Prevalence and concentrations of sedative-hypnotic drugs in blood of drivers involved in road traffic crashes in the Padova region of Italy - not so easy to interpret.

BACKGROUND & OBJECTIVES: This study reports the prevalence and concentrations of sedative-hypnotic drugs as exemplified by benzodiazepines (BZD) and zolpidem (Z-hypnotic) in blood samples from drivers involved in road traffic accidents (RTA) in the Padova region of Italy. Another aim of the study was to estimate the prevalence of these drugs with concentrations in blood above the therapeutic intervals and above specific per se limits. METHODS: A total of 4066 blood samples collected from drivers involved in RTA were analysed for the presence of alcohol, drugs of abuse and medicinal drugs with sedative-hypnotic properties. Prevalence of drivers positive for BZDs and zolpidem were reported according to the reporting limit of our laboratory (1 ng/mL) in a sort of zero tolerance approach and compared with the prevalence according to analytical cut-offs used in the "European Union's research project on Driving Under the Influence of Drugs, Alcohol and Medicines" (DRUID). The impairment-based, per se limits adopted in Norway and in England and Wales and the values used to define "therapeutic ranges" in blood and in plasma/serum were also applied to the case study. RESULTS: 175 blood samples were positive for sedative-hypnotics above 1 ng/mL, with the following prevalence: diazepam 44%, nordazepam 41.8%, lorazepam 32.6%, zolpidem 28%, oxazepam 25.6%, alprazolam 16%, delorazepam 11,6%, lormetazepam 11,6%, temazepam 11.6%, clonazepam 11.6%, triazolam 6.9%, N-desalkylflurazepam 4.6%, bromazepam 2.3%. When applying DRUID analytical cut-offs, the prevalence of BZDs and zolpidem sharply decreases. Applying the impairing cut-offs used in Norway, 56% of positive samples were above the limits equivalent to a BAC of 0.2 g/L, 39% above the limits corresponding to 0.5 g/L, and 23% above the cut-off corresponding to 1.2 g/L. Only 1% of the drivers had drug concentrations above the per se concentration limits adopted in England and Wales [26]. When comparing blood levels with therapeutic ranges in plasma, bromazepam, lormetazepam and delorazepam were often found above the highest limits. The adjustment of the concentrations with the plasma-to-blood ratios causes a significant increase of cases above the therapeutic ranges in plasma. CONCLUSIONS: Sedative-hypnotic drugs are medicinal substances frequently identified in drivers involved in RTA, commonly in concentrations associated with driving impairment. Besides the concentrations of drugs in blood, several factors have to be considered to conclude that a driver was impaired. The frequent association with alcohol, cocaine and other BZDs, confirms the abuse potential of these medications.

Suicide identification during on-site inspection. Proposal and application of an interpretative method for death scene investigation.

Death scene investigation (DSI) is critically important for the identification of the manner of death. The present study aims to present a scoring system for the correct framing of a case as a suicide starting from the DSI and its preliminary application. The method is based on five items: (1) statistical frequency of the method adopted; (2) victim's history of mental illness; (3) circumstantial data; (4) number of means; (5) compatibility of means and injuries with suicidal dynamics; and the application of a correction factor if suicide risk indicators are present. We blindly analyzed 180 cases of violent deaths equally divided into suicides, homicides and accidental deaths and the results obtained were compared with the established dynamics of death. The proposed method has proven to be efficient in the identification of suicide at the DSI, but further on-site studies making use of a wider number of cases is necessary.

Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded nutritional supplements.

Diuretic agents are prohibited in sports in- and out-of-competition according to the regulations of the World Anti-Doping Agency (WADA) because of their possible masking effects on other doping agents in urine samples, and their ability to produce fast acute weight losses. Despite previous studies reported adverse analytical findings (AAFs) resulting from contaminations at ppm level (µg/g) of medicinal products, and recommended to introduce reporting limits for diuretics in doping controls, these are not adopted in analyses performed by WADA-accredited laboratories. We report the case of an athlete with two AAFs for hydrochlorothiazide (HCTZ) at low urinary concentrations (<10 ng/mL), who declared the use of nutritional supplements prepared in a compounding pharmacy. His nutritional supplements were analyzed revealing HCTZ presence in different concentrations, at the ppm level (µg/g and ng/mL). With the aim of testing the plausibility of the observed urinary HCTZ concentrations with the nutritional supplement ingestion, a urinary excretion study with three healthy volunteers was performed. HCTZ-contaminated powder (6.4 µg/g of HCTZ) was administered to each subject in different dosages, reproducing the possible ingestion pattern occurred. Urine specimens were collected before and after ingestion of the powder, up to 24 hours, and underwent liquid-liquid extraction and liquid chromatography-tandem mass spectrometry determination. Post-administration specimens were found to contain HCTZ at concentrations of 5-230 ng/mL, which supported the accidental inadvertent intake of the prohibited substance by the athlete. This study makes the argument that the introduction of reporting limits for diuretics are warranted in doping control samples, in order to protect against inadvertent AAFs due to contaminated products.

Hair analysis to discriminate voluntary doping vs inadvertent ingestion of the aromatase inhibitor letrozole.

Letrozole is an aromatase inhibitor, used to treat postmenopausal women with hormone receptor-positive or unknown advanced breast cancer. It is prohibited in sport because it is used together with androgen anabolizing steroids to avoid their adverse effects. In the case of an adverse analytical finding, it may be important to distinguish between repetitive use due to voluntary administration and occasional use, possibly due to involuntary intake. With the objective to identify the dose capable of producing a positive hair test, and to apply these results to the scenarios of inadvertent letrozole ingestion by an athlete, this study investigates the urinary excretion and incorporation into hair of single doses of letrozole. Seven subjects were recruited for an excretion study of letrozole and its metabolite bis(4-cyanophenyl) methanol (M1) in urine, after the consumption of 0.62 mg, 1.25 mg, and 2.5 mg of letrozole, and to investigate the incorporation in hair after ingestion of 0.62 mg and 2.5 mg of letrozole. Urine and hair samples were also obtained from two women in chronic therapy. Urinary concentrations of letrozole and its metabolite M1 were lower in subjects administered once with 0.62 mg, 1.25 mg, or 2.5 mg letrozole than in women in regular therapy with 2.5 mg/day. In hair collected after a single dosage, concentrations of 16-60 pg/mg were detected while in women in chronic therapy concentrations were higher than 160 pg/mg all along the hair shaft. Hair analysis turned to be a promising possibility for the discrimination of letrozole repetitive use vs occasional/inadvertent administration.

Death by heroin intoxication in a body pusher with an innovative packaging technique: case report and review of the literature.

Death due to mechanical or chemical intoxication of heroin body packers, thanks to the continuous improvement in packaging techniques, are increasingly rare, and almost all the cases reported in the literature refer to drug swallowers. A case of fatal acute heroin intoxication in a body pusher with an unreported packaging technique is presented, and previous deaths due to heroin body packing are reviewed, taking into consideration imaging techniques performed, cause of death, toxicological analysis on biological and non-biological samples, as well as number, position and type of drug packages identified at the dissection of the body. The innovative packaging technique found in the present case, constituted by an external multilayer cellophane casing containing 16 smaller packages of hardened heroin powder, each one covered with cigarette paper and multiple layers of heat-sealed cellophane, was probably used to avoid both chemical complications of package rupture and to create a package with morphological and radiological features different from those reported by previous studies. Drug dealers, in fact, are continually looking for packaging methods that, besides being safer, minimize the risk of detection at the radiological examinations performed, thus increasing the number of false negative findings. The identification of new types of package is therefore important, in order to identify packages that do not have the typical radiological signs, both in order to protect the patient's health and to avoid the non-recognition of a drug carrier. Despite the presence of multilayer composition of both the smaller and the bigger external coverage, these new types of package did not guarantee the greater safety of the drug dealer.

Methodology for the identification of vulnerable asylum seekers.

Asylum seekers often experience situations of vulnerability, being frequently exposed to a heightened risk of harm, and thus require special care, support and protection. The categories of "vulnerable persons", identified by International Legislation, and an individual's classification as a "vulnerable asylum seeker", have important implications in the reception procedures, in the decision-making phase and in the definition of therapeutic needs and rehabilitation. The Istanbul Protocol, the first international guideline approved by the United Nations and applied in different contexts, is not applicable for the assessment of the totality of the conditions (medical and otherwise), and therefore, the identification and assessment of conditions of vulnerability is largely delegated to questionnaires administered by non-medical personnel. The proposed methodology, based on the modificatory reworking of the Guidelines of the International Academy of Legal Medicine concerning the "medicolegal ascertainment of personal injury and damage on the living person", takes into consideration all the medical issues relevant for the decision concerning the applicant, both in the reception procedures and in the outcome of the asylum application.

Post-autopsy computed tomography. Pros and cons in a firearm death.

Many studies have focused on the importance of post-mortem computed tomography (PMCT) prior to or in substitution of standard forensic autopsies in case of firearm death. However, due to the fact that PMCT is not routinely performed in all countries, in cases of death abroad it can happen that a CT scan is performed only after a first autopsy. A case of post-mortem re-examination, including the external examination and a post-autopsy computed tomography (PACT), of a gunshot victim of homicide in a foreign country is presented, and the pros and cons of imaging in post-autopsy setting are discussed. PACT could be a tool for carrying out more complete investigations and for obtaining information on bone injuries and foreign bodies trapped within peripheral soft tissues that can be re-analyzed after the arrival of the first autopsy report. Given that the value of information derived may be strongly influenced by the previously performed autopsy, in order to process the definitive considerations it is necessary to compare and interpret the data obtained through PACT with the results of the first autopsy, and to continue the international cooperation effort and the application of international guidelines in order to share information at the repatriation of the corpse.

Micro-computed tomography of false starts produced on bone by different hand-saws.

The analysis of macro- and microscopic characteristics of saw marks on bones can provide useful information about the class of the tool utilized to produce the injury. The aim of the present study was to test micro-computed tomography (micro-CT) for the analysis of false starts experimentally produced on 32 human bone sections using 4 different hand-saws in order to verify the potential utility of micro-CT for distinguishing false starts produced by different saws and to correlate the morphology of the tool with that of the bone mark. Each sample was analysed through stereomicroscopy and micro-CT. Stereomicroscopic analysis allowed the identification of the false starts and the detection of the number of tool marks left by each saw. Micro-CT scans, through the integration of 3D renders and multiplanar reconstructions (MPR), allowed the identification of the shape of each false start correlating it to the injuring tool. Our results suggest that micro-CT could be a useful technique for assessing false starts produced by different classes of saws, providing accurate morphological profiles of the bone marks with all the advantages of high resolution 3D imaging (e.g., high accuracy, non-destructive analysis, preservation and documentation of evidence). However, further studies are necessary to integrate qualitative data with quantitative metrical analysis in order to further characterize the false start and the related injuring tool.

Alteration of the Death Scene After Self-stabbing: A Case of Sharp Force Suicide Disguised by the Victim as a Homicide?

This paper reports a case of a 72-year-old woman who was found dead in her bedroom with a 4 cm vertical stab wound in the abdomen. A bloodstained knife was found in the top drawer of her bedside table. The clothes worn by the victim showed no damage. A bloodstained vest and a sweater with frontal incisions were found far from the victim, in the bathroom and in the bedroom respectively. Several bloodstains were found in every room of the apartment. The evidence found during the forensic examination and, in particular, the Bloodstain Pattern Analysis, led the investigators to determine the manner of death, being consistent with a suicide with a long-lasting physical activity after self-stabbing. This report describes an unusual case of "disguised suicide," in which the victim tried to cover-up the suicide by changing her clothes and concealing the weapon, in the last minutes of her life.