Publications by authors named "Florian Eyer"

85 Publications

Anticholinergic syndrome after atropine overdose in a supposedly homeopathic solution: a case report.

Clin Toxicol (Phila) 2021 May 14:1-3. Epub 2021 May 14.

Department of Internal Medicine II, Division of Clinical Toxicology and Poison Control Centre Munich, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Background: A 53-year-old male with no pre-existing conditions and no permanent medication presented to our emergency department with an anticholinergic syndrome including confusion, anxiety, ataxia and dysarthria after ingestion of a homeopathic solution containing extract supposedly in a D4 dilution.

Methods: Atropine sulphate was quantitatively analysed in serum and the homeopathic preparation liquid chromatography/mass spectrometry.

Results: Analysis revealed concentrations of approximately 3 mg/mL atropine sulphate in the homeopathic solution and a serum level of 5.7 ng/mL (±1.4) in the patient's blood proving a 600-fold overdose of atropine due to a production error of the homeopathic dilution. The patient was observed and recovered without further intervention.

Conclusion: Rare but possibly dangerous manufacturing errors should be considered when faced with symptoms occurring after ingestion of homeopathic or holistic remedies.
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http://dx.doi.org/10.1080/15563650.2021.1918704DOI Listing
May 2021

Return of the Quaaludes? Prolonged agitated delirium after intentional ingestion of the methaqualone analog SL-164 - a case report.

Subst Abus 2021 Mar 24:1-3. Epub 2021 Mar 24.

Department of Internal Medicine II, Division of Clinical Toxicology and Poison Control Centre Munich, TUM School of Medicine, Technical University of Munich, Munich, Germany.

: A 22-year-old male with a known history of drug abuse presented to our department with prolonged agitated delirium, myocloni, tachycardia and subfebrile temperature after the deliberate ingestion of opium poppy tea ( L.) together with the methaqualone analog SL-164 (5-chloro-3-(4-chloro-2-methylphenyl)-2-methyl-4()-quinazolinone) which is sold online as a designer drug. : SL-164 and its hydroxy metabolites were detected in serum and urine via liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). : The pronounced delirium was treated with benzodiazepines and neuroleptics; temporary medical restraint had to be applied. Symptoms completely resolved over the next 72 h and the patient was discharged on day three able to give consent. : Although methaqualone was a popular and widespread sedative in the 1950s and 60 s before its discontinuation in the USA in 1985, derivatives of the methaqualone class have not previously played a large role as drugs of abuse in the rapidly growing market of new psychoactive substances. To our knowledge, this is the first case of agitated delirium with detection of SL-164 and hydroxylated metabolites in a patient's serum and urine.
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http://dx.doi.org/10.1080/08897077.2021.1903648DOI Listing
March 2021

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

Clin Toxicol (Phila) 2021 Mar 16:1-13. Epub 2021 Mar 16.

Emergency Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.

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;  < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years;  = 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.
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http://dx.doi.org/10.1080/15563650.2021.1884693DOI Listing
March 2021

Mushroom Poisoning.

Dtsch Arztebl Int 2020 10;117(42):701-708

Luxembourg: Prof. Dr. Robert Wennig (formerly Laboratoire National de Santé- Toxicologie, Université du Luxembourg-Campus Limpertsberg); Department of Clinical Toxicology & Poison Control Center Munich, Klinikum rechts der Isar, School of Medicine, Technical University of Munich; GIZ-Nord Poisons Centre,Göttingen University Hospital Faculty of Medicine and University Hospital Cologne and Department of Forensic Toxicology,University Hospital Cologne.

Background: Poisonous mushrooms are eaten by mushroom hunters out of ignorance, after misidentification as edible mushrooms, or as a psychoactive drug. Mushroom poisoning commonly leads to consultation with a poison information center and to hospitalization.

Methods: This review is based on pertinent publications about the syndromes, toxins, and diagnostic modalities that are presented here, which were retrieved by a selective search in PubMed. It is additionally based on the authors' longstanding experience in the diagnosis and treatment of mushroom intoxication, expert consultation in suspected cases, macroscopic identification of wild mushrooms, and analytic techniques.

Results: A distinction is usually drawn between mushroom poisoning with a short latency of less than six hours, presenting with a gastrointestinal syndrome whose course is usually relatively harmless, and cases with a longer latency of six to 24 hours or more, whose course can be life-threatening (e.g., phalloides, gyromitra, orellanus, and rhabdomyolysis syndrome). The DRG diagnosis data for Germany over the period 2000-2018 include a total of 4412 hospitalizations and 22 deaths due to the toxic effects of mushroom consumption. 90% of the fatalities were due to the death cap mushroom (amatoxins). Gastrointestinal syndromes due to mushroom consumption can be caused not only by poisonous mushrooms, but also by the eating of microbially spoiled, raw, or inadequately cooked mushrooms, or by excessively copious or frequent mushroom consumption.

Conclusion: There are few analytic techniques available other than the qualitative demonstration of amatoxins. Thus, the diagnosis is generally made on the basis of the clinical manifestations and their latency, along with meticulous history-taking, assisted by a mushroom expert, about the type(s) of mushroom that were consumed and the manner of their preparation.
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http://dx.doi.org/10.3238/arztebl.2020.0701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868946PMC
October 2020

Effect of plasma exchange on colchicine elimination in overdose - a case report.

Clin Toxicol (Phila) 2021 Feb 8:1-4. Epub 2021 Feb 8.

Division of Clinical Toxicology, Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1080/15563650.2021.1877298DOI Listing
February 2021

Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers.

Am J Gastroenterol 2021 01;116(1):106-115

Drug Health Services, Royal Prince Alfred Hospital, Camperdown, Australia.

Introduction: Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk.

Methods: We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank.

Results: The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption.

Discussion: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.
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http://dx.doi.org/10.14309/ajg.0000000000000833DOI Listing
January 2021

Genome-wide Association Study and Meta-analysis on Alcohol-Associated Liver Cirrhosis Identifies Genetic Risk Factors.

Hepatology 2021 May;73(5):1920-1931

Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, United Kingdom.

Background And Aims: Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC.

Approach And Results: We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes.

Conclusions: Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.
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http://dx.doi.org/10.1002/hep.31535DOI Listing
May 2021

Assessment of α-amanitin toxicity and effects of silibinin and penicillin in different in vitro models.

Toxicol In Vitro 2020 Sep 27;67:104921. Epub 2020 Jun 27.

Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilian-University Munich, Goethestraße 33, 80336 Munich, Germany; Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany.

Silibinin (Sil) is used as hepatoprotective drug and is approved for therapeutic use in amanitin poisoning. In our study we compared Sil-bis-succinate (Sil), a water-soluble drug approved for i.v.-administration, with Sil solved in ethanol (Sil), which is normally used in research. We challenged monocultures or 3D-microtissues consisting of HepG2 cells or primary hepatocytes with α-amanitin and treated with SIL, SIL, penicillin and combinations thereof. Cell viability and the integrity of the microtissues was monitored. Finally, the expression of the transporters OATP1B1 and B3 was analyzed by qRT-PCR. We demonstrated that primary hepatocytes were more sensitive to α-amanitin compared to HepG2. Primary hepatocytes cultures were protected by Sil and Sil independent of penicillin from the cytotoxic effects of α-amanitin. Subsequent studies of the expression profile of the transporters OATP1B1/B3 revealed that primary hepatocytes do express both whereas in HepG2 cells they were hardly detectable. Our study showed that Sil has significant advantage over Sil with no additional benefit of penicillin. Moreover, HepG2 cells may not represent an appropriate model to investigate Amanita phalloides poisoning in vitro with focus on OATP transporters since these cells are lacking sensitivity towards α-amanitin probably due to missing cytotoxicity-associated transporters suggesting that primary hepatocytes should be preferred in this context.
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http://dx.doi.org/10.1016/j.tiv.2020.104921DOI Listing
September 2020

Genome-Wide Association Study for Alcohol-Related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1.

Gastroenterology 2020 10 16;159(4):1276-1289.e7. Epub 2020 Jun 16.

Medical Department 1, University Hospital Dresden, Technische Universität Dresden, Germany.

Background And Aims: Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samples from the United Kingdom Biobank (UKB) to identify polymorphisms associated with risk of alcohol-related liver disease.

Methods: We performed a GWAS of 35,839 participants in the UKB with high intake of alcohol against markers of hepatic fibrosis (FIB-4, APRI, and Forns index scores) and hepatocellular injury (levels of aminotransferases). Loci identified in the discovery analysis were tested for their association with alcohol-related cirrhosis in 3 separate European cohorts (phase 1 validation cohort; n=2545). Variants associated with alcohol-related cirrhosis in the validation at a false discovery rate of less than 20% were then directly genotyped in 2 additional European validation cohorts (phase 2 validation, n=2068).

Results: In the GWAS of the discovery cohort, we identified 50 independent risk loci with genome-wide significance (P < 5 × 10). Nine of these loci were significantly associated with alcohol-related cirrhosis in the phase 1 validation cohort; 6 of these 9 loci were significantly associated with alcohol-related cirrhosis in phase 2 validation cohort, at a false discovery rate below 5%. The loci included variants in the mitochondrial amidoxime reducing component 1 gene (MARC1) and the heterogeneous nuclear ribonucleoprotein U like 1 gene (HNRNPUL1). After we adjusted for age, sex, body mass index, and type-2 diabetes in the phase 2 validation cohort, the minor A allele of MARC1:rs2642438 was associated with reduced risk of alcohol-related cirrhosis (adjusted odds ratio, 0.76; P=.0027); conversely, the minor C allele of HNRNPUL1:rs15052 was associated with an increased risk of alcohol-related cirrhosis (adjusted odds ratio, 1.30; P=.020).

Conclusions: In a GWAS of samples from the UKB, we identified and validated (in 5 European cohorts) single-nucleotide polymorphisms that affect risk of alcohol-related cirrhosis in opposite directions: the minor A allele in MARC1:rs2642438 decreases risk, whereas the minor C allele in HNRNPUL1:rs15052 increases risk.
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http://dx.doi.org/10.1053/j.gastro.2020.06.014DOI Listing
October 2020

A machine learning approach to risk assessment for alcohol withdrawal syndrome.

Eur Neuropsychopharmacol 2020 06 14;35:61-70. Epub 2020 May 14.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich Nussbaumstr. 7, 80336 Munich, Germany.

At present, risk assessment for alcohol withdrawal syndrome relies on clinical judgment. Our aim was to develop accurate machine learning tools to predict alcohol withdrawal outcomes at the individual subject level using information easily attainable at patients' admission. An observational machine learning analysis using nested cross-validation and out-of-sample validation was applied to alcohol-dependent patients at two major detoxification wards (LMU, n = 389; TU, n = 805). 121 retrospectively derived clinical, blood-derived, and sociodemographic measures were used to predict 1) moderate to severe withdrawal defined by the alcohol withdrawal scale, 2) delirium tremens, and 3) withdrawal seizures. Mild and more severe withdrawal cases could be separated with significant, although highly variable accuracy in both samples (LMU, balanced accuracy [BAC] = 69.4%; TU, BAC = 55.9%). Poor outcome predictions were associated with higher cumulative clomethiazole doses during the withdrawal course. Delirium tremens was predicted in the TU cohort with BAC of 75%. No significant model predicting withdrawal seizures could be found. Our models were unique to each treatment site and thus did not generalize. For both treatment sites and withdrawal outcome different variable sets informed our models' decisions. Besides previously described variables (most notably, thrombocytopenia), we identified new predictors (history of blood pressure abnormalities, urine screening for benzodiazepines and educational attainment). In conclusion, machine learning approaches may facilitate generalizable, individualized predictions for alcohol withdrawal severity. Since predictive patterns highly vary for different outcomes of withdrawal severity and across treatment sites, prediction tools should not be recommended for clinical practice unless adequately validated in specific cohorts.
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http://dx.doi.org/10.1016/j.euroneuro.2020.03.016DOI Listing
June 2020

Surviving chlormequat poisoning - pharmacokinetics and the role of atropine.

Clin Toxicol (Phila) 2021 01 27;59(1):74-76. Epub 2020 Apr 27.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, School of Medicine, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1080/15563650.2020.1758326DOI Listing
January 2021

Choking agents and chlorine gas - History, pathophysiology, clinical effects and treatment.

Toxicol Lett 2020 Mar 4;320:73-79. Epub 2019 Dec 4.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Introduction: Choking agent exposure, among them chlorine gas, occurs in household or industrial accidents, chemical warfare and terrorist attacks.

Aims: Review of published animal and human data regarding the history, pathophysiology, clinical effects and management of chlorine exposure.

Pathophysiology: Highly soluble agents cause quick upper respiratory tract symptoms. Chlorine gas has a medium solubility, also causing delayed lower airway symptoms, mainly due to its oxidizing potential by releasing hypochlorous and hydrochloric acid, but also by interacting with Transient Receptor Potential channels.

Symptoms: Eyes may show conjunctival injection, abrasions and corrosions. Burns of the oronasal mucosa and trachea can occur. Dyspnea, bronchospasm and possible retrosternal pain occur frequently. Glottis edema or laryngospasm are acute life-threatening emergencies. Chlorine gas can cause toxic pneumonitis, lung edema and acute respiratory distress syndrome (ARDS).

Management: General management includes physical examination, pulse oximetry and arterial blood gases. Eyes should be irrigated, humidified oxygen and inhalative bronchodilators administered. An EKG, cardiac enzymes and complete-blood-count should be obtained if there is retrosternal pain. Routine chest x-ray is not recommended - except if pulmonary edema is suspected. Laryngoscopy should be performed if glottis edema is suspected. Sodium bicarbonate inhalation after chlorine gas inhalation is discussed controversially. Mechanical ventilation with continuous-positive-airway-pressure or intubation/tracheotomy with high positive-end-expiratory-pressure may be necessary. Glucocorticoids for prevention of pulmonary edema should be applied restrictively. Prophylactic antibiotics are not recommended. In severe ARDS, extracorporeal membrane oxygenation (ECMO) can be considered.

Conclusion: Treatment is mainly symptom oriented. New and promising therapies are in development.
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http://dx.doi.org/10.1016/j.toxlet.2019.12.005DOI Listing
March 2020

Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.

Hepatology 2020 07 20;72(1):88-102. Epub 2020 May 20.

Departments of Gastroenterology and Hepatology, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.

Background And Aims: Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC.

Approach And Results: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol-related cirrhosis and HCC, 1,653 with alcohol-related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.88; P = 8.13 × 10 ) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 × 10 ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54-1.88; P = 1.52 × 10 ) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 × 10 ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (OR , 0.75; 95% CI, 0.64-0.87; P = 1.72 × 10 ).

Conclusions: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population.
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http://dx.doi.org/10.1002/hep.30996DOI Listing
July 2020

[Diagnostics and treatment of selected clinically relevant, acute drug intoxications].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2019 Nov;62(11):1313-1323

Abteilung für Klinische Toxikologie & Giftnotruf München, Universitätsklinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland.

Acute drug poisoning due to accidental or self-damaging overdoses is responsible for 5-10% of emergency medical interventions in Germany. The treatment of asymptomatic to life-threatening courses requires extensive expertise. On the basis of a selective literature search, this article gives an overview of selected clinically relevant, acute drug poisonings with regard to epidemiology, symptomatology, diagnostics, and therapy.Intoxications with psychotropic drugs are the most common drug intoxications. Poisoning with tricyclic antidepressants causes anticholinergic, central nervous, and cardiovascular symptoms. Less toxic are selective serotonin reuptake inhibitors (SSRIs); the intoxication may be characterized by serotonin syndrome. Malignant neuroleptic syndrome is a severe complication of neuroleptic poisoning.Poisoning with analgesics is clinically relevant due to its high availability. For paracetamol poisoning, intravenous acetylcysteine is available as an antidote. Hemodialysis may be indicated for severe salicylate intoxication. Poisoning with nonsteroidal anti-inflammatory drugs is usually only associated with mild signs of intoxication.Poisoning with cardiac drugs (β-blockers and calcium antagonists) can cause life-threatening cardiovascular events. In addition to symptomatic therapy, insulin glucose therapy also plays an important role.The majority of acute drug poisonings can be treated adequately by symptomatic and partly intensive care therapy - if necessary with the application of primary and secondary toxin elimination. Depending on the severity of the intoxication, pharmacology-specific therapy must be initiated.
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http://dx.doi.org/10.1007/s00103-019-03024-7DOI Listing
November 2019

[Mushroom poisoning].

MMW Fortschr Med 2019 Aug;161(14):64-65

Klinik und Poliklinik für Innere Medizin II, Abt. für Klinische Toxikologie und Giftnotruf München, Klinikum rechts der Isar, Ismaninger Straße 22, D-81675, München, Deutschland.

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http://dx.doi.org/10.1007/s15006-019-0787-yDOI Listing
August 2019

The Use of Activated Charcoal to Treat Intoxications.

Dtsch Arztebl Int 2019 May;116(18):311-317

Department of Internal Medicine II, SDepartment of Clinical Toxicology and Poison Control Center Munich, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich; Joint Poisons Information Center for Mecklenburg-West Pomerania, Saxony, Saxony-Anhalt and Thuringia, Erfurt; Poisons Information Center North for Bremen, Hamburg, Lower Saxony and Schleswig-Holstein, Faculty of Medicine, University of Göttingen; Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health Poison Information Center; Poisons Information Center Vienna, Gesundheit Österreich GmbH, Vienna, Austria.

Background: In 2016, according to the German Federal Statistical Office, 178 425 cases of intoxication (poisoning) were treated in German hospitals. The poison control centers in the German-speaking countries gave advice in a total of 268 787 instances of poisoning in that year, and use of activated charcoal was recommended in 4.37% of cases. The application of activated charcoal plays a major role in both primary and secondary detoxification. This article serves as an overview of the mechanism of action, indications, contraindications, modes of application, and dosing of activated charcoal.

Methods: This review is based on pertinent publications retrieved by a selective search in PubMed. The opinions of experts from the poison control centers in the German-speaking countries were considered in the interpretation of the data.

Results: The administration of activated charcoal is indicated to treat moderately severe to life-threatening intoxication. It should be carried out as soon as possible, within the first hour of the ingestion; timed-release preparations can be given up to 6 hours after the ingestion. An important contraindication is impaired consciousness with the danger of aspiration in a patient whose air- way has not yet been secured. Activated charcoal is ineffective or inadequately effective in cases of poisoning with acids or bases, alcohols, organic solvents, inorganic salts, or metals. The proper dosage consists of an amount that is 10 to 40 times as much as that of the intoxicating substance, or else 0.5-1 g/kg body weight in children or 50 g in adults. Repeated application is indicated for intoxications with agents that persist for a longer time in the stomach and for intoxications with timed-release drugs or drugs with a marked enterohepatic or entero-enteric circulation. The routine combination of activated charcoal with a laxative is not recommended.

Conclusion: Even though intoxications are common, there is still no internationally valid guideline concerning the administration of activated charcoal. A precise analysis of the risks and benefits is needed for each administration, and a poison control center should be consulted for this purpose.
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http://dx.doi.org/10.3238/arztebl.2019.0311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620762PMC
May 2019

MAGAM II - prospective observational multicentre poisons centres study on eye exposures caused by cleaning products.

Clin Toxicol (Phila) 2019 Sep 18;57(9):765-772. Epub 2019 Feb 18.

j Poisons Centre - Clinical Toxicology, University Medical Center of the Johannes Gutenberg University Mainz , Mainz , Germany.

Local effects on the eye following cleaning product exposures are frequently reported. According to EU chemicals legislation many cleaning products are labelled with Hazard Phrase 318 indicating risk of irreversible eye damage. The objectives of this study were to identify cleaning products with potential for irreversible eye damage by collecting human exposure data from poisons centres (PC), and to clarify to what degree exact product identification is possible during a PC telephone call. MAGAM II was a multicentre binational prospective observational PC study. All human eye exposures to detergents or maintenance products reported to nine PCs taking calls from the public and medical professionals during an 18-month period were included. The severity of eye effects was rated according to the WHO Poisoning Severity Score. Five hundred and eighty-six cases were included. Product identification by name leading to formula information was successful in 533 cases (91%). Follow-up was successful in 528 exposures. Irrigation was performed in 94% of cases. Duration of symptoms was ≥24 hours in 73 patients (25%). 33 (6%) patients developed moderate eye injury. Healing was reported in all cases. The percentage of moderate cases was highest in the group of drain cleaners (25%), toilet cleaners (18%) and oven cleaners (15%). Products intended for professional use caused relatively more moderate eye injuries than products also intended for consumer use. MAGAM II has shown that PCs are able to identify formulas in sufficiently high quality as needed for product-directed toxicovigilance. The results underline the potential of PC exposure case data for product safety monitoring. The results indicate that irreversible eye damage is very rare after cleaning product exposure.
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http://dx.doi.org/10.1080/15563650.2018.1560462DOI Listing
September 2019

Emergencies related to recreational drug abuse in Spain compared to emergencies attended in 3 European areas.

Emergencias 2018 Dic;30(6):385-394

Área de Urgencias, Hospital Clínic, Barcelona; Grupo de Investigación "Urgencias: Procesos y Patologías", IDIBAPS, Barcelona, España.

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.
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July 2019

Sustained low efficiency dialysis should not be interrupted for performing transpulmonary thermodilution measurements.

Ann Intensive Care 2018 Nov 23;8(1):113. Epub 2018 Nov 23.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Background: Treatment of multiple organ failure frequently requires enhanced hemodynamic monitoring. When renal replacement is indicated, it remains unclear whether transpulmonary thermodilution (TPTD) measurements are influenced by renal replacement therapy (RRT) and whether RRT should be paused for TPTD measurements. Our aim was therefore to investigate the effect of pausing RRT on TPTD results in two dialysis catheter locations.

Materials And Methods: In total, 62 TPTD measurements in 24 patients (APACHE: 32 ± 7 [mean ± standard deviation (SD)]) were performed using the PiCCO™ system (Pulsion, Germany). Patients were treated with sustained low efficiency dialysis (SLED; Genius™ system, Fresenius, Germany) as RRT. Measurements were taken during ongoing hemodialysis (HD, HDO), during paused HD (HDP) and immediately after termination of HD and blood restitution (HDT). Dialysis catheters were placed either in the superior vena cava (SVC, 19 times) or in the inferior vena cava (IVC, 5 times). Statistical analysis was performed to assess the effects of the measurement setting, SLED (blood flow rate) and the catheter location, on cardiac index (CI), global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI) as measured by TPTD. Multilevel models were used for the analysis due to the triplicate measurements and due to 12 out of 19 SVC and 2 out of 5 IVC patients having more than one TPTD measured.

Results: CI and GEDVI were significantly higher at time point HDP compared to both HDO and HDT. In contrast, values for EVLWI were lower at HDP when compared to HDO and HDT. These findings were independent of the site of dialysis catheter insertion and blood flow rate.

Conclusions: PiCCO™ measurements assessed at paused SLED significantly deviate from ongoing and terminated SLED. Therefore, the dialysis system should not be paused for measurements. TPTD measurements in patients with PiCCO monitoring seem sufficiently reliable during ongoing SLED as well as after its termination. An effect of dialysis catheter location (SVC vs IVC) and blood flow rate on PiCCO™ measurements could not be shown.
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http://dx.doi.org/10.1186/s13613-018-0455-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251800PMC
November 2018

Verification of organophosphorus pesticide poisoning: Detection of phosphorylated tyrosines and a cysteine-proline disulfide-adduct from human serum albumin after intoxication with dimethoate/omethoate.

Toxicol Lett 2018 Dec 27;299:11-20. Epub 2018 Aug 27.

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany. Electronic address:

A method is described allowing forensic analysis of plasma samples to prove human poisoning with the organophosphorus pesticides omethoate (OM) and dimethoate (DIM). Upon incubation of human serum albumin (HSA) with both pesticides tyrosine residues were phosphorylated. In addition, a novel disulfide-adduct between the identical thiol-containing leaving group of OM and DIM (2-mercapto-N-methylacetamide, MNMA) and the only free cysteine residue in HSA (Cys) was formed. Following pronase-catalyzed proteolysis either O,O-dimethyl phosphotyrosine (Tyr-dmp) or O,O-dimethyl thiophosphotyrosine (Tyr-dmsp) as well as the cysteine-proline dipeptide disulfide-adduct (MNMA-CysPro) were produced. All biomarkers were simultaneously detected using modern microbore liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (μLC-ESI MS/HR MS). Corresponding limits of identification (LOI) for tyrosine-adducts (LOI: 30 μM, LOI: 120 μM) and disulfide-adducts (LOI: 1.2 μM, LOI: 30 μM) demonstrated that MNMA-CysPro allowed a considerably more sensitive detection. Finally, this novel method was applied to a plasma sample of an 87-year-old man, who had unintentionally ingested the pesticide Roxion containing DIM as active ingredient. Unambiguous proof of poisoning demonstrated suitability of the novel biomarkers for sensitive verification analysis.
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http://dx.doi.org/10.1016/j.toxlet.2018.08.013DOI Listing
December 2018

Health, risk behaviour and consumption of addictive substances among physicians - results of an online survey.

J Occup Med Toxicol 2018 23;13:27. Epub 2018 Aug 23.

3Klinikum rechts der Isar, Department of Clinical Toxicology, Technical University of Munich, Munich, Germany.

Background: Previous studies were able to show that hazardous alcohol and substance abuse among physicians is not rare. Currently no recent data to detect risk groups are available either on the prevalence of hazardous drinking disorders and risky health behaviour among physicians or on influencing factors (age, gender, role, institution, specialization, working hours).

Methods: A 42-item online questionnaire was distributed to 38 university hospitals, 296 teaching hospitals and 1290 physicians in private practice. The questionnaire addressed health behaviour and alcohol/substance consumption as well as demographic and work-related properties.

Results: Out of 1338 a total of 920 questionnaires could be evaluated. 90% of physicians estimate their health status as satisfying. 23% of doctors consume hazard quantities of ethanol, 5% are nicotine addicted, and 8% suffer from obesity. Childlessness ( = 0,004; OR = 1,67; KI = 1,17-2,37) for both genders and the role of a resident for females ( = 0,046, OR = 3,10, KI = 1,02-9,40) poses a risk factor for hazardous alcohol consumption. Weekly working hours of more than 50 h ( = 0,009; OR = 1,56; KI = 1,12-2,18) and a surgical profession ( < 0,001; OR = 2,03; KI = 1,47-2,81) may also be a risk factor towards hazardous and risky health behaviour.

Conclusion: A more structured and frequently repeated education on help offerings and specific institutions for addicted and risk groups seems essential.
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http://dx.doi.org/10.1186/s12995-018-0208-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107952PMC
August 2018

Lethal outcome of granulomatous acanthamoebic encephalitis in a man who was human immunodeficiency virus-positive: a case report.

J Med Case Rep 2018 Jul 12;12(1):201. Epub 2018 Jul 12.

Division of Clinical Toxicology & Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Background: Acanthamoeba species can cause disseminating infections in immunocompromised individuals.

Case Presentation: Here, we report a case of granulomatous acanthamoebic encephalitis with a lethal outcome in a 54-year-old German man who was human immunodeficiency virus-positive. The diagnosis was based on symptoms of progressive neurological deficits, including sensorimotor paralysis of his right leg and deteriorating alertness. Due to the rapid course and rather late diagnosis of the infection, effective treatment could not be applied and he died 12 days after hospital admission.

Conclusions: To the best of our knowledge, this is the second case of granulomatous acanthamoebic encephalitis reported within Germany. Our case highlights the importance of early diagnosis of granulomatous acanthamoebic encephalitis to prevent fatal outcome.
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http://dx.doi.org/10.1186/s13256-018-1734-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042392PMC
July 2018

[Intoxications in Children and Adolescents in Germany].

Klin Padiatr 2018 Jul 18;230(4):205-214. Epub 2018 Jun 18.

Abteilung für Klinische Toxikologie & Giftnotruf München, Klinikum rechts der Isar, Technische Universität München.

Background: In Germany, intoxications cause the bulk of emergencies in children, to be prevented or attenuated by preventive measures. Therefore, knowledge about intoxications is essential for pediatricians. The present work provides general and epidemiologic data about intoxications and most frequent categories and single toxicants.

Methods: Data of intoxications in children and adolescents from 6 German poison centers (2012-2016 and 2002-2016) were retrospectively analyzed. Categorical data are given as mean±standard deviation, most frequent toxicants as a score.

Results: Calls, especially from non-professionals, increased since 2002. Two third of intoxications occurred in small and pre-school children, more frequently in boys (50%) than girls (44%), in adolescents girls predominated (>60%).<14 years intoxications occur mainly at home, day care or school (>95%), in adolescents suicide attempts and abuse come to the fore (13%). 90% of the cases are asymptomatic or mild, with increasing symptoms at higher ages (adolescents 13% vs. small children 1%). Intoxications with drugs are predominantly in adolescents, surfactant containing cleaning agents and cosmetics, sanitary cleaner, tobacco, glow lights and solute descaler in children.

Discussion And Conclusions: Increasing incoming calls from professionals and non-professionals point out the importance of the poison centers. Although intoxications in children and adolescents mainly proceed without or mild symptoms, the relevance of preventive measures especially for children<7 should not be underestimated.
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http://dx.doi.org/10.1055/a-0594-9480DOI Listing
July 2018

A toolbox for microbore liquid chromatography tandem-high-resolution mass spectrometry analysis of albumin-adducts as novel biomarkers of organophosphorus pesticide poisoning.

Toxicol Lett 2018 Aug 25;292:46-54. Epub 2018 Apr 25.

Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937 Munich, Germany. Electronic address:

Exposure to toxic organophosphorus pesticides (OPP) represents a serious problem in the public healthcare sector and might be forced in terroristic attacks. Therefore, reliable verification procedures for OPP-intoxications are required for forensic, toxicological and clinical reasons. We developed and optimized a toolbox of methods to detect adducts of human serum albumin (HSA) with OPP considered as long-term biomarkers. Human serum was incubated with diethyl-oxono and diethyl-thiono pesticides for adduct formation used as reference. Afterwards serum was subjected to proteolysis using three proteases separately thus yielding phosphorylated tyrosine residues (Y*) detected as single amino acid (pronase), as hexadecapeptide LVRY*TKKVPQVSTPTL (pepsin) and as the tripeptide Y*TK (trypsin), respectively. Adducts were analyzed via microbore liquid chromatography coupled to electrospray ionization (μLC-ESI) and tandem-high-resolution mass spectrometry (MS/HR MS). Using paraoxon-ethyl as model OPP for adduct formation, methods were optimized with respect to MS/HR MS-parameters, protease concentrations and incubation time for proteolysis. HSA-adducts were found to be stable in serum in vitro at +37 °C and -30 °C for at least 27 days and resulting biomarkers were stable in the autosampler at 15 °C for at least 24 h. Limits of identification of adducts varied between 0.25 μM and 4.0 μM with respect to the corresponding pesticide concentrations in serum. Applicability of the methods was proven by successful detection of the adducts in samples of OPP-poisoned patients thus demonstrating the methods as a reliable toolbox for forensic and toxicological analysis.
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http://dx.doi.org/10.1016/j.toxlet.2018.04.025DOI Listing
August 2018

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis.

Am J Gastroenterol 2018 10 13;113(10):1475-1483. Epub 2018 Mar 13.

Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland. Medical Department 1, University Hospital Dresden, TU Dresden, Dresden, Germany. Department of Internal Medicine I, University of Bonn, Bonn, Germany. Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany. Hepatology Section, Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. Department of Gastroenterology, University Hospital Halle/Saale, Halle, Germany. Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. Department of Medicine II, Saarland University Medical Center, Homburg, Germany. Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK. Medical Department 1, University of Erlangen, Nuremberg, Bavaria, Germany. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany. Department of Clinical Toxicology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Institute of Laboratory Animal Science, University of Zurich, Schlieren, Switzerland. Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, United Kingdom. These authors have contributed equally to the presented work and share premier authorship: Felix Stickel, Stephan Buch. These authors have contributed equally to the presented work and share senior authorship: Pierre Deltenre, Thomas Berg, Marsha Y. Morgan, and Jochen Hampe.

Objectives: Variants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), and membrane bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis. Within this population, PNPLA3 rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to explore possible risk associations of TM6SF2 rs58542926 and MBOAT7 rs641738 with HCC.

Methods: Risk variants in PNPLA3, TM6SF2, and MBOAT7 were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analyzed using multivariate logistic regression.

Results: The development of HCC was independently associated with PNPLA3 rs738409 (OR 1.84 [95% CI 1.55-2.18], p = 1.85 × 10) and TM6SF2 rs58542926 (OR 1.66 [1.30-2.13], p = 5.13 × 10), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR 1.04 [0.88-1.24], p = 0.61) was not significant. The population-attributable fractions were 43.5% for PNPLA3 rs738409, 11.5% for TM6SF2 rs58542926, and 49.9% for the carriage of both the variants combined.

Conclusions: Carriage of TM6SF2 rs58542926 is an additional risk factor for the development of HCC in people with alcohol-related cirrhosis. Carriage of both PNPLA3 rs738409 and TM6SF2 rs58542926 accounts for half of the attributable risk for HCC in this population. Genotyping will allow for more precise HCC risk-stratification of patients with alcohol-related cirrhosis, and genotype-guided screening algorithms would optimize patient care.
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http://dx.doi.org/10.1038/s41395-018-0041-8DOI Listing
October 2018

Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series.

Medicine (Baltimore) 2018 02;97(5):e9784

Division of Clinical Pharmacology and Toxicology, Basel University Hospital and University of Basel, Basel, Switzerland Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern Clinical Toxicology Unit, Emergency Department, Hospital Universitari Son Espases, Research Institute of Health Sciences (IdISBa), Palma de Mallorca, Spain Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners Clinical Toxicology, Faculty of Life Sciences and Medicine, King's College London, London, UK The Norwegian CBRNe Centre of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway Department of Clinical Toxicology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity.We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project.Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively.In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives.
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http://dx.doi.org/10.1097/MD.0000000000009784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805445PMC
February 2018

Corrigendum to "Fatal Systemic Vasoconstriction in a Case of Metastatic Small-Intestinal NET".

Case Rep Gastrointest Med 2017 3;2017:8694296. Epub 2017 Dec 3.

Department of Clinical Toxicology, Klinikum rechts der Isar, Technical University of Munich, Ismaningerstrasse 22, 81675 Munich, Germany.

[This corrects the article DOI: 10.1155/2017/9810194.].
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http://dx.doi.org/10.1155/2017/8694296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726006PMC
December 2017