Driving Under the Influence of Drugs: A Single Parallel Monitoring-Based Quantification Approach on Whole Blood.

Driving under the influence of psychoactive substances is a major cause of motor vehicle crashes. The identification and quantification of substances most frequently involved in impaired-driving cases in a single analytic procedure could be an important asset in forensic toxicology. In this study, a highly sensitive and selective liquid chromatography (LC) approach hyphenated with Orbitrap high-resolution mass spectrometry (HRMS) was developed for the quantification of the main drugs present in the context of driving under the influence of drugs (DUID) using 100 μL of whole blood. This procedure involves a simple sample preparation and benefit from the selectivity brought by parallel reaction monitoring (PRM) allowing to solve most DUID cases using a single multi-analyte injection. The method was fully validated for the quantification of the major classes of psychoactive substances associated with impaired-driving (cannabinoids, cocaine and its metabolites, amphetamines, opiates and opioids, and the major benzodiazepines and z-drugs). The validation guidelines set by the "Société Française des Sciences et des Techniques Pharmaceutiques" (SFSTP) were respected for 22 psychoactive substances using 15 internal standards. Trueness was measured to be between 95.3 and 107.6% for all the tested concentrations. Precision represented by repeatability and intermediate precision was lower than 12% while recovery (RE) and matrix effect (ME) ranged from 49 to 105% and from -51 to 3%, respectively. The validated procedure provides an efficient approach for the simultaneous and simple quantification of the major drugs associated with impaired driving benefiting from the selectivity of PRM

Managing the consequences of aggressive conservative treatment for refractory retinoblastoma with vitreous seeding

A 4 year-old girl with bilateral, non-familial retinoblastoma (RB) was referred to our care after primary enucleation OS and active tumor OD refractory to multiple therapies (intravenous chemotherapy, laser/cryotherapy, and I-125 plaque radiotherapy). Vitreous seeding OD, initially controlled by several sessions of Ophthalmic Artery Infusion Chemotherapy (OAIC) and periocular chemotherapy, recurred shortly thereafter. The patient underwent intravitreal (IVit) Melphalan injections achieving tumor control despite the concurrent development of keratopathy, pupillary synechiae, cataract, and necrosis of the inferior fornix and the adjacent orbital fat, all secondary to the treatments administered. Repeated amniotic membrane implants and tarsorrhaphy were performed to alleviate the symptoms. Despite being tumor free for 6 months, a poor fundus view and treatment-related complications prompted us to consider enucleation, but parents declined. Following recent negative magnetic resonance imaging (MRI), her cataract was removed. She was then found to have tumor recurrence. Her eye was enucleated 12 months ago and she recovered well from the surgery. As ocular oncology embarks in eye-preserving treatments for retinoblastoma, it is important to address the cumulative effects and associated impact of such treatments and the possibility of failure

Cannabinoids for behavioral symptoms in severe dementia: Safety and feasibility in a long-term pilot observational study in nineteen patients.

The management of behavioral symptoms and rigidity in patients with dementia constitutes a significant challenge. Short-term studies suggest an interest in the use of medical cannabis, but long-term data are lacking. The objective of this study was to investigate the feasibility and long-term safety of administering tetrahydrocannabinol/cannabidiol (THC/CBD) treatment as an additional drug to a poly medicated population with severe dementia, evaluate clinical improvements, and collect information on the pharmacokinetics of cannabinoids and possible drug-drug interactions. A prospective observational study of patients with severe dementia living in a long-term care home to whom the physicians had prescribed a medical cannabis treatment. Data were collected over 2 years. We assessed the changes in medical cannabis dosages, safety parameters, variations in neuropsychiatric problems, agitation, rigidity, the most invalidating daily activity, and disabling behavior trouble scores. We evaluated the pharmacokinetics of cannabinoids by measuring plasma levels and analyzing the enzymatic activity. We assessed 19 patients (81.4 years-17 women and two men) receiving an average of 12.4 mg THC/24.8 mg CBD per day for up to 13 months, with no reported problems related to the treatment and limited adverse drug reactions. Clinical scores showed a marked improvement that was stable over time, deprescription of other medications, and care facilitated. The pharmacokinetic evaluation showed an expected slight reduction in the enzymatic activity of CYP1A2 and CYP2C19. A long-term THC/CBD (1:2) medication can be administered safely and with overall positive clinical improvement to poly medicated older adults with severe dementia and associated problems. The results must be confirmed in a randomized trial

Antiproton-deuteron annihilation at low energies

Recent experimental studies of the antiproton-deuteron system at low energies have shown that the imaginary part of the antiproton-deuteron scattering length is smaller than the antiproton-proton one. Two- and three-body systems with strong annihilation are investigated and a mechanism explaining this unexpected relation between the imaginary parts of the scattering lengths is proposed.Comment: 6 pages, 3 figures, to be published in The European Physical Journal

Driving under drugs in Switzerland : a descriptive cross-sectional study

Objectives: Many drugs, both illicit or for medication, are known to influence driving abilities and increase risks of accidents. We explored the prevalence of psychoactive substances in a random sample of drivers in Switzerland. Methods: Saliva samples from 1078 random drivers were collected at 24 different locations in Western Switzerland from October 2006 to April 2008 for complete toxicological analysis using liquid chromatography/tandem mass spectrometry. Results: Provisional results are available for 437 drivers. 6.2% (CI95% 4.1 to 8.9) were under the influence of illicit drugs and 8.7% under psychoactive medication (CI95% 6.2 to 11.7). 37 drivers (8.5%) were under the influence of alcohol of which 14 (3.2%) were above 0.8 mg/L. 21 drivers (4.8%) were under the combined influence of more than one psychoactive substance; however only 4 drivers (0.9%) were under both the influence of medication and alcohol. Looking more specifically at illicit substances, 22 (5.0%) were positive to cocaine, 5 (1.1%) to cannabis, and 2 (0.5%) to amphetamines ; for psychoactive medication, 17 (3.9%) were positive to benzodiazepines, 16 (3.7%) to antidepressors, 7 (1.6%) to opiates, 7 (1.6%) to neuroleptics, and 3 (0.7%) to other substances influencing driving abilities. 17/21 drivers did not self-report their consumption of drugs whereas only 9/35 failed mentioning their medication. Men drivers were 3.2 times (CI95% 1.1 to 9.5) more likely to be under the influence of illicit drugs than women. Full results will be reported when laboratory data will be available in April. Conclusions: Driving under the influence of psychoactive substances is common. In Western Switzerland, prevention messages could focus on men, driving under medication or cocaine

First measurements at the DAΦNE φ-factory with the DEAR experimental setup

The relevant background for the DEAR experiment } low-energy X rays and ionizing particles } present in the DEAR interaction region of the DA'NE e'e~ collider was investigated using the "rst-stage DEAR setup and CCD detectors. An extensive Monte Carlo simulation was performed for the present setup and beam conditions. Good quantitative agreement between measurements and simulation was achieved. This is a con"rmation that, with respect to the expected background, which gives an important contribution to the statistical precision of the experiment, the con"guration chosen to measure the strong interaction shift and width in kaonic hydrogen and kaonic deuterium can indeed reach the planned level of accuracy. ( 2000 Elsevier Science B.V. All rights reserved

DBnorm as an R package for the comparison and selection of appropriate statistical methods for batch effect correction in metabolomic studies.

As a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed "dbnorm", a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. "dbnorm" integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, "dbnorm" assigns a score that help users identify the best fitting model for each dataset. In this study, we applied "dbnorm" to two large-scale metabolomics datasets as a proof of concept. We demonstrate that "dbnorm" allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets

Xenon detection in human blood: Analytical validation by accuracy profile and identification of critical storage parameters.

Xenon is a rare, mostly inert, noble gas that has applications in a wide range of fields, including medicine. Xenon acts on the human body as a useful organ-protective and anesthetic agent and has also been previously studied for potential applications in fields such as optics, aerospace and medical imaging. Recently, it was discovered that xenon can boost erythropoietin production, and it has been used as a performance-enhancing agent in international sports competitions such as the Sochi Olympic Games. Therefore, screening methods to detect the misuse of xenon by analysis of biological samples and to monitor anesthesia kinetics and efficiency are being investigated. The aim of this study was to develop and validate an analytical method to detect xenon in blood samples using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). Preliminary studies were conducted to determine the best parameters for chromatography and mass spectrometry for xenon. The analysis was performed using the multiple reaction monitoring (MRM) mode using the transitions m/z 129 → 129, 131 → 131 for xenon and 84 → 84, 86 → 86 for krypton, which was chosen as the internal standard. The LOD of GC-MS/MS was found to be 52 pmol on-column. Calibration lines and controls were made to obtain an accuracy profile at a range of 2.08-104 nmol with a β-expectation tolerance interval set at 80% and the acceptability limit set at ±30%. From the accuracy profile, the LOQ of 15 nmol on-column for the range of 2.08-104 nmol was obtained. The method was validated according to the guidelines of the French Society of Pharmaceutical Sciences and Techniques. The detection method was finally validated using blood from test persons subjected to a 15% or 30% xenon mixture with pure oxygen and air for 45 min. Even though the probes were already used for other projects, it was still possible to detect xenon

Assessing the efficacy and impact of a personalised smoking cessation intervention among type 2 diabetic smokers: study protocol for an open-label randomised controlled trial (DISCGO-RCT).

Few studies have assessed the efficacy of smoking cessation interventions in individuals with type 2 diabetes, but interventions adapted to the specific needs of this population are warranted. The aim of this study is to assess the efficacy of a smoking cessation intervention in a population of smokers with type 2 diabetes and to measure the metabolic impact of smoking cessation. The study is an open-label, randomised control trial. Participants recruited from a sanitary region of Switzerland will be randomly allocated to either the intervention or the control arm. The intervention group will have four individual counselling sessions over 12 weeks. Trained research nurses will conduct the behavioural intervention, using motivational interviews and addressing diabetes and gender specificities. The control group will have one short counselling session at baseline and will be given written information on smoking cessation. Both groups will have a follow-up visit at 26 and 52 weeks. Demographic and medical data will be collected at baseline and follow-up, along with blood and urine samples. The primary study outcome is continuous smoking abstinence validated by expired-air carbon monoxide from week 12 to week 52. Secondary study outcomes are continuous and 7-day point prevalence smoking abstinence at 12 and 26 weeks; change in motivation to quit and cigarette consumption; and change in glycosylated haemoglobin levels, body weight, waist circumference and renal function after smoking cessation. In a subsample of 80 participants, change in stool microbiota from baseline will be measured at 3, 8 and 26 weeks after smoking cessation. Ethical approval has been obtained by the competent ethics committee (Commission cantonale d'éthique de la recherche sur l'être humain, CER-VD 2017-00812). The results of the study will be disseminated through publications in peer-reviewed journals and conference presentations. ClinicalTrials.gov NCT03426423 and SNCTP000002762; Pre-results