Independent validation of the Tanta University Risk Model for intensive care requirement in acutely poisoned adults.

OBJECTIVE: To independently validate the predictive value of the Tanta University Risk Model for intensive care requirement in unselected poisoned patients. METHOD: Retrospective chart review of 293 poisoned patients. The Tanta University Risk Model was calculated as follows: Tanta University Risk Model = -1.966*Glasgow Coma Scale - 0.329*oxygen saturation - 0.212*diastolic blood pressure + 0.27*respiratory rate - 0.33*standard bicarbonate. It was then compared to a composite endpoint indicating an intensive care unit requirement (death in hospital, vasopressors, need for intubation). RESULTS: Nineteen of 293 patients had a complicated clinical course as defined by meeting the primary endpoint definition. Receiver operating characteristic analysis revealed the area under the curve to be 0.79 (95% confidence interval 0.73-0.83). A positive Tanta University Risk Model was defined >-73.46. Fifteen out of 84 patients with a positive Tanta University Risk Model had a complicated course, while four of 209 patients with a negative Tanta University risk model had a complicated course (P<0.0001, Fisher's exact test). The negative predictive value of the Tanta University Risk Model was 0.98 (95% confidence interval 0.95-0.99), the sensitivity was 0.79 and that specificity was 0.75. CONCLUSION: Poisoned patients with a negative Tanta University Risk Model score are unlikely to need an intensive care unit level of care.

In vivo neutralization of colchicine toxicity by a PASylated anticalin in a rat model.

We have investigated the pharmacokinetics (PK) and in vivo activity of an Anticalin exhibiting picomolar affinity towards colchicine, a plant toxin with low tolerable dose in humans. PK analysis of the 20-kDa "Colchicalin" protein in male Sprague Dawley rats (n = 3) revealed a very short plasma half-life (3.5 min), which was prolonged 21-fold via genetic fusion with a 200-residue Pro/Ala sequence (PASylation). The scavenging activity of the PASylated Colchicalin was investigated over 3.5 h via stoichiometric application following a sub-toxic i.v. dose of colchicine on anesthetized rats (n = 2) leading to a rapid rise in total plasma colchicine concentration. We then established a 14-day intoxication model in rats (n = 3) at a 30 mg/kg p.o. colchicine dose which was characterized by severe weight loss, elevated neutrophil-to-lymphocyte ratio and shortened survival. PASylated Colchicalin administration at 4.2% of the neutralizing dose (125 mg/kg/day daily for 12 consecutive days) resulted in faster relief of the symptoms in 2/3 of animals (n = 6) compared to the control group without Colchicalin treatment (n = 5). Nevertheless, 1/3 of the rats died suddenly after the first Colchicalin injection, probably due to a steep rise in the total colchicine plasma concentration, which suggests further improvement of the dosing scheme prior to potential application in acute human colchicine poisoning.

ToxNet: an artificial intelligence designed for decision support for toxin prediction.

BACKGROUND: Artificial intelligences (AIs) are emerging in the field of medical informatics in many areas. They are mostly used for diagnosis support in medical imaging but have potential uses in many other fields of medicine where large datasets are available. AIM: To develop an artificial intelligence (AI) "ToxNet", a machine-learning based computer-aided diagnosis (CADx) system, which aims to predict poisons based on patient's symptoms and metadata from our Poison Control Center (PCC) data. To prove its accuracy and compare it against medical doctors (MDs). METHODS: The CADx system was developed and trained using data from 781,278 calls recorded in our PCC database from 2001 to 2019. All cases were mono-intoxications. Patient symptoms and meta-information (e.g., age group, sex, etiology, toxin point of entry, weekday, etc.) were provided. In the pilot phase, the AI was trained on 10 substances, the AI's prediction was compared to naïve matching, literature matching, a multi-layer perceptron (MLP), and the graph attention network (GAT). The trained AI's accuracy was then compared to 10 medical doctors in an individual and in an identical dataset. The dataset was then expanded to 28 substances and the predictions and comparisons repeated. RESULTS: In the pilot, the prediction performance in a set of 8995 patients with 10 substances was 0.66 ± 0.01 (F1 micro score). Our CADx system was significantly superior to naïve matching, literature matching, MLP, and GAT (p < 0.005). It outperformed our physicians experienced in clinical toxicology in the individual and identical dataset. In the extended dataset, our CADx system was able to predict the correct toxin in a set of 36,033 patients with 28 substances with an overall performance of 0.27 ± 0.01 (F1 micro score), also significantly superior to naïve matching, literature matching, MLP, and GAT. It also outperformed our MDs. CONCLUSION: Our AI trained on a large PCC database works well for poison prediction in these experiments. With further research, it might become a valuable aid for physicians in predicting unknown substances and might be the first step into AI use in PCCs.

Characteristics and predictive factors of severe or fatal suicide outcome in patients hospitalized due to deliberate self-poisoning.

Prediction of clinical course of intoxication is essential for timely initiation of appropriate medical treatment in patients hospitalized due to suicidal self-poisoning. In this retrospective single-centre study in patients hospitalized due to suicidal poisoning in a specialized clinical toxicology unit, we aimed to identify predictive factors associated with severe or fatal course of self-poisoning. All patients underwent at least one psychiatric exploration during their inpatient stay. Severity of poisoning was assessed on admission and after 24 hours according to the Poison Severity Score index (PSS). Spearman's rank correlation coefficient was used to test the association of PSS with sociodemographic, anamnestic and (pre-)clinical parameters. Multivariable binomial logistic regression analysis was performed to determine predictive factors for severe and/or fatal self-poisoning. 1090 patients were included in the study. Median age was 39 years (range 13-91), 66.7% of patients were female. PSS was classified in the majority as "minor" (n = 558, 51.2%) or "moderate" (n = 264, 24.2%). 61 patients (5.6%) had PSS "severe"; 14 patients (1.3%) died. A higher severity of poisoning positively correlated with duration of inpatient therapy (p<0.001, Spearman's rho = 0.454) and duration of ventilation (p<0.001, rho = 0.474), and it inversely correlated with initial Glasgow Coma Scale (GCS) score (p<0.001, rho = -0.437). Multivariable analysis identified no alcohol co-ingestion (OR 3.23; 95%CI 1.3, 8.07; p = 0.012) and self-poisoning with non-medicinal substances (OR 5.4; 95%CI 1.78, 16.34; p = 0.003) as factors predictive for "severe" or "fatal" suicide outcome. In contrast, female gender (OR 0.4; 95%CI 0.2, 0.81; p = 0.011), not using an antidepressant as the method for self-poisoning (OR 0.27; 95%CI 0.12, 0.59; p = 0.001) and a higher initial GCS score (OR 0.79; 95%CI 0.73, 0.85; p<0.001) reduced the risk of a severe or fatal course of self-poisoning. The conclusion for clinical practice is that male patients hospitalized due to self-poisoning, with a low initial GCS score, who did not co-ingest alcohol, attempted suicide with non-pharmaceutical substances or antidepressants are at a higher risk of severe/fatal outcome of suicide. Determination of these risk factors at admission could be potentially used to guide treatment intensification in patients hospitalized due to deliberate self-poisoning.

Socio-demographic and psychiatric profile of patients hospitalized due to self-poisoning with suicidal intention.

OBJECTIVE: To identify the psychiatric profile of patients hospitalized due to self-intoxication associated with suicide-related behavior (SRB). METHODS: In this retrospective single-center study, records of consecutive patients treated for suicidal poisoning in our Clinical Toxicology unit between 1st January 2012 and 31st December 2016, who received at least one psychiatric exploration during their inpatient stay, were analyzed with regard to epidemiological data, ingested substances, psychiatric and somatic comorbidities, suicidal circumstances and follow-up therapy. RESULTS: Out of 1289 hospitalized patients, 1090 patients with complete data were analyzed. Mean age was 40.5 ± 17.2 years, 66.7% were female. 32.0% of patients had previously engaged in SRB, in 76.3% intention was suicidal. 64.7% of patients had a pre-existing psychiatric disorder (PD). Patients with a pre-existing PD more often displayed prior SRB than those without PD (40.7% vs 15.3%; p < 0.001; Fisher's exact test), used long-term/on demand medication (70.2% vs 38.9%; p < 0.001), distanced themselves from the current suicide attempt (65.9% vs 50.8%; p < 0.001) and had no detectable trigger (38.7% vs 18.1%; p < 0.001). Partnership conflict was the most commonly named trigger, and it was documented more often in patients without than in those with PD (41.6% vs 25.6%). After psychiatric reevaluation, most patients were diagnosed with mood disorders (29.7%) and stress disorders (17.0%); 32.8% of patients had a combination of two or more PDs. CONCLUSION: Hospitalization due to self-poisoning is associated with pre-existing PD, prior SRB and access to psychiatric medication. Detection of these risk factors could allow timely introduction of effective preventive measures tailored to particularly vulnerable subgroups and appropriate relief. However, lack of a detectable trigger in many cases may hamper the identification of those at risk.

Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

BACKGROUND AND IMPORTANCE: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described. OBJECTIVE: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective multicentre study using data from the Euro-DEN Plus database from January 2014 to December 2019. OUTCOMES MEASURE AND ANALYSIS: Comparison of epidemiologic and clinical characteristics, ED and hospital management of patients with CNS depressant intoxication with or without ethanol co-use. MAIN RESULTS: Although 7644 (17.5%) of the 43 633 presentations were included, ethanol was co-ingested in 3811 (49.9%). In total 53.3% required medical treatment, 14 patients died. Patients with ethanol co-use more frequently presented with a Glasgow Coma Scale (GCS) ≤8 (34.1% vs. 22.4%; P < 0.001), vomiting (8.1% vs. 4.6%; P < 0.001), anxiety (12 % vs. 6.4%; P < 0.001), agitation/aggression (22% vs. 14.7%; P < 0.001), seizures (3.8% vs. 2.4%; P < 0.001) and hypotension (7.5% vs. 4.6%; P < 0.001). They more often required ambulance transport (85.5% vs. 76.5%; P < 0.001), medical treatment (57.3% vs. 48.0%; P < 0.001), hospitalization (27.7% vs. 18.9%; P < 0.001), and admission to intensive care (12.2% vs. 4.0%; P < 0.001). Subgroup analysis showed that GCS ≤8 was particularly common in patients who combined ethanol with opioids or gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL). CONCLUSION: Co-use of ethanol with CNS-depressant drugs appears to increase the risk of adverse effects and is associated with a higher need for medical treatment, especially when ethanol is combined with opioids or GHB/GBL.

Lessons to be learned: identifying high-risk medication and circumstances in patients at risk for suicidal self-poisoning.

BACKGROUND: Although the total number of suicides decreased since the beginning of the 1980s, the number of suicide-related behaviors using self-intoxication increased. Therefore, research on the characteristics of individuals committing self-intoxication becomes of growing importance for risk assessments and the development of preventive measures. METHODS: In this prospective, observational, monocentric cohort study, all incoming calls at our Poisons Control Centre reporting suicide-related behaviors through self-intoxication, were analyzed via a standardized questionnaire over 12 months. Both univariate and bivariate analyses were performed. RESULTS: 1238 cases of deliberate intoxication were included in the study. The majority of cases occurred in the age group between 18 and 44 (n = 607/49%), two-thirds were female (n = 817/66%). The main substances used were antidepressants (n = 420/34%), peripheral analgesics (n = 322/26%) and neuroleptics (n = 282/23%). The majority of patients ingested substances from their prescribed medication (n = 640/82%) with the highest proportion in those aged over 64 years (n = 72/113; 91%, p < 0.001). Substance use was reported for the minority of patients (n = 175/23%). For 704 cases (79%), a psychiatric disorder was documented. Factors associated with recurrent suicide-related behaviors were an underlying psychiatric disorder (OR = 6.2; 95% CI 3.8-10.4), substance use (OR = 2.4; 95% CI 1.5-3.8), and ingestion of neuroleptics (OR = 2.1, 95% CI 1.4-3.0) or antidepressants (OR = 1.6; 95% CI 1.2-2.3). CONCLUSION: This study might contribute to identifying individuals with an increased risk of suicide-related behaviors by deliberate intoxication and to developing preventive strategies for future suicide attempt(s).

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

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.

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

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.

[Intoxications in Children and Adolescents in Germany]. / Deutschlandweites Vergiftungsspektrum im Kindes- und Jugendalter.

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.

An internet-based survey of 96 German-speaking users of "bath salts": frequent complications, risky sexual behavior, violence, and delinquency.

OBJECTIVE: To define the demographics of German-speaking "bath salt" users. DESIGN: Prospective web-based survey of volunteer users of "bath salts". Subject recruitment/exclusion: Participation was solicited by posts in web forums frequented by users of synthetic cathinones. An invitation to participate was also disseminated via regional drug information centers. Responses were discarded if participants refused data analysis, provided incomplete surveys, were under 18 years of age (five cases), and in case of clearly improbable answers (i.e., two cases with profanity typed in free-form input fields). Overall 96 out of 180 participants provided complete questionnaires. These were further analyzed. RESULTS AND CONCLUSIONS: 74% of respondents were male. 41% were under the age of 30 and a further 38% between 30 and 39 years old. Cathinones were used on more than 10 days in the preceding year by 62% of study subjects. The nasal and intravenous routes of administration were most often used. About 80% of respondents reported binge use. There were frequent co-administrations of opioids and opiates. The most common complication was prolonged confusion (47%). 16% had been involuntarily confined. One third had thoughts of violence and 16% acted on these thoughts either against themselves or others. About 44% reported high-risk sexual activity under the influence of cathinones. About 31% had driven or ridden a bike while intoxicated. About 6% had problems with law-enforcement for selling cathinones and 16% for crimes committed under the influence of cathinones. In conclusion, cathinone users are typically young males in their twenties and thirties. Most are experienced drug users, particularly of alcohol and opiates/opioids. The impact on society is tremendous as evidenced by high rates of self-reported violence, high-risk sexual activity, crimes, and traffic violations.

Independent validation of the ICU requirement score in a cohort of acutely poisoned adults.

OBJECTIVE: To independently validate the predictive value of the intensive care requirement score (IRS) in unselected poisoned patients. DESIGN: Retrospective chart review. PATIENTS AND METHODS: Five hundred and seventeen out of 585 admissions for acute intoxications could be analyzed. Eleven were excluded for a condition already requiring intensive care unit (ICU) support at admission (e.g., preclinical intubation). A further 57 admissions were excluded due to missing data. The IRS was calculated using a point-scoring system including age, Glasgow Coma Scale, heart rate, type of intoxication, and preexisting conditions. It was then compared to a composite endpoint indicating an ICU requirement (death in hospital, vasopressors, need for ventilation). The endpoint and the point-scoring system were identical to the original publication of the score. RESULTS AND CONCLUSION: Twenty-three out of 517 patients had a complicated clinical course as defined by meeting the endpoint definition. Twenty-one out of 23 complicated courses had a positive IRS (defined as greater or equal 6 points), as compared to 255/494 patients with an uncomplicated clinical course (p < .001, Fisher's exact test). One patient (with a positive IRS) died. The negative predictive value of the IRS was 0.99 (95% CI: 0.97-1), the sensitivity was 0.91 and the specificity 0.48. In conclusion, the IRS is significantly linked to outcome. While a negative IRS virtually excludes the need for ICU care, a positive IRS has a positive predictive value too low to be used for risk stratification. The IRS could also be applied to unselected admissions of poisoned patients.

Ibuprofen plasma concentration profile in deliberate ibuprofen overdose with circulatory depression treated with therapeutic plasma exchange: a case report.

BACKGROUND: Inquiries relating to ibuprofen overdose have more than tripled in the last ten years in our poison control center. Although the vast majority of cases have a benign clinical course, there are few severe or even fatal cases present with refractory circulatory failure. CASE PRESENTATION: We describe a case of a 48 year-old male with suicidal mono-ingestion of approximately 72 g ibuprofen. Despite an initial rapid spontaneous drop in the total ibuprofen plasma concentration (IPC) from 550 to 275 mcg/mL within the first 5 h after admission, the patient developed a circulatory failure, refractory to aggressive fluid resuscitation and high doses of vasopressors. Due to ibuprofen's favorable pharmacokinetics (>95% bound to albumin, low volume of distribution) and in the absence of specific therapeutic alternatives thereby avoiding escalating vasopressor doses, therapeutic plasma exchange (TPE) for extracorporeal elimination of ibuprofen was considered as a therapeutic rescue option. An improvement of hemodynamics with a significant reduction of vasopressors was observed with TPE-initiation. However, neither the observed IPC-profile nor a pharmacokinetic (PK) simulation provided evidence for a quantitative effective elimination of ibuprofen by TPE. Based on PK-modeling we calculated an overall ibuprofen half-life of 17.2 h for the entire observation period over 5 days. CONCLUSIONS: To our knowledge this is the first report of a severe ibuprofen-mono intoxication treated with TPE and providing serial IPCs over a period of five days, indicating an estimated fivefold overall-elimination half-life of 17.2 h. Despite TPE clinically improved persistent hemodynamic instability, this procedure was neither consistent with the observed IPC-profile nor correlated with a meaningful quantitative elimination of ibuprofen.

Synthetic cathinones in Southern Germany - characteristics of users, substance-patterns, co-ingestions, and complications.

OBJECTIVE: To define the characteristics of synthetic cathinone users admitted to hospital including clinical and laboratory parameters and the complications of use. DESIGN: Retrospective single-center study of patients treated for acute cathinone intoxication and complications of cathinone use between January 2010 and January 2016. SETTING: A specialized clinical toxicology unit at an academic tertiary care center in Southern Germany serving a population of about 4 million. PATIENTS AND METHODS: 81 consecutive patients with laboratory-confirmed use of cathinones who presented for acute intoxication or complications of cathinone use were retrospectively analyzed. RESULTS AND CONCLUSIONS: The patients were predominantly male (64%, 52/81) with a median age of 34 years. 60 were admitted for signs of acute intoxication while 21 suffered from complications of cathinone use. 70% of acutely intoxicated patients had an increased creatinine phosphokinase. Only a minority of patients presented with a sympathomimetic toxidrome. Three patients had infectious complications, 10 prolonged psychosis, 6 rhabdomyolyses and/or kidney failure, and two patients died. Based on presentations, cathinone use has increased with the first cases seen in 2010. Opiates/opioids are the main co-ingested drugs of abuse. The pattern of cathinone use shifted from methylone in 2010/2011 to 3,4-methylenedioxypyrovalerone (MDPV) and 3-methylmethcathinone (3-MMC) in 2014/2015. We conclude that in our setting "typical" cathinone users are males in their thirties. They are seldom drug naïve and regularly co-ingest illicit drugs. Preventive measures have to be tailored to these difficult to reach patients. Present efforts to educate young clubbers in their late teens may fail to reach the pertinent demographic.