Dimetindene-Is the minimum toxic dose for children too strict?

Dimetindene is a sedating antihistamine indicated for the symptomatic treatment of allergic conditions. Dimetindene is marketed among others under the trade name Fenistil (oral solution). Toxicity data are limited, and there is no consensus on the dose at which children require hospitalization. Objective is to determine the potentially toxic dose in children. Data in children with age up to 15 years were obtained from hospital discharge reports. Of 139 paediatric hospital discharge reports, 23 cases (16.5%) were excluded because of uncertain ingestion. In 116 children (46 boys and 70 girls, mean age 2 years and 9 months ± 1 year and 1 month), the majority of children developed no symptoms (87 children, 75%, mean age 3 years±1 year) and the remaining 29 children (25%, mean age 2 years and 11 months ± 1 year and 3 months) developed only mild and spontaneously resolving symptoms of poisoning after a dose of 0.82 ± 0.32 mg/kg b.w. (range 0.26-1.82 mg/kg). In 98% of all cases, hospitalized children were observed for a maximum 24 h, and their condition did not require specific treatment. In conclusion, the prognosis for accidental dimetindene poisoning in children appears to be good and the minimum toxic dose has been determined to be 0.5 mg/kg b.w.

Viper envenomation in Central and Southeastern Europe: a multicentre study.

INTRODUCTION: Snakebite incidence varies across Europe. However, there is limited research from Central and Southeastern Europe. These regions are notable for the presence of the common European adder (Vipera berus) and the more venomous nose-horned viper (Vipera ammodytes). No standard European antivenom protocol exists. The aim was to assess the epidemiology and treatment of viper bites in this region, focusing on a comparison of bites from Vipera berus and Vipera ammodytes. METHODS: We conducted a prospective multicenter study in Central and Southeastern Europe from 2018 to 2020. This study included poison centres and toxicology-associated hospital wards in Poland, the Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, and Bulgaria. The following data were collected: age, gender, Vipera species, snakebite site, clinical picture, laboratory results, Audebert's clinical severity grading score, and antivenom therapy. RESULTS: The annual incidence of viper bites in Central and Southeast Europe was estimated at 2.55 bites per million population. Within their respective geographical distribution areas, the incidence of Vipera ammodytes bites (1.61 bites per million population) was higher than Vipera berus bites (1.00 bites per million population). Patients bitten by Vipera ammodytes more frequently reported local pain and developed thrombocytopenia. Antivenom treatment was more commonly administered in Vipera ammodytes bites (72%) compared to Vipera berus bites (39%). The incidence of Vipera ammodytes bites treated with antivenom within its geographical distribution area was three times higher than Vipera berus bites treated with antivenom (1.16 bites per million population versus 0.39 bites per million population). No deaths were reported. CONCLUSIONS: The estimated incidence of viper bites in Central and Southeastern Europe is at least 2.55 per million population. Vipera ammodytes bites are more common and severe, characterized by higher frequencies of pain and thrombocytopenia. Antivenom is needed more often for Vipera ammodytes bites. It is vital that enough European Medicines Agency-approved Vipera ammodytes antivenom is produced and offered affordably.

Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.

OBJECTIVE: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata. METHODS: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Descriptive data by age and sex are presented and compared among age/sex categories and among drug families. RESULTS: Of 17,371 patients were included during the 39-month period, 17,198 (99.0%) had taken at least one of the investigated drugs (median age: 31 years; 23.9% female; ethanol co-ingestion recorded in 41.5%, unknown in 31.2%; multiple drug use in 37.9%). Opioids (in 31.4% of patients) and amphetamines (23.3%) were the most frequently involved and hallucinogens (1.9%) and ketamine (1.7%) the least. Overall, female patients were younger than males, both in the whole cohort (median age 29 vs. 32 years; p < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years; p = 0.83). The relative proportion of each drug group was different at every age strata and some patterns could be clearly described: cannabis, NPS and hallucinogens were the most common in patients <20 years; amphetamines, ketamine and cocaine in the 20- to 39-year group; GHB/GBL in the 30- to 39-year group; and opioids and benzodiazepines in patients ≥40 years. Ethanol and other drug co-ingestion was more frequent at middle-ages, and multidrug co-ingestion was more common in females than males. CONCLUSION: Differences in the drugs involved in acute drug toxicity presentations according to age and sex may be relevant for developing drug-prevention and education programs for some particular subgroups of the population based on the increased risk of adverse events in specific sex and/or age strata.

Advice to the European Commission as Regards Type and Criteria for Comprehensive Studies to Be Requested From Manufacturers: The Opinion of the Scientific Committee on Health, Environmental, and Emerging Risks (SCHEER).

The European Commission has established a priority list of 15 additives contained in cigarettes and roll-your-own tobacco subject to enhanced reporting obligations. The European Union (EU) Tobacco Products Directive (TPD) prescribes that Member States shall require manufacturers and importers of tobacco products to carry out comprehensive studies on these additives to assess their contribution to any of the properties listed in Article 6 of the TPD: toxicity or addictiveness, characterizing flavor, inhalation facilitation, nicotine uptake, and carcinogenic, mutagenic, or toxic for reproduction. The Scientific Committee on Health, Environmental, and Emerging Risks (SCHEER) has provided guidance on the type and criteria for comprehensive studies, and on the most suitable methodologies to test these 15 tobacco additives as well as additives on future updated lists. The SCHEER proposes a stepwise strategy as the most pragmatic and efficient way to assess the effects of tobacco additives. In addition to proposing specific steps and tests to be considered by industry, some general criteria were also identified such as no comparative testing (testing cigarettes with and without the additive) and no animal studies. As tobacco additives have no benefits for health, but rather may promote use of and addiction to an extremely toxic product, a risk-benefit analysis is not the appropriate paradigm for assessing the additive. When comprehensive studies confirm that additives have any of the properties listed in Article 6 of the TPD, regulatory actions should be considered. If uncertainties cannot be solved by comprehensive studies, the SCHEER recommends that the assessors consider the worst-case evaluation. IMPLICATIONS: In this article, the SCHEER proposes a stepwise strategy to assess (1) the toxic and addictive effects, (2) the characterizing flavor, and (3) facilitating inhalation properties of tobacco additives. The proposed steps and tests provide guidance to (1) Member State on which comprehensive studies should be requested and (2) tobacco industry on which strategy of testing should be applied to address the request and to prepare reports to be sent to the relevant authorities for the evaluation of tobacco additives "safety" to comply with the Tobacco Products Directive 2014/40/EU.

Eye hazard classification according to UN GHS / EU CLP and the severity of eye symptoms caused by accidental exposures to detergents and cleaning products.

The use of lower cut-off values/concentration limits for the calculation of mixture classification in UN GHS/EU CLP versus the previous regulatory scheme (EU Dangerous Preparations Directive, DPD), has resulted in an increased number of classifications in the highest eye hazard category. Herein, a semi-quantitative categorisation of severity of eye effects, following accidental human exposures to detergents, was compared to the classification category of the products. Three schemes were evaluated: EU DPD; EU CLP (based on all available data and information, including weight of evidence); and EU CLP (based entirely on the calculation method). As reported by four EU Poison Centres, the vast majority of exposures had caused minor or no symptoms. Classification was a poor predictor of effects in man subjected to accidental exposure. Note however that this is also because effects are not only driven by the intrinsic hazard (as reflected in the classification), but also by the exposure conditions and mitigation (i.e. rinsing). EU CLP classification using all available data and information was more predictive of medically relevant symptoms than the EU CLP calculation method. The latter led to a poorer differentiation between irritating products versus products potentially causing serious eye damage.

Public health response to methanol mass poisoning in the Czech Republic in 2012: a case study.

OBJECTIVES: The study focuses on the 2012 methanol outbreak in the Czech Republic. The main goal of the present study was to apply analytical and descriptive tools to selected qualitative and quantitative processes related to the 2012 methanol outbreak in the Czech Republic. The secondary goal was to study and evaluate in detail their potential for creating integrated conceptual national policies aimed at eliminating the risk of methanol poisoning in the future. METHODS: The presented qualitative analysis focused on the content of documents published by Czech public authorities - the Ministry of Health, the Ministry of the Interior, the Czech Agriculture and Food Inspection Authority, and the Regional Public Health Authorities - as well as the content of the relevant legal regulations. Moreover, statistical data concerning the number of hospitalisations and deaths due to the methanol intoxication were used to provide a background to a detailed description of the relevant facts. RESULTS: In procedural terms, most of the analysed measures focused on a strongly restrictive regulation of sales, regular information channels designed to protect consumers on the national as well as international level, and elimination of further health and economic risks stemming from the dangerous alcoholic products that had already entered distribution networks. The health, social and economic consequences of such activities are quantified at a highly aggregated level. The analysed institutional ties are evaluated also in the context of international documents: the European Action Plan to Reduce Harmful Use of Alcohol 2012-2020 and the Global Strategy to Reduce Harmful Use of Alcohol, and their current potential for steering public policies is assessed. CONCLUSION: The analysis and evaluation of procedural activities carried out after the methanol outbreak have laid the foundations for a multidimensional study that can contribute to integrated national policy concepts aimed at preventing these and similar negative health, societal and economic consequences. Six years after the methanol outbreak, national and regional health policies have reflected no findings concerning the experience of patients whose health was impaired due to methanol, and the economic cost of the event has not been calculated. The quality of life of these patients has greatly decreased due to permanent or partial incapacity and serious upheavals of their and their families' economic and social conditions. This opens the question of researching and evaluating multiple aspects of health, social and economic impacts of harmful use of alcohol and setting up processes to mitigate these impacts.

Comparación de las urgencias atendidas por drogas de abuso en dos servicios de urgencias españoles con las atendidas en tres áreas europeas distintas / Emergencies related to recreational drug abuse in Spain compared to emergencies attended in 3 European areas

Objetivo. Analizar algunas características epidemiológicas, clínicas y asistenciales de los pacientes atendidos por sintomatología directamente derivada del consumo de drogas de abuso en dos servicios de urgencias hospitalarios (SUH) españoles y compararlas con las observadas en otras regiones de Europa. Método. Análisis secundario del Registro Euro-DEN Plus (14 países europeos, 20 SUH) que incluyó todos los pacientes atendidos por sintomatología derivada del consumo de drogas (excepto etanol aislado) durante 39 meses consecutivos (octubre 2013 a diciembre 2016). Se comparan los casos de los 2 centros españoles (Barcelona, Palma) con los de 5 centros de Reino Unido e Irlanda (Islas Británicas -IB-), 6 del Norte de Europa (NE) y 7 de Europa Central (EC). Resultados. Se recogieron 17.104 pacientes: España 1.186, IB 6.653, NE 6.097 y EC 3.168. En España hubo más urgencias por cocaína (48,4%) y menos por opiáceos (12,4%) que en el resto de zonas; los pacientes eran más jóvenes (32,2 años) que en NE y mayores que en IB y EC; menos frecuentemente mujeres (21,9%) que en NE y EC; llegaron menos frecuentemente en ambulancia (70,0%) que en IB y NE; y en el SUH se registró escasamente la temperatura (29,8%) y frecuencia respiratoria (30,3%). Las manifestaciones clínicas difirieron entre zonas por la distinta prevalencia de cada tipo de droga. Naloxona (9,6%) se utilizó menos que en IB y NE, y flumazenilo (5,6%) más que en las otras zonas, y los porcentajes de ingresos (4,6%) y fugas del SUH (6,2%) fueron los menores de todas las regiones analizadas. La mortalidad, en urgencias (0,4%) y global (0,7%), fue significativamente superior que en NE. Conclusiones. Las características de las urgencias generadas por drogas de abuso son diferentes en España respecto a otras zonas europeas, debido a un diferente patrón de consumo. Su manejo en el SUH, en términos de exploraciones realizadas, tratamientos empleados y disposición tras la asistencia también son diferentes

Objectives. To analyze epidemiologic, clinical, and care characteristics in cases in which patients came to 2 Spanish emergency departments (EDs) with symptoms caused by recreational drug abuse. To compare the characteristics with those reported for other areas of Europe. Methods. Secondary analysis of the registry of the European Drug Emergencies Network (Euro-DEN Plus), which collects cases in 14 European countries and 20 EDs. The registry included all patients attending EDs with symptoms of recreational drug abuse (excepting cases involving alcohol alone) over a period of 39 consecutive months (October 2013 to December 2016). We compared the cases from the 2 Spanish EDs (in Barcelona and Palma de Mallorca) to those from the 5 EDs in Ireland and the UK, 6 in northern Europe, and 7 in central Europe. Results. A total of 17 104 patients' cases were included: Spain, 1186; UK and Ireland, 6653; northern Europe, 6097; and central Europe, 3168. Spain saw more emergencies related to cocaine (48.4%) and fewer related to opioids (12.4%) than the other areas. The Spanish patients were younger (32.2 years) on average than those in northern Europe and older than those in the UK and Ireland and central Europe. Fewer patients were women in Spain (21.9%) than in northern or central Europe. Fewer arrived in ambulances in Spain (70.0%) than in the UK and Ireland or northern Europe. The Spanish EDs recorded the temperature and respiratory frequency of fewer patients (29.8% and 30.3%, respectively). Clinical signs differed between geographical areas attributable to differences in drug-use patterns. In Spain, naloxone was used by fewer patients (9.6%) than in the UK and Ireland and northern Europe, and flumazenil was used by more patients (5.6%) than in other areas. Spain saw lower percentages of admissions (4.6%) and patients who left without an ED discharge (6.2%) in comparison with other areas. Mortality rates in the Spanish EDs (0.4%) and after discharge from them (0.7%) were higher than in northern Europe. Conclusions. The characteristics of emergencies related to recreational drug abuse registered by the Spanish EDs were differed from those registered in other parts of Europe due to different patterns of drug use. We also detected differences between the Spanish and other European EDs with respect to examinations or tests performed, treatment given, and discharge disposition

Emergencies related to recreational drug abuse in Spain compared to emergencies attended in 3 European areas. / Comparación de las urgencias atendidas por drogas de abuso en dos servicios de urgencias españoles con las atendidas en tres áreas europeas distintas.

OBJECTIVES: To analyze epidemiologic, clinical, and care characteristics in cases in which patients came to 2 Spanish emergency departments (EDs) with symptoms caused by recreational drug abuse. To compare the characteristics with those reported for other areas of Europe. MATERIAL AND METHODS: Secondary analysis of the registry of the European Drug Emergencies Network (Euro-DEN Plus), which collects cases in 14 European countries and 20 EDs. The registry included all patients attending EDs with symptoms of recreational drug abuse (excepting cases involving alcohol alone) over a period of 39 consecutive months (October 2013 to December 2016). We compared the cases from the 2 Spanish EDs (in Barcelona and Palma de Mallorca) to those from the 5 EDs in Ireland and the UK, 6 in northern Europe, and 7 in central Europe. RESULTS: A total of 17 104 patients' cases were included: Spain, 1186; UK and Ireland, 6653; northern Europe, 6097; and central Europe, 3168. Spain saw more emergencies related to cocaine (48.4%) and fewer related to opioids (12.4%) than the other areas. The Spanish patients were younger (32.2 years) on average than those in northern Europe and older than those in the UK and Ireland and central Europe. Fewer patients were women in Spain (21.9%) than in northern or central Europe. Fewer arrived in ambulances in Spain (70.0%) than in the UK and Ireland or northern Europe. The Spanish EDs recorded the temperature and respiratory frequency of fewer patients (29.8% and 30.3%, respectively). Clinical signs differed between geographical areas attributable to differences in drug-use patterns. In Spain, naloxone was used by fewer patients (9.6%) than in the UK and Ireland and northern Europe, and flumazenil was used by more patients (5.6%) than in other areas. Spain saw lower percentages of admissions (4.6%) and patients who left without an ED discharge (6.2%) in comparison with other areas. Mortality rates in the Spanish EDs (0.4%) and after discharge from them (0.7%) were higher than in northern Europe. CONCLUSION: The characteristics of emergencies related to recreational drug abuse registered by the Spanish EDs were differed from those registered in other parts of Europe due to different patterns of drug use. We also detected differences between the Spanish and other European EDs with respect to examinations or tests performed, treatment given, and discharge disposition.

OBJETIVO: Analizar algunas características epidemiológicas, clínicas y asistenciales de los pacientes atendidos por sintomatología directamente derivada del consumo de drogas de abuso en dos servicios de urgencias hospitalarios (SUH) españoles y compararlas con las observadas en otras regiones de Europa. METODO: Análisis secundario del Registro Euro-DEN Plus (14 países europeos, 20 SUH) que incluyó todos los pacientes atendidos por sintomatología derivada del consumo de drogas (excepto etanol aislado) durante 39 meses consecutivos (octubre 2013 a diciembre 2016). Se comparan los casos de los 2 centros españoles (Barcelona, Palma) con los de 5 centros de Reino Unido e Irlanda (Islas Británicas ­IB­), 6 del Norte de Europa (NE) y 7 de Europa Central (EC). RESULTADOS: Se recogieron 17.104 pacientes: España 1.186, IB 6.653, NE 6.097 y EC 3.168. En España hubo más urgencias por cocaína (48,4%) y menos por opiáceos (12,4%) que en el resto de zonas; los pacientes eran más jóvenes (32,2 años) que en NE y mayores que en IB y EC; menos frecuentemente mujeres (21,9%) que en NE y EC; llegaron menos frecuentemente en ambulancia (70,0%) que en IB y NE; y en el SUH se registró escasamente la temperatura (29,8%) y frecuencia respiratoria (30,3%). Las manifestaciones clínicas difirieron entre zonas por la distinta prevalencia de cada tipo de droga. Naloxona (9,6%) se utilizó menos que en IB y NE, y flumazenilo (5,6%) más que en las otras zonas, y los porcentajes de ingresos (4,6%) y fugas del SUH (6,2%) fueron los menores de todas las regiones analizadas. La mortalidad, en urgencias (0,4%) y global (0,7%), fue significativamente superior que en NE. CONCLUSIONES: Las características de las urgencias generadas por drogas de abuso son diferentes en España respecto a otras zonas europeas, debido a un diferente patrón de consumo. Su manejo en el SUH, en términos de exploraciones realizadas, tratamientos empleados y disposición tras la asistencia también son diferentes.