Renata Solimini

Acute Intoxications And Fatalities From Illicit Fentanyl And Analogues: An Update

Abstract: Illicit fentanyl and its analogues are very dangerous synthetic opioids, with high abuse potential and severe adverse effects including coma and death. They are used as adulterants in street heroin, cocaine, and methamphetamine, or as heroin substitutes sold to unaware users with a high risk of overdoses. Fentanyl and its analogues have also been identified in counterfeit medicinal products, such as oxycodone, hydrocodone, and alprazolam tablets, or as components of speedball mixtures together with cocaine or other stimulants. In recent years, a number of epidemics involving acute intoxications and deaths related to illicit fentanyl or its analogues have occurred in the United States, Europe, Canada, Australia, and Japan. In several cases, fatalities involved polysubstance use. A review of the most recent case reports or case series of acute intoxications and fatalities involving illicit fentanyl and its newest analogues is herein provided, together with the available information on intoxication symptoms, eventual death cause, and metabolites detected in different biological fluids and reported concentrations.

Development of a new immunoassay for the detection of ethyl glucuronide (EtG) in meconium: validation with authentic specimens analyzed using LC-MS/MS. Preliminary results.

Abstract Background: Ethyl glucuronide (EtG) measurement in neonatal meconium has emerged as a reliable marker to objectively assess prenatal exposure to maternal ethanol complementary to fatty acid ethyl ester (FAEEs) measurement. The detection of EtG in meconium is currently a lengthy, difficult and expensive process using liquid chromatography tandem mass spectrometry (LC-MS/MS) as the analytical procedure. An enzyme-linked immunosorbent assay (ELISA) for the identification of EtG in meconium was developed, validated and applied to authentic meconium specimens from newborns collected in Europe. Methods: The ELISA procedure was calibrated using 0.45, 0.9, 1.35 and 1.8 nmol/g (100, 200 300 and 400 ng/g) standards. Meconium (0.25 g) was mixed thoroughly, with extraction buffer (pH 7.3; 0.5 mL). The tube was capped, sonicated, centrifuged and the supernatant was decanted. An aliquot of the extract (50 μL) was placed in the well of the microplate followed by enzyme conjugate (150 μL). The plate was incubated for 1 h, washed with deionized water, dried and substrate (200 μL) was added. After 30 min incubation, stop solution was added and the plate was read at 450 nm and 650 nm. Samples were also analyzed for EtG and FAEEs by validated LC-MS/MS assays. Results: Using an EtG cut-off of 0.9 nmol/g for both ELISA screening test and confirmatory LC-MS/MS, immunoassay sensitivity was 100%; specificity 78%; positive-predictive value (PPV) 29% and negative-predictive value (NPV) 100%. Conclusions: The assay is proposed as a preliminary screening test for the meconium of newborns suspected of being born to mothers drinking alcohol during pregnancy.

Neurological Disorders in Medical Use of Cannabis : An Update

BACKGROUND & OBJECTIVE Medical cannabis is increasingly used as a treatment or adjunct treatment with different levels of efficacy in several neurological disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and Alzheimer disease, Tourettes syndrome, Huntingtons disease, neuropathic pain, epilepsy, headache), as well as in other medical conditions (e.g. nausea and vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions, asthma). Nevertheless, a number of neurological adverse effects from use of medical cannabis on the short- and on the longterm have been reported, in addition to other adverse health events. CONCLUSION It has been noticed that the use of medical cannabis can lead to a paradoxical effects depending on the amount of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain. Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis, seizures, epilepsy, headache) may be caused or exacerbated by the same treatment supposed to cure them. The current review presents an update of the neurological adverse effects resulting from the use of cannabis for medical purposes, highlighting the need to weigh the benefits and risks, when using cannabinoidbased treatments.

A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context

The reliability of DrugWipe 5A on site test for principal drugs of abuse (cannabis, amphetamines, cocaine, and opiates) detection in oral fluid was assessed by comparing the on-site results with headspace solid-phase microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS) analysis on samples extracted by the device collection pad. Oral fluid samples were collected at recreational settings (e.g., discos, pubs, and music bars) of Rome metropolitan area. Eighty-three club goers underwent the on-site drug screening test with one device. Independently from the result obtained, a second device was used just to collect another oral fluid sample subsequently extracted and analyzed in the laboratory following HS-SPME procedure, gas chromatographic separation by a capillary column, and MS detection by electron impact ionization. DrugWipe 5A on-site test showed 54 samples (65.1%) positive to one or more drugs of abuse, whereas 75 samples (90.4%) tested positive for one or more substances following GC-MS assay. Comparing the obtained results, the device showed sensitivity, specificity, and accuracy around 80% for amphetamines class. Sensitivity (67 and 50%) was obtained for cocaine and opiates, while both sensitivity and accuracy were unsuccessful (29 and 53%, resp.) for cannabis, underlying the limitation of the device for this latter drug class.

Where on earth to publish? A sample survey comparing traditional and open access publishing in the oncological field

BackgroundThe paper intends to help scientific authors to make the best choice of journals in which to publish, by describing and comparing journal features in the area of oncology. For this purpose, the authors identified impact factor (IF) ranking, cost options and copyright conditions offered to authors wishing to publish in full open access (OA), subscription-based or hybrid journals.MethodsData referring to articles published in 2010 by three Italian research institutions (National Institute of Health – Rome (ISS), Regina Elena National Cancer Institute – Rome (IRE), National Cancer Institute – Milan (INT) in journals (78) managed according to different business models, all listed in the Journal Citation Reports, subject category Oncology, were collected and analysed. The journals surveyed were ranked according to IF, position in quartiles, publication charges, usage rights in published articles, self-archiving conditions in OAI-compliant repositories digital archives.ResultsAlmost half (34) the journals surveyed were included in the first quartile, thus revealing authors’ preference for journals with a high IF. The prevalent journal business model was the hybrid formula (based on subscriptions but also offering a paid OA option) with 51 journals, followed by subscription-based only journals accounting for 22, while just 5 full OA journals were identified. In general, no relationship was found between IF and article publication charges, in terms of correspondence between more expensive fees and higher IF.ConclusionsThe issue of OA journals as compared with traditional subscription-based journals is highly debated among stakeholders: library administrators facing financial restrictions, authors seeking to locate the best outlet for their research, publishers wishing to increase their revenues by offering journals with wider appeal. Against this background, factors such as the quest for alternatives to high-cost business models, investments in setting up institutional repositories hosting the published versions of articles and efforts to overcome copyright barriers and gain free access to scientific literature are all crucial.

Epidemiologic Study of Mortality During Summer 2003 in Italian Regional Capitals: Results of a Rapid Survey

Following the unusually hot summer in 2003 and the dramatic news from neighbouring countries such as France, the Italian Minister of Health commissioned an epidemiologic mortality study to investigate whether there had been an excess of deaths in Italy, particularly for the elderly population. Communal offices, which provide vital statistics, were asked to provide data on the number of deaths among residents between June 1 and August 31, for the years 2003 and 2002, for the 21 capital cities of Italy’s regions. A mortality increase of 3,134 deaths was observed, most of which (92 %) occurred among persons aged 75 years and older. The highest increases were observed in northwestern cities (Turin, Milan, Genoa). A clear correlation was observed between mortality and climatic indexes (maximum temperature, Humidex).

Adulteration Practices of Psychoactive Illicit Drugs: An Updated Review

BACKGROUND Powdery drugs such as cocaine and heroin are frequently adulterated or diluted predominantly to obtain more doses and to increase the drug dealers profits, but also to enhance, to modify or to oppose drug effects. The aim of this report is to provide an overview of the recent scientific literature on medicines as well as on new psychoactive substances, used as cutting agents (i.e. pharmacologically active adulterants) and on the related adverse health effects on consumers, possibly due to the synergistic effect of the adulterants laced with substances of abuse. METHOD A literature search up to January 2017 was performed on MEDLINE, Scopus and Web of Science and reports and documents of international agencies or institutions were also searched. RESULTS Pharmacologically active substances such as: paracetamol, caffeine, dextromethorphan, clenbuterol for heroin; levamisole, phenacetine, lidocaine, hydroxyzine and diltiazem for cocaine; caffeine and phentermine for amphetamine, have been identified over the years. Furthermore, since cocaine and morphine (this latter as a precursor of heroin) are both extracted from natural products, some impurities and minor alkaloids can be present in the final preparation. In this context, it is worth considering that new psychoactive substances are also used as cutting agents. CONCLUSION The wide availability of illicit psychotropic drugs is the most serious hazard threatening consumers. Indeed emergency departments are often responsible in evaluating damages caused not only by the base substance, but also by other eventual compounds added to mimic or antagonize drug effects or simply dilute the drug amount, with a possible harmful synergic toxic action.

Ultra-high-pressure liquid chromatography tandem mass spectrometry determination of antidepressant and anxiolytic drugs in neonatal meconium and maternal hair

A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of 22 antidepressant and anxiolytic drugs ad metabolites in the three consecutive maternal hair segments representing the pregnancy trimesters and paired neonatal meconium samples. After hair washing with methyl alcohol and diethyl ether and subsequent addition of internal standards, hair samples were treated with 500 μl VMA-T M3 reagent for 1h at 100 °C. After cooling, 100 μl M3 extract were diluted with 400 μl water and a volume of 10 μl was injected into chromatographic system. Meconium samples were firstly treated with 1 ml methyl alcohol and the organic layer back-extracted twice with 1.5 ml of a mixture of ethylacetate:hexane (80:20, v/v). Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization. The method was linear from the limit of quantification (0.05-1 ng/mg hair and 5-25 ng/g meconium depending on analyte under investigation;) to 10 ng/mg hair and 1000 ng/g meconium, with an intra- and inter-assay imprecision and inaccuracy always less than 20% and an analytical recovery between 66.6% and 95.3%, depending on the considered analyte and biological matrix. Using the validated method, 7 mothers were found positive to one or more hair segments and 5 meconium samples were found positive to one or more antidepressant and anxiolytic drugs, assessing prenatal exposure to these drugs following maternal consumption in one or more pregnancy trimesters.

A Helpline Telephone Service for Tobacco Related Issues: The Italian Experience

Antismoking helplines have become an integral part of tobacco control efforts in many countries, including Italy. The demonstrated efficacy and the convenience of telephone based counselling have led to the fast adoption of antismoking helplines. However, information on how these helplines operate in actual practice is not often readily available. This paper provides an overview of the Italian Antismoking Helpline, an increasingly popular telephone service for tobacco problems operating in Italy since 2000. As many states, regions and nations are contemplating various telephone programs as part of large scale anti-tobacco campaigns, this paper briefly discusses the reasons the helpline is well suited to lead the cessation component of a comprehensive tobacco control program, how it operates and how it can be used in conjunction with other tobacco control activities. The Italian Antismoking Helpline provides Italians with free services that include counselling, cessation related information, self help quit kits and current legislation information. The helpline is promoted statewide by media campaigns, health care providers, local tobacco control programs and public school system. The Helpline is centrally operated through the Istituto Superiore di Sanità and it has served over 17.000 tobacco users and others.

Nails in Forensic Toxicology: an Update

BACKGROUND The analysis of nails as a keratinized matrix to detect drugs or illicit substances has been increasingly used in forensic and clinical toxicology as a complementary test, especially for the specific characteristics of stably accumulating substances for long periods of time. This allows a retrospective investigation of chronic drug abuse, monitoring continuous drug or pharmaceutical use, reveal in utero drug exposure or environmental exposures. METHODS We herein review the recent literature investigating drug incorporation mechanisms and drug detection in nails for forensic toxicological purposes. RESULTS Mechanisms of drug incorporation have not yet been fully elucidated. However, some research has lately contributed to a better understanding of how substances are incorporated into nails, suggesting three potential mechanisms of drug incorporation: contamination from sweat, incorporation from nail bed and incorporation from germinal matrix. In addition, numerous methods dealing with the determination of drugs of abuse, medications and alcohol biomarkers in nails have been reported in studies over the years. The latter methods could find application in clinical and forensic toxicology. CONCLUSION The studies herein reviewed point out how important it is to standardize and harmonize the methodologies (either pre-analytical or analytical) for nails analysis and the optimization of sampling as well as the development of proficiency testing programs and the determination of cut-off values.