that low weight is not predominant in crack users.

Brain-derived neurotrophic factor in substance use disorders: A systematic review and meta-analysis.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is associated with several neurodegenerative and psychiatric disorders. It is not clear, however, whether BDNF levels are modified in substance use disorders (SUDs). METHODS: We conducted a systematic search of electronic databases to identify studies comparing peripheral plasma or serum BDNF levels in adults with SUDs vs. non-user controls. Forty studies were included in the meta-analysis involving a total of 2238 participants with SUDs and 2574 controls. RESULTS: After trim and fill adjustment, current drug users presented lower serum BDNF levels (SMD = -0.99, 95%CI -1.40 to -0.58, I2 = 95.9) than non-user controls. However, this difference disappears during withdrawal. Studies using serum or plasma BDNF samples have shown different results. Subgroup analysis revealed lower levels of serum BDNF in alcohol users (SMD = -0.70, 95%CI -1.15 to -0.25, I2 = 89.81) and crack/cocaine users (SMD = -1.78, 95%CI -2.92 to -0.65, I2 = 97.59) than controls. Meta-regression analysis revealed that gender, age, and age of first use moderate the effects of drug use in peripheral BDNF levels. CONCLUSIONS: Peripheral BDNF levels are decreased in the serum, but not the plasma, of active drug users. Altogether, these findings suggest that BDNF levels may be related to acute use and addiction severity and also point to BDNF's potential utility as a biomarker in this population.