The Emerging Cloud: a survey of vapers, their health and utilization of healthcare within the UK.

BACKGROUND: Recent work in the UK estimated the prevalence of current cannabinoid-based vaping to be higher than in the USA, a factor previously associated with e-cigarette or vaping-associated lung injury (EVALI). Research in the USA has demonstrated that attendances to emergency departments relating to e-cigarettes began to rise before the EVALI outbreak, suggesting that vapers also experience milder forms of vaping-related illness. AIM: Quantify symptom prevalence and healthcare utilization amongst current UK vapers. DESIGN: Voluntary online survey of individuals aged 16 and over within the UK. METHODS: Anonymized data were collected on demographics, vaping/smoking status and vaping substances used. Current vapers were asked about the presence of 10 prevalent symptoms from previous US EVALI case series, healthcare attendances and diagnoses given. Risk-ratios were calculated to compare the likelihood of symptoms and attendances between substances. RESULTS: A total of 2477 complete responses were analysed. In all, 397 respondents were current vapers. Symptom prevalence within the previous 12 months ranged from 3.8% to 30.5% (bloody sputum, cough). Healthcare attendances per symptomatic respondent ranged from 0.1 to 1.4 (bloody sputum, shortness of breath). Current vapers of cannabinoid-based products (alone/in combination) had the most attendances per symptomatic respondent for 9/10 symptoms and were more likely to report symptoms aside from 'cough' (nicotine-free e-liquids [risk ratio = 1.7]). Clinicians reportedly never diagnosed vaping-related illness. CONCLUSIONS: UK vapers experience symptoms previously reported in EVALI cases for which they also seek healthcare. Users of cannabinoid-based products were more likely to report symptoms and accounted for a higher healthcare burden. UK vapers may also experience vaping-related illness that does not meet EVALI case criteria.

Isotonitazene, a novel psychoactive substance opioid, detected in two cases following a local surge in opioid overdoses.

BACKGROUND: Isotonitazene is a novel opioid that was first reported in Europe in 2019. There have been no reports of the detection of isotonitazene in patients presenting to the emergency department with acute drug toxicity. AIM: There was an increase in presentations to our emergency department with acute opioid toxicity in August 2021. We aim to describe this outbreak and provide detail on two cases in which isotonitazene was quantified in serum samples. METHODS: Serum samples were available for comprehensive toxicological analysis for two presentations. Written consent was obtained and the samples were analysed through a Thermo XRS ultrahigh-performance liquid chromatography system, interfaced to a Thermo Q Exactive high-resolution accurate mass spectrometer, operating in heated positive ion electrospray mode. Acquired data were processed using Toxfinder software (Thermo) against a regularly updated in-house database. RESULTS: There was an increase in acute opioid presentations to our emergency department from a median of 10 per month to 36 in August 2021. Twenty were treated with naloxone, and 23 were admitted to the hospital for observation and treatment. Serum sample analysis from two patients with acute opioid toxicity responsive to naloxone detected the presence of isotonitazene (0.18 and 0.81 ng/ml). CONCLUSION: We report a cluster of acute opioid toxicity presentations to our Emergency Department with detection of isotonitazene in two cases. Analytical screening is important in determining the presence of novel psychoactive substances (NPS) and to help inform the public health of the implications of NPS use, particularly during clusters of acute recreational drug toxicity presentations.

The unseen cloud: a survey of vaping practices and the acquisition of vaping products within the UK.

BACKGROUND: Vaping of cannabinoid-based products and informal acquisition of vaping products were associated with the outbreak of E-cigarette or vaping associated lung injury (EVALI) in the USA. Current prevalence of cannabinoid-based vaping within the UK is not known and literature regarding the acquisition of vaping products is limited. AIM: To estimate the prevalence of nicotine-based, nicotine-free and cannabinoid-based product vaping within the UK and to determine where vaping products are acquired. DESIGN AND METHODS: A voluntary online survey of individuals aged 16 and over within the UK was conducted using a convenience sample. Data were collected on respondent demographics, smoking/vaping history and acquisition of e-liquids/products. RESULTS: A total of 2478 responses were included. Median age 45 years (interquartile range 35-57). Prevalence of current vaping of nicotine-based e-liquids, nicotine-free e-liquids and cannabinoid-based products was 14.4%, 11.2% and 5.49%, respectively. Current nicotine-based and nicotine-free vaping was most prevalent in 25-34 years olds (22.4% and 19.2% of respondents). Current cannabinoid-based vaping was most prevalent in 16-24 years olds. The most common 'ever' used cannabinoid-based products were cannabidiol oil/cannabigerol oil and cannabis leaves (4.8%). Specialist vaping stores were the most common source of 'ever' acquisition for all products. 36.8% and 40.5% of respondents who had ever vaped nicotine-based and nicotine-free e-liquids reported prior acquisition from informal sources. CONCLUSION: This survey reported a higher prevalence of current cannabinoid-based vaping within the UK (5.5%) than previously reported in the USA (2.0%). In addition to the informal acquisition of vaping products as demonstrated within the survey, these results highlight potential underestimation of the risk of EVALI within the UK.

Non-medical use of loperamide in the UK and the USA.

BACKGROUND: Loperamide is a mu-opioid receptor agonist that is available as an over-the-counter anti-motility agent in the US and UK; recommended maximum doses of 12-16 mg/day. Anecdotal reports of non-medical use (NMU) have increased over the past decade with supra-therapeutic doses (70-800 mg/day) associated with cardiotoxicity. Little data exists on the prevalence of loperamide NMU. AIM: The aim of this study was to determine the prevalence of loperamide NMU in the UK and US and to describe characteristics of non-medical loperamide users. DESIGN: The Researched, Abuse, Diversion and Addiction Related Surveillance (RADARS® ) Survey of Nonmedical Use of Prescription Drugs (NMURx) was utilized to study NMU of loperamide among the adult population in the UK and US in 2017. The RADARS® NMURx is anonymous and self-administered online. METHODS: A total of 40,029 completed surveys were included (10,019 from the UK and 30,010 from the US). Respondents were asked questions about medical and NMU of loperamide, frequency of and reasons for NMU, route of use problematic drug use markers, and demographics. RESULTS: Prevalence of lifetime loperamide use (95% CI) and lifetime NMU of loperamide were: UK 28.5% (27.67-29.4), and 0.66% (0.5-0.8), respectively; US 33.7% (33.1-34.2), and 5.19% (4.9-5.5), respectively. Problematic drug use markers were elevated in those who reported NMU of loperamide in both the UK and US, however high-risk use was more prevalent in the UK than in the US. CONCLUSION: NMU of loperamide is common. In the current international environment of opioid addiction involving both therapeutic and illicit opioids, awareness of the NMU of loperamide is important.

Presentations to the emergency department with non-medical use of benzodiazepines and Z-drugs: profiling and relation to sales data.

BACKGROUND: Non-medical use of benzodiazepines and Z-drugs is common; however, there is limited information available on the extent of harm related to this in Europe, as well as the relationship between misuse and availability. AIM: To describe presentations to the emergency department in Europe related to the recreational use of benzodiazepines and Z-drugs and compare regional differences in these presentations with legal drug sales of benzodiazepines and Z-drugs within each country. METHODS: Emergency department presentations with recreational misuse of benzodiazepines and Z-drugs were obtained from the Euro-DEN dataset for the period from October 2013 to September 2015; data extracted included demographics, clinical features, reported coused drugs, and outcome data. Sales figures obtained by QuintilesIMS™ (Atlanta, Georgia) were used to compare regional differences in the proportion of benzodiazepines and Z-drugs in the emergency department presentations and legal drug sales across Europe. RESULTS: Over the 2 years, there were 2119 presentations to the Euro-DEN project associated with recreational use of benzodiazepines and/or Z-drugs (19.3% of all Euro-DEN presentations). Presentations with 25 different benzodiazepines and Z-drugs were registered in all countries, most (1809/2340 registered benzodiazepines and Z-drugs, 77.3%) of which were prescription drugs. In 24.9%, the benzodiazepine was not specified. Where the benzodiazepine/Z-drug was known, the most frequently used benzodiazepines and Z-drugs were respectively clonazepam (29.5% of presentations), diazepam (19.9%), alprazolam (11.7%), and zopiclone (9.4%). The proportions of types of benzodiazepines/Z-drugs related to ED-presentations varied between countries. There was a moderate (Spain, UK, Switzerland) to high (France, Ireland, Norway) positive correlation between ED presentations and sales data (Spearman Row's correlation 0.66-0.80, p < 0.005), with higher correlation in countries with higher ED presentation rates. CONCLUSION: Presentations to the emergency department associated with the non-medical use of benzodiazepines and/or Z-drugs are common, with variation in the benzodiazepines and/or Z-drugs between countries. There was a moderate to high correlation with sales data, with higher correlation in countries with higher ED presentation rates. However, this is not the only explanation for the variation in non-medical use and in the harm associated with the non-medical use of benzodiazepines/Z-drugs.

Concurrent Use of Benzodiazepine by Heroin Users-What Are the Prevalence and the Risks Associated with This Pattern of Use?

INTRODUCTION: Polydrug use involving heroin and benzodiazepines is common. The potential risk of additive pharmacological effects may be associated with poorer outcomes in patients who use benzodiazepines together with heroin. The aim of this study was to determine the clinical picture of patients presenting to the emergency department following acute drug toxicity involving heroin and benzodiazepines. METHODS: Exposure information, clinical data and outcome of acute drug toxicity presentations were collected between 1 October 2013 and 30 September 2014 as part of the European Drug Emergencies Network (Euro-DEN) project. The database was interrogated to identify patients who had taken heroin with or without benzodiazepine(s). RESULTS: A total of 1345 presentations involving acute heroin toxicity were identified: 492 had used one or more non-heroin/benzodiazepine drug and were not further considered in this study; 662 were lone heroin users and 191 had co-used heroin with one or more benzodiazepines. Co-users were more likely than lone heroin users to have reduced respiratory rate at presentation 12.7 ± 4.9 vs 13.6 ± 4.4 (p = 0.02) and require admission to hospital 18.3 vs 9.8% (p < 0.01). There were no differences in critical care admission rates 3.1 vs 3.9% (p = 0.83) or length of stay 4 h 59 min vs 5 h 32 min (p = 0.23). The 3 most common benzodiazepines were clonazepam, diazepam, and alprazolam. No differences were observed for clinical features between the three benzodiazepines. CONCLUSION: This study shows that co-use of heroin and benzodiazepines is common, although the overall outcomes between co-users of heroin and benzodiazepines and heroin-only users were similar.

Epidemiology of adolescent substance use in Norfolk schools.

BACKGROUND: The pattern of alcohol and substance use is changing, with the introduction of novel psychoactive substances, the internet as a means of acquisition and variations in drug purity and price. Alcohol and substance use among adolescents is associated with behavioural, mental health, health and social difficulties; arising at a vulnerable period in their development. Little is known about adolescent substance use in the UK, especially in rural areas. AIM: To investigate the prevalence of substance use amongst young people, aged 16-21 years, in Norfolk schools. DESIGN: Cross sectional questionnaire survey. METHOD: Pupils from two, sixth form colleges in Norfolk answered a self-report questionnaire designed to measure prevalence, age of onset and frequency of use for alcohol, tobacco, illicit substances including new psychoactive substances as well as demographic data. RESULTS: A total of 482 students completed the survey (68% participation rate). Life-time use of alcohol was reported by 442 (91.7%) students and over half the pupils had tried tobacco (52.5%, n=253). About 40.7% reported cannabis use and nearly one-fifth (18.9%, n=91) reported using 3,4-methylenedioxymethamphetamine (MDMA); 41.1% (n=198) students reported using 'any drug' and 23.2% (n=112) 'using an illicit drug other than cannabis' and 8.7% (n=42) reported the use of a novel psychoactive substance. CONCLUSION: The most widely used substances were alcohol, tobaccos and cannabis; in keeping with European trends. Over the past decade a decline in alcohol and drug use by adolescents has been seen in the UK. However, since 2010 this decline has slowed with an increase in substance use noted in the past 2 years. This study provides evidence to support this trend. The findings demonstrate differences between the use of substances by pupils in this Norfolk sample compared to national surveys and more urbanized areas. These regional differences can be used to assist the development of local interventions targeting substance use among adolescents.

The dark cloud of recreational drugs and vaping.

Electronic cigarettes (e-cigarettes) are increasing in popularity with 19% of UK smokers reporting to have used them. The ability to regulate the evaporation temperature in newer electronic nicotine delivery systems (ENDS) facilitates the potential for use of these devices to 'vape' cannabis, novel psychoactive substances (NPS) and other recreational drugs. Vaping cannabis does have the potential to reduce tobacco use and combustible cannabis/tobacco-related disease, but with over one-third of UK adults reporting life-time use of recreational drugs and increasing e-cigarette uptake in adolescent groups the misuse of these devices poses a serious potential public health risk. Further work is therefore urgently required to inform the appropriate treatment and primary prevention strategies for this emerging issue.

The impact of the Psychoactive Substances Act 2016 on the online availability of MDMB-CHMICA.

BACKGROUND: In May 2016, the UK Government enacted the Psychoactive Substances Act which made it an offense to produce or supply many drugs including new psychoactive substances (NPS). AIM: We aimed to assess the impact of the Act on the availability of the synthetic cannabinoid receptor agonist methyl 2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate (MDMB-CHMICA) from internet-based suppliers. DESIGN: Internet snapshot availability study. METHODS: We conducted two snapshot availability surveys looking at the number of websites offering to sell MDMB-CHMICA: the first in March prior to implementation of the Act and the second in June, 1 month post-implementation. RESULTS: In March and June 2016, we identified 47 and 38 websites, respectively, which offered to sell MDMB-CHMICA. There were no significant differences in the price of the drug nor the forms available for purchase. In the June survey there was a significant decrease in the number of websites which openly stated they were based in the UK (from 14 down to 2), three websites stated that they did not supply customers based in the UK and two websites stated they had ceased sales of MDMB-CHMICA due to the Act. CONCLUSIONS: This study showed a small but limited reduction in the availability of MDMB-CHMICA from internet-based suppliers following implementation of the Act.

Circulating acetaminophen metabolites are toxicokinetic biomarkers of acute liver injury.

Acetaminophen (paracetamol-APAP) is the most common cause of drug-induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP-metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analyzed from discovery (n = 116) and validation (n = 150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP-metabolites than those without ALI. Receiver operator curve (ROC) analysis demonstrated that at hospital presentation CYP-metabolites were more sensitive/specific for ALI than alanine aminotransferase (ALT) activity and APAP concentration (optimal CYP-metabolite receiver operating characteristic area under the curve (ROC-AUC): 0.91 (95% confidence interval (CI) 0.83-0.98); ALT ROC-AUC: 0.67 (0.50-0.84); APAP ROC-AUC: 0.50 (0.33-0.67)). This enhanced sensitivity/specificity was replicated in the validation cohort. Circulating CYP-metabolites stratify patients by risk of liver injury prior to starting NAC. With development, APAP metabolites have potential utility in stratified trials and for refinement of clinical decision-making.

Healthcare professionals are less confident in managing acute toxicity related to the use of new psychoactive substances (NPS) compared with classical recreational drugs.

BACKGROUND: The features of acute classical recreational drugs or new psychoactive substances (NPS) toxicity fall into three broad groups: (i) stimulant; (ii) hallucinogenic and (iii) depressant. Currently, there is no information available on healthcare professionals knowledge/confidence in managing the acute toxicity related to NPS use. AIM: We have compared knowledge and confidence of managing acute toxicity related to use of NPS with that seen with the use of to classical recreational drugs. DESIGN AND METHODS: Physicians/nurses completed a questionnaire survey to self-assess on a 5-point scale their knowledge (1-little knowledge; 5-very knowledgeable) and confidence (1-little confidence; 5-very confident) of managing acute toxicity related to the use of classical recreational drugs or NPS. Differences between knowledge and confidence for classical recreational drugs and NPS were assessed using paired Student's t-test; comparison between doctors, nurses and the frequency of managing acute classical recreational drug/NPS toxicity was assessed using unpaired Student's t-test. RESULTS: One hundred and eighty-eight (82 physicians, 106 nurses) completed the survey. Classical drug compared with NPS knowledge: nurses 2.9 ± 1.0 vs. 2.1 ± 1.0, P < 0.001; physicians 3.1 ± 0.8 vs. 2.1 ± 1.0, P < 0.001. There was no difference between nurses and physicians in classical drug (P = 0.11) or NPS (P = 0.89) knowledge. Confidence in managing classical drug toxicity compared with NPS confidence: nurses 3.0 ± 1.1 vs. 2.3 ± 1.1, P < 0.001; physicians 3.0 ± 0.9 vs. 2.1 ± 1.0, P < 0.001. There was no difference between nurses and physicians in classical drugs (P = 0.85) or NPS (P = 0.33) confidence. CONCLUSIONS: Physicians/nurses are less confident in managing acute NPS toxicity. Management of toxicity is not dependent on knowing the drug/NPS, but should be on the basis of these clinical signs/symptoms. Training/education should focus on the concept of managing the pattern of toxicity that an individual presents with rather than the actual drug(s).

Epidemiology of adolescent substance use in London schools.

BACKGROUND: Alcohol and substance use in adolescence can be associated with a range of health, emotional, social, behavioural and legal problems. There has been a change in the recreational drugs available to users in recent years; however, little is known about how this impacts the youngest and most vulnerable population of substance users. AIM: To investigate the prevalence of substance use among children aged 15-18 years in London schools. DESIGN: Questionnaire survey. METHOD: Students aged 15-18 years in three London schools self-completed the questionnaire which collected demographic data (age, gender and ethnicity) and data on frequency of use of alcohol, tobacco and classical recreational drugs and novel psychoactive substances. RESULTS: Completed surveys were available from 533 students (47.8% of those invited to participate). One hundred thirteen (20.4%) students reported lifetime use of at least one recreational drug, cannabis (96, 18.7%) was commonly reported and only 6 (1.1%) reported use of a novel psychoactive substance. A total of 250 (47.8%) reported using alcohol at least once; those from White and Mixed ethnic groups were more likely to report using alcohol than those in other ethnic groups. A total of 382 (74.2%) students reported using tobacco at least once, and students from ethnic minorities were more likely to smoke than their White counterparts. CONCLUSION: This study supports previous findings that alcohol and drug use are declining in adolescents in UK. There are different patterns of substance use amongst different ethnic groups; this is important to schools and policymakers planning interventions related to substance use in school-aged children.

Taking stock: UK national antidote availability increasing, but further improvements are required.

BACKGROUND: A 2010/2011 audit of the Royal College of Emergency Medicine (RCEM) National Poisons Information Service (NPIS) UK guidelines on antidote availability demonstrated variable stocking of antidotes for the management of poisoned patients; the guidelines were updated and republished in 2013. AIM: To assess if antidote stocking has improved since the 2010/2011 audit and introduction of the 2013 guidelines. METHODS: Questionnaires were sent to Chief Pharmacists at all 215 acute hospitals in England, Wales and Northern Ireland in October 2014. Data were collected on the timing of availability (category A antidotes should be available immediately, category B within 1 h and category C can be held supraregionally) and stock levels. RESULTS: 169 (78.6%) responses were received. Atropine, calcium gluconate and flumazenil (category A) were the only antidotes available in all hospitals within the recommended time and stock levels. Forty-one (24.3%) hospitals held every category A antidote; this increased to 81 (47.9%) for those holding at least one cyanide antidote and all other category A antidotes. The proportion of hospitals stocking category A/B antidotes within the recommended time increased for 20 (90.9%) category A/B antidotes. Fomepizole (category B) availability increased to 62.1% of hospitals from 11.4% in 2010/2011. Other than penicillamine (63.3% hospitals), there was poor availability (2.4%-36.1%) of category C antidotes. CONCLUSIONS: Availability of category A and B antidotes has improved since the 2010/2011 audit and 2013 guidelines. However, there remains significant variability particularly for category C antidotes. More work is required to ensure that those treating poisoned patients have timely access to antidotes focusing particularly on category C antidotes.

Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury.

Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.

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. We aimed to investigate (i) if a dataset of ED presentations could be produced using a combination of routinely collected clinical and administrative data and (ii) to validate this dataset against another one produced using methods similar to those used in previous studies. 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.

Analysis of anonymized pooled urine in nine UK cities: variation in classical recreational drug, novel psychoactive substance and anabolic steroid use.

BACKGROUND: Analysis of anonymous pooled urine samples from street urinals has been used to demonstrate time-trends in the detection of classical recreational drugs and novel psychoactive substances (NPS). AIM: This study aimed to expand this to undertake a geographical trend analysis of classical recreational drugs/NPS across UK. METHODS: Samples of anonymous pooled urine were collected from street urinals that had been in place for one night in April 2014 in nine cities across the UK. Collected samples were then analysed for the presence of recreational drugs, NPS anabolic steroids using high-performance liquid chromatography coupled to high-resolution accurate mass full-scan mass spectrometry and gas chromatography coupled to electron impact ionization mass spectrometry operating in selected ion monitoring and full-scan modes. RESULTS: Ten classical recreational drugs, nine NPS and four anabolic steroids were detected across the nine cities; the range of detection was from 1 in Leeds to 14 in London. The most common classical drugs were cocaine (9 cities) and 3,4-methylenedioxy-methamphetamine (8 cities); the most common NPS was 4-methylmethcathinone (5 cities). In addition there was variation in the detection of NPS, with methylhexaneamine detected only in Bristol and London, piperazines (3-trifluoromethylphenylpiperazine and 1-benzylpiperazine) and pentedrone only detected in Birmingham and the cathinone methylone only detected in London. CONCLUSIONS: There is variability in the detection of classical recreational drugs, NPS and anabolic steroids across UK, likely reflecting variation in their use. This technique can be used to supplement drug use surveys to determine geographical and time trends in the use of these substances. This is important to ensure appropriate targeting of drug-related interventions.

Reported ingested dose of paracetamol as a predictor of risk following paracetamol overdose.

PURPOSE: To evaluate reported ingested dose of paracetamol as a risk assessment tool in acute paracetamol overdose. METHODS: Data was retrospectively obtained from a clinical toxicology database linked to one Australian and two United Kingdom hospitals. Plasma paracetamol concentrations (PPCs) of adult patients presenting with acute single ingestion, non-staggered paracetamol deliberate self-poisoning between 2006 and 2012 were recorded and plotted on a treatment nomogram to determine accuracy of reported dose ingested as an indicator for antidotal treatment. PPC plotted on a treatment nomogram with a line intersecting a 4-h concentration of 100 mg/L [667 µmol/L] was considered an indication for antidotal treatment in the UK; the corresponding Australasian population utilised a line intersecting 150 mg/L [1000 µmol/L]. RESULTS: Of 1246 patients, 65.7 % were female and 88 % were from the UK. Fifty-two percent of patients reporting ingestion of ≥8 g paracetamol had a PPC above the 100 mg/L treatment line; PPV 52 % [95 % confidence interval (CI) 49 %, 55 %], sensitivity 81 % [95 %CI 78 %, 85 %]. Forty-four of patients reporting percent ingestion of ≥10 g had a PPC above the 150 mg/L treatment line; PPV 44 % [95 % CI 41 %, 49 %], sensitivity 85 % [95 % CI 78 %, 89 %], 72 % of patients reporting ingestion of ≥16 g had a PPC above the 100 mg/L treatment line; PPV 72 % [95% CI 67 %, 77 %], sensitivity 50 % [95 % CI 45 %, 54 %]. Overall, there was moderate correlation (R = 0.58) between reported paracetamol dose ingested and extrapolated 4-h PPC. CONCLUSIONS: There is a positive correlation between reported ingested dose of paracetamol and subsequent chance of a PPC being above a defined treatment line; however, ingested dose of paracetamol alone is a poor risk assessment tool in accurately determining need for treatment with an antidote.

Should computerised tomography replace endoscopy in the evaluation of symptomatic ingestion of corrosive substances?

INTRODUCTION: Corrosive ingestions are common, although most ingestions do not result in clinically significant effects. Limited guidance is available on the role of endoscopy and/or computerised tomography (CT) in the investigation of individuals with corrosive ingestion, and the present data regarding predictors of poor outcome are confusing. Furthermore, whilst there are many case series describing the use of endoscopy in corrosive ingestions, no clear ideal time frame has been established as to when it should be undertaken. More recently, CT has been used to grade injuries, but there are few studies on its role in managing corrosive injuries, and those studies that have been reported are conflicting in their results. METHODS: A Medline search was performed with the terms 'Caustic ingestion' and 'Corrosive ingestion' and a second search by adding the words 'Endoscopy', 'CT', and 'Computerised tomography' as a subject term or keyword. These searches revealed a total of 277 reviews and papers, of which 33 original papers were relevant for analysis. Three further papers were identified during the analysis of these papers and a PubMed search of the same terms added one further paper, bringing the total to 37. There have been no prospective, randomised controlled trials directly comparing endoscopy and CT. Only two retrospective studies compared the use of CT and that of endoscopy. Thirty-five studies examined whether an endoscopy is always needed, and if so, within what time frame this should be done: CT or endoscopy? A review of these studies suggests that the data regarding the use of CT in these circumstances are not yet of sufficient weight to replace endoscopy as the first-line investigation in corrosive ingestion-related injury. Who needs investigation after corrosive ingestion? We believe that signs and symptoms indicate the likelihood of clinically significant injury in adults. Specifically, any evidence of oropharyngeal burns, drooling, vomiting, pain or dysphagia clearly indicates the need for an endoscopy. In children, it appears that an even greater degree of caution is needed. How soon after ingestion should investigation be performed? For whom an endoscopy is required, it is prudent to enable surgery and other specifics regarding management of corrosives to be decided quickly (< 12 h). There are many incidences where endoscopy has been done safely beyond 48 h although this is not needed frequently. Management recommendations Asymptomatic patients, particularly adults with a normal clinical examination and who can eat and drink normally, can be discharged safely without endoscopy. Endoscopy is preferred over CT in the assessment of risk in symptomatic patients with corrosive ingestion. If patients have any oropharyngeal injury and in particular symptoms of drooling, vomiting, dysphagia or pain (retrosternal or otherwise), the risk of having a high-grade injury is higher, and urgent endoscopy should be performed to grade the injury and determine whether surgical intervention is required. Patients who have non-specific symptoms, such as cough, should also undergo endoscopy, but this is less urgent. CONCLUSIONS: Despite the lack of high-quality clinical trial data, the available evidence and clinical experience support the use of early endoscopy (< 12 h) in patients who are symptomatic after ingestion of a corrosive substance. We propose a clinical guideline that can be used to help plan management of corrosives.

Impact of reducing the threshold for acetylcysteine treatment in acute paracetamol poisoning: the recent United Kingdom experience.

BACKGROUND: On 3 September 2012, the licensed indication for acetylcysteine was changed in the United Kingdom (UK) so that all patients with a plasma paracetamol concentration above a "100 mg/L" (4 h post ingestion) nomogram treatment line after an acute paracetamol (acetaminophen) overdose should be treated. This is a lower threshold than that used in the United States, Canada, Australia, and New Zealand. Here we report the impact of this change in the UK on the management of patients with acute overdose in different paracetamol concentration ranges. METHODS: This is a cohort study, consisting of a retrospective analysis conducted on prospectively collected audit data in three UK hospitals. Following appropriate ethical and data protection authority approval, data for patients presenting within 24 h of an acute timed single paracetamol overdose were extracted. Numbers of admissions and use of antidote in relation to different paracetamol concentration bands (< 100 mg/L; 100-149 mg/L; 150-199 mg/L; and ≥ 200 mg/L at 4 h) were analyzed for one-year periods before and after the change. RESULTS: Comparing the year before with the year after the change, there was no change in the numbers of patients presenting to hospital within 24 h of acute timed paracetamol overdose (1246 before and 1251 after), but more patients were admitted (759 before and 849 after) and treated with acetylcysteine (389 before and 539 after). Of the 150 additional patients treated with acetylcysteine in the year following the change, 114 (76%, 95% CI: 68.4-82.6) were in the 100-149 group and 9 (6.0%, 95% CI: 2.8-11.1) in the 150-199 group. CONCLUSIONS: Changes to national guidelines for managing paracetamol poisoning in the UK have increased the numbers of patients with acute overdose treated with acetylcysteine, with most additional treatments occurring in patients in the 100-149 mg/L dose range, a group at low risk of hepatotoxicity and higher risk of adverse reactions.

An Internet snapshot study to compare the international availability of the novel psychoactive substance methiopropamine.

CONTEXT: With the increased use of novel psychoactive substances, there is an increasing availability of these substances from Internet-based suppliers. Methiopropamine, first reported in 2011, is a recreational drug available over the Internet. The aim of this study was to investigate availability and cost of methiopropamine in three different countries: the UK, France, and Canada. METHODS: Using the European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, this study, conducted in June 2013, was undertaken in two different languages: in English (the UK and Canada) and in French (France and Canada), using three Internet searching engines: " google.co.uk ", " google.fr " and " google.ca ". RESULTS: A total of 62 sites were found, most of them were found from the English searches. 45% of the suppliers seemed to originate from the UK. The prices of methiopropamine were comparable between suppliers, no matter which search engine or language was used. The cost of a unit of methiopropamine was inversely related to the purchased quantity, going from 19.49 ± 0.15 GBP per gram for a purchase amount of 500 mg to 3.54 ± 0.13 GBP per gram for a purchase amount of 1 kg. DISCUSSION: The results of the present study demonstrate that the sale of methiopropamine has the potential to reach users across the world. It also appears to support that snapshot studies could be used for toxicovigilance across different countries, by studying the Internet market of novel psychoactive substances. CONCLUSION: To date, snapshot studies, used to monitor the Internet novel psychoactive substances market, have only been undertaken in Europe. We have shown that the flexibility of this methodology enables comparison of the online activity of drug sellers between different countries and continents and that, at least for methiopropamine, the UK is the predominant source for Internet supply.