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Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m(2)]: 91 patients; low-dose [≤0.5 g/m(2)]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

A 22-year-old man was hospitalized after stating he would 'commit suicide in a non-detectable way'. He was admitted with a severe necrotizing pancreatitis and acute kidney injury, evolving to multiple organ failure. His condition rapidly deteriorated, and he died 11 days after hospital admission. Postmortem histopathology confirmed fulminant necrotizing pancreatitis, acute tubular necrosis, cerebral edema, pericentral/midzonal hepatocellular necrosis and acute respiratory distress syndrome. Metabolites of 4F-MDMB-BINACA, a synthetic cannabinoid, were detected in urine and serum collected at hospital admission. The same drug was found in a vapor fluid found in the man's apartment. As cannabis use has been etiologically linked to acute pancreatitis, we hypothesize that the more afferent and potent 4F-MDMB-BINACA could induce acute pancreatitis via stimulation of cannabinoid (CB)1-receptors. Alternatively, terminal fluorination could have induced a dose-dependent toxic effect on a wide range of cellular processes, leading to cell dysfunction and death. This is the first clinicopathological description of a lethal intoxication with 4F-MDMB-BINACA, following extensive vaping. Toxic effects could either relate to CB-receptor binding or to direct fluoride toxicity.

Introduction:There is evidence to suggest that patients delayed seeking urgent medical care during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. A delay in health-seeking behavior could increase the disease severity of patients in the prehospital setting. The combination of COVID-19-related missions and augmented disease severity in the prehospital environment could result in an increase in the number and severity of physician-staffed prehospital interventions, potentially putting a strain on this highly specialized service.Study Objective:The aim was to investigate if the COVID-19 pandemic influences the frequency of physician-staffed prehospital interventions, prehospital mortality, illness severity during prehospital interventions, and the distribution in the prehospital diagnoses.Methods:A retrospective, multicenter cohort study was conducted on prehospital charts from March 14, 2020 through April 30, 2020, compared to the same period in 2019, in an urban area. Recorded data included demographics, prehospital diagnosis, physiological parameters, mortality, and COVID-status. A modified National Health Service (NHS) National Early Warning Score (NEWS) was calculated for each intervention to assess for disease severity. Data were analyzed with univariate and descriptive statistics.Results:There was a 31% decrease in physician-staffed prehospital interventions during the period under investigation in 2020 as compared to 2019 (2019: 644 missions and 2020: 446 missions), with an increase in prehospital mortality (OR = 0.646; 95% CI, 0.435 – 0.959). During the study period, there was a marked decrease in the low and medium NEWS groups, respectively, with an OR of 1.366 (95% CI, 1.036 – 1.802) and 1.376 (0.987 – 1.920). A small increase was seen in the high NEWS group, with an OR of 0.804 (95% CI, 0.566 – 1.140); 2019: 80 (13.67%) and 2020: 69 (16.46%). With an overall decrease in cases in all diagnostic categories, a significant increase was observed for respiratory illness (31%; P = .004) and cardiac arrest (54%; P < .001), combined with a significant decrease for intoxications (-58%; P = .007). Due to the national test strategy at that time, a COVID-19 polymerase chain reaction (PCR) result was available in only 125 (30%) patients, of which 20 (16%) were positive.Conclusion:The frequency of physician-staffed prehospital interventions decreased significantly. There was a marked reduction in interventions for lower illness severity and an increase in higher illness severity and mortality. Further investigation is needed to fully understand the reasons for these changes.

Seizures are a recognized and potentially serious complication of recreational drug use. This study examined a large international data set of presentations to Emergency Departments with acute recreational drug toxicity, the European Drug Emergencies Plus (Euro-DEN Plus) Network, to compare presentations with and without seizures and estimate incidence and associated drugs. Amongst 23,947 presentations between January 2014 and December 2017, there were 1013 (4.2%) with reported seizures. Clinical and demographic features were similar between individuals who had a seizure and those who did not, although rates of coma, cardiac arrest, intubation, intensive care admission, and death were significantly higher in those with seizures. There was a significant association between specific drugs and a higher seizure incidence, including fentanyl (odds ratio 2.63, 95% confidence interval 1.20-5.80), and synthetic cannabinoids (OR 2.90, 95% CI 2.19-3.84). Other drugs were associated with a lower seizure incidence, including heroin (OR 0.46, 95% CI 0.35-0.61), clonazepam (OR 0.22, 95% CI 0.06-0.91), and cannabis (OR 0.65, 95% CI 0.50-0.86). This substantiates observations that the synthetic cannabinoids as a group of novel psychoactive substances are clinically different in consequence of intoxication than cannabis, and that individuals who suffer a seizure in the context of recreational drug intoxication are likely to have worse outcomes overall. Utilising this information of what substances have a greater risk of seizures, could provide tailored harm reduction and education strategies to users to reduce the risk of seizures and their associated complications.

Baclofen toxicity results from intentional self-poisoning (acute baclofen poisoning) or accumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Use of extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation.

Background: Aspiration community-acquired pneumonia (ACAP) and community-acquired pneumonia (CAP) in patients with aspiration risk factors (AspRFs) are infections associated with anaerobes, but limited evidence suggests their pathogenic role. Research Question: What are the aspiration risk factors, microbiology patterns, and empiric anti-anaerobic use in patients hospitalized with CAP? Study Design and Methods: This is a secondary analysis of GLIMP, an international, multicenter, point-prevalence study of adults hospitalized with CAP. Patients were stratified into three groups: (1) ACAP, (2) CAP/AspRF+ (CAP with AspRF), and (3) CAP/AspRF- (CAP without AspRF). Data on demographics, comorbidities, microbiological results, and anti-anaerobic antibiotics were analyzed in all groups. Patients were further stratified in severe and nonsevere CAP groups. Results: We enrolled 2,606 patients with CAP, of which 193 (7.4%) had ACAP. Risk factors independently associated with ACAP were male, bedridden, underweight, a nursing home resident, and having a history of stroke, dementia, mental illness, and enteral tube feeding. Among non-ACAP patients, 1,709 (70.8%) had CAP/AspRF+ and 704 (29.2%) had CAP/AspRF-. Microbiology patterns including anaerobes were similar between CAP/AspRF-, CAP/AspRF+ and ACAP (0.0% vs 1.03% vs 1.64%). Patients with severe ACAP had higher rates of total gram-negative bacteria (64.3% vs 44.3% vs 33.3%, P =.021) and lower rates of total gram-positive bacteria (7.1% vs 38.1% vs 50.0%, P 50% in all groups) independent of AspRFs or ACAP received specific or broad-spectrum anti-anaerobic coverage antibiotics. Interpretation: Hospitalized patients with ACAP or CAP/AspRF+ had similar anaerobic flora compared with patients without aspiration risk factors. Gram-negative bacteria were more prevalent in patients with severe ACAP. Despite having similar microbiological flora between groups, a large proportion of CAP patients received anti-anaerobic antibiotic coverage.

IntroductionChildren, with their specific vulnerabilities and needs, make up to more than 20% of society, so they are at risk of getting involved in disasters. Are the specialists treating them for medical problems in daily life also capable to deal with them in disaster situations?Hypothesis/ProblemThe goals of this study were to evaluate perceived knowledge and capability of tertiary pediatricians to deal with disasters, to identify promoting factors, and to evaluate education need and willingness to work.MethodsA survey looking for demographics, hospital disaster planning, estimated risk and capability for disasters, training, and willingness to work, and a set of six content assessment questions to evaluate knowledge, were presented to emergency pediatricians and pediatric emergency physicians in specialized tertiary centers.ResultsThe response rate was 51%. Thirty-five percent had disaster training and 53% felt that disaster education should be obligatory in their curriculum. Risk for disasters was estimated from 2.4/10 for nuclear incidents to 7.6/10 for major trauma. Self-estimated capability for these situations ranged from 1.8/10 in nuclear incidents to 7.6/10 in major trauma. Unconditional willingness to work ranged from 37% in nuclear situations to 68% in pandemics. Mean score on the questions was 2.06/6. Training, knowledge of antidote and personal protective equipment (PPE) use, self-estimated capability, and exposure were significant predictors for higher scores. Willingness to work correlated significantly with age, self-estimated capability, and risk estimation. In case of chemical and nuclear incidents, there was correlation with knowledge on the use of decontamination, PPE, and radio-detection devices.ConclusionDespite a clear perception of the risks and a high willingness to work, preparedness is limited. The major conclusion is that basics of disaster management should be included in pediatric training.MortelmansLJM, MaebeS, DieltiensG, AnseeuwK, SabbeMB, Van de VoordeP. Are tertiary care paediatricians prepared for disaster situations?Prehosp Disaster Med. 2016;31(2):126–131.

The phosphodiesterase type 5 inhibitor, sildenafil, is not generally known for its use as a self-poisoning drug. However, intoxication cases with lethal outcome have been described. The case presented here is of a 56-year-old man who claimed to have undertaken an unsuccessful suicide attempt by mono-ingestion of 65 tablets of 100 mg sildenafil. He arrived at the emergency department 24 h after intake with severe vomiting and symptoms of blurred vision. Clinical examination revealed no priapism. Of note was a sinus tachycardia of 100 bpm without signs of hypotension. To quantify the sildenafil concentration in serum, an high-performance liquid chromatography photo-diode array method was developed and validated according to European Medicines Agency guidelines. The intoxicated patient had a serum concentration of 22.2 mu g/mL sildenafil, at the time of presentation, which is far above the therapeutic peak concentration. The serum concentration further declined to 9.2 and 2.3 mu g/mL, respectively, 5 and 14 h later, revealing a biological half-life of 4.2 h. To the best of our knowledge, this patient took the highest sildenafil dose, which resulted in the highest serum concentration, ever reported. In this subject, sildenafil showed good tolerability because few symptoms occurred and only moderate supportive therapy was needed for full recovery without sequelae.

The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning.The lead authors reviewed all of the articles from a systematic literature search, extracted the data, summarized the key findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote was conducted to determine the final workgroup recommendations.The latest literature search conducted in November 2014 retrieved a total of 79 articles for final qualitative analysis, including one observational study, one uncontrolled cohort study with aggregate analysis, 70 case reports and case series, and 7 pharmacokinetic studies, yielding a very low quality of evidence for all recommendations. Clinical data were reported for 82 overdose patients while pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration1300 mg/L (9000 μmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration900 mg/L (6250 μmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between 50 and 100 mg/L (350-700 μmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable alternative.VPA is moderately dialyzable in the setting of overdose. ECTR is indicated for VPA poisoning if at least one of the above criteria is present. Intermittent hemodialysis is the preferred ECTR modality in VPA poisoning.

IntroductionBeing one of Europe’s most densely populated countries, and having multiple nuclear installations, a heavy petrochemical industry, and terrorist targets, the Netherlands is at-risk for chemical, biological, or radionuclear (CBRN) incidents. Recent world and continental events show that this threat is real and that authorities may be underprepared.HypothesisThe hypothesis of this study is that Dutch hospitals are underprepared to deal with these incidents.MethodsA descriptive, cross-sectional study was performed. All 93 Dutch hospitals with an emergency department (ED) were sent a link to an online survey on different aspects of CBRN preparedness. Besides specific hospital information, information was obtained on the hospital’s disaster planning; risk perception; and availability of decontamination units, personal protective equipment (PPE), antidotes, radiation detection, infectiologists, isolation measures, and staff training.ResultsResponse rate was 67%. Sixty-two percent of participating hospitals were estimated to be at-risk for CBRN incidents. Only 40% had decontamination facilities and 32% had appropriate PPE available for triage and decontamination teams. Atropine was available in high doses in all hospitals, but specific antidotes that could be used for treating victims of CBRN incidents, such as hydroxycobolamine, thiosulphate, Prussian blue, Diethylenetriaminepentaacetic acid (DTPA), or pralidoxime, were less frequently available (74%, 65%, 18%, 14%, and 42%, respectively). Six percent of hospitals had radioactive detection equipment with an alarm function and 22.5% had a nuclear specialist available 24/7 in case of disasters. Infectiologists were continuously available in 60% of the hospitals. Collective isolation facilities were present in 15% of the hospitals.Conclusion:There is a serious lack of hospital preparedness for CBRN incidents in The Netherlands.MortelmansLJM, GaakeerMI, DieltiensG, AnseeuwK, SabbeMB. Are Dutch hospitals prepared for chemical, biological, or radionuclear incidents? A survey study. Prehosp Disaster Med. 2017;32(5):483–491.

Smoke inhalation is a common cause of cyanide poisoning during fires, resulting in injury and even death. In many cases of smoke inhalation, cyanide has increasingly been recognized as a significant toxicant. The diagnosis of cyanide poisoning remains very difficult, and failure to recognize it may result in inadequate or inappropriate treatment. Findings suggesting cyanide toxicity include the following: (a) a history of enclosed-space fire; (b) any alteration in the level of consciousness; (c) any cardiovascular changes (particularly inexplicable hypotension); and (d) elevated plasma lactate. The feasibility and safety of empiric treatment with hydroxocobalamin for fire smoke victims have been reported in the literature. On the basis of a literature review and a panel discussion, a group of European experts has proposed emergency management protocols for cyanide toxicity in fire smoke victims.

Background No published burden of illness or cost-effectiveness studies on cyanide (CN) poisoning exist. A health economic model has therefore been developed to determine the cost-effectiveness of hydroxocobalamin (Cyanokit) in suspected and known CN poisoning. Objectives To assess the cost-effectiveness of hydroxocobalamin versus standard treatment in known or suspected CN poisoning in Belgium. Methods Probabilities for neurological sequelae and mortality were applied based on phase III trials, literature data and the hydroxocobalamin preclinical trial. Since no cost and utility data for CN poisoning exist, costs and utilities of very comparable or related diseases derived from publicly available Belgian sources and literature were applied. Direct medical costs from the public healthcare payer9s perspective were used. The time horizon was 1 year. Sensitivity analyses were performed to assess the robustness of the results. Results Base-case analyses versus standard treatment revealed cost-effective results (incremental cost-effectiveness ratio=9921€/QALY) in suspected CN poisoning and dominance (more effective and cost-saving) in known CN poisoning. It was determined that 17 lives could be saved and one sequel prevented per year on a national level using hydroxocobalamin treatment. One-way sensitivity analyses varying efficacy, costs, utilities and time horizon demonstrated the robustness of the results. The results were most sensitive to the probability of death and neurological sequelae, but remained within acceptable limits of cost-effectiveness. Furthermore, it was shown that a longer time frame (5 or 10 years) leads to even more favourable cost-effective results. Conclusions Hydroxocobalamin appears cost-effective to dominant compared with standard treatment in CN poisoning from a healthcare payer9s perspective.

Supplemental Digital Content is available in the text., Objective: To provide a management approach for adults with calcium channel blocker poisoning. Data Sources, Study Selection, and Data Extraction: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. Data Synthesis: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D–2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). Conclusion: We offer recommendations for the stepwise management of calcium channel blocker toxicity. For all interventions, the level of evidence was very low.

Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.

Background: γ-hydroxybutyric acid ( GHB ), notorious as a club- and date-rape drug, was quantified in dried blood spots (DBS) by punching out a disc, followed by ‘on-spot’ derivatization and analysis by GC–MS. Results: A homogenous distribution in DBS was demonstrated and accurate results were obtained when analyzing a disc punched out from a 20–35 µl spot, regardless the hematocrit of the blood sample. Validation based on US FDA and European Medicines Agency guidelines was performed, with a calibration range covering 2–100 µg/ml. Conclusion: A sensitive GC–MS method for GHB analysis in DBS was successfully optimized and validated. The successful analysis of DBS collected from GHB abusers suggests the routine applicability of the DBS sampling technique for GHB analysis in toxicological cases.

The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we present our results for digoxin.After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations.Out of 435 articles screened, 77 met inclusion criteria. Only in-vitro, animal studies, case reports and case series were identified yielding a very low quality of evidence for all recommendations. Based on data from 84 patients, including six fatalities, it was concluded that digoxin is slightly dialyzable (level of evidence = B), and that ECTR is unlikely to improve the outcome of digoxin-toxic patients whether or not digoxin immune Fab (Fab) is administered. Despite the lack of robust clinical evidence, the workgroup recommended against the use of ECTR in cases of severe digoxin poisoning when Fab was available (1D) and also suggested against the use of ECTR when Fab was unavailable (2D).ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.

BACKGROUND: Antibiotic resistance is a major global health problem and pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) have become of particular concern in the management of lower respiratory tract infections. However, few data are available on the worldwide prevalence and risk factors for MRSA pneumonia. We aimed to determine the point prevalence of MRSA pneumonia and identify specific MRSA risk factors in community-dwelling patients hospitalised with pneumonia.METHODS: We did an international, multicentre study of community-dwelling, adult patients admitted to hospital with pneumonia who had microbiological tests taken within 24 h of presentation. We recruited investigators from 222 hospitals in 54 countries to gather point-prevalence data for all patients admitted with these characteristics during 4 days randomly selected during the months of March, April, May, and June in 2015. We assessed prevalence of MRSA pneumonia and associated risk factors through logistic regression analysis.FINDINGS: 3702 patients hospitalised with pneumonia were enrolled, with 3193 patients receiving microbiological tests within 24 h of admission, forming the patient population. 1173 (37%) had at least one pathogen isolated (culture-positive population). The overall prevalence of confirmed MRSA pneumonia was 3·0% (n=95), with differing prevalence between continents and countries. Three risk factors were independently associated with MRSA pneumonia: previous MRSA infection or colonisation (odds ratio 6·21, 95% CI 3·25-11·85), recurrent skin infections (2·87, 1·10-7·45), and severe pneumonia disease (2·39, 1·55-3·68).INTERPRETATION: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia.FUNDING: None.

Background Medical students have been deployed in victim care of several disasters throughout history. They are corner stones in first-line care in recent pandemic planning. Furthermore, every physician and senior medical student is expected to assist in case of disaster situations, but are they educated to do so? Being one of Europe’s densest populated countries with multiple nuclear installations, a large petrochemical industry and also at risk for terrorist attacks, The Netherlands bear some risks for incidents. We evaluated the knowledge on Disaster Medicine in the Dutch medical curriculum. Our hypothesis is that Dutch senior medical students are not prepared at all. Methods Senior Dutch medical students were invited through their faculty to complete an online survey on Disaster Medicine, training and knowledge. This reported knowledge was tested by a mixed set of 10 theoretical and practical questions. Results With a mean age of 25.5 years and 60 % females, 999 participants completed the survey. Of the participants, 51 % considered that Disaster Medicine should absolutely be taught in the regular medical curriculum and only 2 % felt it as useless; 13 % stated to have some knowledge on disaster medicine. Self-estimated capability to deal with various disaster situations varied from 1.47/10 in nuclear incidents to 3.92/10 in influenza pandemics. Self-estimated knowledge on these incidents is in the same line (1.71/10 for nuclear incidents and 4.27/10 in pandemics). Despite this limited knowledge and confidence, there is a high willingness to respond (ranging from 4.31/10 in Ebola outbreak over 5.21/10 in nuclear incidents to 7.54/10 in pandemics). The case/theoretical mix gave a mean score of 3.71/10 and raised some food for thought. Although a positive attitude, 48 % will place contaminated walking wounded in a waiting room and 53 % would use iodine tablets as first step in nuclear decontamination. Of the participants, 52 % even believes that these tablets protect against external radiation, 41 % thinks that these tablets limit radiation effects more than shielding and 57 % believes that decontamination of chemical victims consists of a specific antidote spray in military cabins. Conclusions Despite a high willingness to respond, our students are not educated for disaster situations. Electronic supplementary material The online version of this article (doi:10.1186/s12245-015-0077-0) contains supplementary material, which is available to authorized users.

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning.

The Extracorporeal Treatments in Poisoning Workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. Here, the EXTRIP workgroup presents its recommendations for lithium poisoning. After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations. In total, 166 articles met inclusion criteria, which were mostly case reports, yielding a very low quality of evidence for all recommendations. A total of 418 patients were reviewed, 228 of which allowed extraction of patient-level data. The workgroup concluded that lithium is dialyzable (Level of evidence=A) and made the following recommendations: Extracorporeal treatment is recommended in severe lithium poisoning (1D). Extracorporeal treatment is recommended if kidney function is impaired and the [Li(+)] is4.0 mEq/L, or in the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of the [Li(+)] (1D). Extracorporeal treatment is suggested if the [Li(+)] is5.0 mEq/L, significant confusion is present, or the expected time to reduce the [Li(+)] to1.0 mEq/L is36 hours (2D). Extracorporeal treatment should be continued until clinical improvement is apparent or [Li(+)] is1.0 mEq/L (1D). Extracorporeal treatments should be continued for a minimum of 6 hours if the [Li(+)] is not readily measurable (1D). Hemodialysis is the preferred extracorporeal treatment (1D), but continuous RRT is an acceptable alternative (1D). The workgroup supported the use of extracorporeal treatment in severe lithium poisoning. Clinical decisions on when to use extracorporeal treatment should take into account the [Li(+)], kidney function, pattern of lithium toxicity, patient's clinical status, and availability of extracorporeal treatments.

Study objective Salicylate poisoning is a challenging clinical entity associated with substantial morbidity and mortality. The indications for extracorporeal treatments such as hemodialysis are poorly defined. We present a systematic review of the literature along with evidence- and consensus-based recommendations on the use of extracorporeal treatment in salicylate poisoning. Methods The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup is a multidisciplinary group with international representation whose aim is to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. We conducted a systematic literature review followed by data extraction and summarized findings, following a predetermined format. The entire work group voted by a 2-round modified Delphi method to reach consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. Results Eighty-four articles met inclusion criteria, including 1 controlled clinical trial, 3 animal studies, and 80 case reports or case series, yielding an overall very low quality of evidence for all recommendations. Clinical data on 143 patients (130 sets of which could be analyzed for patient-level entry data), including 14 fatalities, were reviewed. Toxicokinetic data on 87 patients were also included. After the second round of voting, the workgroup concluded that salicylates are dialyzable by hemodialysis and hemoperfusion (level of evidence=B) and recommended extracorporeal treatment in patients with severe salicylate poisoning (1D), including any patient with altered mental status (1D), with acute respiratory distress syndrome requiring supplemental oxygen (1D), and for those in whom standard therapy is deemed to be failing (1D) regardless of the salicylate concentration. High salicylate concentrations warrant extracorporeal treatment regardless of signs and symptoms (>7.2 mmol/L [100 mg/dL] [1D]; and >6.5 mmol/L [90 mg/dL] [2D]), with lower thresholds applied for patients with impaired kidney function (>6.5 mmol/L [90 mg/dL] [1D]; >5.8 mmol/L [80 mg/dL] [2D]). Extracorporeal treatment is also suggested for patients with severe acidemia (pH ≤7.20 in the absence of other indications) (2D). Intermittent hemodialysis is the preferred modality (1D), although hemoperfusion (1D) and continuous renal replacement therapies (3D) are acceptable alternatives if hemodialysis is unavailable, as is exchange transfusion in neonates (1D). Conclusion Salicylates are readily removed by extracorporeal treatment, with intermittent hemodialysis being the preferred modality. The signs and symptoms of salicylate toxicity listed warrant extracorporeal treatment, as do high concentrations regardless of clinical status.

The management of methanol poisoning includes early antidote therapy to inhibit the metabolism of methanol to formate. Ethanol and fomepizole are both effective, but recently fomepizole has been preferred, although there is no scientific evidence that the use of fomepizole is a superior therapeutic strategy compared with the use of ethanol combined with haemodialysis. The same patient was admitted twice to our emergency department with methanol poisoning. The first time (methanol 3.24 g/l), she was treated with fomepizole without dialysis owing to the absence of acidosis. The second time (methanol 5.5 g/l), she received ethanol as an antidote and dialysis was started. For both therapeutic strategies, hospital length of stay, observation unit length of stay and costs are compared. In the Belgian healthcare system, we found that fomepizole treatment was three times as expensive as ethanol treatment, and the majority of costs are not reimbursed. Fomepizole antidote therapy, compared with ethanol, has fewer reported side effects, but is more expensive. In hospitals where dialysis is easily available, ethanol antidote therapy should still be considered, especially if similar cost differences exist within the healthcare system one is working in.

Most fire-related deaths are attributable to smoke inhalation rather than burns. The inhalation of fire smoke, which contains not only carbon monoxide but also a complex mixture of gases, seems to be the major cause of morbidity and mortality in fire victims, mainly in enclosed spaces. Cyanide gas exposure is quite common during smoke inhalation, and cyanide is present in the blood of fire victims in most cases and may play an important role in death by smoke inhalation. Cyanide poisoning may, however, be difficult to diagnose and treat. In these children, hydrogen cyanide seems to be a major source of concern, and the rapid administration of the antidote, hydroxocobalamin, may be critical for these children.European experts recently met to formulate an algorithm for prehospital and hospital management of adult patients with acute cyanide poisoning. Subsequently, a group of European pediatric experts met to evaluate and adopt that algorithm for use in the pediatric population.

Summary Background The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). Methods After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. Results Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24–48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is Conclusion Despite Tl’s low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.

Most fire-related deaths are attributable to smoke inhalation rather than burns. The inhalation of fire smoke, which contains not only carbon monoxide but also a complex mixture of gases, seems to be the major cause of morbidity and mortality in fire victims, mainly in enclosed spaces. Cyanide gas exposure is quite common during smoke inhalation, and cyanide is present in the blood of fire victims in most cases and may play an important role in death by smoke inhalation. Cyanide poisoning may, however, be difficult to diagnose and treat. In these children, hydrogen cyanide seems to be a major source of concern, and the rapid administration of the antidote, hydroxocobalamin, may be critical for these children.European experts recently met to formulate an algorithm for prehospital and hospital management of adult patients with acute cyanide poisoning. Subsequently, a group of European pediatric experts met to evaluate and adopt that algorithm for use in the pediatric population.

During out-of hospital cardiac arrest (OHCA) cerebral saturation may provide relevant information on cerebral oxygenation. In this study we examined the time course in cerebral saturation (rSO2) during prehospital ALS comparing patients with a presumed cardiac origin (survivor = Sc, nonsurvivor = NSc) of arrest and noncardiac origin (survivor = Snc, nonsurvivor = NSnc) of arrest.

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence = C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).