Acetaminophen poisoning: an update for the intensivist

Acetaminophen overdose is common and can result from deliberate/nonstaggered or accidental/staggered ingestion. Patients presenting within 24 h of an acetaminophen overdose can safely be managed on medical wards. Early management of nonstaggered overdose is guided by the plasma acetaminophen concentration, whereas management of accidental/staggered ingestion is guided by ingested dose. Ingested dose and time from ingestion to presentation are important prognostic factors in accidental/staggered ingestion. Acetaminophen-induced acute liver failure (ALF) requires meticulous supportive care in an intensive care unit (ICU), with early identification and transfer of patients who are likely to require liver transplantation to a specialist liver centre. The modified King's College Hospital criteria (incorporating lactate into the traditional criteria) represent the best tool for identifying patients who require transplantation

Synthetic cannabinoid availability on darknet drug markets—changes during 2016–2017

open access articleChanges in legislation have affected supply routes of new psychoactive substances such as synthetic cannabinoids with evidence of supply over the darknet. We identified darknet drug markets using an index database and Tor Browser to access markets. We identified SC in product listings using a custom-programmed script. We collected data at bimonthly intervals (August 2016–April 2017). Eleven darknet markets listed SC for sale, the largest number from China, UK, US, Netherlands, and Germany. Formulations available were high purity powder/crystal, smoking preparations and vape preparations. The top five listed compounds from China across the time points were FUB-AMB, ABD-FUBINACA, 5F-NPB-22, MAB-CHMINACA, and NM-2201. 5F-CUMYL-4CN-PINACA was unavailable at early time points but emerged during the study. Cost of high purity formulations from China ranged from 1.3 to 3.1 Euro per gram for quantities ≥1000 g. Europe and North America accounted for 99% smoking preparations predominantly in small packages (<50 g). SC are widely available on the darknet with availability changing over time. High purity formulations are predominantly available from China in quantities up to kilograms with price per gram reducing with increased quantity. Small packages of ready-made smoking mixtures are available from Europe and North America

Case report: Severe mercuric sulphate poisoning treated with 2,3-dimercaptopropane-1-sulphonate and haemodiafiltration

INTRODUCTION: Inorganic mercury poisoning is uncommon, but when it occurs it can result in severe, life-threatening features and acute renal failure. Previous reports on the use of extracorporeal procedures such as haemodialysis and haemoperfusion have shown no significant removal of mercury. We report here the successful use of the chelating agent 2,3-dimercaptopropane-1-sulphonate (DMPS), together with continuous veno-venous haemodiafiltration (CVVHDF), in a patient with severe inorganic mercury poisoning. CASE REPORT: A 40-year-old man presented with haematemesis after ingestion of 1 g mercuric sulphate and rapidly deteriorated in the emergency department, requiring intubation and ventilation. His initial blood mercury was 15 580 μg/l. At 4.5 hours after ingestion he was started on DMPS. He rapidly developed acute renal failure and so he was started on CVVHDF for renal support and in an attempt to improve mercury clearance; CVVHDF was continued for 14 days. METHODS: Regular ultradialysate and pre- and post-filtrate blood samples were taken and in addition all ultradialysate generated was collected to determine its mercury content. RESULTS: The total amount of mercury in the ultrafiltrate was 127 mg (12.7% of the ingested dose). The sieving coefficient ranged from 0.13 at 30-hours to 0.02 at 210-hours after ingestion. He developed no neurological features and was discharged from hospital on day 50. Five months after discharge from hospital he remained asymptomatic, with normal creatinine clearance. DISCUSSION: We describe a patient with severe inorganic mercury poisoning in whom full recovery occurred with the early use of the chelating agent DMPS and CVVHDF. There was removal of a significant amount of mercury by CVVHDF. CONCLUSION: We feel that CVVHDF should be considered in patients with inorganic mercury poisoning, particularly those who develop acute renal failure, together with meticulous supportive care and adequate doses of chelation therapy with DMPS

Using routine clinical and administrative data to produce a dataset of attendances at Emergency Departments following self-harm

Background: Self-harm is a significant public health concern in the UK. This is reflected in the recent addition to the English Public Health Outcomes Framework of rates of attendance at Emergency Departments (EDs) following self-harm. However there is currently no source of data to measure this outcome. Routinely available data for inpatient admissions following self-harm miss the majority of cases presenting to services. Methods: Using the Clinical Record Interactive Search system, the electronic health records (EHRs) used in four EDs were linked to Hospital Episode Statistics to create a dataset of attendances following self-harm. This dataset was compared with an audit dataset of ED attendances created by manual searching of ED records. The proportion of total cases detected by each dataset was compared. Results: There were 1932 attendances detected by the EHR dataset and 1906 by the audit. The EHR and audit datasets detected 77 and 76 of all attendances respectively and both detected 82 of individual patients. There were no differences in terms of age, sex, ethnicity or marital status between those detected and those missed using the EHR method. Both datasets revealed more than double the number of self-harm incidents than could be identified from inpatient admission records. Conclusions: It was possible to use routinely collected EHR data to create a dataset of attendances at EDs following self-harm. The dataset detected the same proportion of attendances and individuals as the audit dataset, proved more comprehensive than the use of inpatient admission records, and did not show a systematic bias in those cases it missed. © 2015 Polling et al

Pharmacokinetics of Mephedrone Enantiomers in Whole Blood after a Controlled Intranasal Administration to Healthy Human Volunteers

Mephedrone, which is one of the most popular synthetic cathinones, has one chiral centre and thus exists as two enantiomers: R-(+)-mephedrone and S-(&minus;)-mephedrone. There are some preliminary data suggesting that the enantiomers of mephedrone may display enantioselective pharmacokinetics and exhibit different neurological effects. In this study, enantiomers of mephedrone were resolved via chromatographic chiral recognition and the absolute configuration was unambiguously determined by a combination of elution order and chiroptical analysis (i.e., circular dichroism). A chiral liquid chromatography tandem mass spectrometry method was fully validated and was applied to the analysis of whole blood samples collected from a controlled intranasal administration of racemic mephedrone hydrochloride to healthy male volunteers. Both enantiomers showed similar kinetics, however, R-(+)-mephedrone had a greater mean Cmax of 48.5 &plusmn; 11.9 ng/mL and a longer mean half-life of 1.92 &plusmn; 0.27 h compared with 44.6 &plusmn; 11.8 ng/mL and 1.63 &plusmn; 0.23 h for S-(&minus;)-mephedrone, respectively. Moreover, R-(+)-mephedrone had a lower mean clearance and roughly 1.3 times greater mean area under the curve than S-(&minus;)-mephedrone. Significant changes in the enantiomeric ratio over time were observed, which suggest that the analytes exhibit enantioselective pharmacokinetics. Even though the clinical significance of this finding is not yet fully understood, the study confirms that the chiral nature, and consequently the enantiomeric purity of mephedrone, can be a crucial consideration when interpreting toxicological results

Using digital social market applications to incentivise active travel: Empirical analysis of a smart city initiative

Information and communication technologies (ICTs), such as mobile communication networks, and behaviour-based approaches for citizen engagement play a key role in making future cities sustainable and tackling persistent problems in high-density urban areas. In the context of Sharing Cities, an EU-funded programme aiming to deliver smart city solutions in areas such as citizen participation and infrastructure improvements of buildings and mobility, a prominent intervention has been the deployment and monitoring of a Digital Social Market (DSM) tool in Milan (Italy). The DSM allows cities to engage with residents and encourage sustainable behaviours by offering non-monetary rewards. This paper aims to evaluate the effectiveness of the DSM approach to promote active travel (cycling and walking) by analysing the data collected through the app as well as through participant surveys. Our model results show that a broader engagement with the DSM app (number of claps to posts, number of posts made, non-monetary rewards earned by participating in non-travel events) is positively correlated with the monitored level of active travel. Lifestyles, attitudes, and social influence also explain the variability in cycling and walking. This highlights the importance of investigating these factors when replicating such initiatives on a large scale

Erratum to: Psychosis associated with acute recreational drug toxicity: a European case series

Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs.; The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset.; Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations.; The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators

Outbreak of Fatal Childhood Lead Poisoning Related to Artisanal Gold Mining in Northwestern Nigeria, 2010.

Background: In May 2010, a team of national and international organizations was assembled to investigate children's deaths due to lead poisoning in villages in northwestern Nigeria. Objectives: To determine the cause of the childhood lead poisoning outbreak, investigate risk factors for child mortality, and identify children aged <5 years in need of emergency chelation therapy for lead poisoning. Methods: We administered a cross-sectional, door-to-door questionnaire in two affected villages, collected blood from children aged 2-59 months, and soil samples from family compounds. Descriptive and bivariate analyses were performed with survey, blood-lead, and environmental data. Multivariate logistic regression techniques were used to determine risk factors for childhood mortality. Results: We surveyed 119 family compounds. One hundred eighteen of 463 (25%) children aged <5 years had died in the last year. We tested 59% (204/345) of children, aged <5 years, and all were lead poisoned (≥10 µg/dL); 97% (198/204) of children had blood-lead levels ≥45 µg/dL, the threshold for initiating chelation therapy. Gold ore was processed inside two-thirds of the family compounds surveyed. In multivariate modeling significant risk factors for death in the previous year from suspected lead poisoning included: the child's age, the mother performing ore-processing activities, community well as primary water source, and the soil-lead concentration in the compound. Conclusion: The high levels of environmental contamination, percentage of children aged <5 years with elevated blood-lead levels (97%, >45 µg/dL), and incidence of convulsions among children prior to death (82%) suggest that most of the recent childhood deaths in the two surveyed villages were caused by acute lead poisoning from gold ore-processing activities. Control measures included environmental remediation, chelation therapy, public health education, and control of mining activities

Improvement in the pre-hospital care of recreational drug users through the development of club specific ambulance referral guidelines

<p>Abstract</p> <p>Background</p> <p>Previously developed 'club guidelines' developed for club owners and promoters have tended to focus more on the legislative aspects of clubs, rather than the medical management of unwell clubbers within club environments. Despite this lack of guidance on the management of unwell clubbers, a significant proportion of clubs have 'club medic' rooms for managing these individuals. However, due to the lack of specific guidance on the training of staff working in these rooms and guidelines on when an ambulance should be called for an unwell clubber, there have been instances previously where clubbers have been inappropriately managed within the club environment, and often referred to hospital only after significant physiological derangement has occurred, thereby leading to an increased risk of morbidity and mortality.</p> <p>Methods</p> <p>We identified owners and promoters of local club venues within the catchment area of our Emergency Department and working jointly with them and other key stakeholders, in particular the London Ambulance Service and Metropolitan Police, identified strategies to improve pre-hospital care for clubbers who become unwell as a result of recreational drug use. These included developing guidelines detailing indications for ambulance transfer to hospital for clubbers with recreational drug toxicity and the training of club medic staff to use the guidelines</p> <p>Results</p> <p>Following the initial development of a pilot set of guidelines, an audit of their use identified training needed relating to the assessment of unwell clubbers with recreational drug toxicity and revisions required to the pilot version of the guidelines. After training related to the revised guidelines, all the club medic staff were confident in their ability to assess unwell clubbers with recreational drug toxicity, the use of the guidelines and also when to call an ambulance.</p> <p>Conclusion</p> <p>Working with key stakeholders in the local community, we have developed guidelines that can be used to improve the pre-hospital care of clubber unwell with recreational drug toxicity, and demonstrated that individuals with a variety of medical knowledge can be trained to use these guidelines. Wider dissemination of these guidelines, both regionally, nationally and potentially internationally, may help to reduce the pre-hospital morbidity and mortality associated with recreational drug toxicity encountered in club environments.</p

Impact of sequence variation in the ul128 locus on production of human cytomegalovirus in fibroblast and epithelial cells

The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, and endothelial cells but limits replication in fibroblasts. Consequently, disrupting mutations in UL128L are rapidly selected when clinical isolates are cultured in fibroblasts. In contrast, bacterial artificial chromosome (BAC)-cloned strains TB40-BAC4, FIX, and TR do not contain overt disruptions in UL128L, yet no virus reconstituted from them has been reported to acquire mutations in UL128L in vitro. We performed BAC mutagenesis and reconstitution experiments to test the hypothesis that these strains contain subtle mutations in UL128L that were acquired during passage prior to BAC cloning. Compared to strain Merlin containing wild-type UL128L, all three strains produced higher yields of cell-free virus. Moreover, TB40-BAC4 and FIX spread cell to cell more rapidly than wild-type Merlin in fibroblasts but more slowly in epithelial cells. The differential growth properties of TB40-BAC4 and FIX (but not TR) were mapped to single-nucleotide substitutions in UL128L. The substitution in TB40-BAC4 reduced the splicing efficiency of UL128, and that in FIX resulted in an amino acid substitution in UL130. Introduction of these substitutions into Merlin dramatically increased yields of cell-free virus and increased cell-to-cell spread in fibroblasts but reduced the abundance of pUL128 in the virion and the efficiency of epithelial cell infection. These substitutions appear to represent mutations in UL128L that permit virus to be propagated in fibroblasts while retaining epithelial cell tropism