Blood alcohol concentration and road accidents: Underestimation due to time of the arrival to the emergency department (ED) or delay in blood sampling. A 4-Year Retrospective Study in Rome.

Alcohol is a significant public health issue, according to the World Health Organization. Our study aims to analyze the correlation between blood alcohol concentrations (BACs) of drivers, their demographic features, and the possible underestimation of BACs due to the time elapsed between hospital admission and blood sampling. Methods: This study includes patients evaluated for BAC levels in the emergency department (ED) of Fondazione Policlinico Universitario A. Gemelli IRCCS from January 2013 to December 2016. BAC levels were compared in patients involved in road crashes according to age group, sex, and time of the accident. The delays in blood sampling and BAC measurement in the ED were recorded for each patient. The time between the accident and access to the hospital in most cases was unknown. Results: A total of 398 patients were included in the analysis, 107 of them had BACs more than 0.05 g/L., and 86 of these individuals had BAC levels more than 0.5 g/L. Road accident patients had higher rates of positive BAC readings at night and on weekends. A significant delay in blood sampling for BAC determination was observed. Discussion: This study demonstrates a critical bias due to the arrival time at the ED and the delay in blood sampling that inevitably influences and underestimates the BAC, resulting in possible false negative results (BAC values below the cutoff). Zero tolerance or a retrospective BAC calculation could mitigate this bias. It is necessary to implement preventive strategies to reduce instances of driving under the influence (DUI) of alcohol.

Drug-impaired driving and traffic collisions: Study on a cross section of the Italian population.

The present study focuses on the association between road accidents and the presence of drugs of abuse markers in the biological fluids of the drivers. Biological fluids collected from 1236 drivers involved in road accidents (54 fatal and 1182 non-fatal crashes) in the Rome area were analyzed for alcohol and psychotropic drugs, as required by judicial authorities. The substance most frequently detected was alcohol (in 19% of non-fatal and 32% of fatal crashes), followed by cannabinoids (12% of non-fatal crashes) and cocaine (9% of non-fatal and 20% of fatal crashes). The results obtained for cocaine and cannabinoids in blood and urine were compared. We observed the absence or low concentrations of the active drug in blood (cocaine was often below 5 ng/ml and THC below 1 ng/ml), whereas urinary concentrations of metabolites were generally high (benzoylecgonine 250-above 5000 ng/ml, THCCOOH 15-270 ng/ml). The risk of being involved in a road accident if cocaine or cannabis markers were present in the urine specimens was evaluated compared to a control population. The odds ratios calculated, being 8.13 for cannabis and 5.32 for cocaine, suggest a strong association between the presence of these drugs in the urine of drivers and traffic accidents, regardless of their presence in blood samples. The present data suggest that the chance of being involved in a road accident is higher than in the control population even if the subject is no longer "under the influence" of cannabis or cocaine at the time of the accident.

Did poisoning play a role in Napoleon's death? A systematic review.

INTRODUCTION: On 5 May 2021 we celebrate the bicentenary of Napoleon's death. Despite autopsy findings of a "gastric cancer" and, more importantly, gastric perforated ulcer complicated with bleeding, the questions about the illness that tormented Napoleon at St. Helena and whether the death was a consequence of a poisoning, maintain an unbroken fascination. PubMed/MEDLINE lists hundreds of articles. We also consulted Index-Cat library for articles dating back to the eighteenth century. The present paper presents for the first time a systematic review on this topic. METHODS: The authors divided the selected articles according to the methodology of the papers: (a) illness and autopsy evidence revised by current pathological knowledge; (b) toxicological tests on Napoleon's hair performed by modern analytical techniques. RESULTS: None of the articles denied the toxicological evidence from Napoleon's hair, although analytical papers did not offer homogeneous results due to several biases. Few of them refuted the hypothesis of death due to primary toxic substances. Most considered gastric bleeding is the primary cause of Napoleon's death due to solely or nearly completely gastric cancer or to medications containing antimony, mercury, or arsenic. CONCLUSIONS: Upon review of the contemporary and modern evidence, we classify Napoleon's 1821 death as "unnatural" with massive gastric bleeding due to primary involvement of toxic substances that may have precipitated or exacerbated an underlying "natural" pathological condition or a disease as likely could be a stomach carcinoma; it does not imply criminal intent.

A data-driven methodology to discover similarities between cocaine samples.

Machine learning has been used for distinct purposes in the science field but no applications on illegal drug have been done before. This study proposes a new web-based system for cocaine classification, profiling relations and comparison, that is capable of producing meaningful output based on a large amount of chemical profiling's data. In particular, the Profiling Relations In Drug trafficking in Europe (PRIDE) system, offers several advantages to intelligence actions across Europe. Thus, it provides a standardized, broad methodology which uses machine learning algorithms to classify and compare drug profiles, highlight how similar drug samples are, and how probable it is that they share a common origin, batch, or preparation process. We evaluated the proposed algorithms using precision and recall metrics and analyzed the quality of predictions performed by the algorithms, with respect to our gold standard. In our experiments, we reached a value of 88% for F0.5-measure, 91% for precision, and 78% for recall, confirming our main hypothesis: machine learning can learn and be applied to have an automatic classification of cocaine profiles.

A Systematic Review of Solid-Phase Microextraction Applications in the Forensic Context.

Since the introduction in 1990, the solid-phase microextraction (SPME) technology has brought significant progress in many fields of forensic sciences due to the versatility of this fast and solventless alternative to conventional extraction techniques. A systematic review about SPME applications in forensic context from January 1995 to June 2018 was carried out according to systematic review guidelines. The majority of the reviewed articles (40/133) aimed to identify drugs (cannabinoids, cocaine, opiates, amphetamines, simultaneous detection of different drugs of abuse, prescribed drugs); 29 of the 133 articles focused on the investigation of fatalities; 28 of the 133 papers used headspace SPME technique for the identification of markers of chronic alcohol abuse. Sixteen papers involved this technique for the isolation of volatile organic compounds for the human odor profile and 20 concerned forensic applications regarding living people. Solid-phase microextraction was preferably employed in the headspace mode and many kinds of fibers were employed, although polydimethylsiloxane was the most adaptable to many forensic realities. Gas chromatography/mass spectrometry was more frequently used, probably for the well-established coupling with SPME. Most of the papers validated their method to harmonize the scientific approaches of procedures development. Good outcomes are reported on biological material collected from living people as well as on cadaveric samples. The results obtained by most of the studies about alcohol biomarkers on scalp hair have been adopted by the "Society of Hair Testing" to demonstrate abstinence over a pre-defined time period and to assess chronic excessive alcohol consumption.

Placenta as alternative specimen to detect in utero cannabis exposure: A systematic review of the literature.

The use of cannabis during pregnancy and lactation is widely recognized as a health concern. The placenta is one of the several biological matrices that can be used to detect in utero drug exposure with the distinct advantage of easy and noninvasive collection. We conducted a PubMed search of selected literature published to June 30, 2016 to investigate the pharmacokinetics of cannabinoids, the active constituent of cannabis, in the placenta. The majority of the selected twelve papers was before 1990 and concerned animals at term gestation with great variability of experimental conditions. Only three were about human population and two of them reported equivocal findings on pre- term placenta. Our systematic review confirms that placental cannabis pharmacokinetics has been scarcely investigated and that further research is needed to determine advantages and disadvantages for monitoring maternal THC use or the degree of in utero exposure.

Cannabinoid Poisoning by Hemp Seed Oil in a Child.

We report a case of mild cannabinoid poisoning in a preschool child, after 3-week ingestion of hemp seed oil prescribed by his pediatrician to strengthen his immune system. The patient presented neurological symptoms that disappeared after intravenous hydration. A possible mild withdrawal syndrome was reported after discharge. The main metabolite of Δ-tetrahydrocannabinol was detected in urine, and very low concentration of Δ-tetrahydrocannabinol was detected in the ingested product. This is, as far as we know, the first report of cannabinoid poisoning after medical prescription of hemp seed oil in a preschool child.

Coronary thrombosis and marijuana smoking: a case report and narrative review of the literature.

We encountered evidence of myocardial infarction due to coronary thrombosis in an autopsy of an occasional marijuana smoker. These findings prompted us to perform a narrative review of the literature to determine when post-mortem toxicological tests may support a temporal relationship between marijuana smoking and cardiovascular disease. Toxicological examination showed the presence of Δ-9-tetrahydrocannabinol, its main metabolite and cannabinol in blood and urine. Quali-quantitative analysis revealed that Δ-9-tetrahydrocannabinol was taken within 2 h of the onset of cardiovascular symptoms, according to circumstantial data. Post-mortem toxicological results must take into account the degradation and post-mortem redistribution of analytes. However, for any inference about the specific cardiovascular triggering effect of Δ-9-tetrahydrocannabinol intake, we maintain that cannabinoid analysis in blood samples must be considered an essential requirement to estimate the time of last intake and avoid incomplete documentation. The literature, combined with the present case report, highlights an association between marijuana use and negative cardiovascular events, although few authors have supported their conclusions with toxicological results. Thus, additional research is needed.

The usefulness of biomarkers of alcohol abuse in hair and serum carbohydrate-deficient transferrin: a case report.

The detection of carbohydrate-deficient transferrin (CDT) in serum is widely accepted to identify chronic alcohol consumption over the previous two weeks, but minor ethanol metabolites detected in hair often complete the information obtained. In particular, ethylglucuronide and cocaethylene (a marker of simultaneous intake of cocaine and alcohol) allow correct interpretation of data obtained in forensic cases. We refer to a negative CDT value obtained from a serum sample collected during hospitalization of a man admitted for cardiac arrest who died about 14 h later. Clinical analysis performed on admission showed a high ethanol level and a positive urinary screening for cocaine. The toxicological analyses of post-mortem samples found cocaine metabolites in his urine and blood. The negative CDT level suggested the ethanol concentration at admission to be an acute episode. Cocaine and cocaethylene well above the cut-off suggested by the literature were found in hair analyzed for the entire length (about 1 cm). Ethylglucuronide detected on the same hair sample confirmed chronic abuse of ethanol in the previous month, at least. The present report suggests caution in the interpretation of biomarkers of alcohol abuse, encouraging the detection of more than one marker to avoid misinterpretation.

Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol effects.

Cocaine and alcohol toxicity is well known, especially when simultaneously abused. These drugs perform both acute and chronic harmfulness, with significant cardiac events such as ventricular arrhythmias, tachycardia, systemic hypertension, acute myocardial infarction, ventricular hypertrophy, and acute coronary syndrome. The present report refers about a patient who died after a documented episode of psychomotor agitation followed by cardiac arrest. At the autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed and confirmed by postmortem molecular analysis revealing a mutation in the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of cocaine, and the death was attributed to cardiac arrhythmias. The detection of cocaine and cocaethylene in hair samples proved chronic simultaneous intake of cocaine and alcohol at least in the last month. The authors discuss the role of these drugs and genetic predisposition of the ARVC in causing the death of the patient.

Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium for detection of alcohol abuse during pregnancy: Correlation study between both biomarkers.

This article presents results from 47 meconium samples, which were analyzed for fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for detection of gestational alcohol consumption. A validated microwave assisted extraction (MAE) method in combination with GC-MS developed in the Institute of Forensic Science (Santiago de Compostela) was used for FAEE and the cumulative concentration of ethyl myristate, ethyl palmitate and ethyl stearate with a cut-off of 600ng/g was applied for interpretation. A simple method for identification and quantification of EtG has been evaluated by ultrasonication followed solid phase extraction (SPE). Successful validation parameters were obtained for both biochemical markers of alcohol intake. FAEE and EtG concentrations in meconium ranged between values lower than LOD and 32,892ng/g or 218ng/g respectively. We have analyzed FAEE and EtG in the same meconium aliquot, enabling comparison of the efficiency of gestational ethanol exposure detection. Certain agreement between the two biomarkers was found as they are both a very specific alcohol markers, making it a useful analysis for confirmation.

Drugs of abuse in hair: application in pediatric patients.

BACKGROUND: We are describing a case of pediatric maltreatment. A 3-year-old boy was brought to the emergency room because of drowsiness that was caused by what his parents described as an 'accidental' intake of a powder contained in a plastic wrapper that was found in a park. METHODS: Urine immunochemical screening for drugs of abuse showed a positive result for opiate exposure. Despite the described 'accident,' the physician suspected abuse and ordered a hair analysis to verify possible intake of drugs of abuse. The child's hair was analyzed along its whole length for drugs of abuse using gas chromatography mass spectrometry in accordance with international guidelines. RESULTS AND DISCUSSION: Morphine and 6-acetylmorphine were identified, and the doctor informed the city's juvenile court. The boy's family was involved with social services for a period of observation to confirm suspected prolonged abuse. Hair analysis proves to be a useful tool for periodical examination of drug exposure to protect children from significant health and social risks.

Sweat testing to monitor drug exposure.

It may be advantageous to use sweat, rather than blood or urine, to monitor individuals' drug exposure for the purposes of drug treatment programs, employment initiatives, and forensic investigations. Forty-eight patients receiving methadone at the Public Service for the Treatment of Drug Dependence of Perugia (Italy) were monitored for 14 days by the analysis of methadone and cocaine present in two sweat patches, each worn for 7 days. The results were compared to those from the analysis of urine samples collected at the beginning of the study and after 7 days, as well as those from the analysis of hair collected on the fourteenth day. Sweat patch analysis was positive for methadone and its metabolite EDDP in 100% of patients. Some individuals were positive for cocaine in urine, sweat, and hair while others were positive for cocaine in only one of those samples. Results suggest analysis of a sweat patch indicates an individual's drug use or drug washout for the previous week, and provides an alternative to blood or urine analyses.

Cocaine and its metabolites in the placenta: a systematic review of the literature.

It is clear that cocaine and cocaine metabolites are present in the placenta and may harm the fetus. The results of the experimental manipulation of cocaine exposure are not reported in the literature in a consistent manner. We conducted a systematic review of selected articles that demonstrated the analytical detection of cocaine and its metabolites in the placenta and that were published from January 1, 1956-June 30, 2011 using Medline, Toxline and Scopus databases. The collected data confirm that the placenta does not act as a barrier to fetal exposure, that cocaine quickly crosses the placenta and that one of the essential roles of the placenta is to metabolize cocaine during pregnancy. Our systematic review summarized the results showing that cocaine, benzoylecgonine and norcocaine are stored in the myometrium and the placental membrane and maintain continuous drug delivery to the amniotic fluid (and to the fetus) probably via diffusion.

Ethanol contamination leads to Fatty acid ethyl esters in hair samples.

The diagnosis of alcoholism is a topical subject of discussion; in fact, many studies have been published on the determination of biochemical markers useful to this target. Fatty acid ethyl esters (FAEE) are minor metabolites of ethanol, and their usefulness has been demonstrated by their detection in hair using a headspace solid-phase microextraction-gas chromatographic-mass spectrometric technique. Environmental contamination in the analysis of drugs of abuse is a well-known focus of discussion between scientists. In the same way, interference from the surroundings could be hypothesized in FAEE detection. To assess the influence of ethanol contamination, an in vitro experiment was performed, leaving hair in an atmosphere saturated with ethanol vapors for 15 days. The spontaneous production of FAEE was demonstrated by analyzing hair day by day. In fact, we observed a constant increase of ethyl myristate, palmitate, and stearate that reached very high concentrations at the end of the investigation. Although the experiment was managed in a stressed way and could not represent real life, its purpose was to focus the attention of researchers on the problem of hair contamination that can occur, for example, with ethanol-containing cosmetics. Therefore, care in interpretation must be taken into account, especially with such a volatile molecule.

Stability of methadone and its main metabolite in oral fluid.

Saliva is a readily available specimen that can be collected by non-invasive procedures and contains many drugs of interest in screening and diagnosis. It is obtained by a painless and non invasive method of sampling; it contains the free fraction of drugs and therefore it is a good indicator of intoxication state. Inspite of its usefulness, only a few studies on long-term storage have been conducted for some drugs of abuse, while methadone stability have not been investigated yet. This lack in standardization and the scarcity of analytical protocols actually restrict saliva applications. Authors studied methadone stability on saliva during 12 months. Fifty-nine saliva samples were collected from heroin addicts in methadone treatment with the Cozart Rapiscan Collection procedure. The samples, spiked with tri-deuterated internal standards analogs of methadone and 2-ethyl-1,5-dimethyl-3,3-diphenyl-pyrrolinium perchlorate (EDDP), were submitted to Solid Phase MicroExtraction-Gas Chromatography/Mass Spectrometry (SPME-GC/MS) technique. Quantitative determinations of methadone and EDDP were performed immediately and after various intervals (one month, two months, twelve months). The results obtained from this experiment show that methadone is sufficiently stable at 4 degrees C until 2 months, while a decrease have been observed for EDDP. These preliminary data prove the need to perform the analysis in a brief time, to avoid loss of EDDP. For the correct use of this biological matrix, more research and guidelines are recommended for drug testing on saliva.

Methadone in hair and sweat from patients in long-term maintenance therapy.

The authors refer to their experience with alternative matrices to supervise the methadone therapy of heroin abusers. For this purpose, hair, sweat, and urine samples were collected from 10 heroin addicts and from a control group and were submitted to gas chromatographic/mass spectroscopic analysis for methadone and its main metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), determination. The advantages of alternative matrices to urine samples in the supervision of methadone maintenance therapy are discussed. In particular, the detection of methadone in sweat could be a preferable option to the urine matrix as a result of the feasibility of sampling that allows noninvasive collection, which is not susceptible to adulteration. The ratio between EDDP and methadone in sweat and hair was also calculated to provide information about program agreement.

The reliability of fatty acid ethyl esters (FAEE) as biological markers for the diagnosis of alcohol abuse.

The search for biochemical markers for the objective diagnosis of alcoholism has been a topic of research because of the important clinical and forensic implications. In the last few years, two minor ethanol metabolites (ethylglucuronide and fatty acid ethyl esters) have been mainly investigated in hair samples for their ability to be incorporated into this biological matrix. The aim of this study was to experience the detection of fatty acid ethyl esters (FAEE) in the hair of alcoholics, social drinkers, and teetotallers in order to give a contribution to the existing literature. Hair samples from 12 alcoholics, 10 social drinkers, and 10 teetotallers were analyzed by gas chromatography-mass spectrometry technique after headspace solid-phase microextraction with deuterated internal standards. A slight overlap in FAEE concentration between the three groups was found, probably because of external contamination. This observation suggests particular attention to the interpretation of the results. Nevertheless, the results obtained show the usefulness of these biochemical markers in the diagnosis of alcoholism.