Cardiotoxicity After Synthetic Cathinone Use; Two Cases, A Case Series and Scoping Review.

The cardiotoxic effects of synthetic cathinones remain largely unknown. In this study, we present two cases, a case series and a scoping review, to explore synthetic cathinone associated cardiotoxicity. Case 1 involved a 28-year-old male with non-ST-elevation myocardial infarction after ingesting a substance containing 4-methylmethcathinone (4-MMC), 3-methylmethcathinon (3-MMC), and methcathinone. Case 2 involved a 49-year-old male with ventricular fibrillation after 4-methylmethcathinone ingestion, who was diagnosed with severe three-vessel disease. A retrospective analysis was performed on self-reported synthetic cathinone poisonings reported to the Dutch Poisons Information Centre from 2012 to 2022. A total of 222 mono-intoxications with cardiotoxicity were included, mostly involving 3-methylmethcathinon (63%). Often tachycardia, hypertension, palpitations, and chest pain were reported. A comprehensive literature search was performed on PubMed to identify the studies reporting cardiac arrest, myocardial infarction, cardiac inflammation, cardiomyopathy, and life-threatening arrhythmias following synthetic cathinone use. A total of 30 articles reporting 40 cases were included. The reported complications included cardiac arrest (n = 28), ventricular tachycardia (n = 4), supraventricular tachycardia (n = 1), ST-elevation myocardial infarction (n = 2), non-ST-elevation myocardial infarction (n = 2), cardiomyopathy (n = 1), and myocarditis (n = 2). A total of ten different associated synthetic cathinones were identified. Cardiac arrest, myocardial infarction, and ventricular arrhythmias have been reported following the use of synthetic cathinones, underscoring the importance of obtaining a detailed recreational drug use history from patients presenting with syncope, chest pain, or palpitations.

Development and evaluation of regression tree models for predicting in-hospital mortality of a national registry of COVID-19 patients over six pandemic surges.

BACKGROUND: Objective prognostic information is essential for good clinical decision making. In case of unknown diseases, scarcity of evidence and limited tacit knowledge prevent obtaining this information. Prediction models can be useful, but need to be not only evaluated on how well they predict, but also how stable these models are under fast changing circumstances with respect to development of the disease and the corresponding clinical response. This study aims to provide interpretable and actionable insights, particularly for clinicians. We developed and evaluated two regression tree predictive models for in-hospital mortality of COVID-19 patient at admission and 24 hours (24 h) after admission, using a national registry. We performed a retrospective analysis of observational routinely collected data. METHODS: Two regression tree models were developed for admission and 24 h after admission. The complexity of the trees was managed via cross validation to prevent overfitting. The predictive ability of the model was assessed via bootstrapping using the Area under the Receiver-Operating-Characteristic curve, Brier score and calibration curves. The tree models were assessed on the stability of their probabilities and predictive ability, on the selected variables, and compared to a full-fledged logistic regression model that uses variable selection and variable transformations using splines. Participants included COVID-19 patients from all ICUs participating in the Dutch National Intensive Care Evaluation (NICE) registry, who were admitted at the ICU between February 27, 2020, and November 23, 2021. From the NICE registry, we included concerned demographic data, minimum and maximum values of physiological data in the first 24 h of ICU admission and diagnoses (reason for admission as well as comorbidities) for model development. The main outcome measure was in-hospital mortality. We additionally analysed the Length-of-Stay (LoS) per patient subgroup per survival status. RESULTS: A total of 13,369 confirmed COVID-19 patients from 70 ICUs were included (with mortality rate of 28%). The optimism-corrected AUROC of the admission tree (with seven paths) was 0.72 (95% CI: 0.71-0.74) and of the 24 h tree (with 11 paths) was 0.74 (0.74-0.77). Both regression trees yielded good calibration and variable selection for both trees was stable. Patient subgroups comprising the tree paths had comparable survival probabilities as the full-fledged logistic regression model, survival probabilities were stable over six COVID-19 surges, and subgroups were shown to have added predictive value over the individual patient variables. CONCLUSIONS: We developed and evaluated regression trees, which operate at par with a carefully crafted logistic regression model. The trees consist of homogenous subgroups of patients that are described by simple interpretable constraints on patient characteristics thereby facilitating shared decision-making.

Evaluation of new alternative methods for the identification of estrogenic, androgenic and steroidogenic effects: a comparative in vitro/in silico study.

A suite of in vitro assays and in silico models were evaluated to identify which best detected the endocrine-disrupting (ED) potential of 10 test chemicals according to their estrogenic, androgenic and steroidogenic (EAS) potential compared to the outcomes from ToxCast. In vitro methods included receptor-binding, CALUX transactivation, H295R steroidogenesis, aromatase activity inhibition and the Yeast oestrogen (YES) and Yeast androgen screen (YAS) assays. The impact of metabolism was also evaluated. The YES/YAS assays exhibited a high sensitivity for ER effects and, despite some challenges in predicting AR effects, is a good initial screening assay. Results from receptor-binding and CALUX assays generally correlated and were in accordance with classifications based on ToxCast assays. ER agonism and AR antagonism of benzyl butyl phthalate were abolished when CALUX assays included liver S9. In silico final calls were mostly in agreement with the in vitro assays, and predicted ER and AR effects well. The efficiency of the in silico models (reflecting applicability domains or inconclusive results) was 43-100%. The percentage of correct calls for ER (50-100%), AR (57-100%) and aromatase (33-100%) effects when compared to the final ToxCast call covered a wide range from highly reliable to less reliable models. In conclusion, Danish (Q)SAR, Opera, ADMET Lab LBD and ProToxII models demonstrated the best overall performance for ER and AR effects. These can be combined with the YES/YAS assays in an initial screen of chemicals in the early tiers of an NGRA to inform on the MoA and the design of mechanistic in vitro assays used later in the assessment. Inhibition of aromatase was best predicted by the Vega, AdmetLab and ProToxII models. Other mechanisms and exposure should be considered when making a conclusion with respect to ED effects.

Further Evidence for Shape Coexistence in

Isomers close to doubly magic _{28}^{78}Ni_{50} provide essential information on the shell evolution and shape coexistence near the Z=28 and N=50 double shell closure. We report the excitation energy measurement of the 1/2^{+} isomer in _{30}^{79}Zn_{49} through independent high-precision mass measurements with the JYFLTRAP double Penning trap and with the ISOLTRAP multi-reflection time-of-flight mass spectrometer. We unambiguously place the 1/2^{+} isomer at 942(10) keV, slightly below the 5/2^{+} state at 983(3) keV. With the use of state-of-the-art shell-model diagonalizations, complemented with discrete nonorthogonal shell-model calculations which are used here for the first time to interpret shape coexistence, we find low-lying deformed intruder states, similar to other N=49 isotones. The 1/2^{+} isomer is interpreted as the bandhead of a low-lying deformed structure akin to a predicted low-lying deformed band in ^{80}Zn, and points to shape coexistence in ^{79,80}Zn similar to the one observed in ^{78}Ni. The results make a strong case for confirming the claim of shape coexistence in this key region of the nuclear chart.

Nitrogen-Phosphorus-Potassium containing liquid fertilizer intoxication presenting with extreme hyperkalemia, metabolic acidosis and ECG changes.

Liquid fertilizers are widely used for fertilizing in- and outdoor vegetation. Despite the easy accessibility and widespread use, serious intoxications are rare. This case report describes a 61-year-old woman who was treated for life-threatening hyperkalemia, metabolic acidosis and ECG changes after intentional ingestion of liquid fertilizer. Our case shows that intake of liquid fertilizer, though infrequent, can cause serious, life threatening complications.

Automated identification of patient subgroups: A case-study on mortality of COVID-19 patients admitted to the ICU.

BACKGROUND: - Subgroup discovery (SGD) is the automated splitting of the data into complex subgroups. Various SGD methods have been applied to the medical domain, but none have been extensively evaluated. We assess the numerical and clinical quality of SGD methods. METHOD: - We applied the improved Subgroup Set Discovery (SSD++), Patient Rule Induction Method (PRIM) and APRIORI - Subgroup Discovery (APRIORI-SD) algorithms to obtain patient subgroups on observational data of 14,548 COVID-19 patients admitted to 73 Dutch intensive care units. Hospital mortality was the clinical outcome. Numerical significance of the subgroups was assessed with information-theoretic measures. Clinical significance of the subgroups was assessed by comparing variable importance on population and subgroup levels and by expert evaluation. RESULTS: - The tested algorithms varied widely in the total number of discovered subgroups (5-62), the number of selected variables, and the predictive value of the subgroups. Qualitative assessment showed that the found subgroups make clinical sense. SSD++ found most subgroups (n = 62), which added predictive value and generally showed high potential for clinical use. APRIORI-SD and PRIM found fewer subgroups (n = 5 and 6), which did not add predictive value and were clinically less relevant. CONCLUSION: - Automated SGD methods find clinical subgroups that are relevant when assessed quantitatively (yield added predictive value) and qualitatively (intensivists consider the subgroups significant). Different methods yield different subgroups with varying degrees of predictive performance and clinical quality. External validation is needed to generalize the results to other populations and future research should explore which algorithm performs best in other settings.

The association of amfetamines and cathinones with acute coronary syndrome - a systematic review.

BACKGROUND: It is well known that cocaine increases the risk of acute coronary syndrome. However, it is uncertain if the use of other stimulants, such as amfetamines and cathinones, is also related to acute coronary syndrome. OBJECTIVES: To identify all reported cases of acute coronary syndrome related to the use of amfetamines and cathinones, the type of acute coronary syndrome, the atherothrombotic aetiology, and the mortality rate. METHODS: A systematic literature search in PubMed, Embase database, Cochrane library, PsycInfo and Web of Science was performed from inception until 31 August 2022. All original articles in English or Dutch describing adult patients with acute coronary syndrome after the use of amfetamines or cathinones were included. The main outcome was the occurrence of acute coronary syndrome associated with amfetamine-type stimulants or cathinones. Data were collected and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 11,605 articles were identified, 56 of which met the inclusion criteria. A total of 160 patients presented with acute coronary syndrome after five different types of amfetamines, namely, amfetamine (n = 48), metamfetamine (n = 98), 3,4-methylenedioxymetamfetamine (n = 11), fenethylline (n = 2), and 4-fluoroamfetamine (n = 1). Khat chewing was associated with acute coronary syndrome (n = 4234), as were three different types of synthetic cathinones, namely, non-defined cathinones (n = 1), 4-methylmethcathinone (n = 1), and α-pyrrolidinopentiophenone (n = 1). In patients with a known acute coronary syndrome type (n = 157), ST-segment elevation myocardial infarction was diagnosed in 53 patients (75%) and non-ST-segment elevation myocardial infarction in 18 patients (25%). Of the ST-segment elevation myocardial infarction patients, 36% were diagnosed with significant coronary stenosis or thrombus. The mortality rate for khat-associated acute coronary syndrome, with more often male and older patients with fewer cardiovascular risk factors, was higher compared to non-khat-associated acute coronary syndrome. For amfetamine, metamfetamine, and 3,4-methylenedioxymetamfetamine, mortality associated with ST--segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction was 14% and 7%, respectively. Risk factors for acute coronary syndrome were infrequently reported, and risk stratification scores were not reported. CONCLUSION: There is evidence that amfetamine-type stimulants and cathinones are associated with the occurrence of acute coronary syndrome. Khat chewing appears to be a risk factor for acute coronary syndrome. Amfetamine, metamfetamine, 3,4-methylenedioxymetamfetamine, fenethylline, 4-fluoroamfetamine, and synthetic cathinones were also reported in relation to acute coronary syndrome. However, this evidence is limited, of low quality and with a low number of reported cases. Further prospective studies need to be conducted.

High-Precision Determination of g Factors and Masses of

We present the measurements of individual bound electron g factors of ^{20}Ne^{9+} and ^{22}Ne^{9+} on the relative level of 0.1 parts per billion. The comparison with theory represents the most stringent test of bound-state QED in strong electric fields. A dedicated mass measurement results in m(^{20}Ne)=19.992 440 168 77(9) u, which improves the current literature value by a factor of 18, disagrees by 4 standard deviations, and represents the most precisely measured mass value in atomic mass units. Together, these measurements yield an electron mass on the relative level of 0.1 ppb with m_{e}=5.485 799 090 99(59)×10^{-4} u as well as a factor of seven improved m(^{22}Ne)=21.991 385 098 2(26) u.

Incidence of Vitis fruit-induced clinical signs and acute kidney injury in dogs and cats.

OBJECTIVES: To determine the incidence of clinical signs and Vitis fruit-induced acute kidney injury in dogs and cats with a Vitis fruit ingestion reported to the Dutch Poisons Information Center, and a description of the therapies instituted by the veterinarians. MATERIALS AND METHODS: All cases of Vitis fruit ingestions in dogs and cats reported to the center between January 1, 2018 and December 31, 2018 were included in this study. Veterinarians and pet owners were contacted by phone or email to obtain follow-up information. Information was collected using a standardised data collection sheet. RESULTS: Ninety-five dogs and 13 cats with proven Vitis fruit ingestion were included. Fourteen dogs and two cats developed clinical signs: emesis (11/16, 68.8%), lethargy (5/16, 31.3%), diarrhoea (3/16, 18.8%), anorexia (3/16, 18.8%), tremor (2/16, 12.5%) and restlessness (1/16, 6.3%). The overall incidence for developing clinical signs was 14.7% in dogs and 15.4% in cats. One (1/95, 1%) dog developed acute kidney injury after ingestion of Vitis fruit. No cats developed acute kidney injury. Induction of emesis and/or administration of activated charcoal was instituted in 72 of 82 (88%) and eight of 11 (73%) of asymptomatic dogs and cats and six of 14 (43%) and two of two (100%) of symptomatic dogs and cats, respectively. Overall, emesis was induced in 72 of 95 (76%) dogs (100% success rate) and removed Vitis fruits in the majority of cases (98% when induced <4 hours after ingestion and 83% when induced 4 to 12 hours after ingestion). Emesis was induced in seven of 13 (54%) cats (86% success rate) and removed Vitis fruits in 83% of the cases. CLINICAL SIGNIFICANCE: In this study, a significant proportion (around 15%) of dogs and cats developed clinical signs after ingestion of Vitis fruits, which were predominantly related to the gastrointestinal tract. Symptomatic acute kidney injury was rare. Our findings suggest the use of decontamination measures, i.e. induction of emesis, may be warranted up to 12 hours after ingestion.

Can we reliably automate clinical prognostic modelling? A retrospective cohort study for ICU triage prediction of in-hospital mortality of COVID-19 patients in the Netherlands.

BACKGROUND: Building Machine Learning (ML) models in healthcare may suffer from time-consuming and potentially biased pre-selection of predictors by hand that can result in limited or trivial selection of suitable models. We aimed to assess the predictive performance of automating the process of building ML models (AutoML) in-hospital mortality prediction modelling of triage COVID-19 patients at ICU admission versus expert-based predictor pre-selection followed by logistic regression. METHODS: We conducted an observational study of all COVID-19 patients admitted to Dutch ICUs between February and July 2020. We included 2,690 COVID-19 patients from 70 ICUs participating in the Dutch National Intensive Care Evaluation (NICE) registry. The main outcome measure was in-hospital mortality. We asessed model performance (at admission and after 24h, respectively) of AutoML compared to the more traditional approach of predictor pre-selection and logistic regression. FINDINGS: Predictive performance of the autoML models with variables available at admission shows fair discrimination (average AUROC = 0·75-0·76 (sdev = 0·03), PPV = 0·70-0·76 (sdev = 0·1) at cut-off = 0·3 (the observed mortality rate), and good calibration. This performance is on par with a logistic regression model with selection of patient variables by three experts (average AUROC = 0·78 (sdev = 0·03) and PPV = 0·79 (sdev = 0·2)). Extending the models with variables that are available at 24h after admission resulted in models with higher predictive performance (average AUROC = 0·77-0·79 (sdev = 0·03) and PPV = 0·79-0·80 (sdev = 0·10-0·17)). CONCLUSIONS: AutoML delivers prediction models with fair discriminatory performance, and good calibration and accuracy, which is as good as regression models with expert-based predictor pre-selection. In the context of the restricted availability of data in an ICU quality registry, extending the models with variables that are available at 24h after admission showed small (but significantly) performance increase.

Alarming increase in poisonings from recreational nitrous oxide use after a change in EU-legislation, inquiries to the Dutch Poisons Information Center.

BACKGROUND: After the change in EU-legislation in 2014, recreational use of nitrous oxide (N2O) increased in the Netherlands from 2015 onwards. We studied the effect on N2O poisonings during an 11 year period. METHODS: A retrospective observational study was performed on the incidence rate of N2O poisonings, relative to all recreational drug poisonings reported to the Dutch Poisons Information Center (DPIC) from 2010-2020. Secondary outcomes were the frequency of heavy use, frequent use, co-exposures, and toxicity in 2019 and 2020. RESULTS: 433 N2O poisonings were included. The incidence rate increased exponentially from 0.12% in 2010 to 11% in 2020, with an average monthly rate of 3.8%. In 2019 and 2020, 79% of the patients indicated heavy use, frequent use or both, and 42% used from large cylinders. Chronic toxicity (signs of peripheral neuropathy) was reported in 38% of the patients. CONCLUSION: The rate of N2O poisonings increased alarmingly in the Netherlands. An increasing proportion of patients reported problematic heavy or frequent use, accompanied by chronic toxicity.

Comparison of outcome and characteristics between 6343 COVID-19 patients and 2256 other community-acquired viral pneumonia patients admitted to Dutch ICUs.

PURPOSE: Describe the differences in characteristics and outcomes between COVID-19 and other viral pneumonia patients admitted to Dutch ICUs. MATERIALS AND METHODS: Data from the National-Intensive-Care-Evaluation-registry of COVID-19 patients admitted between February 15th and January 1th 2021 and other viral pneumonia patients admitted between January 1st 2017 and January 1st 2020 were used. Patients' characteristics, the unadjusted, and adjusted in-hospital mortality were compared. RESULTS: 6343 COVID-19 and 2256 other viral pneumonia patients from 79 ICUs were included. The COVID-19 patients included more male (71.3 vs 49.8%), had a higher Body-Mass-Index (28.1 vs 25.5), less comorbidities (42.2 vs 72.7%), and a prolonged hospital length of stay (19 vs 9 days). The COVID-19 patients had a significantly higher crude in-hospital mortality rate (Odds ratio (OR) = 1.80), after adjustment for patient characteristics and ICU occupancy rate the OR was respectively 3.62 and 3.58. CONCLUSION: Higher mortality among COVID-19 patients could not be explained by patient characteristics and higher ICU occupancy rates, indicating that COVID-19 is more severe compared to other viral pneumonia. Our findings confirm earlier warnings of a high need of ICU capacity and high mortality rates among relatively healthy COVID-19 patients as this may lead to a higher mental workload for the staff.

Direct Q-Value Determination of the ß

The cyclotron frequency ratio of ^{187}Os^{29+} to ^{187}Re^{29+} ions was measured with the Penning-trap mass spectrometer PENTATRAP. The achieved result of R=1.000 000 013 882(5) is to date the most precise such measurement performed on ions. Furthermore, the total binding-energy difference of the 29 missing electrons in Re and Os was calculated by relativistic multiconfiguration methods, yielding the value of ΔE=53.5(10) eV. Finally, using the achieved results, the mass difference between neutral ^{187}Re and ^{187}Os, i.e., the Q value of the ß^{-} decay of ^{187}Re, is determined to be 2470.9(13) eV.

The effect of ICU-tailored drug-drug interaction alerts on medication prescribing and monitoring: protocol for a cluster randomized stepped-wedge trial.

BACKGROUND: Drug-drug interactions (DDIs) can cause patient harm. Between 46 and 90% of patients admitted to the Intensive Care Unit (ICU) are exposed to potential DDIs (pDDIs). This rate is twice as high as patients on general wards. Clinical decision support systems (CDSSs) have shown their potential to prevent pDDIs. However, the literature shows that there is considerable room for improvement of CDSSs, in particular by increasing the clinical relevance of the pDDI alerts they generate and thereby reducing alert fatigue. However, consensus on which pDDIs are clinically relevant in the ICU setting is lacking. The primary aim of this study is to evaluate the effect of alerts based on only clinically relevant interactions for the ICU setting on the prevention of pDDIs among Dutch ICUs. METHODS: To define the clinically relevant pDDIs, we will follow a rigorous two-step Delphi procedure in which a national expert panel will assess which pDDIs are perceived clinically relevant for the Dutch ICU setting. The intervention is the CDSS that generates alerts based on the clinically relevant pDDIs. The intervention will be evaluated in a stepped-wedge trial. A total of 12 Dutch adult ICUs using the same patient data management system, in which the CDSS will operate, were invited to participate in the trial. Of the 12 ICUs, 9 agreed to participate and will be enrolled in the trial. Our primary outcome measure is the incidence of clinically relevant pDDIs per 1000 medication administrations. DISCUSSION: This study will identify pDDIs relevant for the ICU setting. It will also enhance our understanding of the effectiveness of alerts confined to clinically relevant pDDIs. Both of these contributions can facilitate the successful implementation of CDSSs in the ICU and in other domains as well. TRIAL REGISTRATION: Nederlands Trial register Identifier: NL6762 . Registered November 26, 2018.

Multimodal prehabilitation to reduce the incidence of delirium and other adverse events in elderly patients undergoing elective major abdominal surgery: An uncontrolled before-and-after study.

BACKGROUND: Delirium is a common and serious complication in elderly patients undergoing major abdominal surgery, with significant adverse outcomes. Successful strategies or therapies to reduce the incidence of delirium are scarce. The objective of this study was to assess the role of prehabilitation in reducing the incidence of delirium in elderly patients. METHODS: A single-center uncontrolled before-and-after study was conducted, including patients aged 70 years or older who underwent elective abdominal surgery for colorectal carcinoma or an abdominal aortic aneurysm between January 2013 and October 2015 (control group) and between November 2015 and June 2018 (prehabilitation group). The prehabilitation group received interventions to improve patients' physical health, nutritional status, factors of frailty and preoperative anaemia prior to surgery. The primary outcome was incidence of delirium, diagnosed with the DSM-V criteria or the confusion assessment method. Secondary outcomes were additional complications, length of stay, unplanned ICU admission, length of ICU stay, readmission rate, institutionalization, and in-hospital or 30-day mortality. RESULT: A total of 360 control patients and 267 prehabilitation patients were included in the final analysis. The mean number of prehabilitation days was 39 days. The prehabilitation group had a higher burden of comorbidities and was more physically and visually impaired at baseline. At adjusted logistic regression analysis, delirium incidence was reduced significantly from 11.7 to 8.2% (OR 0.56; 95% CI 0.32-0.98; P = 0.043). No statistically significant effects were seen on secondary outcomes. CONCLUSION: Current prehabilitation program is feasible and safe, and can reduce delirium incidence in elderly patients undergoing elective major abdominal surgery. This program merits further evaluation. TRIAL REGISTRATION: Dutch Trial Registration, NTR5932.

Reducing deposition of encrustation in ureteric stents by changing the stent architecture: A microfluidic-based investigation.

Ureteric stents are clinically deployed to retain ureteral patency in the presence of an obstruction of the ureter lumen. Despite the fact that multiple stent designs have been researched in recent years, encrustation and biofilm-associated infections remain significant complications of ureteral stenting, potentially leading to the functional failure of the stent. It has been suggested that "inactive" side-holes of stents may act as anchoring sites for encrusting crystals, as they are associated with low wall shear stress (WSS) levels. Obstruction of side-holes due to encrustation is particularly detrimental to the function of the stent, since holes provide a path for urine to by-pass the occlusion. Therefore, there is an unmet need to develop novel stents to reduce deposition of encrusting particles at side-holes. In this study, we employed a stent-on-chip microfluidic model of the stented and occluded ureter to investigate the effect of stent architecture on WSS distribution and encrustation over its surface. Variations in the stent geometry encompassed (i) the wall thickness and (ii) the shape of side-holes. Stent thickness was varied in the range 0.3-0.7 mm, while streamlined side-holes of triangular shape were evaluated (with a vertex angle in the range 45°-120°). Reducing the thickness of the stent increased WSS and thus reduced the encrustation rate at side-holes. A further improvement in performance was achieved by using side-holes with a triangular shape; notably, a 45° vertex angle showed superior performance compared to other angles investigated, resulting in a significant increase in WSS within "inactive" side-holes. In conclusion, combining the optimal stent thickness (0.3 mm) and hole vertex angle (45°) resulted in a ∼90% reduction in encrustation rate within side-holes, compared to a standard design. If translated to a full-scale ureteric stent, this optimised architecture has the potential for significantly increasing the stent lifetime while reducing clinical complications.

Comparison of the metabolism of 10 chemicals in human and pig skin explants.

Skin metabolism is important to consider when assessing local toxicity and/or penetration of chemicals and their metabolites. If human skin supply is limited, pig skin can be used as an alternative. To identify any species differences, we have investigated the metabolism of 10 chemicals in a pig and human skin explant model. Phase I metabolic pathways in skin from both species included those known to occur via cytochrome P450s, esterases, alcohol dehydrogenases and aldehyde dehydrogenases. Common Phase II pathways were glucuronidation and sulfation but other conjugation pathways were also identified. Chemicals not metabolized by pig skin (caffeine, IQ and 4-chloroaniline) were also not metabolized by human skin. Six chemicals metabolized by pig skin were metabolized to a similar extent (percentage parent remaining) by human skin. Human skin metabolites were also detected in pig skin incubations, except for one unidentified minor vanillin metabolite. Three cinnamyl alcohol metabolites were unique to pig skin but represented minor metabolites. There were notable species differences in the relative amounts of common metabolites. The difference in the abundance of the sulfate conjugates of resorcinol and 4-amino-3-nitrophenol was in accordance with the known lack of aryl sulfotransferase activity in pigs. In conclusion, while qualitative comparisons of metabolic profiles were consistent between pig and human skin, there were some quantitative differences in the percentage of metabolites formed. This preliminary assessment suggests that pig skin is metabolically competent and could be a useful tool for evaluating potential first-pass metabolism before testing in human-derived tissues.

Attitudes of physicians towards the care of critically ill elderly patients - a European survey.

BACKGROUND: Very elderly patients are one of the fastest growing population in ICUs worldwide. There are lots of controversies regarding admission, discharge of critically ill elderly patients, and also on treatment intensity during the ICU stay. As a consequence, practices vary considerably from one ICU to another. In that perspective, we collected opinions of experienced ICU physicians across Europe on statements focusing on patients older than 80. METHODS: We sent an online questionnaire to the coordinator ICU physician of all participating ICUs of an recent European, observational study of Very old critically Ill Patients (VIP1 study). This questionnaire contained 12 statements about admission, triage, treatment and discharge of patients older than 80. RESULTS: We received answers from 162 ICUs (52% of VIP1-study) spanning 20 different European countries. There were major disagreements between ICUs. Responders disagree that: there is clear evidence that ICU admission is beneficial (37%); seeking relatives' opinion is mandatory (17%); written triage guidelines must be available either at the hospital or ICU level (20%); level of care should be reduced (25%); a consultation of a geriatrician should be sought (34%) and a geriatrician should be part of the post-ICU trail (11%). The percentage of disagreement varies between statements and European regions. CONCLUSION: There are major differences in the attitude of European ICU physicians on the admission, triage and treatment policies of patients older than 80 emphasizing the lack of consensus and poor level of evidence for most of the statements and outlining the need for future interventional studies.

[Bitten by an exotic venomous snake]. / Gebeten door een exotische gifslang.

BACKGROUND: Patients who have been bitten by an exotic venomous snake are at risk of severe morbidity and a fatal outcome following an incorrect risk-assessment. Treatment with an antivenom can be necessary and can turn out to be lifesaving. In the Netherlands there are only a few cases of bites from exotic venomous snakes each year. CASE DESCRIPTION: A 28-year-old man presented at the emergency department (ED) after having been bitten by a monocled cobra (Naja kaouthia). Here he developed severe neurotoxicity with respiratory insufficiency requiring intubation and mechanical ventilation. The patient was successfully treated with an antivenom. CONCLUSION: An exotic snakebite victim is always a medical emergency. With early presentation at the ED, proper assessment, treatment and the availability of antivenom from the National Serum Depot, this will not necessarily cause insurmountable problems.