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Background High‐dose chemotherapy (HDCT) with TI‐CE regimen is a valid option for the treatment of relapsed advanced germ cell tumors (GCT). We report a phase II trial with therapeutic drug monitoring of carboplatin for optimizing area under the curve (AUC) of this drug. Methods Patients with unfavorable relapsed GCT were treated according to TI‐CE regimen: two cycles combining paclitaxel and ifosfamide followed by three cycles of HD carboplatin plus etoposide administered on 3 days. Carboplatin dose was adapted on day 3 based on carboplatin clearance (CL) at day 1 in order to reach a target AUC of 24 mg.min/mL per cycle. The primary endpoint was the complete response (CR) rate. Results Eighty‐nine patients who received HDCT were included in the modified intent‐to‐treat (mITT) analysis. Measured mean AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 mg.min/mL for 10th and 90th percentiles). Thirty‐five (44.3%) patients achieved a CR with or without surgery of residual masses and 20 patients achieved a partial response with negative tumor markers. With a median follow‐up of 44 months (m), median PFS was 12.3 m (95% CI: 7.5–25.9) and OS was 46.3 m (95% CI: 18.6–not reached). For high‐ and very high‐risk patients, according to the International Prognostic Score at first relapse or treated after at least one salvage treatment (n = 51), 2‐year PFS rate was 41.1%. Conclusion The rates of complete and favorable responses were clinically relevant in this very poor risk population. Individual monitoring of carboplatin plasma concentration permitted to control more accurately the target AUC and avoided both underexposure and overexposure to the drug., The superiority of HDCT over standard chemotherapy as initial salvage treatment of patients with relapsed or refractory germ cell tumors remains a valid question. In the TI‐CE regimen, TDM was demonstrated to be feasible in routine practice and really allowed to control target AUC more accurately compared to previous reports, avoiding both underexposure and overexposure to carboplatin. In our study, the rate of CR observed in this population with very poor prognosis was 44.3% and increased to 69.6% of favorable responses. Based on our study and if the benefit of HDCT is proven in the TIGER trial, we suggest that the use of carboplatin TDM for dose individualization in current practice should be considered.

Le site de Sanofi situé à Mourenx, dans le bassin industriel de Lacq (64), produit un médicament antiépileptique, la Dépakine®, dont le principe actif est le valproate de sodium (VPS). Ce site est une installation classée pour la protection de l’environnement (ICPE) soumise à autorisation au titre de l’article L.511-1 et suivants du Code de l’environnement. Les rejets dans l’environnement d’une telle installation sont encadrés par des limites établies sur la base d’une évaluation quantitative des risques sanitaires (EQRS). En 2017, Sanofi Chimie a réalisé une évaluation de l’impact sur la santé et l’environnement des rejets atmosphériques de valproate, en utilisant des valeurs toxicologiques de référence (VTR) à seuil par voie orale, cutanée et respiratoire proposées par le bureau d’étude CEHTRA (Consultancy for Environmental & Human Toxicology and Risk Assessment). Parmi les différentes VTR proposées par CEHTRA, Sanofi a utilisé les VTR fondées sur des effets tératogènes. L’EQRS conduite par la société AECOM pour le compte de Sanofi, en vue d’estimer les risques pour les riverains et les professionnels travaillant à proximité du site, a conclu que « les risques sanitaires liés aux rejets actuels et passés de valproate [étaient] inférieurs aux valeurs de référence » proposées par CEHTRA. L’Anses a été saisie le 29 juin 2018 par la DGS et la DGPR afin de mener, en urgence, une analyse critique des VTR du valproate élaborées pour le compte de Sanofi et utilisées dans le cadre de cette EQRS. Dans son avis du 12 juillet 2018, l’Anses n’a pas remis en cause le choix de construire une VTR à seuil mais n’a pas retenu les VTR élaborées par les deux bureaux d’études, EQUITOX (2015) et CEHTRA (2017), à partir des données animales et/ou humaines car de nombreuses données chez l’Homme disponibles dans la littérature n’avaient pas été prises en compte (Anses, 2018). Dans ce contexte, et au titre de la sécurité des professionnels exposés au valproate, une campagne de mesures de la concentration d’acide valproïque (VPA) dans le sang des employés de l’usine a été organisée par le service de santé au travail de l’entreprise du 27 novembre à la mi-décembre 2018. Le groupe d'alerte en santé travail (GAST) de Nouvelle-Aquitaine a été associé au suivi de cette campagne. Pour l’analyse de cette campagne de mesures, l’entreprise Sanofi s’est référée à une valeur biologique repère dans le sang de 5 mg.L-1. Ainsi, la DGT, la DGS et la DGPR ont saisi l’Anses, le 5 avril 2019, pour mener, en urgence, une analyse critique de la valeur biologique utilisée comme repère par Sanofi pour évaluer l’imprégnation de ses travailleurs. Au vu des données disponibles, le choix du dosage du valproate dans le sang n’a pas été remis en cause. Néanmoins, au regard de la cinétique d’élimination plasmatique de cette substance et de l’existence de métabolites urinaires, il n’a pas été exclu qu’un autre biomarqueur puisse être un meilleur témoin de l’exposition agrégée sur une période plus longue. Concernant le calcul de la valeur limite biologique (VLB), l’approche basée sur la dose thérapeutique est à privilégier mais la dose thérapeutique de 1200 mg.j-1 retenue pour le calcul de la VLB est critiquable compte tenu des données actuellement disponibles. En effet, des effets indésirables, notamment reprotoxiques, pourraient être observés à des doses inférieures à 1200 mg.j-1. Par ailleurs, plusieurs incohérences ou un manque de justification de certains choix ont été relevés lors du calcul de VLB, en particulier au niveau de l’application des facteurs d’incertitude/de protection. Par conséquent, la VLB de 5 mg.L-1 utilisée par Sanofi n’a pas été retenue. Enfin, ne disposant pas de suffisamment d’informations, il n’a pas été possible d’apporter un regard critique et de se prononcer sur la méthode d’analyse et les modalités de prélèvement. L’Anses a, par conséquent, recommandé : ‐ de réaliser une revue approfondie de la littérature prenant en compte les données les plus récentes, en particulier chez l’Homme ; ‐ d’évaluer de manière approfondie la possibilité de recommander des valeurs de référence pouvant être utilisées pour la surveillance biologique des expositions professionnelles au valproate (Anses, 2019). Au regard des différents éléments, l’Anses a été saisie le 28 septembre 2018 par la DGS et la DGPR pour élaborer une VTR chronique par inhalation pour le valproate de sodium, puis en avril 2019 par la DGT, la DGS et la DGPR pour définir des valeurs de référence pouvant être utilisées pour la surveillance des expositions professionnelles au valproate.

Background In France, the prevalence of childhood lead poisoning is becoming rare since the avoidance of lead in paints in 1949 and the gradual replacement of water pipes. Chronic lead toxicity is well known and is well correlated to blood lead concentration. Aim Here we report a case of severe lead poisoning occurring in a young female child with a pica behavior. Methods A blood sample and four environmental samples were analyzed using inductively coupled plasma- mass spectrometry (ICP-MS). Lead concentration, lead isotopes and elemental ratios were compared. Results The determination of 208Pb/206Pb, 206Pb/207Pb and Cd/Pb has allowed us to identify the origin of lead poisoning. Discussion-conclusion The source of contamination was eliminated and the child benefited from a psychological and medical follow up. Her outcome was positive. This case illustrated the potential interest of the use of elemental and isotopic ratios for clinical practice as the ICP-MS measurement has allowed a quick response and a rapid eviction of the contamination’s source.

Objective The objectives were to define the maximum tolerated dose (MTD), safety profile and pharmacokinetics (PKs) of intraperitoneal oxaliplatin delivered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal carcinomatosis from gastrointestinal tract cancers. Methods PIPAC was applied every 4–6 weeks, for 5 cycles, in a phase I dose-escalation study using a 3 + 3 design. The first dose level was 90 mg/m2 with planned increases of 50 mg/m2 per level. Platinum concentration was measured in plasma, tissues and intraperitoneal fluid samples. The trial was registered at ClinicalTrials.gov ( NCT03294252 ). Results Ten patients with 33 PIPAC sessions were included. No dose limiting toxicity (DLT) occurred at 90 mg/m2 and two at 140 mg/m2. The MTD was therefore set at 90 mg/m2. Overall treatment included a median number of three PIPAC sessions (range: 1–5) and secondary complete cytoreductive surgery for two patients. Overall safety showed 67 grade I–II and 11 grade III–IV toxicities, usually haematologic, digestive (nausea/vomiting, abdominal pain), and fatigue. Oxaliplatin concentrations were three- to four-fold higher in tissue in contact with aerosol than in muscle without contact. At 140 mg/m2, the plasma oxaliplatin concentration was high with Cmax and area under the curve (AUC)0–48h of 1035 μg/l and 9028 μg h/L, respectively. Conclusions The MTD of oxaliplatin during PIPAC is 90 mg/m2. PK data demonstrate a high tumour concentration and a significant systemic absorption.

Resume Objectif L’objectif de cette revue est de demontrer que la determination d’elements inorganiques ne figurant pas actuellement a la nomenclature des actes de biologie medicale (NABM), peut etre essentielle au diagnostic et a la prise en charge de patients presentant une carence ou une surcharge. Methodes Une recherche des recommandations concernant la determination d’elements inorganiques dans les matrices biologiques a ete effectuee aupres de differentes agences et organismes de sante publique et de societes savantes. Resultats Ces recommandations sont resumees dans cette revue pour les populations a risque du fait de conditions environnementales, nutritionnelles, metaboliques, genetiques ou en lien avec l’introduction de dispositifs medicaux implantables. Conclusion Afin d’eviter un retard dans le diagnostic ou une prise en charge inadaptee conduisant a une perte de chance pour le patient, nous estimons que plusieurs de ces dosages devraient etre integres rapidement a la NABM.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their most frequent side effects (digestive, renal and metabolic disorders) but are lesser known for other effects, such as coagulation disturbances. In this issue, we report the case of a 58-year-old woman who ingested 26 g of naproxen in a suicidal attempt and developed cardiovascular shock, hypocoagulability and thrombopenia. Her outcome was positive (extubation 3 days after admission [D3], correction of haemostatic disruptions on D5 and of thrombopenia on D6). Naproxen plasma concentration was at a toxic concentration of 1320 mg/L at 6 hours after drug ingestion. Only few cases of hypocoagulopathy are reported with the NSAIDs, and this is the first case that can be attributed to naproxen. A possible explanation of this phenomenon following naproxen ingestion is an inhibition of thromboxane A2, usually attributed to NSAIDs, combined with an inhibition of activation of downstream the cascade.

International audience; Emerging evidence suggests that bariatric surgery improves pregnancy outcomes of women with obesity by reducing the rates of gestational diabetes, pregnancy-induced hypertension, and macrosomia. However, it is associated with an increased risk of a small-for-gestational-age fetus and prematurity. Based on the work of a multidisciplinary task force, we propose clinical practice recommendations for pregnancy management following bariatric surgery. They are derived from a comprehensive review of the literature, existing guidelines, and expert opinion covering the preferred type of surgery for women of childbearing age, timing between surgery and pregnancy, contraception, systematic nutritional support and management of nutritional deficiencies, screening and management of gestational diabetes, weight gain during pregnancy, gastric banding management, surgical emergencies, obstetrical management, and specific care in the postpartum period and for newborns.

Introduction: Voluntary drug intoxication with benzodiazepines is common and in most cases without consequences. We report an interesting case of voluntary drug intoxication with clobazam (CLB) in ...

A fixed-dose association of bismuth subcitrate, metronidazole and tetracycline (BMT) (Pylera®, Allergan, NJ, USA) was made available in France in 2013 for the eradication of Helicobacter pylori. Due to a historical issue of bismuth encephalopathy, the French Health Authorities requested a study of blood and plasma bismuth concentrations with BMT in daily practice. The aim of the study was to measure eventual bismuth accumulation and neurological toxicity in patients prescribed BMT. Patients initiating BMT for H. pylori between March 2014 and December 2015 were included. A blood sample was taken before first BMT intake and 24 h after the last intake, for assay of bismuth. A concentration > 50 μg/L was considered abnormal. Neurological complaints were assessed at inclusion, at the end of the 10-day treatment course, and 28 days later. 202 patients were included, of whom 190 took at least one dose of BMT, and 167 provided both required blood samples. Mean blood bismuth concentrations after the BMT course were 16.9 μg/L (95% confidence interval 15.6–18.3). Concentrations were > 50 μg/L (56.0 μg/L and 50.9 μg/L) in two elderly patients, one of whom presented mild, transient memory impairment during treatment. Non-serious neurological symptoms occurred in 20% of all patients and treatment failure was documented in 5% of patients. In this study measuring blood bismuth concentrations in real-life practice, in 50 μg/L. No serious neurological adverse events were observed. EU-PAS register EUPAS3142 at www.encepp.eu ; ENCePP study seal.

Background Therapeutic drug monitoring of carboplatin is based on its unbound clearance (CLU) determined by Bayesian analysis on unbound (U) concentrations. However, the ultrafiltration of plasma samples presents technical and time constraints. Therefore, this study aims to estimate CLU using total plasma (P) concentrations. Methods U and P concentration data of 407 patients were obtained from 2 clinical studies in which actual CLU had been determined for each patient. The patients were then split into development (277 patients) and prospective data sets (130 patients). Two approaches were evaluated. PK-model-only approach: a 3-compartment pharmacokinetic (PK) model based on U and P concentrations and taking into account the protein binding process was developed. The model with patient covariates was also evaluated. Linear regression approach: an equation (CLU = aCLP + b) was obtained by linear regression analysis between actual CLU and CLP, which is the total plasma clearance obtained by analyzing P concentrations according to a 2-compartment PK model. Predictive performance was then assessed within the prospective data set by estimating CLU from P concentrations using each approach and computing the relative percentage error (PE) between estimated CLU and actual CLU. Results The linear regression equation was CLU (L/h) = 1.15 CLP (L/h) + 0.13. The mean PE (MPE) between CLU (estimated using the equation) and the actual CLU was +1.2% (ranging from -31% to +33%) and the mean absolute PE (MAPE) was 9.7%. With the 3-compartment PK model, the MPE was +2.3% (ranging from -41% to +31%) and the MAPE was 11.1%. Inclusion of covariates in the 3-compartment model did not improve the estimation of CLU [MPE = +6.3% (from -33% to +37%); MAPE = 11.4%]. Conclusions The linear equation gives a relatively good estimation of CLU based on P concentrations, making PK-based carboplatin dose adaptation possible for centers without ultrafiltration facilities.

Cerebral Scedosporium infections usually occur in lung transplant recipients as well as in immunocompetent patients in the context of near drowning. Voriconazole is the first-line treatment. The diffusion of voriconazole through the blood-brain barrier in the context of cerebral infection and cyclosporine administration is crucial and remains a matter of debate. To address this issue, the pharmacokinetics of voriconazole was assessed in the plasma, cerebrospinal fluid (CSF), and brain in an experimental model of cerebral scedosporiosis in rats receiving or not receiving cyclosporine. A single dose of voriconazole (30 mg/kg, i.v.) was administered to six groups of rats randomized according to the infection status and the cyclosporine dosing regimen (no cyclosporine, a single dose, or three doses; 15 mg/kg each). Voriconazole concentrations in plasma, CSF, and brain samples were quantified using ultra-performance liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography UV methods and were documented up to 48 hours after administration. Pharmacokinetic parameters were estimated using a noncompartmental approach. Voriconazole pharmacokinetic profiles were similar for plasma, CSF, and brain in all groups studied. The voriconazole Cmax and area under the curve (AUC) (AUC0 ≥ 48 hours) values were significantly higher in plasma than in CSF [CSF/plasma ratio, median (range) = 0.5 (0.39-0.55) for AUC0 ≥ 48 hours and 0.47 (0.35 and 0.75) for Cmax]. Cyclosporine administration was significantly associated with an increase in voriconazole exposure in the plasma, CSF, and brain. In the plasma, but not in the brain, an interaction between the infection and cyclosporine administration reduced the positive impact of cyclosporine on voriconazole exposure. Together, these results emphasize the impact of cyclosporine on brain voriconazole exposure.

International audience; OBJECTIVE: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 μg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 μg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis.METHODS: The second patient's digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi (40mg) capsule.RESULTS: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient's plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method.CONCLUSIONS: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.

International audience; Glioblastoma is the most frequent and aggressive primary malignant tumor of the central nervous system with a gloomy prognosis. Platinum derivatives and one among them, cisplatin, exhibited promising results when locally administered into the brain of glioblastoma bearing rats. Nanovectorization of anticancer agents through polymeric nanoparticles may even promote drug accumulation within cells, thus concentrating the drug efficiently at its target. Anchorage of gadolinium complexes on the corona of such smart drug delivery systems could further allow magnetic resonance imaging (MRI) monitoring of the nanoplat-form biodistribution in the damaged parenchyma and its therapeutic benefit. For this purpose, a biocom-patible amphiphilic triblock copolymer, made of degradable polyester and polycarbonate and bioelimin-able polyethylene oxide (PEO), was synthesized by successive ring-opening polymerizations. After micelli-zation in water, gadolinium complexes were grafted onto the PEO micelle corona and the carboxylate functions, located at the surface of the micelle's core, were able to cross-link with Pt(II) complexes. A macromolecular prodrug was therefore recovered in which more than one third of the carboxylate functions were linked to a platinum atom. By this strategy, stable cisplatin cross-linked nanoparticles were formulated with a mean size in the range of 100.63 ± 12.04 nm consistent with biological investigations. Relaxometry measurements both in water and in plasma at 7 T, 25 °C, confirmed the intrinsic potential of these hybrid nanoparticles as alternative MRI contrast agents with a substantial increase in the r 2 /r 1 ratio by a factor of 3.3 and 2.7, respectively, compared to the conventional low molar mass Gd-DTPA. As a result, their infusion within the striatum of glioblastoma-bearing mice resulted in a hypersignal on T 2-weighted MR images that persisted over time. Ultimately, the formulated prodrug exhibited up to 50-fold increased accumulation in human glioblastoma cell lines and up to 32-fold enhanced subsequent Pt-DNA adduct formation in comparison with free cisplatin, thus supporting the potential of this innovative bimodal tool for further applications.

Purpose: We aimed to evaluate the performance of therapeutic drug monitoring (TDM) approach in controlling interpatient variability of carboplatin exposure (AUC) in patients treated with TI-CE high-dose chemotherapy for advanced germ cell tumors and to assess the possibility of using a formula-based dosing method as a possible alternative. Experimental Design: Eighty-nine patients receiving carboplatin for 3 consecutive days during 3 cycles were evaluable for pharmacokinetic study. Blood samples were taken on day 1 to determine the carboplatin clearance using a Bayesian approach (NONMEM 7.2) and to adjust the dose on day 3 to reach the target AUC of 24 mg.min/mL over 3 days. On days 2 and 3, samples were taken for retrospective assessment of the actual AUC. A population pharmacokinetic analysis was also performed on 58 patients using NONMEM to develop a covariate equation for carboplatin clearance prediction adapted for future TI-CE patients, and its performance was prospectively evaluated on the other 29 patients along with different methods of carboplatin clearance prediction. Results: The mean actual AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 for 10th and 90th percentiles, respectively). The new covariate equation [CL (mL/min) = 130.7 × (Scr/83)−0.826 × (BW/76)+0.907 × (Age/36)−0.223 with Scr in μmol/L, BW in kilograms, age in years] allows unbiased and more accurate prediction of carboplatin clearance compared with other equations. Conclusions: TDM allows controlling and reaching the target AUC. Alternatively, the new equation of carboplatin clearance prediction, better adapted to these young male patients, could be used if TDM cannot be implemented. Clin Cancer Res; 23(23); 7171–9. ©2017 AACR.

International audience; OBJECTIVES: In this study, a novel analytical method to quantify prion inactivating detergent in rinsing waters coming from the washer-disinfector of a hospital sterilization unit has been developed. The final aim was to obtain an easy and functional method in a routine hospital process which does not need the cleaning product manufacturer services.METHODS: An ICP-MS method based on the potassium dosage of the washer-disinfector's rinsing waters was developed. Potassium hydroxide is present on the composition of the three prion inactivating detergent currently on the French market. The detergent used in this study was the Actanios LDI(®) (Anios laboratories). A Passing and Bablok regression compares concentrations measured with this developed method and with the HPLC-UV manufacturer method.RESULTS: According to results obtained, the developed method is easy to use in a routine hospital process. The Passing and Bablok regression showed that there is no statistical difference between the two analytical methods during the second rinsing step. Besides, both methods were linear on the third rinsing step, with a 1.5ppm difference between the concentrations measured for each method.CONCLUSIONS: This study shows that the ICP-MS method developed is nonspecific for the detergent, but specific for the potassium element which is present in all prion inactivating detergent currently on the French market. This method should be functional for all the prion inactivating detergent containing potassium, if the sensibility of the method is sufficient when the potassium concentration is very low in the prion inactivating detergent formulation.; ObjectifsL’objectif principal de cette étude est de développer une méthode analytique de dosage des détergents désinfectants prionicides dans les eaux de rinçage des laveurs désinfecteurs d’un service de stérilisation. Cette méthode doit être simple à mettre en œuvre et utilisable en routine à l’hôpital pour permettre de s’affranchir des dosages réalisés par les fabricants de détergents désinfectants prionicides.MéthodeUne méthode ICP-MS basée sur le dosage du potassium dans les eaux de rinçage d’un laveur désinfecteur a été développée. En effet, les trois détergents désinfectants prionicides actuellement sur le marché contiennent de l’hydroxyde de potassium. Le détergent utilisé dans l’étude a été de l’Actanios® LDI (Laboratoire Anios). Une régression de Passing et Bablok compare des résultats obtenus par cette nouvelle méthode à d’autres obtenus grâce à une méthode (HPLC-UV) développée par le laboratoire Anios.RésultatsLa méthode développée est simple à mettre en œuvre en routine et la régression de Passing et Bablok réalisée montre que les deux méthodes ont été équivalentes sur les 15dosages réalisés dans la deuxième eau de rinçage. Les deux méthodes ont été linéaires mais avec une différence de 1,5ppm sur la troisième eau de rinçage.ConclusionLa méthode ICP-MS développée est non spécifique du détergent étudié mais spécifique de l’élément potassium présent dans tous les détergents désinfectants prionicides actuellement sur le marché. Elle pourrait donc probablement être appliquée à l’ensemble des détergents désinfectants prionicides après avoir vérifié qu’elle est suffisamment sensible lorsque les concentrations en potassium dans le détergent sont faibles.

Objectives Over the last decade, use of phenethylamines has become increasingly prevalent. This study aimed to describe typical aspects of phenethylamine poisoning in order to better inform patient care. Methods Phenethylamine poisoning cases reported to the Poison Control Center of Angers, France, from January, 2007 to December, 2013 were examined. Clinical findings were examined in 105 patients, including phenethylamine used, symptoms and final outcome. Patients were predominantly male (80%), with mean age 26 ± 8 years. Results MDMA (38%), amphetamine (18%) and methamphetamine (14%) were the most commonly reported. Synthetic cathinones (10%) and the 2C series (7%) were also found. Substances most commonly associated with phenethylamine poisoning were cannabis (27%), ethanol (20%) and cocaine (9%). The most frequently reported symptoms included anxiety and hallucinations (49%), mydriasis and headache (41%), tachycardia (40%) and hypertension (15%). Complications such as seizures (7%), cardiac arrest (5%), toxic myocarditis (1%) and hemorrhagic stroke (1%) were also observed. Of the cases, the Poison Severity Score was: null or low, 66%, moderate, 21%, severe or fatal, 13%. Of the patients, 77% received hospital care and 12.4% were admitted to an intensive care unit. Analytical confirmations were obtained for all severe cases. While 93% of patients recovered, there were 5 deaths and 2 patients presented with neurological sequelae. Conclusions Phenethylamine poisonings may be severe in young and healthy individuals. Physicians, toxicologists and analysts should be aware of new phenethylamine consumption trends in order to inform management of patient care and to contribute to a more responsive drug policy.

International audience

International audience; Background: Immunochromatographic drug tests are more and more involved in the initial biological survey of acute poisoning, even with “on site” use at the emergency unit. Specificity of the drug-antibody interaction is both an advantage (rapid, easy-to-perform tests, no apparatus) and a limitation (cross-reactivity, interferences).Patient cases: A 13-year-old girl was admitted at an emergency unit for somnolence and respiratory acidosis. A multi8 rapid drug test was positive for benzodiazepines, methadone (MTD) and phencyclidine (PCP). To avoid false diagnosis, fluorescence polarization immunoassay, liquid- and gas-chromatography were also performed on both plasma and urine. Rapid tests (different batches) from the same and other manufacturers were involved for this patient and other therapeutic, acute or forensic cases.Results:Bromazepam was identified in plasma (0.4 mg/L) and urine but also tramadol (respectively 0.5 and 25 mg/L), its metabolites and, in urine only, norpropoxyphene (NPPX). No methadone was detected. Among 7 other cases with tramadol detected in urine, 5 were positive with PCP test and 5 with MTD. Drug-added urines confirmed false-positive results for PCP with tramadol but for MTD with NPPX. While tramadol cross-reactivity is very low (0.05%), positive tests, even in a therapeutic context, were observed because phencyclidine cut-off is only 25μg/L. Tramadol can also positive MTD test at very high urine level. The NPPX cross-reactivity, initially 100%, was theoretically reduced to less than 0.025% after a modification of antibody by the manufacturer. Structurally-related formulas could explain such positive results but tests from other manufacturers were negative except in one case with tramadol.Conclusion: The analytical performances (sensitivity, specificity) of such rapid tests must be known by clinicians to avoid false-positive diagnosis. The “on site” use at the emergency unit must be considered as a preliminary test that should be confirmed by alternative methods in a laboratory area. Data exchange between biologists, clinicians and manufacturers is needed to improve the quality of results.

International audience; Allergic diseases are characterized by the activation of inflammatory cells and by a massive release of mediators. The aim of this chapter was to describe succinctly the modes of action, indications, and side effects of the major antiallergic and antiasthmatic drugs. When considering the ideal pharmacokinetic characteristics of a drug, a poorly metabolized drug may confer a lower variability in plasma concentrations and metabolism-based drug interactions, although poorly metabolized drugs may be prone to transporter-based disposition and interactions. The ideal pharmacological properties of a drug include high binding affinity, high selectivity, and appropriate association and dissociation rates. Finally, from a patient perspective, the frequency and route of administration are important considerations for ease of use.