Potential drug-drug interactions when managing status epilepticus patients in intensive care: A cohort study.

AIMS: The risk for drug-drug interactions (DDIs) associated with antiseizure drugs (ASDs) used to manage status epilepticus (SE) patients in the intensive care unit (ICU) has been poorly investigated. We aimed to quantify and describe those potential DDIs and determine SE patient risk profiles. METHODS: We conducted an observational bi-centric cohort study including all SE patients admitted to the ICU in the period 2016-2020. RESULTS: Overall, 431 SE patients were included and 5504 potential DDIs were identified including 1772 DDIs (33%) between ASDs, 2610 DDIs (47%) between ASDs and previous usual treatments (PUTs), and 1067 DDIs (20%) between ASDs and ICU treatments (ICUTs). DDIs were moderate (n = 4871), major (n = 562) or severe (n = 16). All patients exhibited potential DDIs, which were major-to-severe DDIs in 47% of the cases. DDIs were pharmacokinetic (n = 1972, 36%), mostly involving cytochrome P450 modulators, and pharmacodynamic (n = 3477, 64%), mainly leading to increased sedation. ASD/PUT DDIs were the most frequent and severe. Age, PUT and ASD drug numbers and length of ICU stay were significantly associated with increased DDI number. We identified four SE patient profiles with different DDI risks and outcomes including (1) epileptic or brain trauma patients, (2) withdrawal syndrome patients, (3) older patients with comorbidities and (4) self-poisoned patients with psychiatric disorders and/or past epilepsy. CONCLUSION: SE patients are subject to potential DDIs between ASDs, ASD/PUT and ASD/ICUT. Major-to-severe DDIs mostly occur between ASDs and PUTs. Physicians should pay attention to SE patient characteristics and history to limit DDI numbers and prevent their consequences.

Quetiapine Poisoning and Factors Influencing Severity.

PURPOSE/BACKGROUND: Quetiapine is a relatively new atypical antipsychotic with fewer adverse effects. It is increasingly prescribed to patients. The purpose of this study was to describe the cases of poisoning observed at the western France Poison Control Centre and identify potential risk factors that increase the severity of the cases. METHODS: This was a retrospective study of self-poisoning with quetiapine as reported by the western France Poison Control Centre between 2007 and 2017. RESULTS: There were 372 cases of quetiapine poisoning. Circumstances are known in 367 of 372 cases. There were 75 cases of null severity (grade 0), 133 cases of mild severity (grade 1), 85 cases of moderate severity (grade 2), and 79 cases of high severity (grade 3). Five deaths were listed in this series. The most commonly observed symptoms were neurological and cardiovascular in nature (drowsiness, coma, tachycardia, hypotension). Of these cases, 79.8% included voluntary ingestions. Among 302 cases with coagents, the most common coagents were benzodiazepines (56%), other psychotropic drugs (41%), and antidepressants (37%). An evaluated ingested dose 1500 mg or greater and 2 or more coagents increase the risk of severe poisoning. In particular, concomitant ingestion of benzodiazepines and antidepressants with quetiapine was associated with high severity (odds ratio, 2.478 [confidence interval, 1.3-4.723]; odds ratio, 1.820 [confidence interval, 1.010-3.316]). CONCLUSIONS: Quetiapine may lead to severe poisoning for which there is currently no specific treatment. Patients and practitioners should be aware of this when quetiapine is prescribed, particularly when used in combination with other medications, and in order to deal with cases of poisoning.

Baclofen Self-Poisoning in the Era of Changing Indication: Multicentric Reports to a French Poison Control Centre.

AIMS: Baclofen has gained interest in treating alcohol use disorder patients. These patients are at risk of voluntary drug intoxications. Understanding the context of baclofen's widespread use for alcohol use disorder, a recent evaluation of the epidemiology, morbidity and mortality of baclofen self-poisoning episodes is necessary. METHODS: All baclofen self-poisoning reported to the Western France Poison Control Centre between January 2008 and December 2015 were included for analysis in this retrospective study. Baclofen poisoning cases were compared to the 31,859 non-baclofen voluntary poisoning cases declared over the same period. RESULTS: Number of baclofen poisoning grew from 8 cases in 2008 to 91 cases in 2015, attributable to patients purposely treated for alcohol use disorder. Overall, 190 cases were considered: 111 patients (59%) had Glasgow coma score (GCS) ≤12 at hospital admission and 77 had GCS > 12 (41%). Eighty patients required mechanical ventilation (42.6%). Neurological severity (GCS ≤ 12) was associated with seizures (n = 24, 22% vs. n = 2, 3%, P < 0.001). Two patients were deceased at first medical evaluation and three died in the hospital (mortality rate 2.6%). Non-baclofen cases had lower rate of endotracheal intubation (n = 1833, 6%, P < 0.001) and mortality rate (n = 299, 0.1%, P = 0.02). CONCLUSIONS: Baclofen self-poisoning cases has risen in recent years due to baclofen intake for alcohol use disorder therapies. The risk-benefit ratio may be evaluated before baclofen is safely prescribed.

First step in assessment of VipGrade®, a computerized clinical decision system to assess Vipera envenomation grading: a single-center interrater reliability study.

METHODS: We conducted a retrospective review of Vipera spp. snakebite cases registered by the PCC of Bordeaux, France, between January 1, 2018, and December 31, 2020, evaluating the agreement between VipGrade® assessments, toxicologists' assessments, and current guidelines. RESULTS: 133 patients with Vipera aspis snakebites were included. There was 100% agreement in severity grading by PCC guidelines and VipGrade®. However, grading by toxicologists and VipGrade® diverged in 19 cases (85% agreement; κ = 0.80; 95% CI: 0.71 to 0.87). CONCLUSIONS: The VipGrade® tool's grading reflects current PCC guidelines, which are authoritative in France, and may allow for a more rapid and standardized determination of management and follow-up of viper-bitten patients. It should be noted, however, that the more complex and dynamic aspects of management are not included in VipGrade®. Its purpose is to supplement, not replace, the advice of the PCC's clinical toxicologists, and this advice should be sought whenever a viper bite is encountered in clinical practice.

Human poisonings by neurotoxic phycotoxins related to the consumption of shellfish: study of cases registered by the French Poison Control Centres from 2012 to 2019.

CONTEXT: In June 2019, a paralytic shellfish poisoning (PSP) case related to the consumption of mussels contaminated by saxitoxins at a concentration below the regulatory threshold came to the attention of the French Agency for Food, Environmental and Occupational Health and Safety (ANSES). This pointed to probable undetected human cases of poisoning by neurotoxic phycotoxins. METHODS: We conducted a retrospective study of poisoning cases by bivalve shellfish (oysters, mussels and scallops) recorded by the French Poison Control Centres (PCC) from 2012 to 2019. All medical records were reviewed by a toxicologist.Cases that could be related to neurotoxic phycotoxins were selected and described. Diagnosis was based on symptoms compatible with ingestion of contaminated shellfish and on contamination data for the shellfish production area (analysed by the French Research Institute for Exploitation of the Sea, Ifremer), or notifications to the European Rapid Alert System for Food and Feed when the origin of the shellfish was known. RESULTS: Among the 619 shellfish poisoning cases recorded by the PCCs from 2012 to 2019, 22% (n = 134) had reported at least one neurological symptom (headache, dizziness or paraesthesia). Review of medical records for the 134 patients led to suspicion of 14 cases of PSP and one case of amnesic shellfish poisoning. Five patients experienced persistent neurological symptoms. Marine toxins were not tested for in the blood or urine of these patients. CONCLUSION: This retrospective identification of cases strongly suspected of being related to neurotoxic phycotoxins led ANSES, PCCs and Ifremer to develop a specific questionnaire and to recommend actions to take when neurological symptoms related to shellfish consumption are reported to a PCC. Daily monitoring of shellfish poisoning cases registered in the national PCCs database was also implemented in order to rapidly detect any suspicious cases, alert the competent authorities, and warn the general population.

Shiitake dermatitis: experience of the Poison Control Centre Network in France from 2014 to 2019.

OBJECTIVE: Shiitake mushrooms (Lentinus edodes) are an edible fungus, initially grown in Japan and China that are increasingly marketed in Europe. We previously presented 15 shiitake dermatitis cases reported to Poison Control Centres (PCCs) in France from January 2000 to December 2013. The aim of this study was to describe changes in the number of shiitake dermatitis cases since 2014, and to better describe the clinical characteristics and risk factors of this reaction. CASE SERIES: This observational study is a retrospective review of cases in the French PCCs database between 1 January 2014 and 31 December 2019. Out of 125 shiitake exposures, we identified 59 cases of dermatitis: sex ratio of 1.80 M/F; ages ranging from 19 to 69 years (median: 39 years). Dermatitis occurred after raw or undercooked shiitake consumption (e.g., from the wok, in soup, or on pizza). The rash appeared 1-168 h (median: 48 h) after shiitake ingestion. Linear, erythematous, urticarial papules and plaques developed across the trunk, arms, and legs within a few hours and persisted for 1-40 d (median 10 d). The amount of shiitake eaten (low vs. medium vs. high) significantly increased the duration of dermatitis (median days 4 vs. 7 vs. 15, respectively; p = .007). In all, 38 patients received corticosteroids, antihistamine drugs, or both without demonstrated benefit. All patients made a complete recovery. CONCLUSIONS: The mechanism of shiitake dermatitis is thought to involve lentinan, a heat-labile polysaccharide component. Inadequate cooking clearly seems to be a driver of the occurrence of shiitake dermatitis. This study highlighted a dose-dependent response, suggesting a partial toxic mechanism or a th1-type hypersensitivity mechanism. Treatment is focused on symptom management. Health professionals and the general population should be aware of both the risk associated with inadequately cooked shiitake consumption and the favourable prognosis of this still poorly known toxic dermatitis.

Ciguatera fish poisoning in France: experience of the French Poison Control Centre Network from 2012 to 2019.

INTRODUCTION: Ciguatera fish poisoning (CFP) is a common Poisoning in the tropical countries. France is directly concerned with French tourists in endemic area and with French citizens living in the French overseas territories. METHOD: Retrospective, descriptive study of CFP cases handled by the French Poison Control Centre Network from 2012 through 2019. RESULTS: Fifty-two events were studied concerning 130 patients. The fish species was identified for 41 events, mainly belonging to five fish families: 14 groupers, 11 snappers, 5 jacks, 4 parrotfishes, 4 barracudas. The origin of the fish was the Atlantic Ocean (23 events), the Indian Ocean (17 events) and the Pacific Ocean (12 events). 91% of the poisonings occurring in the Atlantic Ocean began with gastrointestinal effects while in 44% of events occurring in the Pacific Ocean, the patients had no gastrointestinal effects (onset with neurological symptoms: paraesthesia and dysesthesia). The evolution of the 130 patients has been classic for CFP with persistent symptoms during 1 to 45 weeks. Numerous patients reported exacerbation of neurological signs several months after poisoning following consumption of alcoholic beverages (23 patients) or seafood (19 patients). DISCUSSION: Medical practitioners in Europe must be trained to manage CFP as cases are reported with tourists returning from endemic areas but also with poisoned patients far from tropical areas after consumption of imported fish.

Failure of a Mexican antivenom on recovery from snakebite-related coagulopathy in French Guiana.

INTRODUCTION: In French Guiana, most snakebites are caused by crotalids, with the main signs being tissue damage and bleeding due to venom-induced coagulopathy. Since December 2014 the Western Guiana Hospital (WGH) has used Antivipmyn Tri TM, a Mexican polyvalent antivenom. The aim of the study was to assess its benefit on the correction of snakebite-related coagulopathy. METHODS: This retrospective study included patients hospitalized at the WGH with snakebite and a coagulopathy defined by: a prothrombin rate (PR) lower than 45%, an activated partial thromboplastin time ratio (aPTTr) greater than 2 or a fibrinogen lower than 100 mg.dL-1. The antivenom group included patients receiving Antivipmyn Tri TM from December 2014 to September 2017. The control group included patients admitted between January 2013 and November 2014 (when antivenom was unavailable) or admitted between December 2014 and September 2017 during times of antivenom shortage. We graphically compared the time courses of PR, aPTTr and fibrinogen between groups. Other endpoints were the length of hospital stay and the need for surgery or dialysis. RESULTS: 84 patients were included: 42 in the antivenom group, 42 in the control group. Both groups were similar for age, sex-ratio, proportion of bleedings, necrosis, and severity. Most patients in the antivenom group received 3 vials. There were no significant differences in recovery of PR, aPTTr and fibrinogen through the first 24 h. Fibrinogen declined again in the control group at 30 h and showed a slower rise to normal concentration. There were no significant differences in any secondary endpoint. CONCLUSION: Antivipmyn Tri TM as currently used did not show any benefit in recovery from coagulopathy.

Severe poisoning with naproxen causing coagulopathy.

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.

Baclofen self-poisoning: Is renal replacement therapy efficient in patient with normal kidney function?

AIMS: We aimed at assessing the effectiveness of renal replacement therapy in patients severely self-poisoned with baclofen and with normal kidney function. METHODS: A population pharmacokinetic model was built using analytical data extracted from 26 baclofen poisoning cases reported to a French Poison Centre: 8 patients underwent renal replacement therapy (RRT), 18 did not. In the RRT group, 2 patients suffered from kidney failure. Mechanical ventilation was required for 20 patients with normal kidney function; 15 were not treated by RRT and 5 were. Pharmacokinetic profiles of baclofen were measured in 28 patients and further modelled by a non-parametric approach (PMetrics®). The total data set was divided into a building data set (26 patients, 57 observations) and a validation set (2 external patients, 6 observations). Then, the estimated elimination half-life of baclofen and the duration of intubation were compared in patients with or without RRT using Wilcoxon-Mann-Whitney test. RESULTS: A model using three parameters plus a lag time and bioavailability was necessary to determine the pharmacokinetics of baclofen. Estimated elimination half-life in the 'RRT' group and the 'no RRT' group were respectively 3.1 [2.2-4.8] h (n = 6 patients) and 3.4 [1.4-5.5] h (n = 19 patients, p = 0.53). The median duration of intubation was not significantly different between groups (72 [48-72] h and 72 [24-96] h, respectively; p = 0.38). CONCLUSION: Renal replacement therapy did not appear to significantly increase baclofen clearance in patients without kidney failure.

Snake bites by European vipers in Mainland France in 2017-2018: comparison of two antivenoms Viperfav® and Viperatab®.

Context: Today, immunotherapy with Fab or F(ab')2 fragments is considered as a gold standard treatment for patients bitten by vipers. We compared the efficiency of two antivenoms, Viperfav® and Viperatab®, in mainland France in 2017-2018 with data provided by the French poison control centre (PCC).Methods: Patients with a moderate (2a and 2b) or severe (3) envenomation after a European viper bite and treated with immunotherapy were included and the markers chosen were the risk of post-antivenom treatment worsening, duration of hospital stay and persistent functional discomfort on day 15. Statistical studies were based on multivariate data analysis.Results: Two hundred and ninety-seven cases were recorded. One hundred and eighty-two (61.3%) patients received Viperfav® and 115 (38.7%) received Viperatab®. Compared to Viperfav®, use of Viperatab® significantly increased the risk of post-antivenom treatment worsening (OR* 12.05; 95%CI [3.11; 46.70]; p < .001). No significant difference between these antivenoms was recorded with respect to the duration of hospital stay and persistent functional discomfort on day 15. Viperfav® and Viperatab® have a similar tolerance (p > .21). Otherwise, duration of hospitalisation was significantly increased by a delay of immunotherapy infusion of more than 12 h (OR 2.70; 95%CI [1.45-5.06]; p = .002) or a preventive administration of LMWH (OR 6.55; 95%CI [1.58-27.13]; p=.02).Discussion: While Viperfav® and Viperatab® have a similar tolerance, our data show that Viperatab® was associated with a higher risk of post-antivenom treatment worsening compared to Viperfav®. Furthermore, this study confirms that the antivenom should be used as soon as possible. Indeed, patients receiving the immunotherapy infusion from the grade 2b presented significantly more frequent exacerbated symptoms (OR 3.99; 95%CI [1.16-13.73]; p=.028) after the antivenom infusion compared to grade 2a group.Conclusions: Whereas no significant difference between these antivenoms was recorded with respect to the duration of hospital stay and persistent functional discomfort on day 15, use of Viperatab®, compared to Viperfav®, significantly increased the risk of post-antivenom treatment worsening (OR* 12.05; 95%CI [3.11; 46.70]; p < .001). Taken together, these data show that Viperfav® is the treatment of choice for the management of snake bites in France.

Clinical consequences related to a defective elimination of clobazam caused by homozygous mutated CYP2C19 allele.

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 patient with a homozygous mutated CYP2C19 genotype. Case report: A 63-year-old Caucasian man was admitted to an intensive care unit for voluntary drug intoxication with CLB (1200 mg) complicated by prolonged hospitalization (46 days). The levels of CLB and N-desmethylclobazam (NCLB) in plasma were initially 8.3 and 14.8 mg/L. The persistence of a high concentration of NCLB (14.3 mg/L on day 30) suggested a lack of elimination. A homozygous mutated allele of CYP2C19*2 without enzyme activity was discovered. To overcome this phenotype, NCLB metabolism was induced by administering 100 mg of phenobarbital for 10 days, allowing patient improvement. Discussion: NCLB is the major active metabolite of CLB with a longer half-life and much higher steady-state plasma concentrations compared to the parent drug. The half-life elimination of CLB is 18 h that of NCLB is between 40 and 50 h. However, there is considerable inter-individual variation in the metabolism of CLB and of the report NCLB/CLB under the dependence of genotype of CYP2C19. These polymorphisms are not generally well-known by physicians and may lead to severe poisoning.

Posterior Reversible Encephalopathy Syndrome in Clinical Toxicology: A Systematic Review of Published Case Reports.

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical and radiological entity characterized by a typical brain edema. Although several case reports have described PRES in a context of poisoning, to our knowledge, a comprehensive assessment has not been performed. The aim of this systematic review was to raise awareness on poisoning-specific PRES features and to encourage consistent and detailed reporting of substance abuse-and drug overdose-associated PRES. Methods: Medline/PubMed, Web of Science, and PsycINFO were screened through May 31, 2019, to systematically identify case reports and case series describing PRES associated with poisoning (i.e., alcohol, drugs, illicit drugs, natural toxins, chemical substances) in accidental context, intentional overdose, and substance abuse. The methodological quality of eligible case reports/series was assessed. Patients and exposure characteristics were recorded; relevant toxicological, radiological, and clinical data were extracted. Results: Forty-one case reports and one case series reporting 42 unique cases were included. The median time to PRES onset from the start of exposure was 3 days (IQR 2-10). Acute high blood pressure, visual disturbance, and seizure were reported in 70, 55, and 50% of patients, respectively. The initial clinical presentation was alertness disorders in 64% of patients. Nine patients (21%) required mechanical ventilation. One-third of patients had at least one risk factor for PRES such as chronic hypertension (17%) or acute/chronic kidney failure (24%). The main imaging pattern (67%) was the combination of classical parieto-occipital edema with another anatomical region (e.g., frontal, basal ganglia, posterior fossa involvement). Vasogenic edema was found in 86% of patients. Intracranial hemorrhage occurred in 14% of patients. Both brain infarction and reversible cerebral vasoconstriction syndrome were diagnosed in 5% of patients. Three patients (12%, 3/25) had non-reversible lesions on follow-up magnetic resonance imaging. The median time required to hospital discharge was 14 days (IQR 7-18). Mortality and neurological recurrence rate were null. Conclusions: Comorbidities such as chronic hypertension and kidney failure were less frequent than in patients with other PRES etiologies. Imaging analysis did not highlight a specific pattern for poisoning-induced PRES. Although less described, PRES in the context of poisoning, which shares most of the clinical and radiological characteristics of other etiologies, is not to be ignored.

Metformin overdose: A serious iatrogenic complication-Western France Poison Control Centre Data Analysis.

INTRODUCTION: The prevalence of type 2 diabetes (T2D) continues to rise across the world. Metformin is still considered the "gold standard" and is, therefore, increasingly prescribed. Monitoring of metformin continues to be debated because of its association with lactic acidosis (MALA), a rare but life-threatening complication. The aim of this study was to identify the main individual characteristics associated with severe poisoning in self-poisonings and therapeutic accidents reported at the Western France Poison Control Centre (PCC). METHODS: Retrospective study of metformin poisoning from September 1999 to September 2016 at the Western France PCC recorded in the French PCC's database (SICAP). The end-point was clinically high severity (mortality and/or cardiovascular shock and/or GCS ≤ 7/15). RESULTS: Of the 382 cases included, 197 concerned acute accidental exposures, 127 self-poisonings and 58 therapeutic accidents. MALA concerned 63 patients: 44 therapeutic accidents and 19 self-poisonings. High severity concerned 59 patients: 47 therapeutic accidents and 12 self-poisonings. T2D and age > 60 significantly increase the risk of high severity (OR 7.7, CI [1.54-38.41]; P = 0.013; OR 3.5, CI [1.60-7.84]; P = 0.002, respectively). CONCLUSIONS: Metformin may lead to MALA and severe poisoning in therapeutic accidents but also in self-poisoning circumstances. Among reported cases, T2D history and age >60 increase the risk of serious poisoning. Monitoring of their treatment should be taken seriously especially in the event of digestive symptoms such as diarrhoea.

Risperidone medication errors in children: an analysis of French poison centres data.

OBJECTIVES: To describe clinical consequences of risperidone medication errors in children of less than 13 years and to estimate a clinically relevant toxic dose. METHODS: All cases of risperidone medication errors managed by French Poison Centres from 2001 to 2012 were analyzed. Inclusion criteria were a delay of at least 2 hours between ingestion and request to the FPC in asymptomatic children, an ingested dose above two-fold the maximal daily dose for children above 5 years or any symptomatic patient at the time of first contact. RESULTS: One hundred and sixty cases met our criteria. Median age was 8 years (range 0.9-12) and 28.1% were aged 5 years or less. Causes of the error were an incorrect dose in treated children (84.2%) or a dose given to a wrong child (15.8%). The median ingested dose was 0.1 mg/kg or 3.3-fold the maximum recommended dose. Overall, 59 children had no symptoms, 95 experienced minor symptoms and six moderate symptoms. Somnolence/sedation was the most common (73.3%). Of the 17 children who developed extrapyramidal disorders, all had minor or moderate symptoms and only five required a symptomatic treatment. CONCLUSIONS: Risperidone medication errors in children cause minimal effects. Somnolence and mild to moderate extrapyramidal reactions were the main features of toxicity, and significant cardiac or other neurological features were not observed. No case with severe toxicity was noted. At home surveillance can be proposed for children exposed to a dose ≤0.15 mg/kg.

Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers.

OBJECTIVE: The objectives of this study are to carefully describe the context of methotrexate medication errors, to details medical consequences and management approaches, and to determine the rate of fatal outcome. METHODS: Data on methotrexate medication errors were obtained from the French network of poison control and pharmacovigilance centres, which collected and documented reported drug-induced adverse effects. Cases were included if the intake was more than 2-fold the intended weekly dose or a weekly cumulative dose ≥ 30 mg and a follow-up of at least 4 days after the last dose. Data were analysed for demographics, treatment indication, prescribed dose, drug interactions, clinical complications and medical outcomes. RESULTS: Seventy four patients were included. The causes of methotrexate errors resulted from an erroneous prescription renewal (23.3%), incomprehensiveness of the weekly schedule by patients or at-home caregivers (56.2%) and administration of a wrong dose by a health care professional (20.5%). Of the 70 patients who took methotrexate daily, the mean daily dose received over the whole duration of the error was 9.6 ± 4.1 mg (range 2.5-22.5) with a mean duration of the error of 11.7 ± 12.2 days (range 2 to 90). Thirteen (18%) patients remained asymptomatic and 61 (82%) developed complications of which 46 (62.2%) were severe. Nine (14.8%) patients died within 11 to 45 days after the first dosing error. Compared to patients with no or mild symptoms, those with severe symptoms were more likely to be older (75.6 ± 10.8 vs. 69.5 ± 12.9 years) and to be exposed to a higher cumulative dose (94.8 ± 46.2 vs. 68.0 ± 45.7 mg). CONCLUSIONS: This study confirms that dosing errors with methotrexate can be lethal and persisted despite several warnings from drug agencies. Further measures are awaited from the European Medicine Agency.

Risks linked to accidental inoculation of humans with veterinary vaccines: a 7-year prospective study.

AIM: Accidental inoculation of humans with veterinary vaccines can lead to early and late complications. The aim of our study is to describe these complications and their risk factors. METHODS: Prospective observational study conducted from 2007 to 2014 at Angers University Hospital's Poison Control Centre. The endpoints examined were: early and late locoregional complications, surgical treatment, and absence from work. The statistical analysis was based on a multivariate analysis. DISCUSSION: The presence of mineral oil adjuvants, the injection of the vaccine under pressure and injection in joint and tendon of the hand significantly increased early locoregional complications and surgery but only the presence of mineral oil adjuvant increased significantly late locoregional complications at one month. Absence from work is significantly correlated to the site of injection and the presence of mineral oil adjuvant. CONCLUSION: It is important to know about the contents of the veterinary vaccine in order to anticipate early and late complications that may arise (particularly due to the presence of mineral oil adjuvants). Special attention must also be given do the site of injection. We think that any accidental injection of veterinary vaccine into humans, especially those containing mineral oils, must lead to an early medical consultation. This must also be indicated on the product.

Baclofen and Alcohol-Dependent Patients: A Real Risk of Severe Self-Poisoning.

Baclofen is often prescribed in high doses to fight cravings experienced by alcohol-dependent patients. Such an increase in the availability of baclofen is concerning. This study aimed to determine the change in number and profile of self-poisoning with baclofen over time, as baclofen has become increasingly popular, in order to describe the severity of self-poisoning with baclofen and to focus on co-existing alcohol use disorders, and psychiatric illnesses determine predictors of severity. This was a retrospective study of self-poisoning with baclofen as reported by the western France Poison Control Center (PCC), which represents a population of more than 12 million people from January 2008 to March 2014. One hundred and eleven cases of self-poisoning with baclofen were reported to the western France PCC (62 males and 49 females; average age 39 ± 12). Poisoning severities were as follows: 'null' (nine cases), 'minor' (37 cases), 'moderate' (19 cases) and 'high' (46 cases, including four deaths). The most frequently reported symptoms were neurological (45%) and cardiovascular (27%). The severity was significantly associated with psychiatric disorders (OR = 2.9; p = 0.03). Baclofen, prescribed in high doses, may lead to severe poisoning, particularly in patients with psychiatric illnesses. Authorities should put forward a new policy for prescribing the drug as a treatment for alcohol dependence.

Inpatient Gamma-Hydroxybutyrate Detoxification: A Case Report Describing Day-to-day Therapeutic Management.

BACKGROUND: Gamma-hydroxybutyrate (GHB) is a synthetic drug increasingly used by consumers of psychoactive substances. The sought after psychoactive effects of GHB have resulted in an increase in recreational use in Europe. GHB is considered to have a high dependence potential, and abrupt discontinuation after long-term use can result in a severe withdrawal syndrome. Despite a large number of publications related to GHB withdrawal and detoxification, to date, no evidence-based protocol or consensual international therapeutic guidelines are available (over and above the administration of benzodiazepines). We hereby present a day-to-day description of inpatient GHB detoxification management, from admission to discharge. CASE SUMMARY: This case report pertains to a 47-year-old patient hospitalized for a severe GHB use disorder. The patient had independently made several unsuccessful attempts to stop GHB use. Following to these failures, the patient was oriented to our addiction department for inpatient detoxification. Withdrawal symptoms appeared 4 hours after the last dose of GHB, and consisted of diaphoresis, coenesthetic hallucinations, tremors, motor instability, tachycardia, and a hypertensive peak. Symptoms were successfully managed with diazepam titration and nonpharmacological treatment. The duration of hospitalization was 13 days. At discharge, detoxification was complete and the patient was engaged in relapse prevention therapy. Three months after discharge, the patient had maintained abstinence. CONCLUSIONS: GHB withdrawal, which can be severe, is better prevented or attenuated by daily medical monitoring and adjustment of treatment dosage. Failure of outpatient detoxification should be included in the indication criteria in the guidelines for inpatient detoxification.